Effect of Indian herbal hypoglycemic agents on antioxidant capacity and trace elements content in diabetic rats.

PubMed

Chandra, Anu; Mahdi, Abbas Ali; Singh, Raj Kumar; Mahdi, Farzana; Chander, Ramesh

2008-09-01

In the present investigation we report the protective potential of some herbal hypoglycemic agents on antioxidant status and levels of metal ions in streptozotocin-induced diabetic rats. Furthermore, in vitro antioxidant activity of the herbs was also evaluated. Induction of diabetes mellitus in rats caused an increase in blood lipid peroxide levels that was associated with the reduced activity of red blood cell (RBC) antioxidant enzymes--namely, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase--along with depletion of plasma reduced glutathione (GSH) and copper, zinc, iron, magnesium, and selenium levels. Oral treatment of diabetic rats with Allium sativum, Azadirachta indica, Momordica charantia, and Ocimum sanctum extracts (500 mg/kg of body weight) not only lowered the blood glucose level but also inhibited the formation of lipid peroxides, reactivated the antioxidant enzymes, and restored levels of GSH and metals in the above-mentioned model. The herbal extracts (50-500 microg) inhibited the generation of superoxide anions (O(2)(-.)) in both enzymatic and nonenzymatic in vitro systems. These preparations also inhibited the ferrous-sodium ascorbate-induced formation of lipid peroxides in RBCs. The in vivo and in vitro protective effects of the above-mentioned herbal drugs were also compared with that of glibenclamide. On the basis of our results, we conclude that the above-mentioned herbal plants not only possess hypoglycemic properties, but they also decrease oxidative load in diabetes mellitus. Therefore, we propose that long-term use of such agents might help in the prevention of diabetes-associated complications. However, the extrapolation of these results to humans needs further in-depth study.

Hipoglicemiantes Orais Para Diabetes Mellitus Tipo 2: Comparação de Preços no Brasil e em Outros Sistemas Universais de Saúde.

PubMed

de Oliveira, Gustavo L A; Izidoro, Jans B; Ferré, Felipe; E Sousa, Samuel R A; Acurcio, Francisco A

2018-06-20

To estimate the average price of oral hypoglycemic agents provided by the Brazilian health system (SUS) and to compare them to other public health systems. Cross-sectional study about drug prices purchased by Belo Horizonte (municipal level), Minas Gerais (state level) and federal institutions in January and February of 2014. Average prices were calculated by defined daily dosage (DDD) and were compared to the management levels and the program "Aqui Tem Farmácia Popular" (ATFP). For international comparison, reimbursement values from Spain, Portugal, the United Kingdom and Canada (Province of Quebec) were used. Belo Horizonte had higher average prices than Minas Gerais. In general, essential oral hypoglycemic agents purchased by the SUS had lower prices than ATFP. For example, glibenclamide 5 mg was 1.023% more expensive. Metformin purchased by ATFP was more expensive than by SUS. Eight drugs purchased by SUS had average values above the respective Brazilian price ceiling. As an international comparison, SUS had lower average prices for glibenclamide and metformin. In ATFP, metformin was more expensive than in other countries, while glibenclamide was cheaper than Portugal only. The municipal management level had higher average prices than state level. Oral hypoglycemic agents purchased by SUS are predominantly cheaper than ATFP. Average prices paid by SUS are lower, while the prices paid by ATFP are higher than the reimbursed amounts from other countries. Copyright © 2018. Published by Elsevier Inc.

Nanotechnology based approaches for anti-diabetic drugs delivery.

PubMed

Kesharwani, Prashant; Gorain, Bapi; Low, Siew Yeng; Tan, Siew Ann; Ling, Emily Chai Siaw; Lim, Yin Khai; Chin, Chuan Ming; Lee, Pei Yee; Lee, Chun Mey; Ooi, Chun Haw; Choudhury, Hira; Pandey, Manisha

2018-02-01

Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypoglycemic potency of novel trivalent chromium in hyperglycemic insulin-deficient rats.

PubMed

Machaliński, Bogusław; Walczak, Mieczysław; Syrenicz, Anhelli; Machalińska, Anna; Grymuła, Katarzyna; Stecewicz, Iwona; Wiszniewska, Barbara; Dabkowska, Elzbieta

2006-01-01

Two sources of chromium III, "chromium 454" and "chromium picolinate," were tested in insulin-deficient Streptozocin-treated diabetic rats. This model was selected in order to evaluate the possibility of any hypoglycemic potency of chromium in a relative absence of blood insulin concentration. Three weeks of the treatment with CRC454 and CrP resulted in a 38% and 11% reduction of blood glucose levels, respectively. Body weight gains were equally improved by both treatments. Blood levels of CK, ALT and AST were significantly reduced by CRC454 and CrP. These results might suggest that any hypoglycemic effect of trivalent chromium under insulin-deficient conditions could be largely dependent upon the type of chromium agent and associated characteristics such as solubility and bioavalibility. In contrast, improvement of body weight gains and blood levels of CK, AST and ALT seems to be less dependent on the type of chromium compound under these experimental conditions. In conclusion, CRC454 showed significant reduction of hyperglycemia under insulin-deficient conditions.

[An evaluation of a continuing medical education program for primary care services in the prescription of hypoglycemic agents in diabetes mellitus type 2].

PubMed

Castro-Ríos, Angélica; Reyes-Morales, Hortensia; Pérez-Cuevas, Ricardo

2008-01-01

To evaluate the impact of a continuing medical education program on family doctors to improve prescription of hypoglycemic drugs. An observational study was conducted with two groups of comparison (with-without program) and before-after periods. The unit of analysis was the visit. The period of evaluation comprised six months before and six after implementing the program. The outcome variable was the appropriateness of prescription that was based upon two criteria: appropriate selection and proper indication of the drug. Logistic regression models and the double differences technique were used to analyze the information. Models were adjusted by independent variables related with the patient, the visit and the PCC, the more relevant ones were: sex, obesity, conditions other than diabetes, number of visits in the analyzed period, number of drugs prescribed, size of the PCC and period. the program increases 0.6% the probability of appropriate prescription and 11% the probability of appropriate choice of the hypoglycemic drug in obese patients.

Elements of the Veterans Health Administration Patient-Centered Medical Home are Associated with Greater Adherence to Oral Hypoglycemic Agents in Patients with Diabetes.

PubMed

Meo, Nicholas; Wong, Edwin; Sun, Haili; Curtis, Idamay; Batten, Adam; Fihn, Stephan D; Nelson, Karin

2018-04-01

In 2010, Veterans Health Administration (VHA) primary care clinics adopted a patient-centered medical home (PCMH) model. This study sought to examine the association between the organizational features related to adoption of PCMH and the level of adherence to oral hypoglycemic agents (OHAs) among patients with diabetes. This retrospective cohort study involved 757 VA clinics that provide primary care to 440,971 patients with diabetes who were taking OHAs in fiscal year 2012. One-year refill-based medication possession ratios (MPRs) were calculated at the patient level. Clinic-level adherence was defined as the proportion of clinics with MPR ≥80%. Risk adjustment of adherence was performed using logistic regression to account for differences in patient populations at clinics. Eight domains of the PCMH model (ie, access, continuity, coordination, teamwork, comprehensive care, self-management, communication, shared decision making) were assessed using items from a previously validated index. Multivariate linear regression was applied to identify PCMH components associated with clinic-level adherence. Patients with diabetes per clinic ranged from 100 to 5011. The average level of adherence to OHAs among clinics ranged from 52.8% to 61.9% (interquartile range = 57.9% to 59.4%). In multivariate analysis, organizational features associated with higher clinic-level adherence included access to routine care (standardized beta [Sβ] = .21, P = .004), having a respectful office staff (Sβ = 0.21, P = .002), and utilization of telephone encounters (Sβ = 0.23, P < .001). Among a national cohort of veterans with diabetes, overall PCMH implementation did not significantly increase adherence to oral hypoglycemic agents, although aspects of implementation were associated with increased adherence. Measures of access to care appear the most significant.

Impact of compliance to oral hypoglycemic agents on short-term disability costs in an employer population.

PubMed

Hagen, Susan E; Wright, Douglas W; Finch, Ron; Talamonti, Walter J; Edington, Dee W

2014-02-01

This study evaluated the relationships between compliance with oral hypoglycemic agents and health care/short-term disability costs in a large manufacturing company. The retrospective analysis used an observational cohort drawn from active employees of Ford Motor Company. The study population consisted of 4978 individuals who were continuously eligible for 3 years (between 2001-2007) and who received a prescription for an oral hypoglycemic agent during that time. Medical, pharmacy, and short-term disability claims data were obtained from the University of Michigan Health Management Research Center data warehouse. Pharmacy claims/refill data were used to calculate the proportion of days covered (PDC); an individual was classified as compliant if his/her PDC was ≥80%. Model covariates included age, sex, work type, and Charlson comorbidity scores. The impact of compliance on disability and health care costs was measured by comparing the costs of the compliant with those of the noncompliant during a 1-year follow-up. Among these employees, compliant patients had lower medical, higher pharmacy, and lower short-term disability costs than did the noncompliant. After adjusting for demographics and comorbidity, noncompliance was associated with statistically higher short-term disability costs ($1840 vs. $1161, P<0.0001), longer short-term disability duration, and an increase in short-term disability incidence (21.5% of the noncompliant had a claim compared to 16.0% of the compliant, P<0.0001). These results suggest that medication compliance may be important in curtailing the rise of health care/disability costs in the workplace. Employers concerned with the total costs associated with diabetes should not overlook the impact of compliance on short-term disability.

Discovery of a Phosphodiesterase 9A Inhibitor as a Potential Hypoglycemic Agent

PubMed Central

2015-01-01

Phosphodiesterase 9 (PDE9) inhibitors have been studied as potential therapeutics for treatment of diabetes and Alzheimer’s disease. Here we report a potent PDE9 inhibitor 3r that has an IC50 of 0.6 nM and >150-fold selectivity over other PDEs. The HepG2 cell-based assay shows that 3r inhibits the mRNA expression of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase. These activities of 3r, together with the reasonable pharmacokinetic properties and no acute toxicity at 1200 mg/kg dosage, suggest its potential as a hypoglycemic agent. The crystal structure of PDE9-3r reveals significantly different conformation and hydrogen bonding pattern of 3r from those of previously published 28s. Both 3r and 28s form a hydrogen bond with Tyr424, a unique PDE9 residue (except for PDE8), but 3r shows an additional hydrogen bond with Ala452. This structure information might be useful for design of PDE9 inhibitors. PMID:25432025

Reproducible insulin secretion from isolated rat pancreas preparations using an organ bath.

PubMed

Morita, Asuka; Ouchi, Motoshi; Terada, Misao; Kon, Hiroe; Kishimoto, Satoko; Satoh, Keitaro; Otani, Naoyuki; Hayashi, Keitaro; Fujita, Tomoe; Inoue, Ken-Ichi; Anzai, Naohiko

2018-02-09

Diabetes mellitus is a lifestyle-related disease that is characterized by inappropriate or diminished insulin secretion. Ex vivo pharmacological studies of hypoglycemic agents are often conducted using perfused pancreatic preparations. Pancreas preparations for organ bath experiments do not require cannulation and are therefore less complex than isolated perfused pancreas preparations. However, previous research has generated almost no data on insulin secretion from pancreas preparations using organ bath preparations. The purpose of this study was to investigate the applicability of isolated rat pancreas preparations using the organ bath technique in the quantitative analysis of insulin secretion from β-cells. We found that insulin secretion significantly declined during incubation in the organ bath, whereas it was maintained in the presence of 1 µM GLP-1. Conversely, amylase secretion exhibited a modest increase during incubation and was not altered in the presence of GLP-1. These results demonstrate that the pancreatic organ bath preparation is a sensitive and reproducible method for the ex vivo assessment of the pharmacological properties of hypoglycemic agents.

Molecular modelling and synthesis of spiroimidazolidine-2,4-diones with dual activities as hypoglycemic agents and selective inhibitors of aldose reductase.

PubMed

Salem, Manar G; Abdel Aziz, Yasmine M; Elewa, Marwa; Elshihawy, Hosam A; Said, Mohamed M

2018-05-02

Novel derivatives of spiroimidazolidinedione were synthesized and evaluated as hypoglycemic agents through binding to sulfonylurea receptor 1 (SUR1) in pancreatic beta-cells. Their selectivity index was calculated against both aldehyde reductase (ALR1) and aldose reductase (ALR2). Aldehyde reductase is a key enzyme in the polyol pathway that is involved in the etiology of the secondary diabetic complications. All structures were confirmed by microanalysis and by IR, 1 H NMR, 13 C NMR and EI-MS spectroscopy. The investigated compounds were subjected to molecular docking and an in silico prediction study to determine their free energy of binding (ΔG) values and predict their physicochemical properties and drug-likeness scores. Compound 1'-(5-chlorothiophene-2-ylsulfonyl)spiro[cyclohexane-1,5'-imidazolidine]-2',4'-dione showed IC 50 0.47 µM and 79% reduction in blood glucose level with a selectivity index 127 for ALR2. Copyright © 2018 Elsevier Inc. All rights reserved.

Effervescent Granules Prepared Using Eucommia ulmoides Oliv. and Moso Bamboo Leaves: Hypoglycemic Activity in HepG2 Cells

PubMed Central

Li, Xiang-Zhou

2016-01-01

Eucommia ulmoides Oliv. (E. ulmoides Oliv.) and moso bamboo (Phyllostachys pubescens) leaves are used as folk medicines in central-western China to treat diabetes. To investigate the hypoglycemic activity of the effervescent granules prepared using E. ulmoides Oliv. and moso bamboo leaves (EBEG) in HepG2 cells, EBEG were prepared with 5% of each of polysaccharides and chlorogenic acids from moso bamboo and E. ulmoides Oliv. leaves, respectively. HepG2 cells cultured in a high-glucose medium were classified into different groups. The results displayed EBEG-treated cells showed better glucose utilization than the negative controls; thus, the hypoglycemic effect of EBEG was much greater than that of granules prepared using either component alone, thereby indicating that this effect was due to a synergistic action of the components. Further, glucose consumption levels in the cells treated with EBEG (156.35% at 200 μg/mL) and the positive controls (metformin, 162.29%; insulin, 161.52%) were similar. Thus, EBEG exhibited good potential for use as a natural antidiabetic agent. The hypoglycemic effect of EBEG could be due to the synergistic action of polysaccharides from the moso bamboo leaves and chlorogenic acids from E. ulmoides Oliv. leaves via the inhibition of alpha-glucosidase and glucose-6-phosphate displacement enzyme. PMID:27656239

Bitter melon (Momordica charantia): a review of efficacy and safety.

PubMed

Basch, Ethan; Gabardi, Steven; Ulbricht, Catherine

2003-02-15

The pharmacology, clinical efficacy, adverse effects, drug interactions, and place in therapy of bitter melon are described. Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter melon extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches. Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.

Influence of nopal intake upon fasting glycemia in type II diabetics and healthy subjects.

PubMed

Frati, A C; Gordillo, B E; Altamirano, P; Ariza, C R; Cortés-Franco, R; Chávez-Negrete, A; Islas-Andrade, S

1991-01-01

To assess if the acute hypoglycemic effect of nopal which occurs in diabetic patients also appears in healthy individuals, 500 g of nopal stems (O. streptacantha Lem.) were given orally to 14 healthy volunteers and to 14 patients with NIDDM. Serum glucose and insulin levels were measured at 0, 60, 120 and 180 minutes after nopal ingestion. A control test was performed with the intake of 400 ml of water. The intake of nopal by the NIDDM group was followed by a significant reduction of serum glucose and insulin concentration reaching 40.8 + 4.6 mg/dl (n = 14) (mean+SEM) and 7.8 + 1.5 uU/ml (n = 7) less than basal value, respectively, at 180 minutes. (P less than 0.001 vs control test). No significant changes were noticed in the healthy group as compared with the control test (P greater than 0.05). Acute hypoglycemic effect of nopal was observed in patients with NIDDM but not in healthy subjects, thus the mechanisms of this effect differs from current hypoglycemic agents.

Neuroprotective Role of Exogenous Brain-Derived Neurotrophic Factor in Hypoxia-Hypoglycemia-Induced Hippocampal Neuron Injury via Regulating Trkb/MiR134 Signaling.

PubMed

Huang, Weidong; Meng, Facai; Cao, Jie; Liu, Xiaobin; Zhang, Jie; Li, Min

2017-05-01

Hypoxic-ischemic brain injury is an important cause of neonatal mortality and morbidity. Brain-derived neurotrophic factor (BDNF) has been reported to play a neuroprotective role in hypoxic-ischemic brain injury; however, the specific effects and mechanism of BDNF on hypoxic-hypoglycemic hippocampal neuron injury remains unknown. The current study investigated the action of BDNF in regulating cerebral hypoxic-ischemic injury by simulating hippocampal neuron ischemia and hypoxia. We found that BDNF, p-Trkb, and miR-134 expression levels decreased, and that exogenous BDNF increased survival and reduced apoptosis in hypoxic-hypoglycemic hippocampal neurons. The results also show that BDNF inhibits MiR-134 expression by activating the TrkB pathway. Transfection with TrkB siRNA and pre-miR-134 abrogated the neuroprotective role of BDNF in hypoxic-hypoglycemic hippocampal neurons. Our results suggest that exogenous BDNF alleviates hypoxic-ischemic brain injury through the Trkb/MiR-134 pathway. These findings may help to identify a potential therapeutic agent for the treatment of hypoxic-ischemic brain injury.

Management of type-1 and type-2 diabetes by insulin injections in diabetology clinics - a scientific research review.

PubMed

Aziz, Kamran M A

2012-05-01

Better control of the diabetic metabolic state will prevent the diabetes complications. However in current clinical practice, it is sometimes difficult to achieve this goal. Additionally, physicians find themselves in an equivocal position to initiate insulin therapy, its selection, combining with Oral agents and further management. The current article was written to focus on diabetes pathogenesis at molecular level, its classification and management by insulin injections. Knowledge of basic biochemistry, pharmacology with kinetics of Insulin is essential for diabetes management. Nonetheless, it should be a priority to search for evidence based clinical methodologies for selecting the patients for initiating, modifying or combining the insulin therapy. Type-1 diabetic patients are best controlled on basal bolus insulin regimens. However in type-2 diabetes, metformin with lifestyle modifications should be the first line therapy, thereafter combined with oral hypoglycemic agents or shifting to insulin gradually if diabetes remains uncontrolled. Metformin is recommended to be prescribed with insulin as compared to oral hypoglycemic agents which should be discontinued while starting insulin. Monitoring the insulin therapy on regular visits to diabetologist and diabetes multidisciplinary team remains the integral part of diabetes management. The review also outlines relevant and recent insulin analogue patents for the management of Diabetes.

No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers.

PubMed

Anderson, Denise M; Shelley, Sarah; Crick, Nina; Buraglio, Mauro

2002-12-01

The novel hypoglycemic agent nateglinide is pharmacologically distinct from oral hypoglycemic agents such as sulfonylureas and repaglinide. The present study investigated the effects in healthy volunteers of multiple doses of nateglinide on the pharmacokinetics and pharmacodynamics of warfarin. The study comprised a randomized two-group, two-way crossover, open-label design in 12 healthy male subjects. One group of 6 subjects initially received a single oral dose of warfarin 30 mg and then, after a 7- to 14-day washout, received both warfarin and nateglinide (120 mgnateglinide, 10 min before meals for 4 days and a single dose of 30 mg warfarin on the second day). The alternate group of 6 subjects received treatments in the opposite order. Pharmacokinetic profiles were derived from plasma warfarin and nateglinide concentrations. Prothrombin measurements were evaluated in both periods as a measure of warfarin activity. When administered alone or in combination, there were no statistically significant differences in mean warfarin (R- and S-enantiomers) or nateglinide pharmacokinetic parameters. The concurrent administration of nateglinide and warfarin did not affect the maximal change in prothrombin time that follows warfarin administration. In this study, there was no evidence of an effect of coadministration of nateglinide on the pharmacodynamic action of warfarin or any pharmacokinetic interaction between warfarin and nateglinide.

Methods and compositions for the treatment of niddm

DOEpatents

Wilson, Bary W.; Campbell, James A.; Sasser, Lyle B.; Hortal, Patricio

1996-01-01

A variety of hypoglycemic agents and compositions for use in the maintenance of maturity onset non-insulin dependent diabetes mellitus (NIDDM) are disclosed. The present invention also discloses methods for reducing the blood glucose level in a patient, as well as methods for reducing symptomatic conditions associated with diabetes in a patient.

Self-monitoring of blood glucose among patients with diabetes in Jordan: Perception, adherence, and influential factors.

PubMed

Al-Keilani, Maha S; Almomani, Basima A; Al-Sawalha, Nour A; Shhabat, Batool A

2017-04-01

To investigate the self-monitoring of blood glucose (SMBG) adherence among Jordanian patients with diabetes and to identify the predictive factors. A cross-sectional survey was carried out in 18 hospitals and healthcare centers covering south, north, and middle of Jordan. All patients with diabetes attending endocrinology clinics from May to December, 2015 were approached. The questionnaires were distributed by trained pharmacists and were self-administered. A total of 1079 participants completed the survey. Only 59% of participants were SMBG adherent. Predictors of SMBG adherence were treatment regimen; insulin with oral hypoglycemic agents (p=0.044, CI 1.023-5.274, OR=2.323) or insulin only (p=0.005, CI 1.225-3.115, OR=1.953), and health education on how to use the SMBG meter (p<0.001, CI 10.538-32.497, OR=18.506). The frequency of SMBG was significantly associated with the treatment regimen, with patients who were taking oral hypoglycemic agents (p<0.001) or insulin therapy (p=0.004) tested more frequently as compared to others. Additionally, the frequency of testing was significantly associated with the reason of performing SMBG (p<0.001). Frequency of daily testing was the highest among patients who performed SMBG to know if they were hypoglycemic (48.9%) or hyperglycemic (48.0%), or to inform their doctors (28.4%). SMBG adherence was suboptimal. Predictors of SMBG adherence were treatment regimen and health education about the SMBG meter. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of hepatic lipogenesis by 2-tetradecylglycidic acid.

PubMed

McCune, S A; Nomura, T; Harris, R A

1979-10-01

2-Tetradecylglycidic acid (TDGA), a hypoglycemic agent, has been found to be a very effective inhibitor of de novo fatty acid synthesis by isolated hepatocytes. A comparison was made between the effectiveness of TDGA and 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, on the metabolic processes of isolated hepatocytes. These compounds are structurally related and both inhibit fatty acid synthesis; however, they have opposite effects from each other on the oxidation and esterification of fatty acids. TDGA inhibits whereas TOFA stimulates fatty acid oxidation. TDGA stimulates whereas TOFA inhibits fatty acid esterification.

Prediction of morbidity and mortality in patients with type 2 diabetes.

PubMed

Wells, Brian J; Roth, Rachel; Nowacki, Amy S; Arrigain, Susana; Yu, Changhong; Rosenkrans, Wayne A; Kattan, Michael W

2013-01-01

Introduction. The objective of this study was to create a tool that accurately predicts the risk of morbidity and mortality in patients with type 2 diabetes according to an oral hypoglycemic agent. Materials and Methods. The model was based on a cohort of 33,067 patients with type 2 diabetes who were prescribed a single oral hypoglycemic agent at the Cleveland Clinic between 1998 and 2006. Competing risk regression models were created for coronary heart disease (CHD), heart failure, and stroke, while a Cox regression model was created for mortality. Propensity scores were used to account for possible treatment bias. A prediction tool was created and internally validated using tenfold cross-validation. The results were compared to a Framingham model and a model based on the United Kingdom Prospective Diabetes Study (UKPDS) for CHD and stroke, respectively. Results and Discussion. Median follow-up for the mortality outcome was 769 days. The numbers of patients experiencing events were as follows: CHD (3062), heart failure (1408), stroke (1451), and mortality (3661). The prediction tools demonstrated the following concordance indices (c-statistics) for the specific outcomes: CHD (0.730), heart failure (0.753), stroke (0.688), and mortality (0.719). The prediction tool was superior to the Framingham model at predicting CHD and was at least as accurate as the UKPDS model at predicting stroke. Conclusions. We created an accurate tool for predicting the risk of stroke, coronary heart disease, heart failure, and death in patients with type 2 diabetes. The calculator is available online at http://rcalc.ccf.org under the heading "Type 2 Diabetes" and entitled, "Predicting 5-Year Morbidity and Mortality." This may be a valuable tool to aid the clinician's choice of an oral hypoglycemic, to better inform patients, and to motivate dialogue between physician and patient.

Oral hypoglycemic agents for gestational diabetes mellitus?

PubMed

Maymone, Ana Cristina; Baillargeon, Jean-Patrice; Ménard, Julie; Ardilouze, Jean-Luc

2011-03-01

Gestational diabetes mellitus (GDM), the most frequent medical complication of pregnancy, is associated with several adverse outcomes over the short- and long-term for both mother and offspring. Standard treatment for GDM consists of insulin injections. Oral hypoglycemic agents (OHAs), on the other hand, are still the subject of controversy. Although OHAs are seemingly as efficient as insulin and may provide better quality of life, congenital malformations and unknown long-term effects are still feared. Recent data on the pharmacokinetics of two OHAs (glyburide and metformin) and their clinical use for GDM are reviewed, with a focus on clinical trials and observational studies comparing insulin with glyburide or metformin (1960 - 2010). The review will provide a comprehensive overview of the pros and cons of OHA usage, an appreciation of OHAs' efficiency for the purpose of controlling glycemia and embryogenetic basics relating to congenital malformations. While insulin treatment is an effective therapy for controlling maternal glycemia, it nevertheless requires sufficient education and skills on the part of the patient to manage properly and may cause hypoglycemia, fear and anxiety. Oral treatment as a more user-friendly alternative may thus facilitate the control of GDM in some patients.

Repaglinide, glibenclamide and glimepiride administration to normal and hereditarily diabetic rats.

PubMed

Ladrière, L; Malaisse-Lagae, F; Fuhlendorff, J; Malaisse, W J

1997-09-24

Repaglinide (1 microg/g body wt), glibenclamide (10 microg/g) or glimepiride (10 microg/g) were administered orally to either fed or overnight fasted normal rats and hereditarily diabetic animals (GK rats). In both fed and starved normal rats, repaglinide provoked a greater and more rapid increase in plasma insulin concentration and an earlier fall in glycemia than those observed after administration of the hypoglycemic sulfonylureas. Likewise, in fed GK rats, the plasma insulin concentration was already increased by 30.0 +/- 1.6% 15 min after administration of repaglinide, whilst a sizeable insulinotropic action of the sulfonylureas was only recorded at much later times. Except for a lower glycemia at the 240th min of the test, there was little to distinguish, in starved GK rats, between control experiments including the oral administration of the solution of carboxymethylcellulose used as vehicle and the experiments conducted with the antidiabetic agents. Several converging observations indicated that glimepiride stimulated insulin release more promptly than glibenclamide. It is proposed that advantage can be taken from these vastly different time-courses of the hormonal and metabolic response to distinct hypoglycemic agents to optimize the control of glucose homeostasis in non-insulin-dependent diabetic subjects.

Endocrine Drugs in Aircrew

DTIC Science & Technology

2001-06-01

cells (ICA) present the case, the primary goal of diet therapy is simply in their serum at the time of diagnosis, and some caloric reduction to achieve...transplantation caloric intake and weight gain, and suppresses rejection, pemphigus, and immune hematologic inflammation and the immune system.10 Cortisol...hypoglycemic normal.24𔃼 5 agents is still accompanied by the risk of hypo - glycemia and of the micro- and macrovascular Secondary adrenal

Isolation, purification, and structural features of a polysaccharide from Phellinus linteus and its hypoglycemic effect in alloxan-induced diabetic mice.

PubMed

Zhao, Chao; Liao, Zunsheng; Wu, Xiaoqi; Liu, Yanling; Liu, Xiaoyan; Lin, Zhanxi; Huang, Yifan; Liu, Bin

2014-05-01

Phellinus linteus is a medicinal mushroom that has been used in Oriental countries for centuries for its antitumor, antioxidant, immunomodulatory, and biological activity on hyperglycemia. A water-soluble crude polysaccharide was extracted using hot water from P. linteus mycelia grown under submerged culture. An orthogonal experiment was used to optimize the extraction conditions of P. linteus mycelia polysaccharides (PLP). The crude polysaccharide was purified using DEAE Sephadex A-50 and Sephadex G-200 chromatography. Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance ((1) H NMR) spectroscopy were used to investigate the structure of the purified P. linteus polysaccharide (PLP-I), revealing that it was mainly a branched-type glycan with both α- and β-linkages and a pyranoid sugar ring conformation. PLP orally administered at 100 mg/kg body weight/d could significantly reduce the blood glucose level by 35.60% in alloxan-induced diabetic mice. The results of an oral glucose tolerance test (OGTT) revealed that PLP had an effect on glucose disposal after 28 d of treatment. The result revealed that PLP from a submerged culture of P. linteus mycelia possessed potent hypoglycemic properties. The polysaccharide may be useful as a functional food additive and a hypoglycemic agent. © 2014 Institute of Food Technologists®

QSAR studies in the discovery of novel type-II diabetic therapies.

PubMed

Abuhammad, Areej; Taha, Mutasem O

2016-01-01

Type-II diabetes mellitus (T2DM) is a complex chronic disease that represents a major therapeutic challenge. Despite extensive efforts in T2DM drug development, therapies remain unsatisfactory. Currently, there are many novel and important antidiabetic drug targets under investigation by many research groups worldwide. One of the main challenges to develop effective orally active hypoglycemic agents is off-target effects. Computational tools have impacted drug discovery at many levels. One of the earliest methods is quantitative structure-activity relationship (QSAR) studies. QSAR strategies help medicinal chemists understand the relationship between hypoglycemic activity and molecular properties. Hence, QSAR may hold promise in guiding the synthesis of specifically designed novel ligands that demonstrate high potency and target selectivity. This review aims to provide an overview of the QSAR strategies used to model antidiabetic agents. In particular, this review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market. Special emphasis has been made on studies that led to the identification of novel antidiabetic scaffolds. Computer-aided molecular design and discovery techniques like QSAR have a great potential in designing leads against complex diseases such as T2DM. Combined with other in silico techniques, QSAR can provide more useful and rational insights to facilitate the discovery of novel compounds. However, since T2DM is a complex disease that includes several faulty biological targets, multi-target QSAR studies are recommended in the future to achieve efficient antidiabetic therapies.

Balanites aegyptiaca ameliorates insulin secretion and decreases pancreatic apoptosis in diabetic rats: Role of SAPK/JNK pathway.

PubMed

Hassanin, Kamel M A; Mahmoud, Mohamed O; Hassan, Hossam M; Abdel-Razik, Abdel-Razik H; Aziz, Lourin N; Rateb, Mostafa E

2018-06-01

SAPK-JNK pathway performs a significant role in the pathogenesis of type 2 diabetes. Balanites aegyptiaca (BA) is used as an anti-diabetic agent in folk medicine however its hypoglycemic mechanism is not fully elucidated. The current study aimed to evaluate the effect of crude extract, butanol, and dichloromethane fractions from BA on the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK-JNK) pathway in experimental diabetic rats. Six groups of male Wistar rats were included: normal control, diabetic, diabetic rats treated with crude, butanol or dichloromethane fraction from BA (50 mg/kg BW) and diabetic rats treated with gliclazide as a reference drug for one month. Our results suggested a protective role of treatment of diabetic rats with BA against oxidative stress-induced SAPK-JNK pathway. Moreover, BA treatment produced a reduction in plasma glucose, HbA 1c , lactic acid, lipid profile, malondialdehyde levels and produced an increase in insulin, reduced glutathione levels, catalase and superoxide dismutase activities compared with untreated diabetic rats. Moreover, it decreased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase 1, protein 53 and increased insulin receptor substrate 1 in rat pancreas while it increased glucose transporter 4 in rat muscle. Analysis of BA extracts by LC-HRMS revealed the presence of different saponins with reported hypoglycemic effect. In conclusion, BA exerted hypoglycemic, hypolipidemic, insulinotropic and antioxidant effects. Additionally, it reduced apoptosis in pancreatic β-cells and increased glucose uptake in muscle. These results suggest that the hypoglycemic effect of BA is due to the inhibition of the SAPK-JNK pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Drug-nutrient interactions.

PubMed

Thomas, J A

1995-10-01

Nutrition status plays a significant role in a drug's pharmacodynamics. Some disease states and other special conditions affect nutrient status and a drug's therapeutic efficacy. Many classes of drugs, including antimicrobials, hypoglycemics, and hypocholesterolemic agents, can be affected by the presence of food, with the geriatric patient particularly at risk. While a drug's pharmacokinetic profile can usually be predicted, it can be modified by nutrients and by certain pathophysiologic conditions, including aging, hepatic dysfunction, and micronutrients.

Antiinflammatory, analgesic and hypoglycemic effects of Mangifera indica Linn. (Anacardiaceae) stem-bark aqueous extract.

PubMed

Ojewole, J A O

2005-10-01

Previous studies in our laboratories and elsewhere have shown that some members of Anacardiaceae family possess antiinflammatory, analgesic and hypoglycemic effects in man and mammalian experimental animals. The present study was, therefore, undertaken to examine the antiinflammatory, analgesic and antidiabetic properties of the stem-bark aqueous extract of Mangifera indica Linn., M. indica a member of the Anacardiaceae family, in rats and mice. The stem-bark powder of M. indica was Soxhlet extracted with distilled water and used. The analgesic effect of the plant's extract was evaluated by the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and antidiabetic effects of the stem-bark extract were investigated in rats, using fresh egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), and chlorpropamide (250 mg/kg p.o.) were used respectively as reference analgesic, antiinflammatory, and hypoglycemic agents for comparison. M. indica stem-bark aqueous extract (MIE, 50-800 mg/kg i.p.) produced dose-dependent and significant (p<0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. MIE (50-800 mg/kg i.p.) also significantly (p<0.05-0.001) inhibited fresh egg albumin-induced paw edema, and caused significant (p<0.05-0.001) hypoglycemic effects in rats. It is suggested that the analgesic effects of MIE (50-800 mg/kg i.p.) may be peripherally and centrally mediated. The different chemical constituents of the plant, especially the polyphenolics, flavonoids, triterpenoids, mangiferin, and other chemical compounds present in the plant may be involved in the observed antiinflammatory, analgesic, and hypoglycemic effects of the plant's extract. However, the results of this experimental animal study lend pharmacological credence to the suggested folkloric uses of the plant in the management and control of painful, arthritic and other inflammatory conditions, as well as in the management of adult-onset type 2 diabetes mellitus in some rural African communities. (c) 2005 Prous Science. All rights reserved.

Nateglinide and acarbose are comparably effective reducers of postprandial glycemic excursions in chinese antihyperglycemic agent-naive subjects with type 2 diabetes.

PubMed

Zhou, Jian; Li, Hong; Zhang, Xiuzhen; Peng, Yongde; Mo, Yifei; Bao, Yuqian; Jia, Weiping

2013-06-01

Recent studies have identified postprandial glycemic excursions as risk factors for diabetes complications. This study aimed to compare the effects of nateglinide and acarbose treatments on postprandial glycemic excursions in Chinese subjects with type 2 diabetes. This was a multicenter, open-label, randomized, active-controlled, parallel-group study. One hundred three antihyperglycemic agent-naive subjects with type 2 diabetes (hemoglobin A1c range, 6.5-9.0%) were prospectively recruited from four hospitals in China. The intervention was nateglinide (120 mg three times a day) or acarbose (50 mg three times a day) therapy for 2 weeks. A continuous glucose monitoring system was used to calculate the incremental area under the curve of postprandial blood glucose (AUCpp), the incremental glucose peak (IGP), mean amplitude of glycemic excursions, SD of blood glucose, the mean of daily differences, and 24-h mean blood glucose (MBG). Subjects' serum glycated albumin and the plasma insulin levels were also analyzed. Both agents caused significant reductions on AUCpp and IGP. Similarly, both treatment groups showed significant improvements in the intra- and interday glycemic excursions, as well as the 24-h MBG and serum glycated albumin compared with baseline (P<0.001). However, neither of the agents produced a significantly better effect (P>0.05). Moreover, the nateglinide-treated group had significantly increased insulin levels at 30 min and at 120 min after a standard meal compared with baseline, whereas the acarbose-treated group decreased. No serious adverse events occurred in either group. The rates of hypoglycemic episodes were comparable in the two groups, and no severe hypoglycemic episode occurred in either group. Nateglinide and acarbose were comparably effective in reducing postprandial glycemic excursions in antihyperglycemic agent-naive Chinese patients with type 2 diabetes, possibly through different pathophysiological mechanisms.

[Hypoglycemic treatment in type 2 diabetes patients suffering from moderate to severe renal failure in France. Aim of the study].

PubMed

Bouée, Stéphane; Gaudin, Anne-Françoise; Amelineau, Elisabeth; Bonnet, Fabrice

2013-01-01

The purpose of this study is to describe the hypoglycemic agents prescribed to type 2 diabetes patients (T2D) with renal impairment (RI). Data were extracted from the database LPD-CEGEDIM, based on a sample of 1200 general practitioners. The analysis focused on T2D patients with RI, defined by a glomerular filtration rate (GFR) below 60 mL/min/1.73 m², estimated by the MDRD formula. Of the 36 255 patients identified with T2D, a GFR was calculated for 8 647 patients (23.9%), 1 472 (22%) with a moderate RI (GFR=[30mL/min/1.73 m²-60mL/min/1.73 m²]) and 86 (1.0%) with a severe RI (GFR=[15mL/min/1.73 m-30mL/min/1.73 m²]); 47,6% of T2D patients with a moderate RI and 52,3% of T2D patients with a severe RI were treated with at least one drug contraindicated in patients with moderate or severe RI. These findings suggest better informing doctors of these contraindications and show the value of having new hypoglycemic drugs that can be used in case of RI. © 2013 Société Française de Pharmacologie et de Thérapeutique.

Comparison of the hypoglycemic effect of acarbose monotherapy in patients with type 2 diabetes mellitus consuming an Eastern or Western diet: a systematic meta-analysis.

PubMed

Zhu, Qibo; Tong, Yuzhen; Wu, Taixiang; Li, Jieqing; Tong, Nanwei

2013-06-01

Because of its mechanism of action, the starch content of a diet might alter the hypoglycemic effect of acarbose. We aimed to determine whether differences in this hypoglycemic effect existed between individuals consuming Eastern and Western diets with significantly different starch contents, a systematic meta-analysis of studies comparing acarbose with placebo or other hypoglycemic agents in patients with type 2 diabetes mellitus (T2DM) was performed. Records were retrieved from the Cochrane clinical controlled trials, MEDLINE, EMBASE, Wanfang, Chinese Technical Periodicals, and ongoing trials databases, and full texts and reference lists were screened. Because no study has directly compared patients consuming different types of diet, fixed- and random-effect models were used to indirectly compare the hypoglycemic effect of acarbose monotherapy with that of placebo and/or comparator drugs in patients with T2DM consuming an Eastern (Eastern Asia) or Western (including Europe and North America) diet. A total of 46 studies were included in the meta-analysis. The results revealed that, compared with placebo, hemoglobin A1c (HbA1c) levels were reduced to a significantly greater extent (1.02%) in the Eastern diet (mean [SD], 1.54% [2.00%]) than in the Western diet (mean [SD], 0.52% [1.20%]) P < 0.00001). The ability of acarbose to reduce HbA1c levels in the Eastern (P = 0.20) and Western (P = 0.10) diet groups was similar to that of sulfonylureas, and HbA1c levels were reduced significantly more (0.39%; P < 0.00001) in the Eastern than in the Western diet group. The ability of acarbose to reduce HbA1c levels was similar to those of metformin and nateglinide/repaglinide, but a comparison of its efficacy with different diets was difficult because of the inclusion of few studies in these categories. Analysis of all included studies revealed that acarbose achieved a greater absolute reduction of HbA1c levels in the Eastern diet (mean [SD], 1.26% [1.20%]) than in the Western diet (mean [SD], 0.62% [1.28%]; P < 0.00001) group. However, the poor quality of Eastern diet trials may have affected the outcomes of the meta-analysis. The hypoglycemic effect of acarbose is superior in patients with T2DM consuming an Eastern diet than in those consuming a Western diet and is similar to that of sulfonylureas, metformin, and glinide drugs. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

Effect of hypoglycemic agents on survival outcomes of lung cancer patients with diabetes mellitus

PubMed Central

Xin, Wen-Xiu; Fang, Luo; Fang, Qi-Lu; Zheng, Xiao-Wei; Ding, Hai-Ying; Huang, Ping

2018-01-01

Abstract Background: To assess the association between hypoglycemic agents and prognosis of lung cancer patients with diabetes. Methods: A comprehensive literature search was performed in PubMed, Web of Science, Embase, and Cochrane Library until May 2017. The search yielded 2593 unique citations, of which 18 articles met inclusion criteria. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated by a fixed-effects or random-effects model. Results: The pooled HRs favoring metformin users were 0.77 for overall survival (OS) (n = 15, 95% CI: 0.68–0.86) and 0.50 for disease-free survival (n = 5, 95% CI: 0.39–0.64). One study assessed the relationship between metformin and cancer-specific survival (CSS), reporting no significant results. No significant association between insulin and OS (n = 2, HR: 0.95, 95% CI: 0.79–1.13) or CSS (n = 2, HR: 1.03, 95% CI: 0.76–1.41) was noted. One study evaluated association of sulfonylureas with lung cancer survival and reported no clinical benefit (HR: 1.10, 95% CI: 0.87–1.40). One study reported no association of thiazolidinediones with lung cancer survival (HR: 1.04, 95% CI: 0.65–1.66). Conclusions: This meta-analysis demonstrated that metformin exposure might improve survival outcomes in lung cancer patients with diabetes. PMID:29489653

Prescription of oral hypoglycemic agents for patients with type 2 diabetes mellitus: A retrospective cohort study using a Japanese hospital database.

PubMed

Tanabe, Makito; Motonaga, Ryoko; Terawaki, Yuichi; Nomiyama, Takashi; Yanase, Toshihiko

2017-03-01

In treatment algorithms of type 2 diabetes mellitus in Western countries, biguanides are recommended as first-line agents. In Japan, various oral hypoglycemic agents (OHAs) are available, but prescription patterns are unclear. Data of 7,108 and 2,655 type 2 diabetes mellitus patients in study 1 and study 2, respectively, were extracted from the Medical Data Vision database (2008-2013). Cardiovascular disease history was not considered in study 1, but was in study 2. Initial choice of OHA, adherence to its use, effect on glycated hemoglobin levels for 2 years and the second choice of OHA were investigated. In study 1, α-glucosidase inhibitor, glinide and thiazolidinedione were preferentially medicated in relatively lower glycated hemoglobin cases compared with other OHAs. The two most prevalent first prescriptions of OHAs were biguanides and dipeptidyl peptidase-4 inhibitors, and the greatest adherence was for α-glucosidase inhibitors. In patients treated continuously with a single OHA for 2 years, improvement in glycated hemoglobin levels was greatest for dipeptidyl peptidase-4 inhibitors. As a second OHA added to the first OHA during the first 2 years, dipeptidyl peptidase-4 inhibitors were chosen most often, especially if a biguanide was the first OHA. In study 2, targeting patients with a cardiovascular disease history, a similar tendency to study 1 was observed in the first choice of OHA, adherence and the second choice of OHA. Even in Japanese type 2 diabetes mellitus patients, a Western algorithm seems to be respected to some degree. The OHA choice does not seem to be affected by a cardiovascular disease history. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Development of novel gastroretentive floating particulate drug delivery system of gliclazide.

PubMed

Awasthi, Rajendra; Kulkarni, Giriraj T

2012-09-01

The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.

Risk factors of severe hypoglycemia requiring medical assistance and neurological sequelae in patients with diabetes

PubMed Central

Jeon, Ja Young; Kim, Se Ran; Kim, Hae Jin; Kim, Dae Jung; Lee, Kwan-Woo; Lee, Jung-Dong; Han, Seung Jin

2016-01-01

Abstract Hypoglycemia commonly occurs in patients who are being treated for diabetes. In some cases, these patients suffer from severe hypoglycemia that requires medical assistance and which can unfortunately result in long-term disabilities. Therefore, we investigated risk factors associated with severe hypoglycemia requiring medical assistance (HMA) and the resulting neurological sequelae in patients with diabetes. This investigation was a case–control study that assessed 129 patients with diabetes and documented hypoglycemia from a single tertiary hospital between February 2013 and May 2015. They were treated with oral hypoglycemic agents alone (54%) or with insulin with/without oral hypoglycemic agents (46%). If a patient with diabetes visited the emergency department due to hypoglycemia, this was defined as HMA. The control group was composed of patients with documented, nonsevere hypoglycemia who visited the outpatient clinic during the same period. The degree of neurological disability in the HMA patients was measured using the modified Rankin Scale. A multivariate analysis revealed that independent risk factors of HMA were associated with a lack of the self-monitoring of blood glucose (SMBG) and previous episodes of severe hypoglycemia. In the HMA group, 15 patients (22%) had neurological sequelae at the time of discharge. Patients with neurological sequelae were older than those without sequelae (74.3 years vs 65.8 years, P = 0.006) and had increased psychological evidence of disorders such as insomnia, dementia, and depression (40% vs 11%, P = 0.017). Patients with sequelae were also more likely to live in rural areas (47% vs 19%, P = 0.04) and to have a longer time from last seen normal till glucose administration (5.2 hours vs 1.6 hours, P = 0.027). In the present study, absence of SMBG and previous severe hypoglycemic episodes were independent risk factors of HMA and patients with an older age, a psychological disorder, a rural residence, and a prolonged duration of hypoglycemia had higher risks of neurological sequelae. Therefore, the present findings suggest that physicians should aim to prevent hypoglycemia in patients with a history of hypoglycemia and provide education for these patients regarding regular SMBG. PMID:27893672

Hypoglycemia associated with oleander toxicity in a dog.

PubMed

Page, C; Murtaugh, R J

2015-03-01

Oleander poisoning typically results in cardiac arrhythmias, hyperkalemia, and gastrointestinal irritation, and can be fatal. Oleander extracts have also been studied experimentally as hypoglycemic agents. Here, we describe a dog with confirmed oleander toxicosis presenting with classical symptoms and also hypoglycemia. After excluding other likely causes of hypoglycemia, the finding was attributed to oleander toxicosis, which has not been previously reported in dogs. A 7-year-old female spayed Maltese was presented to the emergency service after ingesting oleander leaves. Toxicosis was confirmed by measurement of digoxin using a competitive binding immunoassay, patient level 0.7 ng/mL (0.9 nmol/L) 24-h post-ingestion. Clinical symptoms included vomiting, cardiac arrhythmia, mild hyperkalemia, and hypoglycemia. Treatment was successful with aggressive supportive care, and the dog was discharged from the hospital after 48 h and made a full recovery. This case reviews the presentation and treatment of oleander toxicity but also highlights possible effects of oleander on blood sugar in dogs. Hypoglycemia in this dog, attributed to oleander poisoning, is interesting as it supports experimental research into hypoglycemic properties of oleander extracts.

Jackfruit (Artocarpus heterophyllus Lam.) peel: A better source of antioxidants and a-glucosidase inhibitors than pulp, flake and seed, and phytochemical profile by HPLC-QTOF-MS/MS.

PubMed

Zhang, Lu; Tu, Zong-Cai; Xie, Xing; Wang, Hui; Wang, Hao; Wang, Zhen-Xing; Sha, Xiao-Mei; Lu, Yu

2017-11-01

Jackfruit (Artocarpus heterophyllus Lam.) peel is an underutilized by-product in both, the production and processing of jackfruit. This research compared the antioxidant and hypoglycemic potential of jackfruit peel with jackfruit pulp, flake and seed for the first time. The phytochemical profile of peel extract was characterized with HPLC-QTOF-MS/MS. Results revealed that peel extract exhibited the highest total phenolic and total flavonoid content, and the phenolics was 4.65, 4.12 and 4.95 times higher than that of pulp, flake and seed extract, respectively. The strongest DPPH and ABTS + scavenging ability, α-glucosidase inhibition were also found in peel extract, and the α-glucosidase inhibition was about 11.8-fold of that of acarbose. The HPLC-QTOF-MS/MS analysis led to the tentative identification of 53 compounds, prenylflavonoids, hydroxycinnamic acids and glycosides are the predominant bioactive compounds. Above results reveal promising potential of jackfruit peel as a new source of natural antioxidants and hypoglycemic agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization and hypoglycemic activity of a β-pyran polysaccharides from bamboo shoot (Leleba oldhami Nakal) shells.

PubMed

Zheng, Yafeng; Zhang, Shuai; Wang, Qi; Lu, Xu; Lin, Liangmei; Tian, Yuting; Xiao, Jianbo; Zheng, Baodong

2016-06-25

The bamboo shoot (Leleba oldhami Nakal) shell is a by-product during bamboo shoot processing. It is a cheap and available resource for dietary polysaccharides. Herein, a novel polysaccharide BSSP2a was isolated and characterized from the bamboo shoot shell polysaccharides, and it was identified as a homogeneous highly-branched beta type pyran polysaccharide with a molecular weight of 1.63×10(4)kDa, which consisted of arabinose, xylose, mannose, glucose and galactose at a molar ratio of 20.4:4.9:1:3.4:20.6. The crude polysaccharides (BSSP) from the bamboo shoots shell showed hypoglycemic activity on the high fat diet and streptozotocin induced diabetic mice in a dose-dependent manner. The administration of high dose BSSP (400mg/kg) improved body weight loss and serum insulin loss, and significantly decreased the blood glucose level, serum triglycerides as well as total cholesterol levels by 48.7%, 34.8% and 26.5%, respectively. The results highlight the potential of the bamboo shoot shell polysaccharides as a natural anti-diabetic agent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bauhinia forficata in the treatment of diabetes mellitus: a patent review.

PubMed

de Souza, Bárbara Verônica Cardoso; Moreira Araújo, Regilda Saraiva Dos Reis; Silva, Oskar Almeida; Faustino, Lucas Costa; Gonçalves, Maria Fabrícia Beserra; Dos Santos, Mirian Lima; Souza, Grasielly Rocha; Rocha, Lindalva Moura; Cardoso, Mônica Larissa Sousa; Nunes, Lívio César Cunha

2018-02-01

Diabetes Mellitus has been considered an epidemic by the World Health Organization, with a high risk of morbidity and mortality. The treatment of this pathology consists in glycemic control, which can be done by oral hypoglycemic agents, insulin therapy, dietary guidance, regular physical activity, and psychosocial support. In addition, other adjuvant treatments are employed, such as phytotherapic, and one of the most used plants is Bauhinia forficata. Areas covered: In the current review, patents using Bauhinia forficata for the Diabetes Mellitus treatment have been analyzed. There were 03 patents in WIPO, 01 in Espacenet, 01 in USPTO, and 02 in INPI. Expert opinion: Patents on the adjuvant treatment of Diabetes Mellitus by Bauhinia forficata are discussed. Although there are some phytotherapy products containing this medicinal plant which has hypoglycemic effect here is still a need for the development of more products based on natural resources, for the treatment of this pathology, without side effects and with other benefits, to assist in the glycemia control in diabetic patients, and to improve their quality of life.

The TRPA1 channel and oral hypoglycemic agents: is there complicity in β-cell exhaustion?

PubMed

Diaz-Garcia, Carlos Manlio

2013-01-01

Diabetes mellitus type 2 (DM2) results from the combination of insulin unresponsiveness in target tissues and the failure of pancreatic β cells to secrete enough insulin. (1) It is a highly prevalent chronic disease that is aggravated with time, leading to major complications, such as cardiovascular disease and peripheral and ocular neuropathies. (2) Interestingly, therapies to improve glucose homeostasis in diabetic patients usually involve the use of glibenclamide, an oral hypoglycemic drug that blocks ATP-sensitive K(+) channels (KATP), (3)(,) (4) forcing β cells to release more insulin to overcome peripheral insulin resistance. However, sulfonylureas are ineffective for long-term treatments and ultimately result in the administration of insulin to control glucose levels. (5) The mechanisms underlying β-cell failure to respond effectively with glibenclamide after long-term treatments still needs clarification. A recent study demonstrating that this drug activates TRPA1, (6) a member of the Transient Receptor Potential (TRP) family of ion channels and a functional protein in insulin secreting cells, (7)(,) (8) has highlighted a possible role for TRPA1 as a potential mediator of sulfonylurea-induced toxicity.

Fear of driving license withdrawal in patients with insulin-treated diabetes mellitus negatively influences their decision to report severe hypoglycemic events to physicians.

PubMed

Brož, Jan; Brabec, Marek; Janíčková Žďárská, Denisa; Fedáková, Zuzana; Hoskovcová, Lucie; You, Jee Young; Doničová, Viera; Hlaďo, Petr; Rahelić, Dario; Kvapil, Milan; Polák, Jan

2015-01-01

Under current European Union legislation, two severe hypoglycemic events within 12 months is grounds for driving license withdrawal. The aim of the study reported here was to determine whether fear of such a withdrawal could lead to patients concealing severe hypoglycemia from physicians, which could negatively impact further treatment decisions. A total of 663 patients with insulin-treated diabetes were anonymously surveyed about whether they would conceal severe hypoglycemic events from their physicians, if revealing them could result in driving license withdrawal. This investigation utilized an adapted and expanded questionnaire by Graveling et al. Of all diabetic patients surveyed, 26.17% would most likely not report hypoglycemia, and 25.86% were undecided. In a group of patients with type 1 diabetes, 31.83% would likely not report hypoglycemic events, and 25.06% were undecided. The patients least likely to report severe hypoglycemic events were those who indicated that vehicles were partly essential for work, and who also had more than two hypoglycemic events monthly. A considerable percentage of diabetic patients would likely conceal severe hypoglycemic events from their physicians due to fear of driving license withdrawal. Patient failure to report severe hypoglycemic events can potentially lead to physicians being misinformed regarding the patient's condition, which could lead to inadequate monitoring and treatment.

77 FR 20876 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of... he has had no severe hypoglycemic reactions resulting [[Page 20877

78 FR 65034 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

... she has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or... no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of...

75 FR 13647 - Qualification of Drivers; Exemption Applications; Diabetes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or... no hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another... had no hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another...

75 FR 25919 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... has had no hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of... no hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another... had no hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another...

77 FR 46149 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or...

Relationship between frequency of hypoglycemic episodes and changes in carotid atherosclerosis in insulin-treated patients with type 2 diabetes mellitus.

PubMed

Mita, Tomoya; Katakami, Naoto; Shiraiwa, Toshihiko; Yoshii, Hidenori; Kuribayashi, Nobuichi; Osonoi, Takeshi; Kaneto, Hideaki; Kosugi, Keisuke; Umayahara, Yutaka; Gosho, Masahiko; Shimomura, Iichiro; Watada, Hirotaka

2017-01-09

The effect of hypoglycemia on the progression of atherosclerosis in patients with type 2 diabetes mellitus (T2DM) remains largely unknown. This is a post hoc analysis of a randomized trial to investigate the relationship between hypoglycemic episodes and changes in carotid intima-media thickness (IMT). Among 274 study subjects, 104 patients experienced hypoglycemic episodes. Increases in the mean IMT and left maximum IMT of the common carotid arteries (CCA) were significantly greater in patients with hypoglycemia compared to those without hypoglycemia. Classification of the patients into three groups according to the frequency of hypoglycemic episodes showed that high frequency of hypoglycemic events was associated with increases in mean IMT-CCA, and left max-IMT-CCA and right max-IMT-CCA. In addition, repetitive episodes of hypoglycemia were associated with a reduction in the beneficial effects of sitagliptin on carotid IMT. Our data suggest that frequency of hypoglycemic episodes was associated with changes in carotid atherosclerosis.

76 FR 9862 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of... endocrinologist examined him in 2010 and certified that he has had no severe hypoglycemic reactions resulting in... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of...

77 FR 65931 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or...

77 FR 5870 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or...

78 FR 56988 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-16

... and certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness... he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the...

76 FR 21792 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-18

... certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of...

77 FR 40941 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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76 FR 71112 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2011-11-16

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77 FR 74271 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2012-12-13

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77 FR 52384 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2012-08-29

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2013-06-26

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2013-08-19

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2013-04-04

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75 FR 69734 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2010-11-15

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2012-03-27

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2010-10-15

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2013-03-18

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76 FR 32012 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2011-06-02

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76 FR 25769 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2011-05-05

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77 FR 33551 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2012-06-06

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2012-01-24

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Baseline Body Mass Index and the Efficacy of Hypoglycemic Treatment in Type 2 Diabetes: A Meta-Analysis.

PubMed

Cai, Xiaoling; Yang, Wenjia; Gao, Xueying; Zhou, Lingli; Han, Xueyao; Ji, Linong

2016-01-01

The aim of this study is to compare the effects of hypoglycemic treatments in groups of patients categorized according to the mean baseline body mass indexes (BMIs). Studies were identified by a literature search and all the studies were double blind, placebo-controlled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. The electronic search was first conducted in January 2015 and repeated in June 2015. 227 studies were included. Treatment with sulfonylureas was compared with placebo in overweight patients and resulted in a significantly greater change in the HbA1c levels (weighted mean difference (WMD), -1.39%) compared to obese patients (WMD, -0.77%)(p<0.05). Treatment with metformin in overweight patients resulted in a comparable change in the HbA1c levels (WMD, -0.99%) compared to obese patients (WMD, -1.06%)(p>0.05). Treatment with alpha glucosidase inhibitors in normal weight patients was associated with a HbA1c change (WMD, -0.94%) that was comparable that in overweight (WMD, -0.72%) and obese patients (WMD, -0.56%)(p>0.05). Treatment with thiazolidinediones in normal weight patients was associated with a HbA1c change (WMD, -1.04%) that was comparable with that in overweight (WMD, -1.02%) and obese patients (WMD, -0.88%)(p>0.05). Treatment with DPP-4 inhibitors in normal weight patients was associated with a HbA1c change (WMD, -0.93%) that was comparable with that in overweight (WMD, -0.66%) and obese patients (WMD, -0.61%)(p>0.05). In total, of the seven hypoglycemic agents, regression analysis indicated that the mean baseline BMI was not associated with the mean HbA1c changes from baseline. In each kind of hypoglycemic therapy in type 2 diabetes, the baseline BMI was not associated with the efficacy of HbA1c changes from baseline.

Baseline Body Mass Index and the Efficacy of Hypoglycemic Treatment in Type 2 Diabetes: A Meta-Analysis

PubMed Central

Cai, Xiaoling; Yang, Wenjia; Gao, Xueying; Zhou, Lingli; Han, Xueyao; Ji, Linong

2016-01-01

Aim The aim of this study is to compare the effects of hypoglycemic treatments in groups of patients categorized according to the mean baseline body mass indexes (BMIs). Methods Studies were identified by a literature search and all the studies were double blind, placebo-controlled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. The electronic search was first conducted in January 2015 and repeated in June 2015. Results 227 studies were included. Treatment with sulfonylureas was compared with placebo in overweight patients and resulted in a significantly greater change in the HbA1c levels (weighted mean difference (WMD), −1.39%) compared to obese patients (WMD, −0.77%)(p<0.05). Treatment with metformin in overweight patients resulted in a comparable change in the HbA1c levels (WMD, −0.99%) compared to obese patients (WMD, −1.06%)(p>0.05). Treatment with alpha glucosidase inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.94%) that was comparable that in overweight (WMD, −0.72%) and obese patients (WMD, −0.56%)(p>0.05). Treatment with thiazolidinediones in normal weight patients was associated with a HbA1c change (WMD, −1.04%) that was comparable with that in overweight (WMD, −1.02%) and obese patients (WMD, −0.88%)(p>0.05). Treatment with DPP-4 inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.93%) that was comparable with that in overweight (WMD, −0.66%) and obese patients (WMD, −0.61%)(p>0.05). In total, of the seven hypoglycemic agents, regression analysis indicated that the mean baseline BMI was not associated with the mean HbA1c changes from baseline. Conclusion In each kind of hypoglycemic therapy in type 2 diabetes, the baseline BMI was not associated with the efficacy of HbA1c changes from baseline. PMID:27935975

Analysis of Risk Factors for Hypoglycemic Coma in 194 Patients with Type 2 Diabetes

PubMed Central

Lu, Zefen; Liu, Jianfeng; He, Qing; Chakraborty, Anindita; Zhu, Tiehong

2017-01-01

Background The present study was conducted to analyze possible risk factors in patients with type 2 diabetes who are in hypoglycemic coma. Material/Methods A total of 194 patients with type 2 diabetic hypoglycemic coma who were admitted to our hospital between January 2010 and January 2016 were included. The patients were all in coma on admission, and their blood glucose levels were lower than 2.8 mmol/L. None of the patients had type I diabetes, specific types of diabetes, or gestational diabetes. Multiple linear regression analysis was used to determine possible factors associated with hypoglycemic coma. Results Among the patients, 82 were male and 112 were female (mean age, 66.88±10.62 years). In addition, 72 patients lived in urban areas and 122 lived in rural areas. Occurrence of hypoglycemic coma was correlated with difference between urban and rural residence, glycosylated hemoglobin (HbA1c) level, combined hypertension, and combined neural complications. Self-purchased drugs resulted in significantly lower blood glucose level at the onset of hypoglycemic coma than insulin, secretagogue, or non-secretagogue drugs. Blood glucose level at onset was correlated with season. Patients living in rural areas or with combined macrovascular or microvascular complications had prolonged hospital stay and poor prognosis. Conclusions Our results demonstrate that rural residence, higher HbA1c level, combined hypertension, and combined neural complications increase the incidence of hypoglycemic coma. Use of self-purchased drugs and colder seasons may result in lower blood glucose levels in patients with hypoglycemic coma. PMID:29180613

78 FR 24795 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2013-04-26

... endocrinologist examined him in 2012 and certified that he has had no severe hypoglycemic reactions resulting in... endocrinologist examined him in 2013 and certified that he has had no severe hypoglycemic reactions resulting in... endocrinologist examined him in 2012 and certified that he has had no severe hypoglycemic reactions resulting in...

77 FR 33554 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2012-06-06

... endocrinologist examined him in 2012 and certified that he has had no severe hypoglycemic reactions resulting in... examined her in 2012 and certified that she has had no severe hypoglycemic reactions resulting in loss of... that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the...

78 FR 16032 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2013-03-13

... examined him in 2012 and certified that he has had no severe hypoglycemic reactions resulting in loss of... that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... endocrinologist examined him in 2013 and certified that he has had no severe hypoglycemic reactions resulting in...

76 FR 17475 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2011-03-29

... 2010 and certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness... endocrinologist examined him in 2011 and certified that he has had no severe hypoglycemic reactions resulting in... endocrinologist examined him in 2011 and certified that he has had no severe hypoglycemic reactions resulting in...

78 FR 79062 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2013-12-27

... endocrinologist examined him in 2013 and certified that he has had no severe hypoglycemic reactions resulting in... examined him in 2013 and certified that he has had no severe hypoglycemic reactions resulting in loss of... 2013 and certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness...

78 FR 1927 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

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2013-01-09

... examined him in 2012 and certified that he has had no severe hypoglycemic reactions resulting in loss of... endocrinologist examined him in 2012 and certified that he has had no severe hypoglycemic reactions resulting in... her in 2012 and certified that she has had no severe hypoglycemic reactions resulting in loss of...

Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes

PubMed Central

Kim, Gyuri; Lee, Yong-ho; Kang, Eun Seok; Cha, Bong-Soo; Lee, Hyun Chul

2016-01-01

Purpose The objective of this study was to investigate clinical and laboratory parameters that could predict which patients could maintain adequate glycemic control after switching from initial insulin therapy to oral hypoglycemic agents (OHAs) among patients with type 2 diabetes (T2D). Materials and Methods We recruited 275 patients with T2D who had been registered in 3 cohorts of initiated insulin therapy and followed up for 33 months. The participants were divided into 2 groups according to whether they switched from insulin to OHAs (Group I) or not (Group II), and Group I was further classified into 2 sub-groups: maintenance on OHAs (Group IA) or resumption of insulin (Group IB). Results Of 275 patients with insulin initiation, 63% switched to OHAs (Group I) and 37% continued insulin (Group II). Of these, 44% were in Group IA and 19% in Group IB. The lowest tertile of baseline postprandial C-peptide-to-glucose ratio (PCGR), higher insulin dose at switching to OHAs, and higher HbA1c level at 6 months after switching to OHAs were all associated with OHA failure (Group IB; p=0.001, 0.046, and 0.014, respectively). The lowest tertile of PCGR was associated with ultimate use of insulin (Group IB and Group II; p=0.029). Conclusion Higher baseline level of PCGR and lower HbA1c levels at 6 months after switching to OHAs may be strong predictors for the successful maintenance of OHAs after switching from insulin therapy in Korean patients with T2D. PMID:27593867

Synthesis and hypoglycemic activity of 9-O-(lipophilic group substituted) berberine derivatives.

PubMed

Zhang, Shanshan; Wang, Xiaohong; Yin, Weicheng; Liu, Zhenbao; Zhou, Mi; Xiao, Daipeng; Liu, Yanfei; Peng, Dongming

2016-10-01

A series of 9-O-(lipophilic group substituted) berberine derivatives were synthesized and evaluated for their cytotoxicity and hypoglycemic activity against HepG2 cells. All the results indicated that most of the synthesized compounds exhibited lower cytotoxicity and a certain degree of hypoglycemic activity. Especially the compounds 5g and 5h displayed dramatically increased hypoglycemic activity compared with berberine, and the cytotoxicity maintained or even lower than berberine, indicating that they are potential candidates for new anti-type 2 diabetes mellitus drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hypoglycemia in Type 2 Diabetes - More Common Than You Think

PubMed Central

Gehlaut, Richa Redhu; Dogbey, Godwin Y.; Schwartz, Frank L.; Marling, Cynthia R.; Shubrook, Jay H.

2015-01-01

Background: Hypoglycemia is often the limiting factor for intensive glucose control in diabetes management, however its actual prevalence in type 2 diabetes (T2DM) is not well documented. Methodology: A total of 108 patients with T2DM wore a continuous glucose monitoring system (CGMS) for 5 days. Rates and patterns of hypoglycemia and glycemic variability (GV) were calculated. Patient and medication factors were correlated with rates, timing, and severity of hypoglycemia. Results: Of the patients, 49.1% had at least 1 hypoglycemic episode (mean 1.74 episodes/patient/ 5 days of CGMS) and 75% of those patients experienced at least 1 asymptomatic hypoglycemic episode. There was no significant difference in the frequency of daytime versus nocturnal hypoglycemia. Hypoglycemia was more frequent in individuals on insulin (alone or in combination) (P = .02) and those on oral hypoglycemic agents (P < .001) compared to noninsulin secretagogues. CGMS analysis resulted in treatment modifications in 64% of the patients. T2DM patients on insulin exhibited higher glycemic variability (GV) scores (2.3 ± 0.6) as compared to those on oral medications (1.8 ± 0.7, P = .017). Conclusions: CGMS can provide rich data that show glucose excursions in diabetes patients throughout the day. Consequently, unwarranted onset of hypo- and hyperglycemic events can be detected, intervened, and prevented by using CGMS. Hypoglycemia was frequently unrecognized by the patients in this study (75%), which increases their potential risk of significant adverse events. Incorporation of CGMS into the routine management of T2DM would increase the detection and self-awareness of hypoglycemia resulting in safer and potentially better overall control. PMID:25917335

Hypoglycemia in Type 2 Diabetes--More Common Than You Think: A Continuous Glucose Monitoring Study.

PubMed

Gehlaut, Richa Redhu; Dogbey, Godwin Y; Schwartz, Frank L; Marling, Cynthia R; Shubrook, Jay H

2015-04-27

Hypoglycemia is often the limiting factor for intensive glucose control in diabetes management, however its actual prevalence in type 2 diabetes (T2DM) is not well documented. A total of 108 patients with T2DM wore a continuous glucose monitoring system (CGMS) for 5 days. Rates and patterns of hypoglycemia and glycemic variability (GV) were calculated. Patient and medication factors were correlated with rates, timing, and severity of hypoglycemia. Of the patients, 49.1% had at least 1 hypoglycemic episode (mean 1.74 episodes/patient/ 5 days of CGMS) and 75% of those patients experienced at least 1 asymptomatic hypoglycemic episode. There was no significant difference in the frequency of daytime versus nocturnal hypoglycemia. Hypoglycemia was more frequent in individuals on insulin (alone or in combination) (P = .02) and those on oral hypoglycemic agents (P < .001) compared to noninsulin secretagogues. CGMS analysis resulted in treatment modifications in 64% of the patients. T2DM patients on insulin exhibited higher glycemic variability (GV) scores (2.3 ± 0.6) as compared to those on oral medications (1.8 ± 0.7, P = .017). CGMS can provide rich data that show glucose excursions in diabetes patients throughout the day. Consequently, unwarranted onset of hypo- and hyperglycemic events can be detected, intervened, and prevented by using CGMS. Hypoglycemia was frequently unrecognized by the patients in this study (75%), which increases their potential risk of significant adverse events. Incorporation of CGMS into the routine management of T2DM would increase the detection and self-awareness of hypoglycemia resulting in safer and potentially better overall control. © 2015 Diabetes Technology Society.

Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats

PubMed Central

2013-01-01

Background The available drugs for diabetes, Insulin or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats. Methods Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/kg.b.w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by DMRT. Results During the short term study the aqueous extract at a dosage of 200 mg/kg.b.w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic property. Conclusions From the above results it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s). PMID:23414307

Review of patient-reported outcome instruments measuring health-related quality of life and satisfaction in patients with type 2 diabetes treated with oral therapy.

PubMed

Roborel de Climens, Aude; Tunceli, Kaan; Arnould, Benoit; Germain, Nicola; Iglay, Kristy; Norquist, Josephine; Brodovicz, Kimberly G

2015-04-01

Treatments and their mode of administration may represent a burden for patients and can therefore impact their health-related quality of life (HRQL) or treatment/health satisfaction. Patients with type 2 diabetes mellitus (T2DM) can be treated with oral hypoglycemic agents (OHAs), injectable medications (such as insulin), or a combination of agents. This review aimed to identify patient-reported outcome (PRO) instruments measuring HRQL and/or satisfaction that could differentiate between oral medications based on medication related attributes such as efficacy, tolerability, weight loss, dosing frequency and pill burden. Medline, Embase, PsycINFO, Cochrane Library and the Patient-Reported Outcome and Quality of Life Questionnaires (PROQOLID) biomedical databases were searched to identify instruments and document their development methodology, content and psychometric properties (i.e. validity, reliability), responsiveness and ability to detect changes between treatments. Nineteen instruments were retained based on their potential to differentiate between OHAs. Ten instruments assessed HRQL, amongst which the Audit of Diabetes Dependent Quality of Life, Diabetes 39, Diabetes Health Profile and Impact of Weight on Quality of Life displayed good psychometric properties in T2DM populations and comprehensive HRQL content. Nine instruments assessed satisfaction. Both the Oral Hypoglycemic Agent Questionnaire (OHAQ) and Diabetes Medication Satisfaction (DiabMedSat) Questionnaire have highly relevant content regarding drug attributes. The OHAQ is specific to oral treatment and the DiabMedSat includes HRQL items. The Diabetes Treatment Satisfaction Questionnaire is a standard instrument that is extensively used and provides conclusive results in studies of patients with T2DM. Very few of the existing PRO instruments are specific to OHAs. Despite satisfaction instruments being recommended to differentiate between OHAs in studies of T2DM based on medication attributes, we find that none of the existing instruments appear to be useful in detecting differences between treatments, therefore limiting their use in clinical and observational research.

Oral hypoglycemic activity of culinary-medicinal mushrooms Pleurotus ostreatus and P. cystidiosus (higher basidiomycetes) in normal and alloxan-induced diabetic Wistar rats.

PubMed

Jayasuriya, W J A B; Suresh, T S; Abeytunga, D; Fernando, G H; Wanigatunga, C A

2012-01-01

This study investigates the oral hypoglycemic activity of Pleurotus ostreatus (P.o.) and P. cystidiosus (P.c.) mushrooms on normal and alloxan-induced diabetic Wistar rats. Different doses (250, 500, 750, 1000, and 1250 mg/kg/body weight) of suspensions of freeze-dried and powdered (SFDP) P.o. and P.c. were administered to normal rats, and postprandial serum glucose levels were measured. Optimal time of activity was investigated using the dose 500 mg/kg. Hypoglycemic effect of a single dose of SFDP P.o. and P.c. (500 mg/kg) were investigated using diabetic male and female rats at different stages of estrous cycle and compared with metformin and glibenclamide. Chronic hypoglycemic activity of SFDP P.o. and P.c. (500 mg/kg) was studied using serum glucose levels and glycosylated hemoglobin levels. Maximally effective dose of SFDP P.o. and P.c. was 500 mg/kg. The highest reduction in the serum glucose level was observed 120 minutes after administration of mushrooms. A single dose of P.o. and P.c. significantly (P < 0.05) reduced the serum glucose levels of male diabetic rats. The hypoglycemic activity in female rats was highest in proestrous stage. The hypoglycemic effect of P.o. and P.c. is comparable with metformin and glibenclamide. Daily single administrations of P.o. and P.c. to diabetic rats exert apparent control on the homeostasis of blood glucose. SFDP P.o. and P.c. possessed marked and significant oral hypoglycemic activity. This study suggests the consumption of P.o. and P.c. mushrooms might bring health benefits to mankind as it shows hypoglycemic activity in rats.

Reduction of Insulin Related Preventable Severe Hypoglycemic Events in Hospitalized Children

PubMed Central

Poppy, Amy; Retamal-Munoz, Claudia; Cree-Green, Melanie; Wood, Colleen; Davis, Shanlee; Clements, Scott A.; Majidi, Shideh; Steck, Andrea K.; Alonso, G. Todd; Chambers, Christina; Rewers, Arleta

2018-01-01

OBJECTIVE Insulin is a commonly used, high-risk medication in the inpatient setting. Incorrect insulin administration can lead to preventable hypoglycemic events, which are a significant morbidity in inpatient diabetes care. The goal of this intervention was to decrease preventable insulin-related hypoglycemic events in an inpatient setting in a tertiary care pediatric hospital. METHODS Methods included the institution of several interventions such as nursing and physician education, electronic medical record order sets, electronic communication note templates, and the development of new care guidelines. RESULTS After the institution of multiple interventions, the rate of preventable hypoglycemic events decreased from 1.4 preventable events per 100 insulin days to 0.4 preventable events per 100 insulin days. CONCLUSIONS Through the use of a multi-interventional approach with oversight of a multidisciplinary insulin safety committee, a sustained decreased rate of severe preventable hypoglycemic events in hospitalized pediatric patients receiving insulin was achieved. PMID:27317577

Reduction of Insulin Related Preventable Severe Hypoglycemic Events in Hospitalized Children.

PubMed

Poppy, Amy; Retamal-Munoz, Claudia; Cree-Green, Melanie; Wood, Colleen; Davis, Shanlee; Clements, Scott A; Majidi, Shideh; Steck, Andrea K; Alonso, G Todd; Chambers, Christina; Rewers, Arleta

2016-07-01

Insulin is a commonly used, high-risk medication in the inpatient setting. Incorrect insulin administration can lead to preventable hypoglycemic events, which are a significant morbidity in inpatient diabetes care. The goal of this intervention was to decrease preventable insulin-related hypoglycemic events in an inpatient setting in a tertiary care pediatric hospital. Methods included the institution of several interventions such as nursing and physician education, electronic medical record order sets, electronic communication note templates, and the development of new care guidelines. After the institution of multiple interventions, the rate of preventable hypoglycemic events decreased from 1.4 preventable events per 100 insulin days to 0.4 preventable events per 100 insulin days. Through the use of a multi-interventional approach with oversight of a multidisciplinary insulin safety committee, a sustained decreased rate of severe preventable hypoglycemic events in hospitalized pediatric patients receiving insulin was achieved. Copyright © 2016 by the American Academy of Pediatrics.

The effects of hypoglycemic and alcoholic coma on the blood-brain barrier permeability

PubMed Central

Yorulmaz, Hatice; Seker, Fatma Burcu; Oztas, Baria

2011-01-01

In this investigation, the effects of hypoglycemic coma and alcoholic coma on the blood-brain barrier (BBB) permeability have been compared. Female adult Wistar albino rats weighing 180-230 g were divided into three groups: Control group (n=8), Alcoholic Coma Group (n=18), and Hypoglycemic Coma group (n=12). The animals went into coma approximately 3-4 hours after insulin administration and 3-5 minutes after alcohol administration. Evans blue (4mL/kg) was injected intravenously as BBB tracer. It was observed that the alcoholic coma did not significantly increase the BBB permeability in any of the brain regions when compared to control group. Changes in BBB permeability were significantly increased by the hypoglycemic coma in comparison to the control group values (p<0.01). Our findings suggest that hypoglycemic and alcoholic coma have different effects on the BBB permeability depending on the energy metabolism. PMID:21619558

Environmentally relevant concentrations of glibenclamide induce oxidative stress in common carp (Cyprinus carpio).

PubMed

Guadalupe Martínez-Viveros, Ericka María; Islas-Flores, Hariz; Dublán-García, Octavio; Galar-Martínez, Marcela; SanJuan-Reyes, Nely; García-Medina, Sandra; Hernández-Navarro, María Dolores; Gómez-Oliván, Leobardo Manuel

2018-04-01

The hypoglycemic pharmaceutical glibenclamide (GLB) is widely used around the world. This medication is released into the environment by municipal, hospital and industrial wastewater discharges. Although there are reports of its environmental occurrence in the scientific literature, toxicity studies on aquatic species of commercial interest such as the common carp Cyprinus carpio are scarce. The present study aimed to evaluate the oxidative stress induced on C. carpio by environmentally relevant concentrations of GLB. Biomarkers of oxidative damage such as hydroperoxide content, lipid peroxidation and protein carbonyl content were evaluated as well as the activity of the antioxidant enzymes superoxide dismutase and catalase. The concentration of GLB was determined in water as well as in gill, liver, muscle, brain and blood of carp at 12, 24, 48, 72 and 96 h. The findings obtained in the study prove that GLB induces increases in biomarkers of oxidative damage and antioxidant enzyme activity in the teleost C. carpio, that this response is not concentration dependent and that the organs evaluated bioconcentrate this hypoglycemic agent. These findings permit us to conclude that the presence of GLB in water bodies represents a risk for aquatic species. Copyright © 2018 Elsevier Ltd. All rights reserved.

Persistent hypoglycemia of unknown etiology in a patient without diabetes: a case report and review.

PubMed

White, Bryan P; Southwood, Robin

2013-04-01

This case report reviews the presentation, evaluation, and treatment of persistent hypoglycemia in a patient without a history of diabetes. The use of laboratory tests to differentiate between drug-induced and disease-induced hypoglycemia is reviewed. A 51-year-old female with multiple medical conditions including bipolar disorder and no history of diabetes was admitted for evaluation and treatment of hypoglycemia. Pharmacotherapy included intravenous dextrose infusions and bolus doses. A battery of tests was ordered to evaluate intrinsic and extrinsic causes. Endocrine Society guidelines for hypoglycemia exist and have recommendations for testing and strategies to rule out drug-related causes. Her insulin level was 57 IU/mL (normal range < 17). Her proinsulin level was 356.8 pmol/L (normal range <8.8). The guidelines recommend a battery of laboratory tests; however, the results are not rapidly available necessitating a structured follow-up process. In our patient, exposure to hypoglycemic agents and exogenous insulin can be ruled out. Autoimmune hypoglycemia or a hypoglycemic reaction to one of her home medications is very unlikely, but cannot be ruled out. An insulinoma is the most likely etiology of her hypoglycemia, but that cannot be confirmed.

A review of thiazolidinediones and metformin in the treatment of type 2 diabetes with focus on cardiovascular complications

PubMed Central

Behzad, Molavi; Negah, Rassouli; Suveer, Bagwe; Neda, Rasouli

2007-01-01

The rising incidence of obesity and insulin resistance to epidemic proportions has closely paralleled the surge in the prevalence of diabetes and outpaced therapeutic advances in diabetes prevention and treatment. Current evidence points to obesity induced oxidative stress and chronic inflammation as the common denominators in the evolution of insulin resistance and diabetes. Of all the hypoglycemic agents in the pharmacological arsenal against diabetes, thiazolidinediones, in particular pioglitazone, as well as metformin appear to have additional effects in ameliorating oxidative stress and inflammation; rendering them attractive tools for prevention of insulin resistance and diabetes. In addition to their hypoglycemic and lipid modifying properties, pioglitazone and metformin have been shown to exert anti-oxidative and anti-inflammatory effects in vascular beds, potentially slowing the accelerated atherosclerosis in diabetes, which is the major cause of morbidity and mortality in the affected population. The combination of pioglitazone and metformin would thus appear to be an effective pharmacological intervention in prevention and treatment of diabetes. Finally, this review will address the currently available evidence on diabetic cardiomyopathy and the potential role of combination therapy with pioglitazone and metformin. PMID:18200815

Murraya paniculata (L.) (Orange Jasmine): Potential Nutraceuticals with Ameliorative Effect in Alloxan-Induced Diabetic Rats.

PubMed

Menezes, Cicero Diego Almino; de Oliveira Garcia, Francisca Adilfa; de Barros Viana, Glauce Socorro; Pinheiro, Patricia Gonçalves; Felipe, Cícero Francisco Bezerra; de Albuquerque, Thaís Rodrigues; Moreira, Alisson Cordeiro; Santos, Enaide Soares; Cavalcante, Maynara Rodrigues; Garcia, Tatiana Rodrigues; Silva, Thiago Fonseca; Coutinho, Henrique Douglas Melo; de Menezes, Irwin Rose Alencar

2017-11-01

Orange jasmine, Murraya paniculata (Rutaceae), is a plant from India widely used in folk medicine as antinociceptive, antiinflammatory, and antioxidant. Although oral hypoglycemic agents and insulin are the mainstays of treatment of diabetes mellitus (DM), there is a significant demand for new natural products to reduce the development of diabetic complications. Alloxan-induced diabetic rats were treated for 60 days with a hydroalcoholic extract of M. paniculata (MPE), at doses of 100, 200, and 400 mg/kg. MPE decreased glycemia and also cholesterol and triglyceride levels, starting 1 week after treatments, as compared with the same group before treatments. Glucose values were reduced toward normality after 1 week of treatment. MPE hypoglycemic effects were potentiated by glibenclamide and metformin. MPE also decreased fructosamine and glycated hemoglobin values. MPE reduced diabetes-induced morphological alterations of the kidney, pancreas, and liver. MPE acts similarly to glibenclamide and metformin, and its glucose-lowering action is partly a consequence of ATP-sensitive K + channel inhibition. MPE may be a potential therapeutic alternative for the treatment of diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Unraveling the active hypoglycemic agent trigonelline in Balanites aegyptiaca date fruit using metabolite fingerprinting by NMR.

PubMed

Farag, Mohamed A; Porzel, Andrea; Wessjohann, Ludger A

2015-11-10

Trigonelline (3-carboxy-1-methyl pyridinium) was identified as a relevant bioactivity and taste imparting component in Balanites aegyptiaca fruit, using (1)H NMR of crude extracts without any fractionation or isolation step. The structural integrity of trigonelline was established within the extract matrix via(1)H NMR, (1)H-(1)H COSY, HMQC and HMBC and by comparison with authentic standard. A quantitative (1)H NMR method (qHNMR) was used to determine trigonelline concentrations in the peel and pulp of B. aegyptiaca fruit of 8 and 13mgg(-1), respectively. Trigonelline so far has not been reported from B. aegyptiaca or its genus as it easily escapes LC-MS based detection. Its discovery provides novel insight into the balanite fruits antidiabetic properties as the compound is known for a pronounced hypoglycemic effect. In addition, it is likely to impart the perceptible bitter taste portion to balanites sweet bitter taste. UPLC-MS of the crude extract additionally revealed the fruit flavonoid pattern showing quercetin/isorhamnetin flavonol conjugates in addition to epicatechin, the latter being present at much lower levels. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel D-phenylalanine-derivative hypoglycemic agent A-4166 increases cytosolic free Ca2+ in rat pancreatic beta-cells by stimulating Ca2+ influx.

PubMed

Fujitani, S; Yada, T

1994-03-01

It has recently been shown that N-[(trans-4-isopropylcyclohexyl)-carbonyl]D-phenylalanine (A-4166), a new nonsulfonylurea oral hypoglycemic agent, reduces blood glucose levels in nondiabetic and diabetic animals in a quicker and shorter lasting manner than sulfonylureas, and that the hypoglycemic effect of A-4166 is due to the stimulation of insulin release. However, the mechanism by which A-4166 stimulates insulin release is still unknown. In the present study, we investigated the effect of A-4166 on the cytosolic free Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells from normal rats by dual wavelength fura-2 microfluorometry. In the presence of 2.8 mM glucose, A-4166 produced a rapid increase in [Ca2+]i in a concentration-dependent manner over the range of 3-30 microM. The increase in [Ca2+]i was transient, oscillatory, or sustained. A-4166 did not evoke any decrease in [Ca2+]i, whereas a high concentration of glucose (16.7 mM), a metabolized secretagogue, produced an initial decrease and a subsequent increase in [Ca2+]i. In the presence of 16.7 mM glucose, low concentrations (0.03-1 microM) of A-4166 produced an increase in [Ca2+]i in some of the beta-cells tested. The [Ca2+]i response to A-4166 was completely and reversibly inhibited under Ca(2+)-free conditions as well as by nitrendipine, a blocker of the L-type Ca2+ channel. Nitrendipine also inhibited insulin release from perfused rat pancreases stimulated by A-4166. Diazoxide, an opener of the ATP-sensitive K+ channel, blocked the [Ca2+]i response to A-4166. Sulfonylureas such as tolbutamide and glibenclamide increased [Ca2+]i in a manner similar to A-4166. These results indicate that at basal glucose concentrations, A-4166 increases [Ca2+]i in rat pancreatic beta-cells by stimulating Ca2+ influx through L-type Ca2+ channels, and that this effect is markedly augmented at elevated glucose concentrations. It appears that the increase in [Ca2+]i is related to the stimulation of insulin release by A-4166. Inhibition of ATP-sensitive potassium channels, but not stimulation of beta-cell metabolism, may be involved in the increase in [Ca2+]i by A-4166.

The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats.

PubMed

Pushparaj, P N; Tan, B K; Tan, C H

2001-12-21

In the present study, we have examined the possible mechanism of the hypoglycemic action of the semi-purified fractions of an ethanolic extract of Averrhoa bilimbi Linn (Oxalidaceae) leaves (ABe) in streptozotocin-diabetic male Sprague-Dawley (SD) rats. The ABe was partitioned with water and butanol to yield a butanol-soluble fraction (BuF) and a water-soluble fraction (AF). The AF was further partitioned with ethyl acetate and hexane to obtain ethyl acetate (EF) and hexane (HF) soluble fractions. The hypoglycemic property of each fraction was assessed by the oral glucose tolerance test (OGTT) at a dose of 125-mg/kg-body weight in streptozotocin (STZ)-diabetic rats (STZ 60 mg/kg i.p.). Fractions AF, BuF and the reference drug metformin (500 mg/kg body weight), produced significant blood glucose-lowering effect in the diabetic rats when compared to the vehicle (distilled water). In the long-term study, the diabetic rats were randomly divided into 4 groups and treated orally by gavage with vehicle, AF (125 mg/kg body weight), BuF (125 mg/kg body weight), and metformin (500 mg/kg body weight) respectively twice a day for 14 days. On day 7 and day 14, AF and BuF, like the reference drug, metformin, lowered the fasting blood glucose concentration significantly (P < 0.05) when compared with the vehicle. The serum insulin level was significantly increased in the AF-treated rats only on day 14 when compared to that in the vehicle-treated rats on day zero (P < 0.05). The serum insulin level in BuF-treated rats was also significantly higher (P < 0.05) on both day 7 and day 14 compared to that on day zero. Hepatic glucose-6-phosphatase activity was significantly lower (P<0.05) in AF- and metformin-treated groups, but not in BuF-treated groups, compared to that in vehicle-treated group. However, there was no change in hepatic glycogen content in AF-, BuF- and metformin-treated group compared to the vehicle-treated group. These results indicate that AF is more potent than BuF in the amelioration of hyperglycemia in STZ-diabetic rats and is a potential source for the isolation of new orally active agent(s) for anti-diabetic therapy.

Hypoglycemic effects of Trichosanthes kirilowii and its protein constituent in diabetic mice: the involvement of insulin receptor pathway.

PubMed

Lo, Hsin-Yi; Li, Tsai-Chung; Yang, Tse-Yen; Li, Chia-Cheng; Chiang, Jen-Huai; Hsiang, Chien-Yun; Ho, Tin-Yun

2017-01-18

Diabetes is a serious chronic metabolic disorder. Trichosanthes kirilowii Maxim. (TK) is traditionally used for the treatment of diabetes in traditional Chinese medicine (TCM). However, the clinical application of TK on diabetic patients and the hypoglycemic efficacies of TK are still unclear. A retrospective cohort study was conducted to analyze the usage of Chinese herbs in patients with type 2 diabetes in Taiwan. Glucose tolerance test was performed to analyze the hypoglycemic effect of TK. Proteomic approach was performed to identify the protein constituents of TK. Insulin receptor (IR) kinase activity assay and glucose tolerance tests in diabetic mice were further used to elucidate the hypoglycemic mechanisms and efficacies of TK. By a retrospective cohort study, we found that TK was the most frequently used Chinese medicinal herb in type 2 diabetic patients in Taiwan. Oral administration of aqueous extract of TK displayed hypoglycemic effects in a dose-dependent manner in mice. An abundant novel TK protein (TKP) was further identified by proteomic approach. TKP interacted with IR by docking analysis and activated the kinase activity of IR. In addition, TKP enhanced the clearance of glucose in diabetic mice in a dose-dependent manner. In conclusion, this study applied a bed-to-bench approach to elucidate the hypoglycemic efficacies and mechanisms of TK on clinical usage. In addition, we newly identified a hypoglycemic protein TKP from TK. Our findings might provide a reasonable explanation of TK on the treatment of diabetes in TCM.

[Study on the extraction technology and hypoglycemic activity of lectin from Trichosanthes kirilowi].

PubMed

Li, Qiong; Ye, Xiao-Li; Zeng, Hong; Chen, Xin; Li, Xue-Gang

2012-03-01

To extract lectins from Trichosanthes kirilowi and study their hypoglycemic activity. The optimal extraction process included the following parameters were conformed by optimization analysis,lectins extracted from Trichosanthes kirilowi was achieved by ammonium sulfate precipitation; The agglutinate activity was determined by using the agglutination test with 5% human blood cells. Human hepatocarcinoma cell HepG2 and the alloxan-induced diabetic mice model were used to assess hypoglycemic activity of Lectin in Trichosanthes kirilowi. The agglutination indexes of lectins extraction buffer were 32; The cell and mice tests indicated that the lectins exhibited hypoglycemic activity in the 70% saturation. The optimum extraction technology is as follows: extraction with PBS, the material-water ratio is 1:30, the extraction time is 24 h, while the concentration of sodium chloride is 0 mol/L and pH is 7.2. Precipitate lectins by ammonium sulfate in the 70% saturation, centrifugal speed is 10 000 tracted from Trichosanthes kirilowi exposes proper hypoglycemic activity.

Combination of HPLC chromatogram and hypoglycemic effect identifies isoflavones as the principal active fraction of Belamcanda chinensis leaf extract in diabetes treatment.

PubMed

Chen, Yan; Wu, Chong-Ming; Dai, Rong-Ji; Li, Liang; Yu, Yu-Hong; Li, Yan; Meng, Wei-Wei; Zhang, Liang; Zhang, Yongqian; Deng, Yu-Lin

2011-02-15

In previous study, we demonstrated the hypoglycemic effect of aqueous extract of Belamcanda chinensis leaves in rats. Here, we separated the aqueous extract of B. chinensis leaves and investigated the spectrum-effect relationships between HPLC chromatograms and hypoglycemic activities of different isolates from B. chinensis leaf extract. Sequential solvent extraction with petroleum ether, chloroform, acetic ester and n-butanol provided several isolates showing similar hypoglycemic activities, making it difficult to discriminate the active fractions. Stepwise elution through HP20 macroporous resin by water, 40% and 95% ethanol provided isolates with distinct hypoglycemic activities, representing a simple, rapid and efficient preparative separation method. Combination of HPLC chromatogram and pharmacological effect targeted a hypoglycemic activity-related region in HPLC chromatogram. Each peak in this region was analyzed by UV spectrum scan. Most of them were flavonoids in which tectoridin and swertisin were known flavonoids with anti-diabetic activities. In together, this work provides a general model of combination of HPLC chromatography and pharmacological effect to study the spectrum-effect relationships of aqueous extract from B. chinensis leaves, which can be used to find principle components of B. chinensis on pharmacological activity. Copyright © 2011 Elsevier B.V. All rights reserved.

Safety of once-daily insulin detemir in patients with type 2 diabetes treated with oral hypoglycemic agents in routine clinical practice.

PubMed

Ross, Stuart; Dzida, Grzegorz; Ji, Qiuhe; Kaiser, Marcel; Ligthelm, Robert; Meneghini, Luigi; Nazeri, Avideh; Orozco-Beltran, Domingo; Pan, Changyu; Svendsen, Anne Louise

2014-05-01

The aim of the present study was to identify demographic and treatment factors that were predictive of hypoglycemia in a large cohort of type 2 diabetic patients initiating insulin detemir. The present 24-week observational study of insulin initiation included 17 374 participants from 10 countries. Severe hypoglycemia was defined as an event requiring third party assistance; minor hypoglycemia was defined as a daytime or nocturnal glucose measurement <3.1 mmol/L. Prior to initiating insulin therapy, 4.9% of the cohort reported hypoglycemia (pre-insulin hypoglycemia), with most (94.2%) reporting minor events and 9.6% reporting severe events. Compared with patients without pre-insulin hypoglycemia, those with pre-insulin hypoglycemia had a higher incidence of events of minor hypoglycemia (1.72 vs 4.46 events per patient-year [ppy], respectively), nocturnal hypoglycemia (0.25 vs 1.09 events ppy, respectively), and severe hypoglycemia (<0.01 vs 0.04 events ppy, respectively) at final visit. Age (P < 0.047), body mass index (P < 0.001), a prior history of microvascular disease (P < 0.001), pre-insulin hypoglycemia (P < 0.001), increased number of oral hypoglycemic agents (OHAs; P < 0.001), OHA intensification (P < 0.001), and the use of glinides (P = 0.004) were all found to be independently associated with the occurrence of hypoglycemia during the study. Once-daily insulin detemir therapy was safe and effective, and rates of hypoglycemia were low. Concerns about hypoglycemia should not deter the initiation of basal insulin analogs. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Collaborative care for patients with depression and diabetes mellitus: a systematic review and meta-analysis.

PubMed

Huang, Yafang; Wei, Xiaoming; Wu, Tao; Chen, Rui; Guo, Aimin

2013-10-14

Diabetic patients with depression are often inadequately treated within primary care. These comorbid conditions are associated with poor outcomes. The aim of this systematic review was to examine whether collaborative care can improve depression and diabetes outcomes in patients with both depression and diabetes. Medline, Embase, Cochrane library and PsyINFO were systematically searched to identify relevant publications. All randomized controlled trials of collaborative care for diabetic patients with depression of all ages who were reported by depression treatment response, depression remission, hemoglobin A1c (HbA1c) values, adherence to antidepressant medication and/or oral hypoglycemic agent were included. Two authors independently screened search results and extracted data from eligible studies. Dichotomous and continuous measures of outcomes were combined using risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) either by fixed or random-effects models. Eight studies containing 2,238 patients met the inclusion criteria. Collaborative care showed a significant improvement in depression treatment response (RR = 1.33, 95% CI = 1.05-1.68), depression remission (adjusted RR = 1.53, 95% CI =1.11-2.12), higher rates of adherence to antidepressant medication (RR = 1.79, 95% CI = 1.19-2.69) and oral hypoglycemic agent (RR = 2.18, 95% CI = 1.61-2.96), but indicated a non-significant reduction in HbA1c values (MD = -0.13, 95% CI = -0.46-0.19). Improving depression care in diabetic patients is very necessary and important. Comparing with usual care, collaborative care was associated with significantly better depressive outcomes and adherence in patients with depression and diabetes. These findings emphasize the implications for collaborative care of diabetic patients with depression in the future.

Prescription drug therapy in the podiatric outpatient population: interactions and precautions.

PubMed

Dickinson, B D; Alley, P; Price, T W; Simeone, L A

1988-04-01

A survey of 2,000 outpatients at the clinic of the Dr. William M. Scholl College of Podiatric Medicine was conducted analyzing both medications reported by the patients at the time of treatment and drugs by the attending podiatrist. The major groups of medications already used by the patients included diuretics, vitamins and minerals, nonsteroidal antiinflammatory drugs, cardiovascular medications, insulin and oral hypoglycemics, estrogen and thyroid hormone replacement, and antibiotics. Patients with asthma, ulcers, epilepsy, affective disorders and Parkinsonism represented significant subgroups. The major drugs used by podiatrists in the outpatient clinic included analgesics and antiinflammatory agents, local anesthetics, antibiotics, sedative-hypnotics, and a variety of topical agents. These two sources of medication serve as the basis for a review of drug interactions in the podiatric outpatient population. In addition, precautions for the use of drugs commonly administered by podiatrists are reviewed.

Evaluation of a novel continuous glucose measurement device in patients with diabetes mellitus across the glycemic range.

PubMed

Morrow, Linda; Hompesch, Marcus; Tideman, Ann M; Matson, Jennifer; Dunne, Nancy; Pardo, Scott; Parkes, Joan L; Schachner, Holly C; Simmons, David A

2011-07-01

This glucose clamp study assessed the performance of an electrochemical continuous glucose monitoring (CGM) system for monitoring levels of interstitial glucose. This novel system does not require use of a trocar or needle for sensor insertion. Continuous glucose monitoring sensors were inserted subcutaneously into the abdominal tissue of 14 adults with type 1 or type 2 diabetes. Subjects underwent an automated glucose clamp procedure with four consecutive post-steady-state glucose plateau periods (40 min each): (a) hypoglycemic (50 mg/dl), (b) hyperglycemic (250 mg/dl), (c) second hypoglycemic (50 mg/dl), and (d) euglycemic (90 mg/dl). Plasma glucose results obtained with YSI glucose analyzers were used for sensor calibration. Accuracy was assessed retrospectively for plateau periods and transition states, when glucose levels were changing rapidly (approximately 2 mg/dl/min). Mean absolute percent difference (APD) was lowest during hypoglycemic plateaus (11.68%, 14.15%) and the euglycemic-to-hypoglycemic transition (14.21%). Mean APD during the hyperglycemic plateau was 17.11%; mean APDs were 18.12% and 19.25% during the hypoglycemic-to-hyperglycemic and hyperglycemic-to-hypoglycemic transitions, respectively. Parkes (consensus) error grid analysis (EGA) and rate EGA of the plateaus and transition periods, respectively, yielded 86.8% and 68.6% accurate results (zone A) and 12.1% and 20.0% benign errors (zone B). Continuous EGA yielded 88.5%, 75.4%, and 79.3% accurate results and 8.3%, 14.3%, and 2.4% benign errors for the euglycemic, hyperglycemic, and hypoglycemic transition periods, respectively. Adverse events were mild and unlikely to be device related. This novel CGM system was safe and accurate across the clinically relevant glucose range. © 2011 Diabetes Technology Society.

Evaluation of a Novel Continuous Glucose Measurement Device in Patients with Diabetes Mellitus across the Glycemic Range

PubMed Central

Morrow, Linda; Hompesch, Marcus; Tideman, Ann M; Matson, Jennifer; Dunne, Nancy; Pardo, Scott; Parkes, Joan L; Schachner, Holly C; Simmons, David A

2011-01-01

Background This glucose clamp study assessed the performance of an electrochemical continuous glucose monitoring (CGM) system for monitoring levels of interstitial glucose. This novel system does not require use of a trocar or needle for sensor insertion. Method Continuous glucose monitoring sensors were inserted subcutaneously into the abdominal tissue of 14 adults with type 1 or type 2 diabetes. Subjects underwent an automated glucose clamp procedure with four consecutive post-steady-state glucose plateau periods (40 min each): (a) hypoglycemic (50 mg/dl), (b) hyperglycemic (250 mg/dl), (c) second hypoglycemic (50 mg/dl), and (d) euglycemic (90 mg/dl). Plasma glucose results obtained with YSI glucose analyzers were used for sensor calibration. Accuracy was assessed retrospectively for plateau periods and transition states, when glucose levels were changing rapidly (approximately 2 mg/dl/min). Results Mean absolute percent difference (APD) was lowest during hypoglycemic plateaus (11.68%, 14.15%) and the euglycemic-to-hypoglycemic transition (14.21%). Mean APD during the hyperglycemic plateau was 17.11%; mean APDs were 18.12% and 19.25% during the hypoglycemic-to-hyperglycemic and hyperglycemic-to-hypoglycemic transitions, respectively. Parkes (consensus) error grid analysis (EGA) and rate EGA of the plateaus and transition periods, respectively, yielded 86.8% and 68.6% accurate results (zone A) and 12.1% and 20.0% benign errors (zone B). Continuous EGA yielded 88.5%, 75.4%, and 79.3% accurate results and 8.3%, 14.3%, and 2.4% benign errors for the euglycemic, hyperglycemic, and hypoglycemic transition periods, respectively. Adverse events were mild and unlikely to be device related. Conclusion This novel CGM system was safe and accurate across the clinically relevant glucose range. PMID:21880226

Impact of Retrospective Calibration Algorithms on Hypoglycemia Detection in Newborn Infants Using Continuous Glucose Monitoring

PubMed Central

Signal, Matthew; Le Compte, Aaron; Harris, Deborah L.; Weston, Philip J.; Harding, Jane E.

2012-01-01

Abstract Background Neonatal hypoglycemia is common and may cause serious brain injury. Diagnosis is by blood glucose (BG) measurements, often taken several hours apart. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing the number of BG measurements. Calibration algorithms convert sensor signals into CGM output. Thus, these algorithms directly affect measures used to quantify hypoglycemia. This study was designed to quantify the effects of recalibration and filtering of CGM data on measures of hypoglycemia (BG <2.6 mmol/L) in neonates. Subjects and Methods CGM data from 50 infants were recalibrated using an algorithm that explicitly recognized the high-accuracy BG measurements available in this study. CGM data were analyzed as (1) original CGM output, (2) recalibrated CGM output, (3) recalibrated CGM output with postcalibration median filtering, and (4) recalibrated CGM output with precalibration median filtering. Hypoglycemia was classified by number of episodes, duration, severity, and hypoglycemic index. Results Recalibration increased the number of hypoglycemic events (from 161 to 193), hypoglycemia duration (from 2.2% to 2.6%), and hypoglycemic index (from 4.9 to 7.1 μmol/L). Median filtering postrecalibration reduced hypoglycemic events from 193 to 131, with little change in duration (from 2.6% to 2.5%) and hypoglycemic index (from 7.1 to 6.9 μmol/L). Median filtering prerecalibration resulted in 146 hypoglycemic events, a total duration of hypoglycemia of 2.6%, and a hypoglycemic index of 6.8 μmol/L. Conclusions Hypoglycemia metrics, especially counting events, are heavily dependent on CGM calibration BG error, and the calibration algorithm. CGM devices tended to read high at lower levels, so when high accuracy calibration measurements are available it may be more appropriate to recalibrate the data. PMID:22856622

Impact of retrospective calibration algorithms on hypoglycemia detection in newborn infants using continuous glucose monitoring.

PubMed

Signal, Matthew; Le Compte, Aaron; Harris, Deborah L; Weston, Philip J; Harding, Jane E; Chase, J Geoffrey

2012-10-01

Neonatal hypoglycemia is common and may cause serious brain injury. Diagnosis is by blood glucose (BG) measurements, often taken several hours apart. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing the number of BG measurements. Calibration algorithms convert sensor signals into CGM output. Thus, these algorithms directly affect measures used to quantify hypoglycemia. This study was designed to quantify the effects of recalibration and filtering of CGM data on measures of hypoglycemia (BG <2.6 mmol/L) in neonates. CGM data from 50 infants were recalibrated using an algorithm that explicitly recognized the high-accuracy BG measurements available in this study. CGM data were analyzed as (1) original CGM output, (2) recalibrated CGM output, (3) recalibrated CGM output with postcalibration median filtering, and (4) recalibrated CGM output with precalibration median filtering. Hypoglycemia was classified by number of episodes, duration, severity, and hypoglycemic index. Recalibration increased the number of hypoglycemic events (from 161 to 193), hypoglycemia duration (from 2.2% to 2.6%), and hypoglycemic index (from 4.9 to 7.1 μmol/L). Median filtering postrecalibration reduced hypoglycemic events from 193 to 131, with little change in duration (from 2.6% to 2.5%) and hypoglycemic index (from 7.1 to 6.9 μmol/L). Median filtering prerecalibration resulted in 146 hypoglycemic events, a total duration of hypoglycemia of 2.6%, and a hypoglycemic index of 6.8 μmol/L. Hypoglycemia metrics, especially counting events, are heavily dependent on CGM calibration BG error, and the calibration algorithm. CGM devices tended to read high at lower levels, so when high accuracy calibration measurements are available it may be more appropriate to recalibrate the data.

Evaluation of the In Vivo Therapeutic Effects of Radix Paeoniae Rubra Ethanol Extract with the Hypoglycemic Activities Measured from Multiple Cell-Based Assays

PubMed Central

Chang, Chia-Chuan; Yuan, Wei; Lin, Yun-Lian; Liu, Ren-Shyan; Juan, Yi-Chen; Sun, Wan-Hua; Tsay, Huey Jen; Lee, Yu-Ching

2016-01-01

Background. Radix Paeoniae Rubra (Chi Shao) contains several phytochemicals with hypoglycemic actions. Current research aims to explore potential insulinotropic effects and long-term therapeutic efficacy of such herb against type 2 diabetes. Methods. Composition analysis for the ethanol extract (PRExt) was executed by high performance liquid chromatography. Polyphenol-enriched fraction was characterized by high pressure size exclusion chromatography. Multiple cell platforms were employed to evaluate hypoglycemic bioactivities. In animal experiments, blood glucose, the homeostasis model assessment (HOMA)-index assessment, glucose tolerance test, and in vivo glucose uptake were all measured. Additional effects of PRExt on obesity and hepatic steatosis were evaluated by serum and histological analysis. Results. PRExt provides multiple hypoglycemic effects including the enhancement of glucose-mediated insulin secretion. Pentagalloylglucose and polyphenol-enriched fraction are two insulinotropic constituents. Moreover, PRExt intraperitoneal injection causes acute hypoglycemic effects on fasted db/db mice. Oral administration of PRExt (200 mg/kg b.w.) gradually reduces blood glucose in db/db mice to the level similar to that in C57J/B6 mice after 30 days. The improvement of glucose intolerance, HOMA-index, and in vivo glucose uptake is evident in addition to the weight loss effect and attenuation of hepatic steatosis. Conclusion. PRExt is an effective antidiabetic herbal extract with multiple hypoglycemic bioactivities. PMID:28018473

A review of the efficacy and safety of oral antidiabetic drugs

PubMed Central

Stein, Stephanie Aleskow; Lamos, Elizabeth Mary; Davis, Stephen N

2014-01-01

Introduction Additional oral antidiabetic agents to metformin, sulfonylureas (SU) and thiazolidinediones (TZD) are approved for the treatment of type 2 diabetes. Areas covered The efficacy and safety of metformin, SUs, TZDs, dipeptidyl peptidase-IV (DPP-4) inhibitors, meglitinide analogs, α-glucosidase inhibitors (AGIs), bile-acid sequestrants (BAS) and bromocriptine will be reviewed. Expert opinion Several new oral agents have been approved for type 2 diabetes management in recent years. It is important to understand the efficacy and safety of these medications in addition to the older agents to best maximize oral drug therapy for diabetes. Of the recently introduced oral hypoglycemic/antihyperglycemic agents, the DPP-4 inhibitors are moderately efficacious compared with mainstay treatment with metformin with a low side-effect profile and have good efficacy in combination with other oral agents and insulin. They are a recommended alternative when metformin use is limited by gastrointestinal (GI) side effects or when SU treatment results in significant hypoglycemia or weight gain. Meglitinide analogs are limited by their frequent dosing, expense and hypoglycemia (repaglinide > nateglinide), while AGIs are also limited by their dosing schedule and GI side-effect profile. BAS and bromocriptine have the lowest efficacy with regard to HbA1c reduction, also are plagued by GI adverse reactions, but have a low risk of hypoglycemia. PMID:23241069

[Type 2 diabetes mellitus: new treatments].

PubMed

Ascaso, Juan F

2014-08-04

The benefits and problems associated with traditional hypoglycemic drugs, such as failure of beta cells, hypoglycemia and weight gain, that lead to a worsening of diabetes, are reviewed. New hypoglycemic drugs with incretin effect (glucagon-like peptide-1 agonists and dipeptidyl peptidase 4 inhibitors), achieve, in a glucose dependent manner, an glycosylated hemoglobin reduction without hypoglycemia or increase in body weight. Recently, another group of oral hypoglycemic drugs, sodium-glucose cotransporter type 2 inhibitors, have demonstrated efficacy in diabetes control by inhibiting renal glucose reabsorption. However, long-term effects and cardiovascular prevention remain to be demonstrated. We have more and better drugs nowadays. Hypoglycemic treatment should be customized (glycosylated hemoglobin levels, risk-benefit, risk of hypoglycemia, weight changes, cardiovascular risk), with a combination of drugs being necessary in most cases. However, we do not have yet an ideal hypoglycemic drug. Moreover we must remember that an early and intensive treatment of dyslipidemia and hypertension is essential for the prevention of cardiovascular disease in patients with type 2 diabetes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Microencapsulation Approach for Orally Extended Delivery of Glipizide: In vitro and in vivo Evaluation

PubMed Central

Abdelbary, A.; El-gendy, N. A.; Hosny, A.

2012-01-01

Glipizide is an effective antidiabetic agent, however, it suffers from relatively short biological half-life. To solve this encumbrance, it is a prospective candidate for fabricating glipizide extended release microcapsules. Microencapsulation of glipizde with a coat of alginate alone or in combination with chitosan or carbomer 934P was prepared employing ionotropic gelation process. The prepared microcapsules were evaluated in vitro by microscopical examination, determination of the particle size, yield and microencapsulation efficiency. The filled capsules were assessed for content uniformity and drug release characteristics. Stability study of the optimised formulas was carried out at three different temperatures over 12 weeks. In vivo bioavailability study and hypoglycemic activity of C9 microcapsules were done on albino rabbits. All formulas achieved high yield, microencapsulation efficiency and extended t1/2. C9 and C19 microcapsules attained the most optimised results in all tests and complied with the dissolution requirements for extended release dosage forms. These two formulas were selected for stability studies. C9 exhibited longer shelf-life and hence was chosen for in vivo studies. C9 microcapsules showed an improvement in the drug bioavailability and significant hypoglycemic activity compared to immediate release tablets (Minidiab® 5 mg). The optimised microcapsule formulation developed was found to produce extended antidiabetic activity. PMID:23626387

Structure determination of metabolites isolated from urine and bile after administration of AY4166, a novel D-phenylalanine-derivative hypoglycemic agent.

PubMed

Takesada, H; Matsuda, K; Ohtake, R; Mihara, R; Ono, I; Tanaka, K; Naito, M; Yatagai, M; Suzuki, E

1996-10-01

Molecular structures of 10 metabolites, which were isolated from urine (M1-M8) or bile (M9 and M10) after administration of AY4166 (N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine), a novel amino acid derivative with hypoglycemic activity, have been elucidated by mass spectrometry and nuclear magnetic resonance. Four of these (M1, M2, M3 and M8) were determined to be hydroxyl derivatives of AY4166, two (M9 and M10) were carboxylate derivatives via oxidization of M2 and M3, three (M4, M5 and M6) were glucronic acid conjugates and the other (M7) was a dehydro derivative. The estimated structures for M1, M2, M3, M7, M8, M9 and M10 were confirmed by the coincidence of the retention time of HPLC, MS and 1H NMR spectra between the isolated metabolites and authentic synthesized substances. For three glucronic acid conjugates, M4, M5 and M6, structural confirmation was performed by a selective enzymatic digestion with beta-glucronidase. M1 and M2/3 were about 5-6 and 3 times less potent than AY4166, respectively, and M7 was almost as potent as AY4166.

Hypoglycemic effect of hawthorn in type II diabetes mellitus rat model.

PubMed

Aierken, Aili; Buchholz, Tina; Chen, Chen; Zhang, Xiaoying; Melzig, Matthias F

2017-10-01

Hawthorn is a popular herb in many different traditional medicine systems, including traditional Chinese medicine, where it has long been used for the treatment of hyperglycemia. However, most of its varied biological activities remain unexplored. This study investigated the hypoglycemic effect of hawthorn extracts in type II diabetic (T2DM) rat model. A total of 54 rats were randomly divided into six groups: normal control group; type II diabetic model group (T2DM; these rats were induced by high-fat diet and streptozotocin); high, middle and low concentrations of hawthorn treatment (HT H , HT M and HT L T2DM rats were given hawthorn extract at a dose of 50, 100 and 200 mg kg -1 body weight, respectively); and positive control group (orlistat 40 mg kg -1 body weight). Triglyceride and total cholesterol serum levels were lower in the hawthorn extract-treated groups than in the T2DM control group (P < 0.01). Furthermore, hawthorn extracts decreased blood glucose level and increased plasma insulin release from pancreas. Positive effects of hawthorn against streptozotocin-induced T2DM were demonstrated. This study suggests that hawthorn extract represents a useful agent for the prevention or treatment of T2DM. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Biological activity studies of the novel glucagon-like peptide-1 derivative HJ07.

PubMed

Han, Jing; Sun, Li-Dan; Qian, Hai; Huang, Wen-Long

2014-08-01

To identify the glucose lowering ability and chronic treatment effects of a novel coumarin-glucagon-like peptide-1 (GLP-1) conjugate HJ07. A receptor activation experiment was performed in HEK 293 cells and the glucose lowering ability was evaluated with hypoglycemic duration and glucose stabilizing tests. Chronic treatment was performed by daily injection of exendin-4, saline, and HJ07. Body weight and HbA1c were measured every week, and an intraperitoneal glucose tolerance test was performed before treatment and after treatment. HJ07 showed well-preserved receptor activation efficacy. The hypoglycemic duration test showed that HJ07 possessed a long-acting, glucose-lowering effect and the glucose stabilizing test showed that the antihyperglycemic activity of HJ07 was still evident at a predetermined time (12 h) prior to the glucose challenge (0 h). The long time glucose-lowering effect of HJ07 was better than native GLP-1 and exendin-4. Furthermore, once daily injection of HJ07 to db/db mice achieved long-term beneficial effects on HbA1c lowering and glucose tolerance. The biological activity results of HJ07 suggest that HJ07 is a potential long-acting agent for the treatment of type 2 diabetes. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Hypoglycemic effects of an aqueous extract of Bauhinia forficata on the salivary glands of diabetic mice.

PubMed

Curcio, Sergio Augusto Fudaba; Stefan, Luciana Francine Bocchi; Randi, Bruno Azevedo; Dias, Marco Antonio; da Silva, Rodrigo Eduardo; Caldeira, Eduardo José

2012-07-01

The objective of this study was to evaluate the salivary glands in diabetic mice, analyzing alterations in the secretory epithelium and interactions with the stromal compartment acquired during a prolonged period of treatment with Bauhinia forficata extract. Female mice were divided into two groups: Nonobese diabetic (NOD) mice treated with Bauhinia forficata (I), and NOD mice not treated with the hypoglycemic agent (II). After treatment, the salivary glands were collected for analysis by transmitted and polarized light microscopy, complemented by three-dimensional analysis of these tissues. The results showed weight loss in animals of group II and weight recovery in treated animals. Glucose levels were elevated in group II, but declined in group I. In the two groups, the salivary glands were characterized by involution of the secretory epithelium, presence of an inflammatory infiltrate and an increase of extracellular fibrillar components. It can be concluded that treatment with Bauhinia forficata reduced glucose levels and contributed to weight recovery in treated animals. However, the observation of tissue destructuring and compromised epithelial-stromal interactions, with consequent impairment of glandular function, demonstrates that Bauhinia forficata exerts an effect on the recovery of body metabolism but this improvement does not influence in the tissue recovery.

Guar by-product improves carbohydrate tolerance in healthy human subjects.

PubMed

Track, N S; Lai, V W; Chiu, S S

1985-08-01

Guar gum possesses distinct hypoglycemic properties. The other fraction of the guar bean, guar by-product (GBP), was studied to determine if it possesses any hypoglycemic properties. When 25 g GBP or wheat bran were consumed with a carbohydrate test meal by 10 healthy subjects, at 15 and 30 min after the GBP test meal significantly lower normalized plasma glucose responses were measured. Postprandial plasma insulin responses were similar after both test meals. During the first 60 min postprandially, the mean integrated plasma glucose response area was significantly lower after the GBP test meal. These data indicate that GBP, like guar gum, possesses hypoglycemic properties; because of the different chemical characteristics of these 2 guar bean fractions, it seems that their hypoglycemic properties are due probably to different mechanisms.

Hypoglycemia induced behavioural deficit and decreased GABA receptor, CREB expression in the cerebellum of streptozoticin induced diabetic rats.

PubMed

Sherin, A; Peeyush, K T; Naijil, G; Chinthu, R; Paulose, C S

2010-11-20

Intensive glycemic control during diabetes is associated with an increased incidence of hypoglycemia, which is the major barrier in blood glucose homeostasis during diabetes therapy. The CNS neurotransmitters play an important role in the regulation of glucose homeostasis. In the present study, we showed the effects of hypoglycemia in diabetic and non- diabetic rats on motor functions and alterations of GABA receptor and CREB expression in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. Scatchard analysis of [(3)H]GABA binding in the cerebellum of diabetic hypoglycemic and control hypoglycemic rats showed significant (P<0.01) decrease in B(max) and K(d) compared to diabetic and control rats. Real-time PCR amplification of GABA receptor subunit GABA(Aα1) and GAD showed significant (P<0.001) down-regulation in the cerebellum of hypoglycemic rats compared to diabetic and control rats. Confocal imaging study confirmed the decreased GABA receptors in hypoglycemic rats. CREB mRNA expression was down-regulated during recurrent hypoglycemia. Both diabetic and non-diabetic hypoglycemic rats showed impaired performance in grid walk test compared to diabetic and control. Impaired GABA receptor and CREB expression along with motor function deficit were more prominent in hypoglycemic rats than hyperglycemic which showed that hypoglycemia is causing more neuronal damage at molecular level. These molecular changes observed during hypo/hyperglycemia contribute to motor and learning deficits which has clinical significance in diabetes treatment. 2010 Elsevier Inc. All rights reserved.

Probable hypoglycemic adverse drug reaction associated with prickly pear cactus, glipizide, and metformin in a patient with type 2 diabetes mellitus.

PubMed

Sobieraj, Diana M; Freyer, Craig W

2010-01-01

To report a case of an adverse drug reaction (ADR) in a patient with type 2 diabetes mellitus taking prickly pear cactus (PPC), glipizide, and metformin. A 58-year-old Mexican male with type 2 diabetes mellitus being treated with metformin 1000 mg twice daily and extended-release glipizide 10 mg daily was referred to the pharmacist for medication education. He denied taking herbal supplements or experiencing hypoglycemia. Two hemoglobin A(1c) values (6.8% and 6.7%) obtained over the past year demonstrated glycemic control, which was supported by his reported fasting blood glucose readings of 113-132 mg/dL. One month later, the patient reported 4 hypoglycemic events with blood glucose readings of 49-68 mg/dL, which resulted in discontinuation of glipizide. One month later, the patient denied any further hypoglycemia. During medication reconciliation he reported consuming crude PPC pads daily for 2 months for glucose control. Literature suggests that PPC has an effect on lowering blood glucose levels in patients with type 2 diabetes mellitus, although few identified data describe ADRs from combining PPC with other agents used in treating type 2 diabetes mellitus. A literature search of MEDLINE (through December 2009) using the search terms diabetes mellitus, prickly pear cactus, nopal, opuntia, metformin, glipizide, glyburide, glimepiride, and sulfonylurea revealed no case reports of the described ADR. One case report describing the blood glucose-lowering effect of PPC in a patient concurrently taking oral antihyperglycemics documented an episode of hypoglycemia, although the Naranjo probability scale was not applied. One patient survey discovered the most common drug-herbal interaction in the given population to be between PPC and antihyperglycemic agents, resulting in hypoglycemia. In our case, use of the Naranjo probability scale suggests the ADR to be probable. The mechanism may be due to the additive glucose lowering of the 3 agents consumed concurrently by the patient. Patients with type 2 diabetes mellitus should be routinely counseled about the use of herbal products to minimize the risk of ADRs.

Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.

PubMed

Zou, Zhen; He, Dinggeng; Cai, Linli; He, Xiaoxiao; Wang, Kemin; Yang, Xue; Li, Liling; Li, Siqi; Su, Xiaoya

2016-04-06

The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.

Glycemic control in patients with type 2 diabetes mellitus in Spain.

PubMed

Pérez, A; Mediavilla, J J; Miñambres, I; González-Segura, D

2014-11-01

To evaluate the degree of glycemic control in patients with type 2 diabetes in Spain and identify factors associated with glycemic control. This was a cross-sectional, multicenter, epidemiological study that used consecutive sampling and was conducted in primary care practices in Spain. A total of 5591 patients with type 2 diabetes mellitus lasting more than 1 year and who were treated with hypoglycemic agents for more than 3 months were included in the study. At a single visit, HbA1c levels were measured (A1cNow+ system) and demographic and clinical variables related to diabetes and its treatment were recorded. During the visit, CV risk factors (CVRF), the presence of target-organ damage (TOD), the presence of hypoglycemia and body weight changes within the previous year were recorded. We analyzed data from 5382 patients (mean age 66.7 [10.8] years, mean duration of the diabetes 8.8 [6.3] years). TOD was present in 43.6% of the patients and 59.1% were taking 2 or more drugs. The patients' mean HbA1c was 7.1 (1.1)%, and 48.6% had HbA1c levels <7.0%. The patients with HbA1c levels ≥7.0% had longer-standing diabetes, a higher prevalence of TOD and CVRF, used more complex therapies, experienced more hypoglycemic episodes in the previous year and had more weight gain. In the multivariate analysis, the absence of insulin treatment, the absence of abdominal obesity and atherogenic dyslipidemia, a duration of the diabetes <10 years and an age >70 years were associated with improved glycemic control. Patients with poorly controlled type 2 diabetes mellitus are highly prevalent in Spain. Factors associated with poorer glycemic control include the complexity of both the disease and the hypoglycemic therapy, a history of hypoglycemia and weight gain. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Evaluation of Hypoglycemic and Genotoxic Effect of Polyphenolic Bark Extract from Quercus sideroxyla

PubMed Central

Soto-García, Marcela; Rosales-Castro, Martha; Escalona-Cardoso, Gerardo N.

2016-01-01

Quercus sideroxyla is a wood species whose bark has phenolic compound and should be considered to be bioactive; the hypoglycemic and genotoxic properties of Q. sideroxyla bark were evaluated in this study. Total phenolic compound was determined in crude extract (CE) and organic extract (OE). The OE has the highest amount of phenols (724.1 ± 12.0 GAE/g). Besides, both CE and OE demonstrated effect over the inhibition of α-amylase in vitro. Hypoglycemic activity was assessed by glucose tolerance curve and the area under curve (UAC); OE showed the highest hypoglycemic activity. In addition, diabetes was induced by streptozotocin (65 mg/kg) and the extracts (50 mg/kg) were administered for 10 days; OE showed hypoglycemic effect compared with diabetic control and decreased hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE; results of acute toxicity did not show any mortality. Besides, the comet assay showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the formation of type 1 comets. PMID:27867402

Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro.

PubMed

Shen, Xin; Zhou, Nan; Mi, Le; Hu, Zishuo; Wang, Libin; Liu, Xueying; Zhang, Shengyong

2017-01-01

The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph). In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6) myotubes. Daily oral treatment with Ph for 4 weeks significantly ( P <0.05) reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD-POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of type 2 diabetes (T2D) rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes.

Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro

PubMed Central

Shen, Xin; Zhou, Nan; Mi, Le; Hu, Zishuo; Wang, Libin; Liu, Xueying; Zhang, Shengyong

2017-01-01

The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph). In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6) myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05) reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD–POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of type 2 diabetes (T2D) rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes. PMID:28223777

Complementary and comparative study on hypoglycemic and antihyperglycemic activity of various extracts of Eugenia jambolana seed, Momordica charantia fruits, Gymnema sylvestre, and Trigonella foenum graecum seeds in rats.

PubMed

Yadav, Mukesh; Lavania, Amita; Tomar, Radha; Prasad, G B K S; Jain, Shalini; Yadav, Hariom

2010-04-01

In present study, we investigated hypoglycemic and antihyperglycemic potential of five extracts (water, ethanol, methanol, hexane, and chloroform) of four plants (i.e., seeds of Eugenia jambolana, fruits of Momordica charantia, leaves of Gymnema sylvestre, and seeds of Trigonella foenum graecum) alone and/or in combination with glimepiride in rats. Ethanol extract of E. jambolana, water extract of M. charantia, ethanol extract of G. sylvestre, and water extract of T. graecum exhibited highest hypoglycemic and antihyperglycemic activity (most active) in rats among all the extracts, while hexane extracts exhibited least activities. Most active extracts were further studied to dose-dependent (200, 100, and 50 mg/kg body weight (bw)) hypoglycemic and antihyperglycemic effects alone and in combination with glimepiride (20, 10, and 5 mg/kg bw). The combination of most active extracts (200 mg/kg bw) and lower dose of glimepiride (5 mg/kg bw) showed safer and potent hypoglycemic as well as antihyperglycemic activities without creating severe hypoglycemia in normal rats, while higher doses (200 mg/kg bw of most active extracts, and 10 and 20 mg/kg bw of glimepiride) were generated lethal hypoglycemia in normal rats. From this study, it may be concluded that the ethanol extract of E. jambolana seeds, water extract of M. charantia fruits, ethanol extract of G. sylvestre leaves, and water extract of T. graecum seeds have higher hypoglycemic and antihyperglycemic potential and may use as complementary medicine to treat the diabetic population by significantly reducing dose of standard drugs.

Hypoglycemia in glyburide-treated gestational diabetes: is it dose-dependent?

PubMed

Brustman, Lois; Langer, Oded; Scarpelli, Sophia; El Daouk, Manal; Fuchs, Anna; Rosenn, Barak

2011-02-01

To estimate whether there is a relationship between glyburide dose and the rate of hypoglycemic episodes in women with gestational diabetes mellitus (GDM). We studied 674 women with GDM who were treated with glyburide and diagnosed from 2000 to 2009. Glucose data were downloaded from memory-based meters at each visit and analyzed to estimate the incidence of recorded episodes of hypoglycemia and the association with concurrent dose of glyburide therapy (2.5, 5, 10, 15, or 20 mg). Hypoglycemia was defined as a blood glucose of less than 50 mg/dL, further classified as "severe hypoglycemia" if the event required the assistance of another person for resuscitation, "symptomatic hypoglycemia" if it was associated with typical neurogenic symptoms, or "asymptomatic hypoglycemia" if the biochemical reading was less than 50 mg/dL with no symptoms or accompanied by mild symptoms that did not impair the patient's ability to function. Patients recorded a mean of 272 glucose values. Sixty-seven percent of the patients experienced no blood glucose values in the hypoglycemic range. 33% had 1-7% of their total blood glucose values within the hypoglycemic range. All recordings of hypoglycemic episodes were asymptomatic; no patient reported a severe or symptomatic hypoglycemic episode. A significant association was found between the incidence of asymptomatic hypoglycemia and mean blood glucose (P<.001). No association was found between glyburide dose and incidence of asymptomatic hypoglycemia. No association between glyburide dose or mean blood glucose value and the incidence of neonatal hypoglycemia was found. Incremental increases in glyburide dose are not associated with an increase in the incidence of hypoglycemic episodes. II.

Effective Utilization of Oral Hypoglycemic Agents to Achieve Individualized HbA1c Targets in Patients with Type 2 Diabetes Mellitus.

PubMed

Bannister, Margaret; Berlanga, Jenny

2016-09-01

Type 2 diabetes is a progressive condition that may require the combination of three oral treatments to achieve optimal glycemic management to prevent microvascular and macrovascular complications whilst minimizing the risk of acute complications and side effects or adverse reactions to treatments. With the widening availability of treatment options and increasing importance of individualized treatment pathways, including personalized HbA1c targets, this article will explore the mode of action of currently available oral treatments, factors to consider when individualizing HbA1c targets, the relevance of estimated glomerular filtration rate assessment, and the importance of reviewing the clinical impact of all treatment decisions.

A Protein Isolate from Moringa oleifera Leaves Has Hypoglycemic and Antioxidant Effects in Alloxan-Induced Diabetic Mice.

PubMed

Paula, Paulo C; Sousa, Daniele O B; Oliveira, Jose T A; Carvalho, Ana F U; Alves, Bella G T; Pereira, Mirella L; Farias, Davi F; Viana, Martonio P; Santos, Flavia A; Morais, Talita C; Vasconcelos, Ilka M

2017-02-11

Moringa oleifera has been used in traditional medicine to treat diabetes. However, few studies have been conducted to relate its antidiabetic properties to proteins. In this study, a leaf protein isolate was obtained from M. oleifera leaves, named Mo -LPI, and the hypoglycemic and antioxidant effects on alloxan-induced diabetic mice were assessed. Mo -LPI was obtained by aqueous extraction, ammonium sulphate precipitation and dialysis. The electrophoresis profile and proteolytic hydrolysis confirmed its protein nature. Mo -LPI showed hemagglutinating activity, cross-reaction with anti-insulin antibodies and precipitation after zinc addition. Single-dose intraperitoneal (i.p.) administration of Mo -LPI (500 mg/kg·bw) reduced the blood glucose level (reductions of 34.3%, 60.9% and 66.4% after 1, 3 and 5 h, respectively). The effect of Mo -LPI was also evidenced in the repeated dose test with a 56.2% reduction in the blood glucose level on the 7th day after i.p. administration. Mo -LPI did not stimulate insulin secretion in diabetic mice. Mo- LPI was also effective in reducing the oxidative stress in diabetic mice by a decrease in malondialdehyde level and increase in catalase activity. Mo -LPI (2500 mg/kg·bw) did not cause acute toxicity to mice. Mo -LPI is a promising alternative or complementary agent to treat diabetes.

78 FR 26419 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-06

... Safety Administration (FMCSA). ACTION: Notice of applications for exemption from the diabetes mellitus... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or... hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another person, or...

75 FR 14652 - Qualification of Drivers; Exemption Applications; Diabetes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

... Administration (FMCSA), DOT. ACTION: Notice of applications for exemptions from the diabetes standard; request... no hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another... had no hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another...

Antiobesity Pharmacotherapy for Patients with Type 2 Diabetes: Focus on Long-Term Management

PubMed Central

Jeon, Won Seon

2014-01-01

Type 2 diabetes and obesity have a complex relationship; obesity is linked to insulin resistance, the precursor to type 2 diabetes. The management of obesity is an important method to delay onset of diabetes and improve the glycemic durability of antidiabetic agents. However, insulin and some of the oral hypoglycemic agents used to treat diabetes cause significant weight gain, and it is difficult for patients with diabetes to reduce and maintain their weight by life-style changes alone. Thus, antiobesity medications or bariatric surgery may be a necessary adjunct for certain obese patients with diabetes. In 2012, the U.S. Food and Drug Administration (FDA) approved lorcaserin and phentermine/topiramate extended-release for the management of chronic weight, and approval for naltrexone/bupropion sustained-release as an adjunct to exercise and reduced caloric intake followed in 2014. Liraglutide is pending FDA approval for antiobesity drug. Here we review the efficacy of approved and new promising drugs for the management of obesity. PMID:25559569

Honey and Diabetes: The Importance of Natural Simple Sugars in Diet for Preventing and Treating Different Type of Diabetes

PubMed Central

Dezmirean, Daniel S.

2018-01-01

Diabetes is a metabolic disorder with multifactorial and heterogeneous etiologies. Two types of diabetes are common among humans: type 1 diabetes that occurs when the immune system attacks and destroys insulin and type 2 diabetes, the most common form, that may be caused by several factors, the most important being lifestyle, but also may be determined by different genes. Honey was used in folk medicine for a long time, but the health benefits were explained in the last decades, when the scientific world was concerned in testing and thus explaining the benefits of honey. Different studies demonstrate the hypoglycemic effect of honey, but the mechanism of this effect remains unclear. This review presents the experimental studies completed in the recent years, which support honey as a novel antidiabetic agent that might be of potential significance for the management of diabetes and its complications and also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. PMID:29507651

78 FR 14406 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... reactions resulting in loss of consciousness, requiring the assistance of another person, or resulting in... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of... had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of...

Effect of water extract of Psidium guajava leaves on alloxan-induced diabetic rats.

PubMed

Mukhtar, H M; Ansari, S H; Ali, M; Naved, T; Bhat, Z A

2004-09-01

A water extract of Psidium guajava leaves was screened for hypoglycemic activity on alloxan-induced diabetic rats. In both acute and sub-acute tests, the water extract, at an oral dose of 250 mg/kg, showed statistically significant hypoglycemic activity.

77 FR 48587 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Safety Administration (FMCSA), DOT. ACTION: Notice of applications for exemption from the diabetes... certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance of another...

A comparison of adherence to hypoglycemic medications between Type 2 diabetes patients with and without serious mental illness

PubMed Central

Kreyenbuhl, Julie; Leith, Jaclyn; Medoff, Deborah R.; Fang, LiJuan; Dickerson, Faith B.; Brown, Clayton H.; Goldberg, Richard W.; Potts, Wendy; Dixon, Lisa B.

2011-01-01

Inadequate self-management of chronic medical conditions like Type 2 diabetes may play a role in the poor health status of individuals with serious mental illnesses. We compared adherence to hypoglycemic medications and blood glucose control between 44 diabetes patients with a serious mental illness and 30 patients without a psychiatric illness. The two groups did not differ in their ability to manage a complex medication regimen as assessed by a performance-based measure of medication management capacity. However, significantly fewer patients with a mental illness self-reported nonadherence to their hypoglycemic regimens compared to those without a mental illness. Although individuals with mental illnesses also had better control of blood glucose, this metabolic parameter was not correlated with adherence to hypoglycemic medications in either patient group. The experience of managing a chronic mental illness may confer advantages to individuals with serious mental illnesses in the self-care of co-occurring medical conditions like Type 2 diabetes. PMID:21459458

Efficacy and safety of empagliflozin in combination with other oral hypoglycemic agents in patients with type 2 diabetes mellitus.

PubMed

Romera, Irene; Ampudia-Blasco, Francisco Javier; Pérez, Antonio; Ariño, Bernat; Pfarr, Egon; Giljanovic Kis, Sanja; Naderali, Ebrahim

2016-12-01

To analyze the efficacy and safety of empagliflozin combined with other oral hypoglycemic agents in patients with type 2 diabetes mellitus. Pooled analysis of three phase III trials in patients with type 2 diabetes mellitus (n=1,801) who received placebo or empagliflozin 10 or 25mg once daily for 24 weeks, in combination with metformin, metformin+sulphonylurea or pioglitazone ± metformin. Empagliflozin significantly decreased HbA1c (adjusted mean reduction vs placebo with empagliflozin 10mg: -0.58% [95% CI: -0.66; -0.49]; P<.0001, and with empagliflozin 25mg: -0.62% [95% CI: -0.70; -0.53], P<.0001), weight (adjusted mean reduction vs placebo with empagliflozin 10mg: -1.77kg [95% CI: -2.05; -1.48]; P<.0001, and with empagliflozin 25mg: -1.96kg [95% CI: -2.24; -1.67], P<.0001), and systolic and diastolic blood pressure (SBP/DBP). Adverse effect rates were 64% with placebo, 63.9% with empagliflozin 10mg, and 60.9% with empagliflozin 25mg. Documented episodes of hypoglycemia (≤70mg/dL and/or requiring care) occurred in 3.9% of patients with placebo, 6.9% of patients with empagliflozin 10mg, and 5.3% of patients with empagliflozin 25mg. Urinary tract infections developed in 9.4% of patients with placebo, 10.2% of patients with empagliflozin 10mg, and 8.3% of patients with empagliflozin 25mg. Genital infections were reported in 1.0% of patients with placebo, 4.6% of patients with empagliflozin 10mg, and 3.5% of patients with empagliflozin 25mg. Empagliflozin combined with other oral treatments decreased HbA1c, body weight, and SBP/DBP as compared to placebo, with a good safety and tolerability profile. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Delay of insulin initiation in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycemic agents (analysis of patient- and physician-related factors): A prospective observational DIPP-FACTOR study in Korea.

PubMed

Kim, Sin Gon; Kim, Nam Hoon; Ku, Bon Jeong; Shon, Ho Sang; Kim, Doo Man; Park, Tae Sun; Kim, Yong-Seong; Kim, In Joo; Choi, Dong Seop

2017-05-01

To assess the time to initiation of insulin therapy, and concurrently investigate both patient- and physician-related factors associated with delaying insulin therapy in Korean patients with type 2 diabetes uncontrolled by oral hypoglycemic agents (OHAs). This prospective, observational disease registry study was carried out across 69 centers in Korea. Type 2 diabetes patients who had received two or more OHAs within the past 5 years, had a glycated hemoglobin ≥8% in the past 6 months and had not received insulin were included. Data recorded on data collection forms during a 12-month period were analyzed. Of 2168 patients enrolled, 1959 were evaluated and classified as the insulin-initiated or insulin-delayed group. Insulin was prescribed for just 20% of the patients during a 1-year follow-up period, and less than half (44.5%) of the patients who were taking two OHAs started insulin after 6 years. Patient-related factors for delay in insulin initiation included older age, shorter duration of diabetes and lower glycated hemoglobin. Physician-related factors included age (~50 to <60 years), sex (women) and number (<1000) of patients consulted per month. Patient refusal (33.6%) and physicians' concerns of patient non-compliance (26.5%) were the major physician-reported reasons for delaying insulin therapy. Inconvenience of insulin therapy (51.6%) and fear of injection (48.2%) were the major reasons for patient refusal. Insulin initiation is delayed in patients with type 2 diabetes uncontrolled by two or more OHAs in Korea. Patient- and physician-related factors associated with this delay need to be addressed for better diabetes management. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Nateglinide and Acarbose Are Comparably Effective Reducers of Postprandial Glycemic Excursions in Chinese Antihyperglycemic Agent–Naive Subjects with Type 2 Diabetes

PubMed Central

Zhou, Jian; Li, Hong; Zhang, Xiuzhen; Peng, Yongde; Mo, Yifei; Bao, Yuqian

2013-01-01

Abstract Background Recent studies have identified postprandial glycemic excursions as risk factors for diabetes complications. This study aimed to compare the effects of nateglinide and acarbose treatments on postprandial glycemic excursions in Chinese subjects with type 2 diabetes. Subjects and Methods This was a multicenter, open-label, randomized, active-controlled, parallel-group study. One hundred three antihyperglycemic agent–naive subjects with type 2 diabetes (hemoglobin A1c range, 6.5–9.0%) were prospectively recruited from four hospitals in China. The intervention was nateglinide (120 mg three times a day) or acarbose (50 mg three times a day) therapy for 2 weeks. A continuous glucose monitoring system was used to calculate the incremental area under the curve of postprandial blood glucose (AUCpp), the incremental glucose peak (IGP), mean amplitude of glycemic excursions, SD of blood glucose, the mean of daily differences, and 24-h mean blood glucose (MBG). Subjects' serum glycated albumin and the plasma insulin levels were also analyzed. Results Both agents caused significant reductions on AUCpp and IGP. Similarly, both treatment groups showed significant improvements in the intra- and interday glycemic excursions, as well as the 24-h MBG and serum glycated albumin compared with baseline (P<0.001). However, neither of the agents produced a significantly better effect (P>0.05). Moreover, the nateglinide-treated group had significantly increased insulin levels at 30 min and at 120 min after a standard meal compared with baseline, whereas the acarbose-treated group decreased. No serious adverse events occurred in either group. The rates of hypoglycemic episodes were comparable in the two groups, and no severe hypoglycemic episode occurred in either group. Conclusions Nateglinide and acarbose were comparably effective in reducing postprandial glycemic excursions in antihyperglycemic agent–naive Chinese patients with type 2 diabetes, possibly through different pathophysiological mechanisms. PMID:23631607

Hypoglycemic action of karanjin.

PubMed

Mandal, B; Maity, C R

1986-01-01

The hypoglycemic activity of karanjin, 3-methoxy flavono 7,8-furan, was investigated in normal and alloxan-induced diabetic albino rats. Oral administration of karanjin at a dose of 2 mg/kg/day for 7 days caused a significant reduction in blood sugar level both in normal and in alloxan-induced diabetic rats. Acute treatment with a single dose of karanjin, 0.5 mg/kg i.p., produced a significant fall in blood sugar level in normal rats while in alloxan-induced diabetic rats it was ineffective. Impaired glucose tolerance was also improved by karanjin treatment. It is concluded that karanjin has a significant hypoglycemic effect in albino rats.

76 FR 66120 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... reactions resulting in loss of consciousness, requiring the assistance of another person, or resulting in...

77 FR 36333 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-18

... certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the... has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the assistance... reactions resulting in loss of consciousness, requiring the assistance of another person, or resulting in...

77 FR 59447 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-27

... Safety Administration (FMCSA), DOT. ACTION: Notice of applications for exemption from the diabetes... and certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness... in 2012 and certified that he has had no severe hypoglycemic reactions resulting in loss of...

Hazardous factors besides infection in hypoglycemia.

PubMed

Su, Yu-Jang; Lai, Yen-Chun; Liao, Chia-Jung

2017-04-01

Hypoglycemia is one of the most common issues encountered in daily emergency practice. In addition to the treatment of hypoglycemia, certain other situations concomitant with hypoglycemia require further treatment. The aim of the present study was to compare demographic and clinical characteristics of infected [urinary tract infection (UTI), pneumonia or biliary tract infection (BTI)] vs. non-infected hypoglycemic patients to establish which hypoglycemic patients required further observation or hospitalization. This was a retrospective cross-sectional study of hypoglycemic (<60 mg/dl) hospitalized patients. The patients were divided into two groups: Those with hypoglycemia and concurrent infection (UTIs, pneumonia or BTIs; n=103) and non-infected hypoglycemic patients (n=83). Student's t-test was performed to analyze continuous data and the χ 2 test was used to analyze categorical data. Infections included 62 UTI, 43 pneumonia and 5 BTI. Comparing between the infected and non-infected groups, no significant differences were identified between mean glucose or body temperature, concurrent diagnosis (liver cirrhosis, uremia, acute renal failure, stroke or cancer) or mortality rate. Compared with the non-infected subjects, the infected patients were significantly older and had a significantly higher female ratio, as well as increased heart rates, white blood cell count and C-reactive protein levels. The present study proposes that characteristics, including concurrent stroke, liver cirrhosis and cancer are a point of focus in the initial management of hospitalized hypoglycemic patients.

78 FR 64267 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... reactions resulting in loss of consciousness, requiring the assistance of another person, or resulting in... him in 2013 and certified that he has had no severe hypoglycemic reactions resulting in loss of... he has had no severe hypoglycemic reactions resulting in loss of consciousness, requiring the...

76 FR 47291 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-04

... Safety Administration (FMCSA), DOT. ACTION: Notice of applications for exemption from the diabetes... 2011 and certified that he has had no severe hypoglycemic reactions resulting in loss of consciousness... endocrinologist examined him in 2011 and certified that he has had no severe hypoglycemic reactions resulting in...

[The vanadium compounds: chemistry, synthesis, insulinomimetic properties].

PubMed

Fedorova, E V; Buriakina, A V; Vorob'eva, N M; Baranova, N I

2014-01-01

The review considers the biological role of vanadium, its participation in various processes in humans and other mammals, and the anti-diabetic effect of its compounds. Vanadium salts have persistent hypoglycemic and antihyperlipidemic effects and reduce the probability of secondary complications in animals with experimental diabetes. The review contains a detailed description of all major synthesized vanadium complexes having antidiabetic activity. Currently, vanadium complexes with organic ligands are more effective and safer than the inorganic salts. Despite the proven efficacy of these compounds as the anti-diabetic agents in animal models, only one organic complex of vanadium is currently under the second phase of clinical trials. All of the considered data suggest that vanadium compound are a new promising class of drugs in modern pharmacotherapy of diabetes.

Citrullus colocynthis as the Cause of Acute Rectorrhagia

PubMed Central

Javadzadeh, Hamid Reza; Davoudi, Farnoush; Valizadegan, Ghasem; Goodarzi, Hasan; Mahmoodi, Sadrollah; Ghane, Mohammad Reza; Faraji, Mehrdad

2013-01-01

Introduction. Citrullus colocynthis Schrad. is a commonly used medicinal plant especially as a hypoglycemic agent. Case Presentation. Four patients with colocynth intoxication are presented. The main clinical feature was acute rectorrhagia preceeded by mucosal diarrhea with tenesmus, which gradually progressed to bloody diarrhea and overt rectorrhagia within 3 to 4 hours. The only colonoscopic observation was mucosal erosion which was completely resolved in follow-up colonoscopy after 14 days. Conclusion. The membranolytic activity of some C. colocynthis ingredients is responsible for the intestinal damage. Patients and herbalists should be acquainted with the proper use and side effects of the herb. Clinicians should also be aware of C. colocynthis as a probable cause of lower GI bleeding in patients with no other suggestive history, especially diabetics. PMID:23819072

[Advance of Forensic Research in Insulin Poisoning].

PubMed

Tong, F; Liang, Y; Shi, Q; Zhang, L; L, W H; Zhou, Y W

2017-02-01

Insulin as a common clinical hypoglycemic agent can effectively control serves to lower the concentration of blood glucose. However, insulin overdose can lead to death. In the whole fatal cases of insulin overdose, medical accident is the most common, followed by suicide. Though insulin homicide is extremely rare, it deserves great attention. Though there are some researches about insulin poisoning on forensic toxicology and pathology, it is still a difficult task in forensic practice. In this paper, the mechanism of death, pathological changes, detection methods and diagnose criteria of insulin overdose will be discussed in the view of forensic toxicology and pathology. We hope that this paper could enhance relative knowledges of insulin poisoning for medical examiners. Copyright© by the Editorial Department of Journal of Forensic Medicine.

Antioxidant and Hypoglycemic Activities of Exopolysaccharide by Submerged Culture of Inocutus Hispidus.

PubMed

Liu, S H; Sun, S W; Tian, Z F; Wu, J Y; Li, X L; Xu, C P

2015-01-01

This work was to investigate the hypoglycemic and antioxidant activities of the exopolysaccharides produced in a stirred-tank bioreactor by Inocutus hispidus. The exopolysaccharides showed significant antioxidant activities, up to 70.7±2.5% inhibition of hydroxyl radicals, 50% inhibition of 2,2-diphenyl-1-picrylhydrazyl radicals, and a Trolox equivalent antioxidant capacity of 3.3 mM. The exopolysaccharide also showed notable hypoglycemic effects in streptozotocin-induced diabetic mice, reducing the plasma glucose, total cholesterol and triacylglycerol concentrations by 18.2±1.5, 20.9±0.8 and 14.4±0.4, respectively. The results demonstrated the potential of this EPS for human health protection against oxidative damage and hyperglycemia.

What Can I Do to Prevent Serious Hypoglycemic Episodes When I Am Hypoglycemic Unaware?

MedlinePlus

... important because they start at a blood glucose level where you should still be able to independently treat yourself. These early mental symptoms are subtle and have to be distinguished from normal performance; for example, most people are slower at math when their blood glucose is low, but if ...

75 FR 28677 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... reactions resulting in loss of consciousness, requiring the assistance of another person, or resulting in... endocrinologist examined him in 2010 and certified that he has had no hypoglycemic reactions resulting in loss of... endocrinologist examined him in 2010 and certified that he has had no hypoglycemic reactions resulting in loss of...

Hypoglycemic Effect of Chinese Yam (Dioscorea opposita rhizoma) Polysaccharide in Different Structure and Molecular Weight.

PubMed

Li, Qian; Li, Wenzhi; Gao, Qunyu; Zou, Yuxiao

2017-10-01

Three new Chinese yam polysaccharides (namely HSY, huaishanyao in Chinese) were isolated using the methods of boiled water extraction and stepwise ethanolic precipitation, combined with the tangential flow ultrafiltration membrane system. Their molecular weights were determined by high performance gel permeation chromatography. Three type yam polysaccharides in different molecular weight were isolated: HSY-I (>50 kDa), HSY-II (10 to 50 kDa), HSY-III (<10 kDa). The monosaccharide and glycosidic bond links composition were analyzed with GC and Smith degradation. The structure characteristics were further discussed combined with infrared spectrophotometry. Dexamethasone-induced insulin resistance glucose/lipid metabolism diabetic mice model was established to evaluate the hypoglycemic effect of different concentration of HSY and different molecular weights polysaccharide HSY-I, HSY-II, and HSY-III. The results indicated that the HSY polysaccharide mixture, HSY-I and HSY-II had hypoglycemic effect. Three polysaccharides from Chinese yam tuber were isolated in this study. Their structures were characterized and hypoglycemic effects were evaluated. The result clearly identified the benefits of this plant as a healthy functional food. © 2017 Institute of Food Technologists®.

Influence of erythropoietin on cognitive performance during experimental hypoglycemia in patients with type 1 diabetes mellitus: a randomized cross-over trial.

PubMed

Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik; Kjær, Troels Wesenberg; Olsen, Niels Vidiendal; Dela, Flemming; Holst, Jens Juul; Faber, Jens; Tarnow, Lise; Thorsteinsson, Birger

2013-01-01

The incidence of severe hypoglycemia in type 1 diabetes has not decreased over the past decades. New treatment modalities minimizing the risk of hypoglycemic episodes and attenuating hypoglycemic cognitive dysfunction are needed. We studied if treatment with the neuroprotective hormone erythropoietin (EPO) enhances cognitive function during hypoglycemia. Eleven patients with type 1 diabetes, hypoglycemia unawareness and recurrent severe hypoglycemia completed the study. In a double-blind, randomized, balanced, cross-over study using clamped hypoglycemia they were treated with 40,000 IU of EPO or placebo administered intravenously six days before the two experiments. Cognitive function (primary endpoint), hypoglycemic symptoms, and counter-regulatory hormonal response were recorded. Compared with placebo, EPO treatment was associated with a significant reduction in errors in the most complex reaction time task (-4.7 (-8.1 to -1.3), p = 0.01) and a less reaction time prolongation (-66 (-117 to -16) msec, p = 0.02). EPO treatment did not change performance in other measures of cognition. Hypoglycemic symptoms, EEG-changes, and counter-regulatory hormone concentrations did not differ between EPO and placebo treatment. In patients with type 1 diabetes and hypoglycemia unawareness, treatment with EPO is associated with a beneficial effect on cognitive function in a complex reaction time task assessing sustained attention/working memory. Hypoglycemic symptoms and hormonal responses were not changed by EPO treatment. ClinicalTrials.gov NCT00615368.

Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties

PubMed Central

Das, Narhari; Abdur Rahman, S. M.

2016-01-01

Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand. PMID:27478435

[Impact of hypoglycemic episodes on nerves conduction and auditory and visual evoked potentials in children with type 1 diabetes].

PubMed

Wysocka-Mincewicz, Marta; Trippenbach-Dulska, Hanna; Emeryk-Szajewska, Barbara; Zakrzewska-Pniewska, Beata; Kochanek, Krzysztof; Pańkowska, Ewa

2007-01-01

Hypoglycemia is an acute disturbance of energy, especially impacting the central nervous system, but direct influence on peripheral nervous function is not detected. The aim of the study was to establish the influence of hypoglycemic moderate and severe episodes on the function of peripheral nerves, hearing and visual pathway. 97 children with type 1 diabetes (mean age 15.4+/-2.16 years, mean duration of diabetes 8.11+/-2.9 years, mean HbA1c 8,58+/-1.06%), at least 10 years old and with at least 3 years duration of diabetes, were included to study. Nerve conduction studies, visual (VEP) and auditory (ABR) evoked potentials were performed with standard surface stimulating and recording techniques. Moderate hypoglycemic episodes were defined as events of low glycemia requiring help of another person but without loss of consciousness and/or convulsions but recurrent frequently in at least one year. Severe hypoglycemia was defined as events with loss of consciousness and/or convulsions. Univariate ANOVA tests of significance or H Kruskal-Wallis test were used, depending on normality of distribution. The subgroups with a history of hypoglycemic episodes had significant delay in all conduction parameters in the sural nerve (amplitude p<0.05, sensory latency p<0.05, and velocity p<0.005) and in motor potential amplitude of tibial nerve (p<0.005). In ABR wave III latency and interval I-III in subgroups with episodes of hypoglycemia (p<0,05) were significantly prolonged. In analyses of VEP parameters no differences were detected. The study showed influence of hypoglycemic episodes on function of all sural nerve parameters and tibial motor amplitude, and in ABR on wave III and interval I-III. Frequent moderate hypoglycemic episodes were strong risk factors for damage of the peripheral and central nervous systems, comparable with impact of several severe hypoglycemias.

Comparative evaluation of polysaccharides isolated from Astragalus, oyster mushroom, and yacon as inhibitors of α-glucosidase.

PubMed

Zhu, Zhen-Yuan; Zhang, Jing-Yi; Chen, Li-Jing; Liu, Xiao-Cui; Liu, Yang; Wang, Wan-Xiao; Zhang, Yong-Min

2014-04-01

The incidence of diabetes has increased considerably, and become the third serious chronic disease following cancer and cardiovascular diseases. Though acarbose, metformin, and 1-deoxynojirimycin have good efficacy for clinical application as hypoglycemic drugs, their expensive costs and some degree of side effects have limited their clinical application. Recently, increasing attention has concentrated on the polysaccharides from natural plant and animal sources for diabetes. In order to illustrate the pharmaceutical activity of polysaccharides as natural hypoglycemic agents, polysaccharides isolated from Astragalus, oyster mushroom, and Yacon were evaluated for their inhibitory effects on α-glucosidase. Polysaccharides were extracted and purified from Astragalus, Oyster mushroom, and Yacon with hot water at 90 °C for 3 h, respectively. The total sugar content of the polysaccharide was determined by the phenol-sulfuric acid method. The α-glucosidase inhibitory activity was measured by the glucose oxidase method. The results exhibited that the inhibitory effects on α-glucosidase were in decreasing order, Astragalus > oyster mushroom > Yacon. The α-glucosidase inhibition percentage of Astragalus polysaccharide and oyster mushroom polysaccharide were over 40% at the polysaccharide concentration of 0.4 mg·mL(-1). The IC50 of Astragalus polysaccharide and oyster mushroom polysaccharide were 0.28 and 0.424 mg·mL(-1), respectively. The information obtained from this work is beneficial for the use polysaccharides as a dietary supplement for health foods and therapeutics for diabetes. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Diabetes mellitus: An overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity

PubMed Central

Patel, DK; Kumar, R; Laloo, D; Hemalatha, S

2012-01-01

Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge number of population in the world. It is mainly characterized by chronic hyperglycemia, resulting from defects in insulin secretion or insulin action. It is predicated that the number of diabetes person in the world could reach upto 366 million by the year 2030. Even though the cases of diabetes are increasing day by day, except insulin and oral hypoglycemic drugs no other way of treatment has been successfully developed so far. Thus, the objective of the present review is to provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along with the remedies available for this metabolic disorder. The review also contains brief idea about diabetes mellitus and the experimental screening model with their relevant mechanism and significance mainly used nowadays. Alloxan and streptozotocin are mainly used for evaluating the antidiabetic activity of a particular drug. This review contain list of medicinal plants which have been tested for their antidiabetic activity in the alloxan induced diabetic rat model. From the available data in the literature, it was found that plant having antidiabetic activity is mainly due to the presence of the secondary metabolite. Thus, the information provided in this review will help the researchers for the development of an alternative methods rather than insulin and oral hypoglycemic agents for the treatment of diabetes mellitus, which will minimize the complication associated with the diabetes and related disorder. PMID:23569941

Hypoglycemic and Hypocholesterolemic Effects of Botryosphaeran from Botryosphaeria rhodina MAMB-05 in Diabetes-Induced and Hyperlipidemia Conditions in Rats

PubMed Central

Miranda-Nantes, Carolina C. B. O.; Fonseca, Eveline A. I.; Zaia, Cassia T. B. V.; Dekker, Robert F. H.; Khaper, Neelam; Castro, Inar A.

2011-01-01

Botryosphaeran, a water-soluble exopolysaccharide of the β-(1 → 3;1 → 6)-D-glucan type that has been isolated from the culture medium of Botryosphaeria rhodina MAMB-05 grown in submerged fermentation using glucose as the sole carbon source, was previously demonstrated to be non-genotoxic in peripheral blood and bone marrow, and exhibited strong anticlastogenic activity. In the present study, the effects of botryosphaeran were investigated in streptozotocin-induced diabetic rats as well as in high-fat diet-fed hyperlipidemic Wistar rats. The plasma glucose level was reduced by 52% in the diabetic group of rats after administration of 12 mg botryosphaeran/kg body weight of the rats (b.w.)/day by gavage over 15 days. A reduction in the median ration intake was accompanied by an increase in the median body weight gain, as well as the efficiency of food conversion. These results demonstrate that botryosphaeran has protective effects by reducing the symptoms of cachexia in Diabetes mellitus. Botryosphaeran administered by gavage at a concentration of 12 mg botryosphaeran/kg b.w./day over 15 days also reduced the plasma levels of total cholesterol and low density lipoprotein-cholesterol by 18% and 27%, respectively, in hyperlipidemic rats. Based on these findings, we conclude that botryosphaeran possesses hypoglycemic and hypocholesterolemic properties in conditions of diabetes mellitus and hyperlipidemia, respectively, and may be used as an oral anti-diabetic agent. PMID:22783102

Hypoglycemic and Hypocholesterolemic Effects of Botryosphaeran from Botryosphaeria rhodina MAMB-05 in Diabetes-Induced and Hyperlipidemia Conditions in Rats.

PubMed

Miranda-Nantes, Carolina C B O; Fonseca, Eveline A I; Zaia, Cassia T B V; Dekker, Robert F H; Khaper, Neelam; Castro, Inar A; Barbosa, Aneli M

2011-09-01

Botryosphaeran, a water-soluble exopolysaccharide of the β-(1 → 3;1 → 6)-D-glucan type that has been isolated from the culture medium of Botryosphaeria rhodina MAMB-05 grown in submerged fermentation using glucose as the sole carbon source, was previously demonstrated to be non-genotoxic in peripheral blood and bone marrow, and exhibited strong anticlastogenic activity. In the present study, the effects of botryosphaeran were investigated in streptozotocin-induced diabetic rats as well as in high-fat diet-fed hyperlipidemic Wistar rats. The plasma glucose level was reduced by 52% in the diabetic group of rats after administration of 12 mg botryosphaeran/kg body weight of the rats (b.w.)/day by gavage over 15 days. A reduction in the median ration intake was accompanied by an increase in the median body weight gain, as well as the efficiency of food conversion. These results demonstrate that botryosphaeran has protective effects by reducing the symptoms of cachexia in Diabetes mellitus. Botryosphaeran administered by gavage at a concentration of 12 mg botryosphaeran/kg b.w./day over 15 days also reduced the plasma levels of total cholesterol and low density lipoprotein-cholesterol by 18% and 27%, respectively, in hyperlipidemic rats. Based on these findings, we conclude that botryosphaeran possesses hypoglycemic and hypocholesterolemic properties in conditions of diabetes mellitus and hyperlipidemia, respectively, and may be used as an oral anti-diabetic agent.

78 FR 38439 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

... the past 12 months and no recurrent (2 or more) severe hypoglycemic episodes in the last 5 years. His... the past 12 months and no recurrent (2 or more) severe hypoglycemic episodes in the last 5 years. His... holidays. The Federal Docket Management System (FDMS) is available 24 hours each day, 365 days each year...

Insulin autoimmune syndrome caused by an adhesive skin patch containing loxoprofen-sodium.

PubMed

Okazaki-Sakai, Satoko; Yoshimoto, Sachiko; Yagi, Kunimasa; Wakasugi, Takanobu; Takeda, Yoshiyu; Yamagishi, Masakazu

2013-01-01

A 62-year-old woman complained of repeated hypoglycemic events. A 75 g oral glucose tolerance test (75 gOGTT) showed a marked increase in the plasma insulin level and impaired glucose tolerance. The patient exhibited a high titer of plasma anti-insulin autoantibodies. Her diagnosis was insulin autoimmune syndrome (IAS). Following the cessation of loxoprofen-sodium (LOXs), she experienced no further hypoglycemic episodes. However, the hypoglycemic attacks recurred following the accidental readministration of LOXs in an adhesive skin patch. Considering the changes in the titer of anti-insulin autoantibodies, the repeated 75 gOGTT and the repeated Scatchard analysis, we determined LOXs to be the cause of the IAS and evaluated the characteristics of the autoantibodies.

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

PubMed Central

Betônico, Carolina C R; Titan, Silvia M O; Correa-Giannella, Maria Lúcia C; Nery, Márcia; Queiroz, Márcia

2016-01-01

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. PMID:26872083

Therapeutic potential of α-glucosidase inhibitors in type 2 diabetes mellitus: an evidence-based review.

PubMed

Joshi, Shashank R; Standl, Eberhard; Tong, Nanwei; Shah, Parag; Kalra, Sanjay; Rathod, Rahul

2015-01-01

Postprandial hyperglycemia (PPHG) contributes to micro- and macro-vascular complications more than fasting hyperglycemia in patients with type 2 diabetes mellitus. Due to the traditional carbohydrate-rich diet, Asians, particularly Indians and Chinese need agents to control the higher risk of uncontrolled PPHG. Targeting PPHG with α-glucosidase inhibitors (AGIs), either alone or in combination with other oral hypoglycemic agents and insulin, provide overall glycemic control with transient mild gastrointestinal disorders. Treatment with AGIs, especially acarbose, has also shown to provide beneficial effects on lipid levels, blood pressure, coagulation factors, carotid intima-media thickness and endothelial dysfunction. New insights of acarbose therapy obtained like increased activity of gut hormones and improved gut microbiota may explain the benefits on weight, whereas increased production of H2 may explains its cardiovascular benefits to some extent. A systematic search strategy was developed to identify randomized controlled trials in MEDLINE, PubMed, EMBASE and ongoing trials databases. AGIs as a class and acarbose in particular, are most useful in combatting PPHG and glucose variability across the spectrum of diabetes therapy, particularly in Asian patients. Together with their effects on incretin hormones and gut-microbiota AGIs can be considered beyond glycemic control as 'cardio-protective agents.'

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients.

PubMed

Aziz, Kamran Ma

2015-01-01

Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs) and sulfonylureas (SUs), which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin) during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME), pre-Ramadan assessments, and patient care.

Fasting during Ramadan: efficacy, safety, and patient acceptability of vildagliptin in diabetic patients

PubMed Central

Aziz, Kamran MA

2015-01-01

Diabetes management during Ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia. As compared to oral hypoglycemic agents (OHAs) and sulfonylureas (SUs), which carry a higher and significant risk of hypoglycemia, newer antidiabetic agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated lower risk of hypoglycemia during Ramadan fasting, with better patient compliance. In addition to diabetes education and pre-Ramadan assessments, the physician should also consider use of DPP-4 inhibitors (such as vildagliptin) during Ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects. Severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with OHAs/SUs. Conversely, these research observations have also demonstrated comparative safety and efficacy with lower risk of hypoglycemia associated with vildagliptin. Current research review has collected evidence-based clinical trials and observations for the drug vildagliptin to minimize the risk of hypoglycemia during Ramadan fasting, while at the same time focusing the role of diabetes self-management education (DSME), pre-Ramadan assessments, and patient care. PMID:25931826

Hypoglycemic property of soy isoflavones from hypocotyl in Goto-Kakizaki diabetic rats.

PubMed

Jin, Ming; Shen, Ming-Hua; Jin, Mei-Hua; Jin, Ai-Hua; Yin, Xue-Zhe; Quan, Ji-Shu

2018-03-01

The present study was carried out to investigate the hypoglycemic effect of soy isoflavones from hypocotyl in GK diabetic rats. A single administration and long-term administration tests were conducted in GK diabetic rats to test the hypoglycemic effect of soy isoflavones. At the end of long-term administration trial, blood protein, cholesterol, triglyceride, glycosylated serum protein, C-reactive protein, insulin, aminotransferase, lipid peroxide, interleukin-6, tumor necrosis factor-α were estimated. Inhibition of soy isoflavones against α-amylase and α-glucosidase, as well as on glucose uptake into brush border membrane vesicles or Caco-2 cells were determined in vitro . In single administration experiment, soy isoflavones reduced postprandial blood glucose levels in GK rats. In long-term administration, hypoglycemic effect of soy isoflavones was first observed at week 12 and maintained till week 16. A significant reduction in fasting blood glucose, C-reactive protein, and lipid peroxide was noted at week 16. However, there was no significant treatment effect on blood insulin. Furthermore, soy isoflavone administration resulted in significant decreases in glycosylated serum protein, tumor necrosis factor-α, and interleukin-6. Other biochemical parameters, such as protein, cholesterol, triglyceride and aminotransferases were not modified, however. The results in vitro showed that soy isoflavones showed a potent inhibitory effect on intestinal α-glucosidase, but not on pancreatic α-amylase. Soy isoflavones also decreased glucose transport potency into brush border membrane vesicles or Caco-2 cells. It is concluded that soy isoflavones from hypocotyl, performs hypoglycemic function in GK rats with type 2 diabetes, maybe via suppression of carbohydrate digestion and glucose uptake in small intestine.

Real-time hypoglycemia detection from continuous glucose monitoring data of subjects with type 1 diabetes.

PubMed

Jensen, Morten Hasselstrøm; Christensen, Toke Folke; Tarnow, Lise; Seto, Edmund; Dencker Johansen, Mette; Hejlesen, Ole Kristian

2013-07-01

Hypoglycemia is a potentially fatal condition. Continuous glucose monitoring (CGM) has the potential to detect hypoglycemia in real time and thereby reduce time in hypoglycemia and avoid any further decline in blood glucose level. However, CGM is inaccurate and shows a substantial number of cases in which the hypoglycemic event is not detected by the CGM. The aim of this study was to develop a pattern classification model to optimize real-time hypoglycemia detection. Features such as time since last insulin injection and linear regression, kurtosis, and skewness of the CGM signal in different time intervals were extracted from data of 10 male subjects experiencing 17 insulin-induced hypoglycemic events in an experimental setting. Nondiscriminative features were eliminated with SEPCOR and forward selection. The feature combinations were used in a Support Vector Machine model and the performance assessed by sample-based sensitivity and specificity and event-based sensitivity and number of false-positives. The best model was composed by using seven features and was able to detect 17 of 17 hypoglycemic events with one false-positive compared with 12 of 17 hypoglycemic events with zero false-positives for the CGM alone. Lead-time was 14 min and 0 min for the model and the CGM alone, respectively. This optimized real-time hypoglycemia detection provides a unique approach for the diabetes patient to reduce time in hypoglycemia and learn about patterns in glucose excursions. Although these results are promising, the model needs to be validated on CGM data from patients with spontaneous hypoglycemic events.

Hypoglycemia Prevents Increase in Lactic Acidosis During Reperfusion After Temporary Cerebral Ischemia in Rats

PubMed Central

Sappey-Marinier, Dominique; Chileuitt, Laureano; Weiner, Michael W.; Faden, Alan I.; Weinstein, Philip R.

2009-01-01

Sequential 31P and 1H MRS was used to measure cerebral phosphate metabolites, intracellular pH, and lactate in normoglycemic and hypoglycemic rats during 30 min of complete cerebral ischemia and 5.5 h of reperfusion. These results were correlated with brain levels of free fatty acids (FFAs), excitatory amino acids, cations, and water content at death. The lactate/N-acetyl aspartate ratio was not significantly different between groups before or during occlusion. During reperfusion, the ratio was higher in normoglycemic rats from 3 to 85 min (p≤ 0.05), and recovery time was faster in hypoglycemic rats (29 vs 45 min; p = 0.04), suggesting reduced lactate production and faster recovery of aerobic metabolism. During occlusion, significant but comparable decrease of intracellular pH occurred in each group. Intracellular pH was higher in hypoglycemic rats at 140 min and 260 min of reperfusion. Water content, Na and K+ concentrations, and FFA and excitatory amino acid levels were not significantly different between groups, but hypoglycemic rats had less depletion of levels of Mg2+ (p=0.011). These results show that hypoglycemia has a limited but potentially beneficial effect on postischemic lactic acidosis. PMID:8771092

Insulin and oral agents for managing cystic fibrosis-related diabetes.

PubMed

Onady, Gary M; Stolfi, Adrienne

2016-04-18

The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or oral glucose tolerance tests greater than 11.11 mmol/liter (200 mg/deciliter) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%. To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 18 February 2016. Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes. Two authors independently extracted data and assessed the risk of bias in the included studies. The searches identified 22 trials (34 references). Four trials (200 participants) are included: one short-term single-center trial (n = 7) comparing insulin with oral repaglinide and no medication in people with cystic fibrosis-related diabetes and normal fasting glucose; one long-term multicenter trial (n = 100, 74 of whom had cystic fibrosis-related diabetes) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (n = 73) comparing insulin with oral repaglinide; and one 12-week single-center trial (n = 20) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin.Two trials with data for the comparison of insulin to placebo did not report any significant differences between groups for the primary outcomes of blood glucose levels, lung function and nutritional status. This was also true for the single trial with data for the comparison of repaglinide to placebo. Two trials (one lasting one year and one lasting two years) contributed data for the comparison of insulin versus repaglinide. There were no significant differences for the primary outcomes at any time point, except at one year (in the two-year trial) when the insulin group had significant improvement in z score for body mass index compared to the repaglinide group. The single trial comparing glargine to neutral protamine Hagedorn insulin also did not report any significant differences in the review's primary outcomes. A few cases of hypoglycemia were seen in three out of the four trials (none in the longest trial), but these events resolved without further treatment.There was an unclear risk of bias from randomization and allocation concealment in two of the four included trials as the authors did not report any details; in the remaining two studies details for randomization led to a low risk of bias, but only one had sufficient details on allocation concealment to allow a low risk judgement, the second was unclear. There was a high risk from blinding for all trials (except for the comparison of oral repaglinide versus placebo) due to the nature of the interventions. Complete data for all outcomes were not available from any trial leading to a high risk of reporting bias. The amounts of insulin and repaglinide administered were not comparable and this may lead to bias in the results. None of the included trials were powered to show a significant improvement in lung function. This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority.There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further trials need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.

Saxagliptin versus glipizide as add-on therapy to metformin: assessment of hypoglycemia.

PubMed

Mintz, Matthew L; Minervini, Gianmaria

2014-05-01

To compare characteristics of hypoglycemic episodes in patients with type 2 diabetes receiving saxagliptin or glipizide add-on therapy to metformin. This was a post hoc analysis of an international, randomized, parallel-group, double-blind, active-controlled, phase 3 trial. The 52-week trial and 52-week extension were conducted from December 2007 to August 2010. Patients aged ≥18 years with glycated hemoglobin (HbA1c) >6.5% to 10.0% receiving stable metformin doses (≥1500 mg/d) were randomized 1:1 to add-on therapy with saxagliptin 5 mg/d or glipizide 5 to 20 mg/d (titrated to optimal effect or highest tolerable dose during the initial 18 weeks). Hypoglycemic episodes were recorded in patient diaries. Confirmed hypoglycemic events were defined as fingerstick glucose ≤50 mg/dL (≤2.8 mmol/L) with associated symptoms. Of 858 patients randomized, 428 received saxagliptin + metformin, and 430 received glipizide + metformin. Saxagliptin was noninferior to glipizide in lowering HbA1c. Hypoglycemia with saxagliptin + metformin and glipizide + metformin was reported by 15 (24 events) and 165 (896 events) patients, respectively, through week 104. The mean (SD) number of hypoglycemic events per patient reporting hypoglycemia was lower with saxagliptin + metformin versus glipizide + metformin through weeks 52 (1.5 [SD 0.88] vs 4.8 [SD 4.9], respectively) and 104 (1.6 [SD 0.99] vs 5.4 [SD 5.8]). Most patients receiving glipizide + metformin with hypoglycemia had multiple events (124/165 patients [75%]). Confirmed hypoglycemia, major events, and severe events occurred only with glipizide + metformin. Time to first hypoglycemic event was shorter with glipizide versus saxagliptin. Limitations of this analysis include its post hoc nature, a high rate of study discontinuation, and exclusion of patients with serious comorbidities and complications. Saxagliptin + metformin was associated with fewer patients reporting hypoglycemia and fewer and less severe hypoglycemic events in those experiencing hypoglycemia compared with glipizide + metformin. ClinicalTrials.gov registration number: NCT00575588.

Hypoglycemia in patients with type 2 diabetes from India and Malaysia treated with sitagliptin or a sulfonylurea during Ramadan: a randomized, pragmatic study.

PubMed

Aravind, S R; Ismail, Shaiful Bahari; Balamurugan, R; Gupta, Jugal Bihari; Wadhwa, Tarun; Loh, Sze Min; Suryawanshi, Shailaja; Davies, Michael J; Girman, Cynthia J; Katzeff, Harvey L; Radican, Larry; Engel, Samuel S; Wolthers, Troels

2012-08-01

To compare the incidence of symptomatic hypoglycemia between sitagliptin and sulfonylurea in Muslim patients with type 2 diabetes who fasted during Ramadan. In a multicenter, pragmatic, randomized study, patients with type 2 diabetes were recruited from clinical centers in India (n = 765) and Malaysia (n = 105). Eligible patients (age ≥ 18 yrs) expressed their intention to daytime fast during Ramadan, were treated with a stable dose of sulfonylurea with or without metformin for ≥3 months prior to screening visit, and had an HbA(1c) ≤ 10%. Patients were randomized in a 1:1 ratio to either switch to sitagliptin 100 mg q.d. or remain on their pre-study sulfonylurea. Daily diary cards were completed to document information on hypoglycemic symptoms and complications. The primary endpoint was the overall incidence of symptomatic hypoglycemia during Ramadan. Of the 870 patients randomized, 848 (n = 421 for sitagliptin and 427 for sulfonylurea) returned ≥1 completed diary card and were included in the analysis. The proportion of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan was lower with sitagliptin (3.8%) compared to sulfonylurea (7.3%). The risk of symptomatic hypoglycemia was significantly lower with sitagliptin (risk ratio [95% CI] = 0.52 [0.29, 0.94]; p = 0.028). By country, the proportions of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan were 4.1% vs. 7.7% in India and 1.9% vs. 3.8% in Malaysia for sitagliptin and sulfonylurea, respectively. No patient discontinued treatment due to a hypoglycemic event. One patient on sitagliptin and seven on sulfonylurea had an event that required non-medical assistance. No events required medical assistance. Both treatments were generally well tolerated. Symptomatic hypoglycemic events did not require a confirmatory blood glucose measurement, which may have overestimated hypoglycemic events. Measures of glycemic control and body weight were not assessed. Switching antihyperglycemic treatment to sitagliptin from a sulfonylurea reduced the risk of symptomatic hypoglycemia by approximately 50% for Muslim patients with type 2 diabetes who fasted during Ramadan. Clinicaltrials.gov: NCT01340768.

Cassia grandis fruit extract reduces the blood glucose level in alloxan-induced diabetic rats.

PubMed

Prada, Ariadna Lafourcade; Amado, Jesús Rafael Rodríguez; Keita, Hady; Zapata, Edgar Puente; Carvalho, Helison; Lima, Emersom Silva; de Sousa, Tatiane Pereira; Carvalho, José Carlos Tavares

2018-04-16

Cassia grandis Lf fruits are ethnobotanically used for digestive disorders, anemia, and for reducing blood glucose. However, there are no studies about the antidiabetic activity nor the oral toxicity of the plant fruit-extracts. This paper aims to evaluate the hypoglycemic effect of C. grandis fruits extract in vivo, and assess the acute oral toxicity, and sub-acute oral toxicity. The antioxidant activity and the α-glycosidase inhibitor effect were also evaluated. The extract was obtained by maceration of the fruit pulp with 70% hydroalcoholic solution (1:2, m:v). The extractive solution was concentrated in a vacuum rotary evaporator, up to a drug: solvent ratio of 2:1 (g/ml). Soluble solids, relative density, refractive index, pH, total phenolics, and flavonoids were determined. A preliminary phytochemical screening was made, followed by the quantitation of volatiles by GC/MS. The acute and sub-acute oral toxicity was evaluated in Sprague Dawley rats, by using biochemical and hematological parameters. The radical scavenging activity (DPPH, ABTS) and α-glycosidase inhibitory effect were tested. The hypoglycemic effect was assessed in alloxan-induced diabetic rats. The extract of C. grandis contains alkaloids, coumarins, flavonoids, free amino acids, amines, phenols, tannins, reduced sugars, resins, saponins, steroids, and triterpenes, plus 38 volatile compounds, being linalool the most abundant (1,66%). The extract exhibited an LD 50  > 2000 mg/kg, and after a continuous administration (1000 mg/kg, 28-days), the hematological and biochemical parameters were normal. The extract showed hypoglycemic effect, being the dose 200 mg/kg no statistically different from glibenclamide at 25 mg/kg. Good antioxidant activity and a potent α-glycosidase inhibitory effect were also observed. C. grandis extract is an excellent hypoglycemic and non-toxic plant product. The hypoglycemic mechanism could be associated with the antioxidant effect and with the α-glycosidase inhibition. Up to the best of our knowledge, this is the first report on the hypoglycemic effect in vivo of C. grandis fruits extract. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Factitious hyperinsulinism leading to pancreatectomy: severe forms of Munchausen syndrome by proxy.

PubMed

Giurgea, Irina; Ulinski, Tim; Touati, Guy; Sempoux, Christine; Mochel, Fanny; Brunelle, Francis; Saudubray, Jean-Marie; Fekete, Claire; de Lonlay, Pascale

2005-07-01

Clinical history and inappropriate insulin secretion during hypoglycemic episodes permit the diagnosis of hyperinsulinism. We report 2 cases of factitious hyperinsulinism leading to partial pancreatectomy. Case 1 was an 8-year-old girl who presented with severe hypoglycemia and elevated insulin and C-peptide levels. Catheterization of pancreatic veins was performed to localize the excess insulin secretion. Insulinoma was suspected, and partial pancreatectomy was performed. Ten days after surgery, severe hypoglycemia recurred with severely elevated plasma insulin levels (x100) but very low C-peptide plasma levels, suggesting factitious hyperinsulinemia. Hypoglycemic episodes before surgery were provoked by oral sulfonamides; postoperative episodes were caused by parenteral insulin. Falsified prescriptions for sulfonamides and insulin by the mother, a nurse, were found. Case 2 was a 6-month-old girl who presented with seizures and hypoglycemia but had a symptom-free interval of many months afterward. At 2 years of age, repeated hypoglycemic seizures and elevated insulin plasma levels suggested congenital hyperinsulinism. C-peptide plasma level, measured once, was normal, but blood sampling was performed 15 minutes after a hypoglycemic episode. Partial pancreatectomy was performed. Two weeks after surgery, hypoglycemic seizures recurred, and the patient was admitted for pancreatic vein catheterization. This investigation was performed during hypoglycemia and revealed high insulin levels and undetectable C-peptide levels, suggesting factitious hypoglycemia. Insulin/C-peptide ratio analysis is crucial to assess factitious hypoglycemia, although sulfonamide-induced hypoglycemia is not thereby detected. One percent (2 of 250) of all cases of hyperinsulinemic hypoglycemia in our unit have been identified as Munchausen syndrome by proxy. Atypical disease history should raise the question of factitious hypoglycemia.

Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus.

PubMed

Yaffe, Kristine; Falvey, Cherie M; Hamilton, Nathan; Harris, Tamara B; Simonsick, Eleanor M; Strotmeyer, Elsa S; Shorr, Ronald I; Metti, Andrea; Schwartz, Ann V

2013-07-22

Hypoglycemia commonly occurs in patients with diabetes mellitus (DM) and may negatively influence cognitive performance. Cognitive impairment in turn can compromise DM management and lead to hypoglycemia. To prospectively evaluate the association between hypoglycemia and dementia in a biracial cohort of older adults with DM. Prospective population-based study. We studied 783 older adults with DM (mean age, 74.0 years; 47.0% of black race/ethnicity; and 47.6% female) who were participating in the prospective population-based Health, Aging, and Body Composition Study beginning in 1997 and who had baseline Modified Mini-Mental State Examination scores of 80 or higher. Dementia diagnosis was determined during the follow-up period from hospital records indicating an admission associated with dementia or the use of prescribed dementia medications. Hypoglycemic events were determined during the follow-up period by hospital records. During the 12-year follow-up period, 61 participants (7.8%) had a reported hypoglycemic event, and 148 (18.9%) developed dementia. Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia compared with those who did not have a hypoglycemic event (34.4% vs 17.6%, P < .001; multivariate-adjusted hazard ratio, 2.1; 95% CI, 1.0-4.4). Similarly, older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycemic event compared with participants who did not develop dementia (14.2% vs 6.3%, P < .001; multivariate-adjusted hazard ratio, 3.1; 95% CI, 1.5-6.6). Further adjustment for stroke, hypertension, myocardial infarction, and cognitive change scores produced similar results. Among older adults with DM, there seems to be a bidirectional association between hypoglycemia and dementia.

Hypoglycemic drugs induce antioxidant aldehyde dehydrogenase activity and remain high in patients with glycemic control in type 2 diabetes.

PubMed

Picazo, Alejandra; Jiménez-Osorio, Angélica S; Zúñiga-Mejía, Porfirio; Pedraza-Chaverri, José; Monroy, Adriana; Rodríguez-Arellano, M Eunice; Barrera-Oviedo, Diana

2017-04-05

The antioxidant system results essential to control and prevent lipid peroxidation due to stress damage in type 2 diabetes. An example is aldehyde dehydrogenase (ALDH), an enzyme that is involved in the detoxification of aldehydes formed during lipid peroxidation. This study was conducted to evaluate ALDH activity and to determine their association with hypoglycemic treatment in type 2 diabetes patients. The study population consisted of 422 Mexican subjects: a control group and type 2 diabetes patients. Type 2 diabetes patients were re-classified as those with or without hypoglycemic treatment and those with or without glycemic control (according to glycated hemoglobin (HbA1c)). Clinical parameters, antioxidant enzyme activities (ALDH, superoxide dismutase (SOD), catalase and glutathione peroxidase) and oxidative markers (reactive oxygen species and thiobarbituric acid reactive substances (TBARS)) were evaluated. The activity of antioxidant enzymes and oxidative stress markers were higher in type 2 diabetes patients with hypoglycemic treatment and without glycemic control than control group. The activity of ALDH and SOD remained high in type 2 diabetes patients with moderate glycemic control while only ALDH's remained high in type 2 diabetes patients with tight glycemic control. Increased ALDH and SOD activities were associated with hypoglycemic therapy. TBARS levels were associated with glycemic control. The persistence of high ALDH and SOD activities in type 2 diabetes patients with glycemic control may be to avoid a significant damage due to the increase in reactive oxygen species and TBARS. It is possible that this new oxidative status prevented the development the classical complications of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypoglycemic effect of Mucuna pruriens seed extract on normal and streptozotocin-diabetic rats.

PubMed

Bhaskar, Anusha; Vidhya, V G; Ramya, M

2008-12-01

The hypoglycemic effect of the aqueous extract of the seeds of Mucuna pruriens was investigated in normal, glucose load conditions and streptozotocin (STZ)-induced diabetic rats. In normal rats, the aqueous extract of the seeds of Mucuna pririens (100 and 200 mg/kg body weight) significantly (P<0.001) reduced the blood glucose levels after an oral glucose load from 127.5+/-3.2 to 75.6+/-4.8 mg% 2 h after oral administration of seed extract. It also significantly lowered the blood glucose in STZ diabetic rats from 240.5+/-7.2 to 90.6+/-5.6 mg% after 21 days of daily oral administration of the extract (P<0.001). Thus, this study shows that M. pruriens has an anti-hyperglycemic action and it could be a source of hypoglycemic compounds.

Effect of Cuscuta reflexa stem and Calotropis procera leaf extracts on glucose tolerance in glucose-induced hyperglycemic rats and mice.

PubMed

Rahmatullah, Mohammed; Sultan, Shamsuddin; Toma, Tanzila Taher; Lucky, Sayeda-A-Safa; Chowdhury, Majeedul H; Haque, Wahid Mozammel; Annay, Eashmat Ara; Jahan, Rownak

2009-12-30

Cuscuta reflexa (whole plant) and Calotropis procera (leaves) are used in folk medicine of Bangladesh to control blood sugar in patients suffering from diabetes mellitus. The hypoglycemic effects of methanol and chloroform extracts of whole plants of Cuscuta reflexa, and methanol extract of leaves of Calotropis procera were investigated in oral glucose tolerance tests in Long Evans rats and Swiss albino mice, respectively. Both methanol and chloroform extracts of Cuscuta reflexa whole plant demonstrated significant oral hypoglycemic activity in glucose-loaded rats at doses of 50, 100 and 200 mg/kg body weight. The methanol extract of leaves of Calotropis procera, when tested at doses of 100 and 250 mg/kg body weight did not demonstrate any oral hypoglycemic effect when tested in glucose-loaded mice.

Effect of Hypoglycemic Agents on Ischemic Preconditioning in Patients With Type 2 Diabetes and Symptomatic Coronary Artery Disease

PubMed Central

Rahmi, Rosa Maria; Uchida, Augusto Hiroshi; Rezende, Paulo Cury; Lima, Eduardo Gomes; Garzillo, Cibele Larrosa; Favarato, Desiderio; Strunz, Celia M.C.; Takiuti, Myrthes; Girardi, Priscyla; Hueb, Whady; Kalil Filho, Roberto; Ramires, José A.F.

2013-01-01

OBJECTIVE To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS We performed a prospective study of 96 consecutive patients allocated into two groups: 42 to group repaglinide (R) and 54 to group vildagliptin (V). All patients underwent two consecutive exercise tests (ET1 and ET2) in phase 1 without drugs. In phase 2, 1 day after ET1 and -2, 2 mg repaglinide three times daily or 50 mg vildagliptin twice daily was given orally to patients in the respective group for 6 days. On the seventh day, 60 min after 6 mg repaglinide or 100 mg vildagliptin, all patients underwent two consecutive exercise tests (ET3 and ET4). RESULTS In phase 1, IPC was demonstrated by improvement in the time to 1.0 mm ST-segment depression and rate pressure product (RPP). All patients developed ischemia in ET3; however, 83.3% of patients in group R experienced ischemia earlier in ET4, without significant improvement in RPP, indicating the cessation of IPC (P < 0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still having the protective effect (P < 0.0069). CONCLUSIONS Repaglinide eliminated myocardial IPC, probably by its effect on the KATP channel. Vildagliptin did not damage this protective mechanism in a relevant way in patients with type 2 diabetes and CAD, suggesting a good alternative treatment in this population. PMID:23250803

Hypoglycemic effect of Opuntia cactus.

PubMed

Ibañez-Camacho, R; Roman-Ramos, R

1979-01-01

Nopal (Opuntia sp.) has been traditionally used by the Mexican population for the treatment of diabetes mellitus. The purpose of this work is to describe effects produced by directly liquified nopal and extracts from this plant in healthy and pancreatectomized rabbits. Preliminary results allow us to conclude that Opuntia streptacantha, Lemaire, has hypoglycemic properties when orally administered, in animals with experimentally induced diabetes as well as in healthy ones with physiologic hyperglycemia.

Hypoglycemic effect of Bromelia plumieri (E. Morren) L.B. Sm., leaves in STZ-NA-induced diabetic rats

PubMed Central

Andrade-Cetto, Adolfo; Medina-Hernández, Anamarel E.

2013-01-01

This study confirms the hypoglycemic effects of two extracts obtained from the Bromelia plumieri (BP) plant in streptozotocin-nicotinamide-induced diabetic rats (STZ-NA). BP has been traditionally used in the municipality of Tlanchinol Hidalgo, Mexico, to treat type 2 diabetes. Two different BP extracts were prepared and tested. The first extract was a water extract (WE), similar to that traditionally used to make tea, and the second extract was an ethanol:water extract (EWE). The extracts (WE at 35 and 350 mg/kg, and EWE at 30 and 300 mg/kg) were tested in STZ-NA-induced diabetic rats to determine whether hypoglycemia occurred after oral administration of the extracts. Phytochemistry: Two different extracts were prepared, n-hexane and butanol, to determine the presence of alkaloids, terpenes and flavonoids. The extracts that were administered to the STZ-NA-induced diabetic rats produced a significant hypoglycemic effect as compared with the control group, similar to that achieved with glibenclamide. We also determined that flavonoids were the main components of BP leaves. The results presented here support the hypothesis that extracts obtained from this plant have hypoglycemic effects, which are in agreement with the traditional uses of this plant. PMID:23576986

Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase

PubMed Central

Suh, Sang Won; Gum, Elizabeth T.; Hamby, Aaron M.; Chan, Pak H.; Swanson, Raymond A.

2007-01-01

Hypoglycemic coma and brain injury are potential complications of insulin therapy. Certain neurons in the hippocampus and cerebral cortex are uniquely vulnerable to hypoglycemic cell death, and oxidative stress is a key event in this cell death process. Here we show that hypoglycemia-induced oxidative stress and neuronal death are attributable primarily to the activation of neuronal NADPH oxidase during glucose reperfusion. Superoxide production and neuronal death were blocked by the NADPH oxidase inhibitor apocynin in both cell culture and in vivo models of insulin-induced hypoglycemia. Superoxide production and neuronal death were also blocked in studies using mice or cultured neurons deficient in the p47phox subunit of NADPH oxidase. Chelation of zinc with calcium disodium EDTA blocked both the assembly of the neuronal NADPH oxidase complex and superoxide production. Inhibition of the hexose monophosphate shunt, which utilizes glucose to regenerate NADPH, also prevented superoxide formation and neuronal death, suggesting a mechanism linking glucose reperfusion to superoxide formation. Moreover, the degree of superoxide production and neuronal death increased with increasing glucose concentrations during the reperfusion period. These results suggest that high blood glucose concentrations following hypoglycemic coma can initiate neuronal death by a mechanism involving extracellular zinc release and activation of neuronal NADPH oxidase. PMID:17404617

[Type 2 diabetes, is it just a case of hyperglycemia? Confusion between the interests of science, humanity and the economy].

PubMed

Ruiz, Juan

2009-06-03

The recommendations for the treatment of type 2 diabetic patients are often centered on the glycemia. These clinical trials based on this approach show only a beneficial effects on the prevention of microangiopathy. The coronary artery disease which is the main cause of mortality among these patients, is not reduced. These data should be interpreted with a systemic prospect. The diabetes vascular complications have multifactorial causes and these clinical trials are motivated for the promotion of hypoglycemic agents. Fortunately, the STENO study offers another glance on the treatment of the diabetes, associating multirisk approach and patients' accompaniment. It obliges to have a critical glance on the research often moved by economic issues and gives to the center a humanistic approach based on the therapeutic relation.

[Acupuncture Intervention Reduced Weight Gain Induced by Hypoglycemic Agents through Food Intake-related Targets in Central Nervous System].

PubMed

Jing, Xin-yue; Ou, Chen; Lu, Sheng-feng; Zhu, Bing-mei

2015-12-01

Clinical practice shows that thiazolidinediones (TZDs) induce weight gain in patients with type-II diabetes mellitus during treatment, which restrains its application and generalization clinically. It has been demonstrated that acupuncture therapy is useful in easing obesity in clinical trials. In the present paper, we summarize the underlying mechanism of weight gain induced by TZDs through food intake-related targets in the central nervous system and analyze the possible effects of acupuncture therapy. Acupuncture therapy is expected to reduce weight gain side effect of TZDs through 1) lowering permeability of blood brain barrier to reduce TZDs concentration in the brain, 2) upregulating the expression of hypothalamic leptin and inhibiting hypothalamic neuropiptide Y expression, and 3) down-regulating activities of peroxisome proliferator-activated receptor to reduce energy intake and fat syntheses.

Orthosiphol A from the aerial parts of Orthosiphon aristatus is putatively responsible for hypoglycemic effect via alpha-glucosidase inhibition.

PubMed

Damsud, Thanakorn; Grace, Mary H; Adisakwattana, Sirichai; Phuwapraisirisan, Preecha

2014-05-01

An infusion of Orthosiphon aristatus has long been used for diabetes therapy; however, the active principles remained unknown. Herein, we report the identification of the putative agents responsible for this antidiabetic activity using an a-glucosidase-guided isolation. Four flavonoids named sinensetin (1), salvigenin (2), tetramethylscutellarein (3) and 3,7,4'-tri-O-methylkaempferol (4), together with a diterpenoid named orthosiphol A (5), were characterized, based on analysis of their spectroscopic data. Flavonoids 3 and 4 inhibited yeast a-glucosidase with IC,o values of 6.34 and 0.75 mM, respectively, whereas orthosiphol A (5) selectively inhibited intestinal maltase with an IC5o, value of 6.54 mM. A kinetic investigation of 5 indicated that it retarded maltase function in a noncompetitive manner.

Evaluation of the Hypoglycemic Effect of Composite Rice Flour in Diabetic Mice.

PubMed

Ding, Zhigang; Gao, Hongmei; Du, Chuanlai; Zheng, Yimei; Guo, Yuanxin; Pan, Dongmei

2016-03-01

To study the hypoglycemic effect of composite rice flour, the diabetic mouse model was established through the intraperitoneal injection of alloxan saline (twice, 200 mg/kg bw). The mice were randomly divided into 4 groups: negative control, positive control, metformin medication group, and composite rice flour feed group. After 21 days, the fasting blood glucose levels were determined by glucose oxidase method and followed with a glucose tolerance test. The results show that the body weight growth rate of mice in the rice flour group was significantly higher than that of the medication group (P < 0.01). Comparing with the positive control group, the fasting blood glucose levels of medication group and rice flour group were significantly lower, and the glucose tolerance was significantly increased in rice flour group (P < 0.01). In conclusion, the composite rice flour has obvious hypoglycemic and protective effect for diabetic mouse model.

[Hypoglycemic action of different doses of nopal (Opuntia streptacantha Lemaire) in patients with type II diabetes mellitus].

PubMed

Frati-Munari, A C; Del Valle-Martínez, L M; Ariza-Andraca, C R; Islas-Andrade, S; Chávez-Negrete, A

1989-01-01

To assess the relationship between the doses of O. streptacantha Lem. and its acute hypoglycemic action in diabetics, eight patients with type II diabetes mellitus were studied. Four test were performed to each patient with the intake of: (a) 400 ml of water, (b) 100 g (c) 300 g and (d) 500 g of broiled stems of O. streptacantha Lem. Serum glucose was measured at 0, 60, 120 and 180 minutes. Maximal decrease of serum glucose was noticed at 180 minutes, with a mean of 2.3, 10, 30.1 and 46.7 mg/dl less than basal value with 0, 100, 300 and 500 g respectively (P = NS, less than 0.05, less than 0.001 and less than 0.001 respectively). A significant direct correlation (r = 0.690, P less than 0.001) was noticed between the doses and the hypoglycemic effect.

Identification of 3-hydroxy-3-methylglutaric acid (HMG) as a hypoglycemic principle of Spanish moss (Tillandsia usneoides).

PubMed

Witherup, K M; McLaughlin, J L; Judd, R L; Ziegler, M H; Medon, P J; Keller, W J

1995-08-01

Bioactivity-directed fractionation, using brine shrimp lethality and murine hypoglycemia, of an ethanol extract prepared from Tillandsia usneoides, led to the isolation of four apparently bioactive compounds from the water-soluble fraction. The compounds were identified as citric acid, succinic acid, 3-hydroxy-3-methylglutaric acid (HMG), and 3,6,3',5'-tetramethoxy-5,7,4'-trihydroxyflavone-7-O-beta-D-g lucoside. The brine shrimp lethality of the acids was simply due to acidity; however, HMG elicited significant hypoglycemic responses in fasting normal mice. Ethyl and methyl esters of citric acid were prepared and tested in the murine hypoglycemic assay. Five of the predominant sugars were identified by tlc. Free thymidine was also isolated. Further evaluation of HMG and other potential inhibitors of HMG CoA lyase, in the treatment of symptoms of diabetes mellitus, is suggested.

Lifelong consumption of sodium selenite: gender differences on blood-brain barrier permeability in convulsive, hypoglycemic rats.

PubMed

Seker, F Burcu; Akgul, Sibel; Oztas, Baria

2008-07-01

The aim of this study was to compare the effects of hypoglycemia and induced convulsions on the blood-brain barrier permeability in rats with or without lifelong administration of sodium selenite. There is a significant decrease of the blood-brain barrier permeability in three brain regions of convulsive, hypoglycemic male rats treated with sodium selenite when compared to sex-matched untreated rats (p<0.05), but the decrease was not significant in female rats (p>0.05). The blood-brain barrier permeability of the left and right hemispheres of untreated, moderately hypoglycemic convulsive rats of both genders was better than their untreated counterparts (p<0.05). Our results suggest that moderate hypoglycemia and lifelong treatment with sodium selenite have a protective effect against blood-brain barrier permeability during convulsions and that the effects of sodium selenite are gender-dependent.

Hypoglycemic Effects of Exo-biopolymers Produced by Five Different Medicinal Mushrooms in STZ-induced Diabetic Rats

PubMed Central

Yang, Byung-Keun; Kim, Guk-Nam; Jeong, Yong-Tae; Jeong, Hun; Mehta, Pradeep

2008-01-01

Hypoglycemic effects of exo-biopolymers (EBP) produced by submerged mycelial cultures of Coriolus versicolor, Cordyceps sinensis, Paecilomyces japonica, Armillariella mellea, and Fomes fomentarius were investigated in streptozotocin (STZ)-induced diabetic rats. The rats from each experimental group were orally administered with EBPs (100 mg/kg BW) daily for 2 weeks. Though the hypoglycemic effect was achieved in all the cases, however, C. versicolor EBP proved as the most potent one. The administration of the C. versicolor EBP substantially reduced (29.9%) the plasma glucose level as compared to the saline administered group (control). It also reduced the plasma total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and, alanine aminotransferase (ALT) levels by 9.22, 23.83, 16.93, and 27.31%, respectively. The sugar and amino acid compositions of this EBP were also analyzed in detail. PMID:23997607

A case of hypoglycemic hemiparesis and literature review

PubMed Central

Meguro, Shu; Soeda, Yukie; Itoh, Arata; Kawai, Toshihide; Itoh, Hiroshi

2012-01-01

An 89-year-old man with diabetes treated with metformin 500 mg/day and glimepiride 4 mg/day was hospitalized because of hypoglycemic right hemiparesis and dysarthria (casual glucose value 1.8 mmol/L), which resolved quickly following administration of 40 mL of 40% dextrose. Hemiparesis is a rare symptom (4.2%) of hypoglycemia. There are about 200 case reports of hypoglycemic hemiparesis. The average glucose level at which hemiparesis developed was 1.8 mmol/L. Right-sided hemiparesis predominated (R 66%; L 34%). On imaging studies, abnormal findings were frequently observed in the internal capsule or splenium of the corpus callosum. The mechanism of hemiparesis is not fully understood. The existence of cases in which hypoglycemia cannot be distinguished from stroke on imaging studies suggests the importance of measurement of the blood glucose level when the symptoms of stroke are first recognized. PMID:22247979

A case of hypoglycemic hemiparesis and literature review.

PubMed

Yoshino, Tetsuhiro; Meguro, Shu; Soeda, Yukie; Itoh, Arata; Kawai, Toshihide; Itoh, Hiroshi

2012-08-01

An 89-year-old man with diabetes treated with metformin 500 mg/day and glimepiride 4 mg/day was hospitalized because of hypoglycemic right hemiparesis and dysarthria (casual glucose value 1.8 mmol/L), which resolved quickly following administration of 40 mL of 40% dextrose. Hemiparesis is a rare symptom (4.2%) of hypoglycemia. There are about 200 case reports of hypoglycemic hemiparesis. The average glucose level at which hemiparesis developed was 1.8 mmol/L. Right-sided hemiparesis predominated (R 66%; L 34%). On imaging studies, abnormal findings were frequently observed in the internal capsule or splenium of the corpus callosum. The mechanism of hemiparesis is not fully understood. The existence of cases in which hypoglycemia cannot be distinguished from stroke on imaging studies suggests the importance of measurement of the blood glucose level when the symptoms of stroke are first recognized.

Prescription drug advertising trends: a study of oral hypoglycemics.

PubMed

Mehta, K K; Sorofman, B A; Rowland, C R

1989-01-01

A content analysis of oral hypoglycemic drug advertisements was performed in selected medical journals published in the United States from 1963 to 1986. The 665 advertisements subsequently examined were studied for certain predetermined parameters in order to indicate trends. The trend results may be summarized as follows. As an extension of prescription drug advertising trends in general, oral hypoglycemic drug advertising showed an increasing length along with a subsequent decrease in the amount of space devoted to the copy portion of the advertisement. They also showed a decrease in the use of statistical information and rarely made references to competitors. Nongender specific, colored advertisements with product and use related appeals have become more common with the passage of time. Although the rationale and purpose behind advertising is unchanged, the format has changed considerably. These changes are primarily due to the enhancement of print technology and to some extent, the changing social environment.

Paramedic Checklists do not Accurately Identify Post-ictal or Hypoglycaemic Patients Suitable for Discharge at the Scene.

PubMed

Tohira, Hideo; Fatovich, Daniel; Williams, Teresa A; Bremner, Alexandra; Arendts, Glenn; Rogers, Ian R; Celenza, Antonio; Mountain, David; Cameron, Peter; Sprivulis, Peter; Ahern, Tony; Finn, Judith

2016-06-01

The objective of this study was to assess the accuracy and safety of two pre-defined checklists to identify prehospital post-ictal or hypoglycemic patients who could be discharged at the scene. A retrospective cohort study of lower acuity, adult patients attended by paramedics in 2013, and who were either post-ictal or hypoglycemic, was conducted. Two self-care pathway assessment checklists (one each for post-ictal and hypoglycemia) designed as clinical decision tools for paramedics to identify patients suitable for discharge at the scene were used. The intention of the checklists was to provide paramedics with justification to not transport a patient if all checklist criteria were met. Actual patient destination (emergency department [ED] or discharge at the scene) and subsequent events (eg, ambulance requests) were compared between patients who did and did not fulfill the checklists. The performance of the checklists against the destination determined by paramedics was also assessed. Totals of 629 post-ictal and 609 hypoglycemic patients were identified. Of these, 91 (14.5%) and 37 (6.1%) patients fulfilled the respective checklist. Among those who fulfilled the checklist, 25 (27.5%) post-ictal and 18 (48.6%) hypoglycemic patients were discharged at the scene, and 21 (23.1%) and seven (18.9%) were admitted to hospital after ED assessment. Amongst post-ictal patients, those fulfilling the checklist had more subsequent ambulance requests (P=.01) and ED attendances with seizure-related conditions (P=.04) within three days than those who did not. Amongst hypoglycemic patients, there were no significant differences in subsequent events between those who did and did not meet the criteria. Paramedics discharged five times more hypoglycemic patients at the scene than the checklist predicted with no significant differences in the rate of subsequent events. Four deaths (0.66%) occurred within seven days in the hypoglycemic cohort, and none of them were attributed directly to hypoglycemia. The checklists did not accurately identify patients suitable for discharge at the scene within the Emergency Medical Service. Patients who fulfilled the post-ictal checklist made more subsequent health care service requests within three days than those who did not. Both checklists showed similar occurrence of subsequent events to paramedics' decision, but the hypoglycemia checklist identified fewer patients who could be discharged at the scene than paramedics actually discharged. Reliance on these checklists may increase transportations to ED and delay initiation of appropriate treatment at a hospital. Tohira H , Fatovich D , Williams TA , Bremner A , Arendts G , Rogers IR , Celenza A , Mountain D , Cameron P , Sprivulis P , Ahern T , Finn J . Paramedic checklists do not accurately identify post-ictal or hypoglycaemic patients suitable for discharge at the scene. Prehosp Disaster Med. 2016;31(3):282-293.

Kidney in diabetes: from organ damage target to therapeutic target.

PubMed

Salvatore, Teresa; Carbonara, Ornella; Cozzolino, Domenico; Torella, Roberto; Nasti, Rodolfo; Lascar, Nadia; Sasso, Ferdinando Carlo

2011-09-01

Despite the growing of pharmacological options for the treatment of diabetes, epidemiological studies suggest that a substantial proportion of patients does not achieve glycemic goals and so suffers from the risk of chronic complications. This review explores the inhibition of renal glucose reabsorption as a novel approach to treat hyperglycemia. Sodium-glucose cotransporter 2 (SGLT2), a low-affinity high-capacity transporter located in the brush-border membrane of the early segment (S1) of the proximal renal tubule, accounts for about 90% of the reabsorption of glucose from tubular fluid. Competitive inhibitors of SGLT2 that are responsible for renal excretion of glucose provide a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. They act independently of insulin secretion, thereby minimizing the risk of hypoglycemia and weight gain, to control energy balance in a negative direction, a distinctive advantage of this class of drugs over existing oral hypoglycemic agents. Although this group of medications is still under investigation, it appears to be safe and generally well tolerated and it would be expected to improve the treatment of type 2 diabetes as monotherapy or in combination with other oral or parenteral agents. Dapagliflozin is the first agent within this class, which induces clinically meaningful reductions in FPG, PPG, HbA1c, and body weight in type 2 diabetes.

Medications and impaired driving.

PubMed

Hetland, Amanda; Carr, David B

2014-04-01

To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on classes of medications associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Only English-language articles that contained findings from observational or interventional designs with ≥ 10 participants were included in this review. Cross-sectional studies, case series, and case reports were excluded. Driving is an important task and activity for the majority of adults. Some commonly prescribed medications have been associated with driving impairment measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, hypnotics, antidepressants, opioid and nonsteroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies of medication impact on sedation, sleep latency, and psychomotor function, as well as the role of alcohol, are also discussed. Psychotropic agents and those with central nervous system side effects were associated with measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific classes of medications, educate their patients, and/or consider safer alternatives.

Effect of Yeonryeonggobon-dan (YRGBD), an herbal complex, on glycemic control in patients with Type 2 diabetes mellitus: a case series.

PubMed

Kim, Jiman; Byun, A Ri; Kwon, Seungwon

2014-12-01

Diabetes mellitus has significant effects on the human body. Recently, herbal medicines have received attention as complementary anti-diabetic agents on the basis of the results of several experimental studies. We present a series of 38 cases that demonstrate the positive effect of Yeonryeonggobon-dan (YRGBD), an herbal complex, in lowering blood sugar levels in patients with uncontrolled type 2 diabetes mellitus. We reviewed the medical records of 38 patients treated with YRGBD. The types and doses of other hypoglycemic agents administered to the patients remained unchanged during treatment with YRGBD. After YRGBD therapy, the glycated haemoglobin level decreased from 76.16±19.90mmol/mol (9.11±1.82%) to 51.21±8.82mmol/mol (6.84±0.81%). There was a statistically significant difference between the glycated haemoglobin levels measured before and after treatment (paired t test, p<0.001). In the present study, we show the clinical effects of YRGBD on blood sugar control in patients with type 2 diabetes mellitus. Further clinical studies investigating the effects of YRGBD are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metformin inhibition of neuroblastoma cell proliferation is differently modulated by cell differentiation induced by retinoic acid or overexpression of NDM29 non-coding RNA.

PubMed

Costa, Delfina; Gigoni, Arianna; Würth, Roberto; Cancedda, Ranieri; Florio, Tullio; Pagano, Aldo

2014-01-01

Metformin is a widely used oral hypoglycemizing agent recently proposed as potential anti-cancer drug. In this study we report the antiproliferative effect of metformin treatment in a high risk neuroblastoma cell model, focusing on possible effects associated to different levels of differentiation and/or tumor initiating potential. Antiproliferative and cytotoxic effects of metformin were tested in human SKNBE2 and SH-SY5Y neuroblastoma cell lines and in SKNBE2 cells in which differentiation is induced by retinoic acid treatment or stable overexpression of NDM29 non-coding RNA, both conditions characterized by a neuron-like differentiated phenotype. We found that metformin significantly inhibits the proliferation of NB cells, an effect that correlates with the inhibition of Akt, while AMPK activity resulted unchanged. Notably, metformin effects were modulated in a different ways by differentiating stimuli, being abolished after retinoic acid treatment but potentiated by overexpression of NDM29. These data suggest the efficacy of metformin as neuroblastoma anticancer agent, and support the requirement of further studies on the possible role of the differentiation status on the antiproliferative effects of this drug.

Efficacy and safety of sotagliflozin in treating diabetes type 1.

PubMed

Rendell, Marc S

2018-02-01

Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other agents as a result of decreased glucose absorption. The primary development effort to date has been in Type 1 diabetes. Areas covered: The published information on sotagliflozin is reviewed, along with the recent results of several pivotal Type 1 diabetes trials. Expert opinion: Sotagliflozin treatment lowers HbA1c and reduces glucose variability, with a trend to less hypoglycemic events. In the Type 1 trials, sotagliflozin treated individuals experienced DKA at a higher rate than placebo treated patients. An additional safety issue arises from the as yet unknown potential risks in women of child bearing potential in whom DKA is of utmost concern. The sotagliflozin development program has now been extended to trials in Type 2 diabetes, and long term studies will be needed to assess the benefits and risks of the agent in comparison to other currently marketed SGLT2 inhibitors.

Hypoglycemia and endurance exercise: dietary considerations.

PubMed

Rutherford, W J

1990-01-01

Until recently, common dietary prescription for chronic hypoglycemia has been a high-protein, low-carbohydrate regimen (Airola, 1977; Danowski, 1978). Increasing evidence suggests, however, that a diet rich in complex carbohydrates may be more suitable for those involved in endurance exercise (Costill & Miller, 1980; Sherman & Costill, 1984). Although little original research has been undertaken which deals with the effects of performance-enhancing nutritional techniques on the hypoglycemic exerciser, such practices need to be examined in order to understand the mechanisms involved. Specifically, carbohydrate loading would seem to be as important, if not more so, to the hypoglycemic individual as a means of supercompensating glycogen stores prior to endurance performance. The roles of pre-exercise supplements and carbohydrate feedings during exercise in this context are less clear. Although results are mixed, increasing evidence (Snyder et al., 1983; Okano et al., 1988) suggests that carbohydrates may be consumed before exercise with beneficial effects on performance. Because of rapid gastric emptying characteristic of reactive hypoglycemia, it would appear that pre-exercise supplementation may be of particular value to the hypoglycemic exerciser. Further, recent studies (Bergstrom & Hultman, 1967; Coyle et al., 1983; Foster et al., 1986; Leatt & Jacobs, 1986; Horton, 1988) indicate that carbohydrate solutions taken during exercise are effective in maintaining serum glucose levels and improving endurance performance. Careful monitoring of nutritional factors would appear to be critical in creating a suitable dietary environment for the hypoglycemic endurance exerciser.

Epidemiology and outcomes of hypoglycemia in patients with advanced diabetic kidney disease on dialysis: A national cohort study

PubMed Central

Wang, Jhi-Joung; Weng, Shih-Feng; Lin, Chih-Ching; Chien, Chih-Chiang

2017-01-01

Background Patients with advanced diabetic kidney disease (DKD) behave differently to diabetic patients without kidney disease. We aimed to investigate the associations of hypoglycemia and outcomes after initiation of dialysis in patients with advanced DKD on dialysis. Methods Using National Health Insurance Research Database, 20,845 advanced DKD patients beginning long-term dialysis between 2002 and 2006 were enrolled. We investigated the incidence of severe hypoglycemia episodes before initiation of dialysis. Patients were followed from date of first dialysis to death, end of dialysis, or 2008. Main outcomes measured were all-cause mortality, myocardial infarction (MI), and subsequent severe hypoglycemic episodes after dialysis. Results 19.18% patients had at least one hypoglycemia episode during 1-year period before initiation of dialysis. Advanced DKD patients with higher adapted Diabetes Complications Severity Index (aDCSI) scores were associated with more frequent hypoglycemia (P for trend < 0.001). Mortality and subsequent severe hypoglycemia after dialysis both increased with number of hypoglycemic episodes. Compared to those who had no hypoglycemic episodes, those who had one had a 15% higher risk of death and a 2.3-fold higher risk of subsequent severe hypoglycemia. Those with two or more episodes had a 19% higher risk of death and a 3.9-fold higher risk of subsequent severe hypoglycemia. However, previous severe hypoglycemia was not correlated with risk of MI after dialysis. Conclusions The rate of severe hypoglycemia was high in advanced DKD patients. Patients with higher aDCSI scores tended to have more hypoglycemic episodes. Hypoglycemic episodes were associated with subsequent hypoglycemia and mortality after initiation of dialysis. We studied the associations and further study is needed to establish cause. In addition, more attention is needed for hypoglycemia prevention in advanced DKD patients, especially for those at risk patients. PMID:28355264

Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling Pathway.

PubMed

Wang, Caijuan; Deng, Yujiao; Yue, Yenan; Chen, Wenting; Zhang, Yu; Shi, Guifang; Wu, Zhongming

2018-03-01

BACKGROUND Diabetes mellitus (DM) is characterized by a decreased blood level of glutamine (Gln), which may contribute to the disturbance in the effect of insulin on skeletal muscle. Therefore, it is crucial to study how to improve the effect of insulin on skeletal muscle by increasing Gln. In the present study, we investigated the effect of Gln on the hypoglycemic action of insulin in skeletal muscle L6 cells at high glucose levels through the insulin signaling pathway and glycogen synthesis pathway. MATERIAL AND METHODS The L6 cells were cultured in and stimulated by Gln and insulin. The glutamine analogue, L-Gamma-Glutamyl-p-nitroanilide (GPNA), was used for verifying the effect of Gln. The expression of insulin signaling molecules, including phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B (AKT), protein kinase C zeta (PKCz), and glucose transporter 4 (GLUT4), were detected by real-time PCR and Western blot analysis, GLUT4 translocation was observed by immunofluorescence staining, glycogen synthase kinase (GSK) was analyzed by Western blotting, and glucose uptake was measured by glucose oxidase method (GOD). RESULTS The results demonstrated that Gln combined with insulin remarkably up-regulated PI3K and PDK1 and also increased AKT and PKCz phosphorylation. The present study shows that Gln enhanced the impact of insulin on GLUT4 and its translocation. The results of glucose uptake and GSK phosphorylation further confirmed the hypoglycemic effect of Gln accompanied with insulin. The hypoglycemic effect of Gln was reversed by GPNA. CONCLUSIONS These findings suggest that Gln enhances the hypoglycemic role of insulin through the PI3K/AKT/GLUT4 signaling pathway and glycogen synthesis pathway.

CHEMICAL CHARACTERIZATION OF A HYPOGLYCEMIC EXTRACT FROM CUCURBITA FICIFOLIA BOUCHE THAT INDUCES LIVER GLYCOGEN ACCUMULATION IN DIABETIC MICE

PubMed Central

Jessica, Garcia Gonzalez; Mario, Garcia Lorenzana; Alejandro, Zamilpa; Cesar, Almanza Perez Julio; Ivan, Jasso Villagomez E; Ruben, Roman Ramos; Javier, Alarcon-Aguilar Francisco

2017-01-01

Background: The aqueous extract of Cucurbita ficifolia (C. ficifolia) fruit has demonstrated hypoglycemic effect, which may be attributed to some components in the extract. However, the major secondary metabolites in this fruit have not yet been identified and little is known about its extra-pancreatic action, in particular, on liver carbohydrate metabolism. Therefore, in addition to the isolation and structural elucidation of the principal components in the aqueous extract of C. ficifolia, the aim of this study was to determine whether or not the hypoglycemic effect of the aqueous extract of Cucurbita ficifolia (C. ficifolia) fruit is due to accumulation of liver glycogen in diabetic mice. Materials and Methods: The aqueous extract from fruit of C. ficifolia was fractionated and its main secondary metabolites were purified and chemically characterized (NMR and GC-MS). Alloxan-induced diabetic mice received daily by gavage the aqueous extract (30 days). The liver glycogen content was quantified by spectroscopic method and by PAS stain; ALT and AST by spectrometric method; glycogen synthase, glycogen phosphorylase and GLUT2 by Western blot; the mRNA expression of GLUT2 and glucagon-receptor by RT-PCR; while serum insulin was quantified by ELISA method. A liver histological analysis was also performed by H&E stain. Results: Chemical fingerprint showed five majoritarian compounds in the aqueous extract of C. ficifolia: p-coumaric acid, p-hydroxybenzoic acid, salicin, stigmast-7,2,2-dien-3-ol and stigmast-7-en-3-ol. The histological analysis showed accumulation of liver glycogen. Also, increased glycogen synthase and decreased glycogen phosphorylase were observed. Interestingly, the histological architecture evidenced a liver-protective effect due the extract. Conclusion: Five compounds were identified in C. ficifolia aqueous extract. The hypoglycemic effect of this extract may be partially explained by liver glycogen accumulation. The bioactive compound responsible for the hypoglycemic effect of this extract will be elucidated in subsequent studies. PMID:28480434

Hypoglycemic Accuracy and Improved Low Glucose Alerts of the Latest Dexcom G4 Platinum Continuous Glucose Monitoring System.

PubMed

Peyser, Thomas A; Nakamura, Katherine; Price, David; Bohnett, Lucas C; Hirsch, Irl B; Balo, Andrew

2015-08-01

Accuracy of continuous glucose monitoring (CGM) devices in hypoglycemia has been a widely reported shortcoming of this technology. We report the accuracy in hypoglycemia of a new version of the Dexcom (San Diego, CA) G4 Platinum CGM system (software 505) and present results regarding the optimum setting of CGM hypoglycemic alerts. CGM values were compared with YSI analyzer (YSI Life Sciences, Yellow Springs, OH) measurements every 15 min. We reviewed the accuracy of the CGM system in the hypoglycemic range using standard metrics. We analyzed the time required for the CGM system to detect biochemical hypoglycemia (70 mg/dL) compared with the YSI with alert settings at 70 mg/dL and 80 mg/dL. We also analyzed the time between the YSI value crossing 55 mg/dL, defined as the threshold for cognitive impairment due to hypoglycemia, and when the CGM system alerted for hypoglycemia. The mean absolute difference for a glucose level of less than 70 mg/dL was 6 mg/dL. Ninety-six percent of CGM values were within 20 mg/dL of the YSI values between 40 and 80 mg/dL. When the CGM hypoglycemic alert was set at 80 mg/dL, the device provided an alert for biochemical hypoglycemia within 10 min in 95% of instances and at least a 10-min advance warning before the cognitive impairment threshold in 91% of instances in the study. Use of an 80 mg/dL threshold setting for hypoglycemic alerts on the G4 Platinum (software 505) may provide patients with timely warning of hypoglycemia before the onset of cognitive impairment, enabling them to treat themselves for hypoglycemia with fast-acting carbohydrates and prevent neuroglycopenia associated with very low glucose levels.

A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes.

PubMed

Goldberg, R B; Einhorn, D; Lucas, C P; Rendell, M S; Damsbo, P; Huang, W C; Strange, P; Brodows, R G

1998-11-01

The objective of the study was to assess the efficacy and safety of repaglinide compared with placebo in the treatment of patients with type 2 diabetes. This was a phase II multicenter, double-blind, placebo-controlled, randomized, dose-adjustment and maintenance trial. After screening and a 2-week washout period, 99 patients were randomized to receive either repaglinide (n = 66) or placebo (n = 33). Patients underwent 6 weeks of dose adjustment followed by 12 weeks of dose maintenance. Fasting and stimulated glycosylated hemoglobin (HbA1c), plasma glucose, insulin, and C-peptide were measured at predetermined intervals. Adverse events and hypoglycemic episodes were recorded. From baseline to last visit, mean HbA1c decreased from 8.5 to 7.8% in patients treated with repaglinide and increased from 8.1 to 9.3% in patients receiving placebo, with a statistically significant difference of - 1.7% (P < 0.0001) between treatment groups at the last visit. Mean fasting plasma glucose and postprandial glucose increased in patients receiving placebo and decreased in patients treated with repaglinide, with statistically significant (P < 0.01) differences between groups at the last visit. Concentrations of fasting and postprandial insulin and C-peptide were lower at the last visit compared with baseline for patients treated with placebo and higher for patients treated with repaglinide, and the differences between groups were statistically significant (P < 0.05). Overall, repaglinide was well tolerated. This study demonstrated that repaglinide was safe and efficacious in lowering blood glucose concentrations. In addition to overall improvement in glycemic control noted with repaglinide in both sulfonylurea-treated patients and oral hypoglycemic agent-naive patients, repaglinide had a potent glucose-lowering effect in the postprandial period.

Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes.

PubMed

Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria; Arafah, Baha M

2017-09-01

Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.

Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes

PubMed Central

Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria

2017-01-01

Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients. PMID:29264578

Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes

PubMed Central

Dardano, Angela; Bianchi, Cristina; Del Prato, Stefano; Miccoli, Roberto

2014-01-01

Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients’ preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal–bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients’ viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients. PMID:25143741

Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez, Veronica; Saraff, Kumuda; Medh, Jheem D., E-mail: jheem.medh@csun.edu

2009-11-06

Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted inmore » a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.« less

New steroid derivative with hypoglycemic activity

PubMed Central

Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Lenin, Hau-Heredia; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Bety, Sarabia-Alcocer

2014-01-01

Data indicates that some steroid derivatives may induce changes on glucose levels; nevertheless, data are very confusing. Therefore, more pharmacological data are needed to characterize the activity induced by the steroid derivatives on glucose levels. The aim of this study was to synthesize a new steroid derivative for evaluate its hypoglycemic activity. The effects of steroid derivative on glucose concentration were evaluated in a diabetic animal model using glibenclamide and metformin as controls. In addition, the pregnenolone-dihydrotestosterone conjugate was bound to Tc-99m using radioimmunoassay methods, to evaluate the pharmacokinetics of the steroid derivative over time. The results showed that the pregnenolone-dihydrotestosterone conjugate induces changes on the glucose levels in similar form than glibenclamide. Other data showed that the biodistribution of Tc-99m-steroid derivativein brain was higher in comparison with spleen, stomach, intestine liver and kidney. In conclusion, the pregnenolone-dihydrotestosterone conjugate exerts hypoglycemic activity and this phenomenon could depend of its physicochemical properties which could be related to the degree of lipophilicity of the steroidderivative. PMID:25550906

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

PubMed Central

Santos, Laura M.; Mattiace, Linda A.; Costa, Manoel L.; Ferreira, Luciano C.; Benabou, Kelly; Kim, Ana H.; Abrahams, John; Bennett, Michael V. L.; Rozental, Renato

2012-01-01

Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide. PMID:22308470

Peruvioses A to F, sucrose esters from the exudate of Physalis peruviana fruit as α-amylase inhibitors.

PubMed

Bernal, Carlos-A; Castellanos, Leonardo; Aragón, Diana M; Martínez-Matamoros, Diana; Jiménez, Carlos; Baena, Yolima; Ramos, Freddy A

2018-05-22

The fruit of Physalis peruviana is widely used in traditional Colombian medicine as an antidiabetic treatment. The aim of the study reported here was to identify the compounds responsible for the hypoglycemic activity using the α-amylase inhibition test. Bioguided fractionation of a dichloromethane extract of the sticky exudate that covers the fruit allowed the isolation and identification of three new sucrose esters, named as peruvioses C-E (1-3), along with the known peruvioses A (6), B (5) and F (4), the structures of which were elucidated by extensive NMR and MS experiments. These compounds proved to be responsible for the hypoglycemic activity observed in the extract. Peruviose D (2) showed the highest activity, with an inhibitory activity value of 84.8%. This is the first study to establish the potential of sucrose esters as α-amylase inhibitors and to explain the hypoglycemic effect that has traditionally been attributed to gooseberry fruit. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats

PubMed Central

Nayak, B. Shivananda; Marshall, Julien R.; Isitor, Godwin; Adogwa, Andrew

2011-01-01

Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density = 1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50 mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2 ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150 mg/dl ±15.88 and 125 mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS = 360.0 mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2 g, 5.11%) which increased significantly by the 20th day (6 g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia. PMID:20981320

Repaglinide plus single-dose insulin glargine: a safe regimen for low-risk type 2 diabetic patients who insist on fasting in Ramadan.

PubMed

Bakiner, Okan; Ertorer, Melek E; Bozkirli, Emre; Tutuncu, Neslihan B; Demirag, Nilgun G

2009-03-01

Aim of this prospective study is to evaluate the effect of repaglinide t.i.d. (three times a day) plus single-dose insulin glargine regimen in low-risk type 2 diabetic patients during Ramadan fasting. Participants had been taking the regimen for at least 3 months. Patients with a history of diabetic coma, severe hypoglycemic crisis or repeating attacks of hypoglycemia were excluded. Hypoglycemic unawareness, kidney or liver disease or HbA1c over 8% were also accepted as exclusion criteria. Eleven patients who insisted on this worship and eight non-fasting cases were involved. All were told to make home-glucose-monitorisation weekly and report any hypoglycemic event throughout Ramadan. Fasting blood glucose (FBG), post-prandial blood glucose (PBG) and fructosamine levels, body weights and blood pressures were recorded just before and after Ramadan. Seven patients in each group concluded the follow-up. Any significant change was detected in the parameters in either groups (P>0.05). Glucose control remained unchanged; fructosamine 318.14+/-65.38 versus 317.28+/-52.80 mmol/L in fasting group, 290.71+/-38.48 versus 290+/-38.56 mmol/L in non-fasting group. None of them exhibited either a major or a minor hypoglycemic event. The results of this pilot study indicated that repaglinide t.i.d. plus single-dose insulin glargine regimen was safe for low-risk type 2 diabetic patients who insisted on fasting during Ramadan.

Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data.

PubMed

Kurosaki, Eiji; Ogasawara, Hideaki

2013-07-01

Sodium-glucose cotransporter-2 (SGLT2) is expressed in the proximal tubules of the kidneys and plays a key role in renal glucose reabsorption. A novel class of antidiabetic medications, SGLT2-selective inhibitors attempt to improve glycemic control in diabetics by preventing glucose from being reabsorbed through SGLT2 and re-entering circulation. Ipragliflozin is an SGLT2 inhibitor in Phase 3 clinical development for the treatment of type 2 diabetes mellitus (T2DM). In this review, we summarize recent animal and human studies on ipragliflozin and other SGLT2 inhibitors including dapagliflozin, canagliflozin, empagliflozin, tofogliflozin, and luseogliflozin. These agents all show potent and selective SGLT2 inhibition in vitro and reduce blood glucose levels and HbA1c in both diabetic animal models and patients with T2DM. SGLT2 inhibitors offer several advantages over other classes of hypoglycemic agents. Due to their insulin-independent mode of action, SGLT2 inhibitors provide steady glucose control without major risk for hypoglycemia and may also reverse β-cell dysfunction and insulin resistance. Other favorable effects of SGLT2 inhibitors include a reduction in both body weight and blood pressure. SGLT2 inhibitors are safe and well tolerated and can easily be combined with other classes of antidiabetic medications to achieve tighter glycemic control. The long-term safety and efficacy of these agents are under evaluation. Copyright © 2013 Elsevier Inc. All rights reserved.

Potential of the chlorogenic acid as multitarget agent: Insulin-secretagogue and PPAR α/γ dual agonist.

PubMed

Sanchez, Maetzin Becerra; Miranda-Perez, Elizabeth; Verjan, Juan Carlos Gomez; de Los Angeles Fortis Barrera, Maria; Perez-Ramos, Julia; Alarcon-Aguilar, Francisco Javier

2017-10-01

The chlorogenic acid (CGA) is a natural product isolated from Cecropia obtusifolia, which possesses several pharmacological properties, such as: anti-carcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic. In relation to its effects on the hyperglycemia and hypertriglyceridemia, few is known about the mechanisms in which this compound may be acting, therefore, the aim of the present study was to determine if CGA acts as an insulin secretagogue increasing intracellular calcium concentrations ([Ca 2+ ] i ) in RINm5F cells; or as an insulin sensitizer and lipid-lowering agent stimulating the expression of PPARγ and PPARα, respectively, in 3T3-L1 adipocytes. As results, RINm5F cells treated with 200μM of CGA showed an increase in [Ca 2+ ] i of 9-times versus control and 4-times as compared to positive control; in addition, an increase in insulin secretion was observed similarly to those of positive control. CGA also significantly increased the mRNA expression of PPARγ (150%) and GLUT4 (220%), as well PPARα (40%) and FATP (25%) as it was appreciated by RT-PCR. Additionally, a chemoinformatic analysis suggested that CGA has suitable physicochemical properties to be considered as leader bioactive molecule for the development of novel agents with similar properties. Together, our results indicate that CGA possesses multiple mechanisms of action for the development of highly effective therapeutics in the treatment of metabolic diseases such as type 2 diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Toxic hypoglycemic syndrome--Jamaica, 1989-1991.

PubMed

1992-01-31

In January and February 1991, the health officer in the parish of St. Ann, Jamaica, received reports of eight persons with toxic hypoglycemic syndrome (THS), an illness associated with consumption of unripe ackee fruit and, possibly, renta yam; two cases were fatal. On July 25, the Jamaican Ministry of Health (JMH) contacted CDC for assistance in investigating the continued occurrence of THS; the collaborative JMH and CDC epidemiologic investigation focused on characterizing the epidemiology of THS in Jamaica and assessing the role of ackee fruit, renta yams, and other factors.

Medications and Impaired Driving: A Review of the Literature

PubMed Central

Hetland, Amanda; Carr, David B

2013-01-01

Objective To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. Data sources The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on specific classes of medications known to be associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Study selection and data extraction Only English-language articles that contained findings from observational or interventional designs were included. Cross-sectional studies, case series, and case reports were excluded. Studies of ≥ 10 subjects were included in this review. Data synthesis Driving is an important task and activity for the majority of adults. Unfortunately, some specific classes of commonly prescribed medications have been associated with driving impairment as measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, certain non-benzodiazepine hypnotics, various antidepressants, opioid and non-steroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies identifying medication impacts on sedation, sleep latency, and psychomotor function – as well as the role of alcohol – are also discussed. Conclusions Psychotropic agents and those with CNS side effects were associated with various measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or perhaps the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific populations and classes of medications when prescribing these agents, educate their patients, and/or consider safer alternatives. PMID:24473486

Increased Risk of Severe Hypoglycemic Events with Increasing Frequency of Non-severe Hypoglycemic Events in Patients with Type 1 and Type 2 Diabetes.

PubMed

Sreenan, Seamus; Andersen, Marc; Thorsted, Brian Larsen; Wolden, Michael L; Evans, Marc

2014-12-01

Severe hypoglycemic events (SHEs) are associated with significant morbidity, mortality and costs. However, the more common non-severe hypoglycemic events (NSHEs) are less well explored. We investigated the association between reported frequency of NSHEs and SHEs among patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the PREDICTIVE study. PREDICTIVE was a global, prospective, observational study. Patients with T1DM (n = 7,420) or T2DM (n = 12,981), starting treatment with insulin detemir, reported the number of NSHEs and SHEs experienced during the 4 weeks prior to baseline and follow-up visits (mean 14.4 weeks). Logistic regression was used to determine the odds ratio (OR) of experiencing ≥1 SHE, in patients having 1-4 or ≥5 NSHEs, versus those having 0 NSHEs, while controlling for baseline covariates. Hypoglycemia rates were lower at follow-up than baseline. At baseline 59.2% (T1DM) and 18.8% (T2DM) reported any hypoglycemia and at follow-up 39.5% (T1DM) and 8.6% (T2DM). There was a significant (P < 0.0001) increase in the odds of ≥1 SHEs with increasing frequency of NSHEs in T1DM and T2DM, for both crude and adjusted estimates. At baseline, in T1DM, ORs for ≥1 SHE were 1.92 and 2.13 for 1-4 and ≥5 NSHEs, respectively; the corresponding ORs in T2DM were 10.83 and 15.36, respectively. At follow-up, the ORs for ≥1 SHE were 2.01 and 3.20 (T1DM) and 18.99 and 24.29 (T2DM) for 1-4 and ≥5 NSHEs, respectively. A statistically significant association between NSHE and SHE frequency was found in T1DM and T2DM. These data provide a clear rationale for the reduction of hypoglycemic events, regardless of severity, while striving for optimal glycemic control.

A Retrospective Cohort Study of Patients with Type 2 Diabetes in China: Associations of Hypoglycemia with Health Care Resource Utilization and Associated Costs.

PubMed

Yi, Yingping; Li, Yawei; Hou, Anran; Ge, Yanqiu; Xu, Yuan; Xiong, Gang; Yang, Xinlei; Acevedo, Stephanie Ann; Shi, Lizheng; Xu, Hua

2018-06-01

This study aimed to examine the associations of hypoglycemia with health care resource utilization (HCRU) and health care costs among patients with type 2 diabetes mellitus (T2DM) in China. This retrospective cohort study was conducted with 23,680 T2DM patients >18 years old who visited the Second Affiliated Hospital of Nanchang University between 1 January 2011 and 31 December 2015. Univariate descriptive statistics were used to relate the HCRU and associated costs to patient characteristics, and regression analysis was used to examine the association between hypoglycemia and HCRU, controlling for other confounding factors. In the T2DM patients with or without insulin treatment, when compared with nonhypoglycemic patients, hypoglycemia was associated with more medical visits (all T2DM patients 19.48 vs. 10.46, insulin users 23.45 vs. 14.12) and higher diabetes-related medical costs (all T2DM patients ¥5187.54 vs. ¥3525.00, insulin users ¥6948.84 vs. ¥3401.15) and medication costs (T2DM patients ¥1349.40 vs. ¥641.92, insulin users: ¥1363.87 vs. ¥853.96). Controlling for age, gender, and Charlson comorbidity index (CCI) score, hypoglycemia and insulin intake were associated with greater health care resource utilization. As compared to nonhypoglycemic patients, hypoglycemic T2DM patients and those on insulin therapy performed more outpatient visits (proportions of hypoglycemic vs nonhypoglycemic T2DM patients performing 3+ visits: 72.69% vs. 65.49%; proportions of hypoglycemic vs nonhypoglycemic patients on insulin therapy performing 3+ visits: 78.26% vs. 71.73%) and were hospitalized more often (proportions of hypoglycemic vs nonhypoglycemic T2DM patients with 3+ admissions 75.90% vs. 50.24%; proportions of hypoglycemic vs nonhypoglycemic patients on insulin therapy with 3+ admissions: 83.19% vs. 58.51%). Hypoglycemia in diabetes patients was associated with increased healthcare resource utilization and health-related expenditure, especially for patients on insulin treatment. Insulin treatment regimens should be more individualized and account for hypoglycemia risk.

Metabolomics-based evidence of the hypoglycemic effect of Ge-Gen-Jiao-Tai-Wan in type 2 diabetic rats via UHPLC-QTOF/MS analysis.

PubMed

Wang, Wenbo; Zhao, Linlin; He, Zhenyu; Wu, Ning; Li, Qiuxia; Qiu, Xinjian; Zhou, Lu; Wang, Dongsheng

2018-06-12

Ge-Gen-Jiao-Tai-Wan (GGJTW) formula, derived from traditional Chinese herbal medicine, is composed of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (Ge-Gen in Chinese), Coptis chinensis Franch (Huang-Lian), and Cinnamomum cassia (L.) J. Presl (Rou-Gui). GGJTW is used for treatment of diabetes in China, reflecting the potent hypoglycemic effect of its ingredients. However, little is known of the hypoglycemic effect of GGJTW and the underlying metabolic mechanism. This study aimed to investigate the hypoglycemic effect of GGJTW in type 2 diabetic rats and the metabolic mechanism of action. Ultra high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomics approach was used for monitoring hyperglycaemia induced by high-sugar high-fat fodder and streptozotocin (STZ), and the protective effect of GGJTW. Dynamic fasting blood glucose (FBG) levels, body weight, and biochemical parameters, including lipid levels, hepatic-renal function, and hepatic histopathology were used to confirm the hyperglycaemic toxicity and attenuation effects. An orthogonal partial least squared-discriminant analysis (OPLS-DA) approach highlighted significant differences in the metabolome of the healthy control, diabetic, and drug-treated rats. The metabolomics pathway analysis (MetPA) and Kyoto encyclopedia of genes and genomes (KEGG) database were used to investigate the underlying metabolic pathways. Metabolic profiling revealed 37 metabolites as the most potential biomarker metabolites distinguishing GGJTW-treated rats from model rats. Most of the metabolites were primarily associated with bile acid metabolism and lipid metabolism. The most critical pathway was primary bile acid biosynthesis pathway involving the up-regulation of the levels of cholic acid (CA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), glycocholic acid (GCA), taurochenodesoxycholic acid (TCDCA), and taurine. The significantly-altered metabolite levels indicated the hypoglycemic effect of GGJTW on diabetic rats and the underlying metabolic mechanism. This study will be meaningful for the clinical application of GGJTW and valuable for further exploration of the mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

Review of antidiabetic fruits, vegetables, beverages, oils and spices commonly consumed in the diet.

PubMed

Beidokhti, Maliheh Najari; Jäger, Anna K

2017-04-06

Type 2 diabetes is the most common type of diabetes and its prevalence is rapidly increasing throughout the world. Modifications of lifestyle such as suitable diet and exercise programs along with pharmacotherapy and education of patients are beneficial therapies for patients with type 2 diabetes. The ethnopharmacological use of herbal medicines, many of them part of our diet as spices, vegetables and fruits, has been developed for the treatment of diabetes due to inexpensiveness, easy availability and few side effects. Our aim is to present a review for researchers who are interested in the biologically active dietary plants traditionally utilized in the treatment of diabetes. Information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed, Sci Finder and Cochrane. Common and scientific name of the fruits, vegetables, beverages, oils and spices and the words 'antidiabetic', 'hypoglycemic', 'anti-hyperglycemic', 'type 2 diabetes' were used as keywords for search. Certain fruits and vegetables are functional foods and their consumption reduces the incidence of type 2 diabetes. Hypoglycemic effects of fruits and vegetables may be due to their inducing nature on pancreatic β-cells for insulin secretion, or bioactive compounds such as flavonoids, alkaloids and anthocyanins, which act as insulin-like molecules or insulin secretagogues. This write-up covers hypoglycemic, anti-hyperglycemic and anti-diabetic activities of some dietary fruits, vegetables, beverages, oils and spices and their active hypoglycemic constituents. Including such plant species in the diet might improve management of type 2 diabetes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Semipurified fractions from the submerged-culture broth of Agaricus blazei Murill reduce blood glucose levels in streptozotocin-induced diabetic rats.

PubMed

Oh, Tae W; Kim, Yun A; Jang, Wook J; Byeon, Jae I; Ryu, Chung H; Kim, Jeong O; Ha, Yeong L

2010-04-14

Hypoglycemic action of semipurified fractions from hot-water extracts of the submerged-culture broth of Agaricus blazei Murill was examined in streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic male Sprague-Dawley rats, relative to the diabetes drug metformin. The hot-water extract, treated with ethanol to remove beta-glucans and glycoproteins, was freeze-dried, and fractionated into hexane, chloroform, ethyl acetate (EA), and butanol fractions. The EA fraction (EAF; 200 mg/kg body weight) reduced (p < 0.05) the blood glucose level in the oral glucose tolerance test, relative to the other fractions and control. In a 14 day-treatment study, diabetic rats treated with the EAF displayed a suppressed blood glucose level and elevated plasma insulin and glucose transport-4 proteins; the reactions occurred in a dose-dependent manner (200 and 400 mg/kg body weight) compared to those in control animals. The EAF reduced the levels of triglyceride and cholesterol in plasma, the activity of glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase in blood, and the content of thiobarbituric acid reactive substance in the liver and kidney. The hypoglycemic efficacy of the EAF (400 mg/kg body weight) was similar to that of metformin (500 mg/kg body weight). The EAF contained substantial amounts of isoflavonoids including genistein, genistin, daidzein, and daidzin, which could have contributed to the fraction's hypoglycemic action. These results indicate that the hot-water extract of the submerged-culture broth of Agaricus blazei contains an EAF having potent hypoglycemic action, which could be useful in the treatment of diabetes mellitus.

Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats.

PubMed

Juárez-Rojop, Isela Esther; Díaz-Zagoya, Juan C; Ble-Castillo, Jorge L; Miranda-Osorio, Pedro H; Castell-Rodríguez, Andrés E; Tovilla-Zárate, Carlos A; Rodríguez-Hernández, Arturo; Aguilar-Mariscal, Hidemi; Ramón-Frías, Teresa; Bermúdez-Ocaña, Deysi Y

2012-11-28

Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans. Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks. The aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, C. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats. This study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas.

Hypoglycemic activity of dried extracts of Bauhinia forficata Link.

PubMed

da Cunha, A M; Menon, S; Menon, R; Couto, A G; Bürger, C; Biavatti, M W

2010-01-01

Leaves of the pantropical genus Bauhinia (Fabaceae) are known popularly as cow's foot, due to their unique characteristic bilobed aspect. The species Bauhinia forficata (Brazilian Orchid-tree) is widely used in folk medicine as an antidiabetic. The present work investigates the hypoglycemic activity of the dried extracts of Bauhinia forficata leaves in vivo, as well as the influence of the drying and granulation processes on this activity. The fluid extract was dried to generate oven-dried (ODE), spray-dried (SDE) and wet granulation (WGE) extracts, with the aid of colloidal silicon dioxide and/or cellulose:lactose mixture. The dried extracts were characterized by spectrophotometric, chromatographic and photo microscopy image analysis. 200 mg/kg body wt., p.o. of each dried product were administered orally to male Wistar rats over 7 days old, for biomonitoring of the hypoglycemic activity profile. The effect of the extracts was studied in STZ-induced diabetic rats. After 7 days of treatment, fasting glucose was determined, and the livers were removed, dried on tissue paper, weighed, and stored at -20 degrees C to estimate hepatic glycogen. Our results show that spray-drying or oven-drying processes applied to B. forficata extracts did not significantly alter its flavonoid profile or its hypoglycemic activity. Indeed, the dried extracts of B. forficata act differently from glibenclamide. Despite the lower active content in WGE, because of the higher concentration of adjuvants, the use of the granulation process improved the manufacturing properties of the ODE, making this material more appropriate for use in tablets or capsules.

Hypoglycemic activity of polysaccharide fractions containing beta-glucans from extracts of Rhynchelytrum repens (Willd.) C.E. Hubb., Poaceae.

PubMed

De Paula, A C C F F; Sousa, R V; Figueiredo-Ribeiro, R C L; Buckeridge, M S

2005-06-01

Beta-glucans are soluble fibers with physiological functions, such as interference with absorption of sugars and reduction of serum lipid levels. The objective of the present study was to analyze the distribution of beta-glucans in different tissues of the African grass species Rhynchelytrum repens and also to evaluate their hypoglycemic activity. Leaf blades, sheaths, stems, and young leaves of R. repens were submitted to extraction with 4 M KOH. Analysis of the fractions revealed the presence of arabinose, glucose, xylose, and traces of rhamnose and galactose. The presence of beta-glucan in these fractions was confirmed by hydrolyzing the polymers with endo-beta-glucanase from Bacillus subtilis, followed by HPLC analysis of the characteristic oligosaccharides produced. The 4 M KOH fractions from different tissues were subjected to gel permeation chromatography on Sepharose 4B, with separation of polysaccharides with different degrees of polymerization, the highest molecular mass (above 2000 kDa) being found in young leaves. The molecular mass of the leaf blade polymers was similar (250 kDa) to that of maize coleoptile beta-glucan used for comparison. The 4 M KOH fraction injected into rats with streptozotocin-induced diabetes showed hypoglycemic activity, reducing blood sugar to normal levels for approximately 24 h. This performance was better than that obtained with pure beta-glucan from barley, which decreased blood sugar levels for about 4 h. These results suggest that the activity of beta-glucans from R. repens is responsible for the use of this plant extract as a hypoglycemic drug in folk medicine.

Insulin sensitizing and alpha-glucoamylase inhibitory action of sennosides, rheins and rhaponticin in Rhei Rhizoma.

PubMed

Choi, Soo Bong; Ko, Byoung Seob; Park, Seong Kyu; Jang, Jin Sun; Park, Sunmin

2006-01-25

Extracts from Rhei Rhizoma extracts (RR) have been reported to attenuate metabolic disorders such as diabetic nephropathy, hypercholesterolemia and platelet aggregation. With this study we investigated the anti-diabetic action of 70% ethanol RR extract in streptozotocin-induced diabetic mice, and determined the action mechanism of active compounds of RR in vitro. In the diabetic mice, serum glucose levels at fasting and post-prandial states and glucose area under the curve at modified oral glucose tolerance tests were lowered without altering serum insulin levels, indicating that RR contained potential anti-diabetic agents. The fractions fractionated from RR extracts by XAD-4 column revealed that 60%, 80% and 100% methanol fractions enhanced insulin sensitivity and inhibited alpha-glucoamylase activity. The major compounds of these fractions were sennosides, rhein and rhaponticin. Rhaponticin and rhein enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Rhaponticin increased adipocytes with a differentiating effect similar to pioglitazone, but rhein and sennoside B decreased triglyceride accumulation. Sennoside A and B inhibited alpha-glucoamylase activity as much as acarbose. In conclusion, a crude extract of RR improves glucose intolerance by enhancing insulin-stimulated glucose uptake and decreasing carbohydrate digestion via inhibiting alpha-glucoamylase activity. Rhein and rhaponticin are potential candidates for hypoglycemic agents.

Hypoglycemic activity of Pyrus biossieriana Buhse leaf extract and arbutin: Inhibitory effects on alpha amylase and alpha glucosidase

PubMed Central

Yousefi, Fatemeh; Mahjoub, Soleiman; Pouramir, Mahdi; Khadir, Fatemeh

2013-01-01

Background: The mechanism of hypoglycemic and hypolipidemic activities of Pyrus biossieriana Buhse leaf extract (PbBLE) and its phytochemical component arbutin, have not been well determined. The present study was performed to understand the hypoglycemic activity mechanisms of pbBLE and arbutin more clearly. Methods: In vitro enzymatic carbohydrate digestion with PbBLE and arbutin was assessed using α-amylase and α-glucosidase powders. The enzyme solutions were premixed with PbBLE and arbutin at different concentrations (0.1, 1, 10 and 100 mg/ml). Substrate solutions and colorimetric reagents were added to the reaction. The release of glucose was determined by spectrophotometric method. Acarbose was used as the positive control. Results: The extract (10, 100 mg/ ml) completely inhibit α- amylase and α- glucosidase activities. The extract produced higher reduction of α-amylase and α-glucosidase activity than arbutin. Inhibition at various concentrations (0.1, 1, 10, 100 mg/ml) were significantly different (p<0.05). Conclusion: Our results exhibited that both the extract and arbutin were able to suppress the enzymes strongly. PMID:24294470

Anti-diabetic effects of Ganoderma lucidum.

PubMed

Ma, Haou-Tzong; Hsieh, Jung-Feng; Chen, Shui-Tein

2015-06-01

Ganoderma lucidum is a white rot fungus widely used as a tonic for the promotion of longevity and health. Extracts of G. lucidum have been recognized as an alternative adjuvant treatment for diabetes. Among the many biologically active constituents of G. lucidum, polysaccharides, proteoglycans, proteins and triterpenoids have been shown to have hypoglycemic effects. G. lucidum polysaccharides have been reported to have hypoglycemic activity by increasing plasma insulin levels and decreasing plasma sugar levels in mice. Protein tyrosine phosphatase 1B is a promising therapeutic target in diabetes, and G. lucidum proteoglycan can inhibit this enzyme in vitro. Moreover, G. lucidum triterpenoids were shown to have inhibitory activity on aldose reductase and α-glucosidase that can suppress postprandial hyperglycemia. In addition, a protein Ling Zhi-8 extracted from G. lucidum significantly decreased lymphocyte infiltration and increased the antibody detection of insulin in diabetic mice. This review summarizes most of the research about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins and tritrerpenoids from G. lucidum as a guide for future research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats.

PubMed

Pushparaj, P; Tan, C H; Tan, B K

2000-09-01

The present study was designed to investigate the hypoglycemic and hypolipidemic activities of an ethanolic extract of Averrhoa bilimbi Linn. leaves (Oxalidaceae, Common name: Bilimbi) in streptozotocin (STZ)-diabetic rats. The optimal hypoglycemic dose (125 mg kg(-1)) was determined by performing the oral glucose tolerance test (OGTT) in both normal and STZ-diabetic rats. To investigate the effect of repeated administration of an ethanolic extract of Averrhoa bilimbi (ABe) leaves, diabetic rats were treated with vehicle (distilled water), ABe (125 mg kg(-1)) or metformin (500 mg kg(-1)) twice a day for 2 weeks. Like metformin, ABe significantly lowered blood glucose by 50% and blood triglyceride by 130% when compared with the vehicle. ABe also significantly increased the HDL-cholesterol concentrations by 60% compared with the vehicle. ABe thus significantly increased the anti-atherogenic index and HDL-cholesterol/total cholesterol ratio. However, like metformin, ABe did not affect total cholesterol and LDL-cholesterol concentrations, but significantly reduced the kidney lipid peroxidation level. These data show that ABe has hypoglycemic, hypotriglyceridemic, anti-lipid peroxidative and anti-atherogenic properties in STZ-diabetic rats.

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

PubMed

Sathya, S; Kokilavani, R; Gurusamy, K

2008-10-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level.

Glucagon-like peptide-1 receptor agonists versus insulin glargine for type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Li, Wei-Xin; Gou, Jian-Feng; Tian, Jin-Hui; Yan, Xiang; Yang, Lin

2010-01-01

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of hypoglycemic drugs, including exenatide, liraglutide, albiglutide, lixisenatide, and taspoglutide. Insulin glargine is a standard agent used to supplement basal insulin in type 2 diabetes mellitus (T2DM). Objective: The aim of this study was to review the efficacy and safety profiles of GLP-1 receptor agonists versus insulin glargine in type 2 diabetic patients who have not achieved treatment goals with oral hypoglycemic agents. Methods: The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and the database of ongoing trials were searched from inception through April 2010. Additional data were sought from relevant Web sites, the American Diabetes Association, reference lists of included trials and related (systematic) reviews, and industry. Randomized controlled trials (RCTs) were selected if they were ≥3 months in duration, compared GLP-1 receptor agonists with insulin glargine in patients with T2DM, and included ≥1 of the following outcomes: mortality, complications of T2DM, glycemie control, weight, lipids, blood pressure, adverse effects, and health-related quality of life. Quasirandomized controlled trials were excluded. The quality of the eligible studies was assessed on the basis of the following aspects: randomization procedure, allocation concealment, blinding, incomplete outcome data (intent-to-treat [ITT] analysis), selective outcome reporting, and publication bias. Results: A total of 410 citations were retrieved; 5 multicenter RCTs that met the inclusion criteria were identified. They were all open-label designs with an insulin glargine arm, predefined outcomes reported, and ITT analysis. One trial had an unclear randomization procedure and allocation concealment. Publication bias was not able to be determined. No data wete found with regard to mortality or diabetes-associated complications, and few data were found on quality of life. The results of the metaanalysis suggest that insulin glargine was significantly better in reducing the fasting blood glucose (mean difference [MD] [95% CI], 1.31 [1.04 to 1.58]; P < 0.001), but exhibits greater incidence of nocturnal hypoglycemia (risk ratio [RR] [95% CI], 0.40 [0.23 to 0.71]; P = 0.002) and influenza (RR [95% CI], 0.56 [0.32 to 0.98]; P = 0.04). GLP-1 receptor agonists are more conducive to reducing weight (MD [95% CI], −3.96 [−5.14 to -2.77]; P < 0.001), postprandial blood glucose (after breakfast, P < 0.001; after dinner, P < 0.001), and LDL-C (MD [95% CI], −0.18 [−0.28 to −0.08]; P < 0.001), but have significantly more gastrointestinal adverse effects (eg, nausea/ vomiting, P < 0.001). There were no significant differences between GLP-1 receptor agonists and insulin glargine in reducing glycosylated hemoglobin (HbA1c) levels (MD [95% CI], −0.03 [−0.13 to 0.08]) and the overall incidence of hypoglycemia (RR [95% CI], 0.69 [0.42 to 1.14]). Conclusions: Compared with insulin glargine, GLP-1 receptor agonists did not have a significant difference in regard to reducing HbA1c levels and they were significantly associated with decreased weight but increased gastrointestinal adverse events. It remains unclear whether GLP-1 receptor agonists influence mortality or diabetes-associated complications in patients with T2DM. More trials with longer follow-up are needed to determine the exact long-term efficacy and safety profiles of this new class of hypoglycemic drugs. PMID:24688145

Prevention of Hypoglycemia With Predictive Low Glucose Insulin Suspension in Children With Type 1 Diabetes: A Randomized Controlled Trial.

PubMed

Battelino, Tadej; Nimri, Revital; Dovc, Klemen; Phillip, Moshe; Bratina, Natasa

2017-06-01

To investigate whether predictive low glucose management (PLGM) of the MiniMed 640G system significantly reduces the rate of hypoglycemia compared with the sensor-augmented insulin pump in children with type 1 diabetes. This randomized, two-arm, parallel, controlled, two-center open-label study included 100 children and adolescents with type 1 diabetes and glycated hemoglobin A 1c ≤10% (≤86 mmol/mol) and using continuous subcutaneous insulin infusion. Patients were randomly assigned to either an intervention group with PLGM features enabled (PLGM ON) or a control group (PLGM OFF), in a 1:1 ratio, all using the same type of sensor-augmented insulin pump. The primary end point was the number of hypoglycemic events below 65 mg/dL (3.6 mmol/L), based on sensor glucose readings, during a 14-day study treatment. The analysis was performed by intention to treat for all randomized patients. The number of hypoglycemic events below 65 mg/dL (3.6 mmol/L) was significantly smaller in the PLGM ON compared with the PLGM OFF group (mean ± SD 4.4 ± 4.5 and 7.4 ± 6.3, respectively; P = 0.008). This was also true when calculated separately for night ( P = 0.025) and day ( P = 0.022). No severe hypoglycemic events occurred; however, there was a significant increase in time spent above 140 mg/dL (7.8 mmol/L) in the PLGM ON group ( P = 0.0165). The PLGM insulin suspension was associated with a significantly reduced number of hypoglycemic events. Although this was achieved at the expense of increased time in moderate hyperglycemia, there were no serious adverse effects in young patients with type 1 diabetes. © 2017 by the American Diabetes Association.

Hypoglycemia prediction with subject-specific recursive time-series models.

PubMed

Eren-Oruklu, Meriyan; Cinar, Ali; Quinn, Lauretta

2010-01-01

Avoiding hypoglycemia while keeping glucose within the narrow normoglycemic range (70-120 mg/dl) is a major challenge for patients with type 1 diabetes. Continuous glucose monitors can provide hypoglycemic alarms when the measured glucose decreases below a threshold. However, a better approach is to provide an early alarm that predicts a hypoglycemic episode before it occurs, allowing enough time for the patient to take the necessary precaution to avoid hypoglycemia. We have previously proposed subject-specific recursive models for the prediction of future glucose concentrations and evaluated their prediction performance. In this work, our objective was to evaluate this algorithm further to predict hypoglycemia and provide early hypoglycemic alarms. Three different methods were proposed for alarm decision, where (A) absolute predicted glucose values, (B) cumulative-sum (CUSUM) control chart, and (C) exponentially weighted moving-average (EWMA) control chart were used. Each method was validated using data from the Diabetes Research in Children Network, which consist of measurements from a continuous glucose sensor during an insulin-induced hypoglycemia. Reference serum glucose measurements were used to determine the sensitivity to predict hypoglycemia and the false alarm rate. With the hypoglycemic threshold set to 60 mg/dl, sensitivity of 89, 87.5, and 89% and specificity of 67, 74, and 78% were reported for methods A, B, and C, respectively. Mean values for time to detection were 30 +/- 5.51 (A), 25.8 +/- 6.46 (B), and 27.7 +/- 5.32 (C) minutes. Compared to the absolute value method, both CUSUM and EWMA methods behaved more conservatively before raising an alarm (reduced time to detection), which significantly decreased the false alarm rate and increased the specificity. 2010 Diabetes Technology Society.

Isolation, Purification, Characterization and Effect upon HepG2 Cells of Anemaran from Rhizome Anemarrhena.

PubMed

Jiang, Qian-Qian; Zhao, Yun-Ping; Gao, Wen-Yuan; Li, Xia; Huang, Lu-Qi; Xiao, Pei-Gen

2013-01-01

The rhizome of Anemarrhena asphodeloides is used as food and traditional Chinese medicine for its hypoglycemic effect. The aim of this study was to investigate the isolation, purification and hypoglycemic activity of Anemaran as the active component. The influence factors (isolation duration, ratio of residuals to water and extracting times) during the isolation process were evaluated. The optimal conditions for NA and AA were extraction temperature 90ºC and 100ºC, duration 1h and 1.5 h, extraction time 3 and 3, and the solid-liquor ratio 1:20 and 1:15, respectively. Neutral and acid Anemaran (NA and AA) were isolated from the rhizome of Anemarrhena asphodeloides. Five fractions of NA-1, NA-2, NA-3, AA-1 and AA-2 were obtained after crude neutral and acid Anemaran purified through DEAE- 52 cellulose anion-exchange column. The characterizations of Anemaran and its different fractions were both analyzed by Fourier transform infrared spectroscopy (FT-IR) and scanning electron micrographs (SEM). Structural properties of different fractions were examined by FT-IR. Strong characteristic absorption peaks were observed at around 1744 cm(-1)and 1650 cm(-1) caused by the C=O group of uronic acids, and the band between 1440 cm(-1) and 1395 cm(-1) associated with the stretching vibration of C-O of galacturonic acid. Neither the crude neutral, nor the acid anemaran significantly inhibited the growth of HepG2 cells in-vitro, which indicated the low cytotoxicity of the anemaran. Furthermore, both neutral and acid anemaran showed hypoglycemic effect. The hypoglycemic effect of neutral anemaran was much higher than that of acid anemaran.

In vivo Investigation of Anti-diabetic Properties of Ripe Onion Juice in Normal and Streptozotocin-induced Diabetic Rats

PubMed Central

Lee, Chul-Won; Lee, Hyung-Seok; Cha, Yong-Jun; Joo, Woo-Hong; Kang, Dae-Ook; Moon, Ja-Young

2013-01-01

The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is “Black Onion Extract”) were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyper-glycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product “Black Onion Extract” may possess anti-hyperglycemic potential in diabetes. PMID:24471128

Hypoglycemic effect of polysaccharides with different molecular weight of Pseudostellaria heterophylla

PubMed Central

2013-01-01

Abstracts Background The aims of this study were to evaluate the antidiabetic activity and to detect molecular size of Pseudostellaria heterophylla polysaccharide (PHP). Pseudostellaria heterophylla is a medicine extensively used in traditional Chinese medicine formulas to treat diabetes and its complications. Methods Molecular weight of PHP was determined by gel permeation chromatography combined with phenol-sulphuric acid method and the monosaccharides composition was determined by HPLC with a precolumn derivatization. Four polysaccharides with different molecular weight were compared for hypoglycemic active on two animal models both high does alloxan induced type1 diabetic mellitus (T1DM) and high-fat/lower does streptozotocin induced type2 diabetic mellitus (T2DM). Blood sugar, glucose tolerance, and insulin tolerance were detected. Rat serum IL-1β, IL-2, IL-10, Leptin, TNF-α, Acrp30 and CRP were also analyzed by sandwich-ELISA approaches to preliminary probe the hypoglycemic mechanism of PHP. Results The hypoglycemic effects related to molecular size of polysaccharide were more effective against T2DM than T1DM. PHP comprise four monosaccharides of galacturonic acid, glucose, galactose and arabinos. T2DM rats daily receiving oral dose of polysaccharide(100 ~ 400 mg/kg) with 50 ~ 210 kDa molecular weight (PF40) could not only significantly lower blood sugar but also reduce total triglyceride level in serum. PF40 improves in insulin tolerance inhibited the expression of some biomarkers including inflammatory cytokine TNF-α and elevated anti-inflammatory cytokine IL-10, regulated adiponectin Acrp30 and leptin. Conclusions PF40 prevent the cascade of inflammatory events in the treatment of T2DM to block overweight progresses to obesity. PMID:24131482

Investigation of hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats

PubMed Central

Ramachandran, Subramaniam; Rajasekaran, Aiyalu; Manisenthilkumar, KT

2012-01-01

Objective To investigate the hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark (AETPB) in streptozotocin (STZ)-induced diabetic rats. Methods Acute toxicity was studied in rats after the oral administration of AETPB to determine the dose to assess hypoglycemic activity. In rats, diabetes was induced by injection of STZ (60 mg/kg, i.p.) and diabetes was confirmed 72 h after induction, and then allowed for 14 days to stabilize blood glucose level. In diabetic rats, AETPB was orally given for 28 days and its effect on blood glucose and body weight was determined on a weekly basis. At the end of the experimental day, fasting blood sample was collected to estimate the haemoglobin (Hb), glycosylated haemoglobin (HbA1c), serum creatinine, urea, serum glutamate-pyruvate transaminase (SGPT), serum glutamate-oxaloacetate transaminase (SGOT) and insulin levels. The liver and kidney were collected to determine antioxidants levels in diabetic rats. Results Oral administration of AETPB did not exhibit toxicity and death at a dose of 2 000 mg/kg. AETPB treated diabetic rats significantly (P<0.001, P<0.01 and P<0.05) reduced elevated blood glucose, HbA1c, creatinine, urea, SGPT and SGOT levels when compared with diabetic control rats. The body weight, Hb, insulin and total protein levels were significantly (P<0.001, P<0.01 and P<0.05) increased in diabetic rats treated with AETPB compared to diabetic control rats. In diabetic rats, AETPB treatment significantly reversed abnormal status of antioxidants and lipid profile levels towards near normal levels compared to diabetic control rats. Conclusions Present study results confirm that AETPB possesses significant hypoglycemic, hypolipidemic and antioxidant activities in diabetic condition. PMID:23569911

Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats

PubMed Central

2012-01-01

Background Traditional plant treatment for diabetes has shown a surging interest in the last few decades. Therefore, the purpose of this study was to assess the hypoglycemic effect of the aqueous extract of C. papaya leaves in diabetic rats. Several studies have reported that some parts of the C. papaya plant exert hypoglycemic effects in both animals and humans. Methods Diabetes was induced in rats by intraperitoneal administration of 60 mg/kg of streptozotocin (STZ). The aqueous extract of C. papaya was administered in three different doses (0.75, 1.5 and 3 g/100 mL) as drinking water to both diabetic and non-diabetic animals during 4 weeks. Results The aqueous extract of Carica papaya (0.75 g and 1.5 g/100 mL) significantly decreased blood glucose levels (p<0.05) in diabetic rats. It also decreased cholesterol, triacylglycerol and amino-transferases blood levels. Low plasma insulin levels did not change after treatment in diabetic rats, but they significantly increased in non-diabetic animals. Pancreatic islet cells were normal in non-diabetic treated animals, whereas in diabetic treated rats, C. papaya could help islet regeneration manifested as preservation of cell size. In the liver of diabetic treated rats, C. papaya prevented hepatocyte disruption, as well as accumulation of glycogen and lipids. Finally, an antioxidant effect of C. papaya extract was also detected in diabetic rats. Conclusions This study showed that the aqueous extract of C. papaya exerted a hypoglycemic and antioxidant effect; it also improved the lipid profile in diabetic rats. In addition, the leaf extract positively affected integrity and function of both liver and pancreas. PMID:23190471

Monoglycerides and fatty acids from Ibervillea sonorae root: isolation and hypoglycemic activity.

PubMed

Hernández-Galicia, Erica; Calzada, Fernando; Roman-Ramos, Rubén; Alarcón-Aguilar, Francisco J

2007-03-01

Eleven monoglycerides (MG), 1-monopalmitin (1), glyceryl 1-monomargarate (2), 1-monostearin (3), glyceryl 1-monononadecylate ( 4), glyceryl 1-monoarachidate (5), glyceryl 1-monobehenate (6), glyceryl 1-monotricosanoate (7), glyceryl 1-monotetracosanoate (8), glyceryl 1-monopentacosanoate (9), glyceryl 1-monohexacosanoate (10) and glyceryl 1-monooctacosanoate (11), together with five fatty acids (FA), lauric acid (12), myristic acid (13), pentadecanoic acid (14), palmitic acid (15) and stearic acid (16) were isolated of the root of IBERVILLEA SONORAE Greene (Cucurbitaceae). Their structures were determined by spectroscopic and chemical methods as well as GC-MS analysis. The hypoglycemic activity of the dichloromethane (DCM) extract, of fractions (F1-F10 and SF1-SF5), of monoglycerides (MG) and of fatty acids (FA) mixtures obtained of the root from I. SONORAE was evaluated in normoglycemic and alloxan-induced diabetic mice. The results showed that by intraperitoneal administration the DCM extract (300 mg/kg), F9 (300 mg/kg) and SF1 (150 mg/kg) significantly reduced glucose levels in both models. For fraction SF1, the hypoglycemic activity was more pronounced than that of tolbutamide (150 mg/kg) used as control. However, neither MG (75 mg/kg) nor FA (75 mg/kg) mixtures isolated from SF1 exhibited a significant hypoglycemic effect. However, when MG and FA were combined in equal proportions (75 mg: 75 mg/kg), their effect was comparable to that of SF1. The observed activity for the DCM extract, F9, SF1 and the MG-FA mixture provides additional support for the popular use of this plant in the treatment of diabetes mellitus in Mexican traditional medicine.

Remote glucose monitoring in cAMP setting reduces the risk of prolonged nocturnal hypoglycemia.

PubMed

DeSalvo, Daniel J; Keith-Hynes, Patrick; Peyser, Thomas; Place, Jérôme; Caswell, Kim; Wilson, Darrell M; Harris, Breanne; Clinton, Paula; Kovatchev, Boris; Buckingham, Bruce A

2014-01-01

This study tested the feasibility and effectiveness of remote continuous glucose monitoring (CGM) in a diabetes camp setting. Twenty campers (7-21 years old) with type 1 diabetes were enrolled at each of three camp sessions lasting 5-6 days. On alternating nights, 10 campers were randomized to usual wear of a Dexcom (San Diego, CA) G4™ PLATINUM CGM system, and 10 were randomized to remote monitoring with the Dexcom G4 PLATINUM communicating with the Diabetes Assistant, a cell phone platform, to allow wireless transmission of CGM values. Up to 15 individual graphs and sensor values could be displayed on a single remote monitor or portable tablet. An alarm was triggered for values <70 mg/dL, and treatment was given for meter-confirmed hypoglycemia. The primary end point was to decrease the duration of hypoglycemic episodes <50 mg/dL. There were 320 nights of CGM data and 197 hypoglycemic events. Of the remote monitoring alarms, 79% were true (meter reading of <70 mg/dL). With remote monitoring, 100% of alarms were responded to, whereas without remote monitoring only 54% of alarms were responded to. The median duration of hypoglycemic events <70 mg/dL was 35 min without remote monitoring and 30 min with remote monitoring (P=0.078). Remote monitoring significantly decreased prolonged hypoglycemic events, eliminating all events <50 mg/dL lasting longer than 30 min as well as all events <70 mg/dL lasting more than 2 h. Remote monitoring is feasible at diabetes camps and effective in reducing the risk of prolonged nocturnal hypoglycemia. This technology will facilitate forthcoming studies to evaluate the efficacy of automated closed-loop systems in the camp setting.

Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice.

PubMed

Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Afrin, Mst Rejina; Sreedhar, Remya; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nakamura, Takashi; Suzuki, Kenji; Nakamura, Masahiko; Ueno, Kazuyuki; Watanabe, Kenichi

2016-09-01

Fasting (48h) in mice causes resistance to insulin-induced hypoglycemic seizures (IIHS) but in rats fasting (14-16h) predisposes IIHS. So we suspect the duration of fasting may possibly affect the onset of seizures and in this study, we investigated the IIHS by administering 8 Units (U) insulin (INS)/k.g., intraperitoneally to 8 weeks old male C57BL6/J mice. The mice were divided into group 1 (non-fasted), group 2 (6h fasted) and group 3 (24h fasted) and we administered the 8U INS. The first behavioral hypoglycemic seizure symptoms such as jump, clonus or barrel rotations considered as seizure onset and we analyzed the blood glucose level (BGL) and serum beta-hydroxybutyrate (BHB) level. The time of first seizure onset in group 1 was 109.7±4.3min, group 2 was 46.50±3.9min and group 3 was 165.4±13.26min. The seizure onset time in group 2 was significantly decreased compared to group 1. The seizure onset time in group 3 was significantly increased compared to group 1 and group 2. The decreased BGL after INS administration was correlated with the seizure onset time in group 1 and group 2 but not in group 3. The BHB level in group 3 was significantly higher compared to group 1 and 2. Our data show that the fasting time duration significantly modulates the onset of hypoglycemic seizures. The opposite effect of 6h or 24h fasting time duration is likely caused by different BHB levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Management of diabetic complications through fruit flavonoids as a natural remedy.

PubMed

Tanveer, Amna; Akram, Kashif; Farooq, Umar; Hayat, Zafar; Shafi, Afshan

2017-05-03

Diabetes mellitus is a global disorder, and a major issue for health care systems. The current review outlooks the use of fruit flavonoids as natural remedy in the prevention of diabetes mellitus. The onset of diabetes mainly depends upon genetics and lifestyle issues. Currently used therapeutic options for the control of diabetes, like dietary amendments, oral hypoglycemic drugs, and insulin, have their own limitations. Fruit flavonoids possess various antidiabetic, anti-inflammatory, and antioxidant potentials and act on various cellular signaling pathways in pancreas, white adipose tissue, skeletal muscle, and liver function, which in result induces antidiabetic effects. Recently, antidiabetic effect of fruit flavonoids has been studied using various animal models and clinical trials. Research studies revealed a statistically significant potential of fruit flavonoids in managing the altered glucose and oxidative metabolisms in diabetes. Unlike synthetic antidiabetic agents, fruit flavonoids manage diabetes without compromising cellular homeostasis thereby posing no side effects. Further studies are required in purification and characterization of different fruit flavonoids with respect to their beneficial effect for diabetic patients.

Aspergillus flavus epidural abscess and osteomyelitis in a diabetic patient.

PubMed

Chi, Chih-Yu; Fung, Chang-Phone; Liu, Cheng-Yi

2003-06-01

A 63-year-old man had a history of diabetes mellitus for more than 10 years and took oral hypoglycemic agents regularly. He visited Taipei Veterans General Hospital with the complaint of progressive weakness in all 4 limbs and neck pain for 6 months. Computed tomography of the cervical spine revealed increased soft tissue density in the epidural space from C2 to C5 with cord compression. Surgical decompression was done and Aspergillus flavus was isolated from the inflammatory tissue. He was initially treated with oral itraconazole 200 mg 3 times per day for 4 days and then twice daily. Later, the treatment regimen was shifted to intravenous amphotericin B 25 mg/d. He died of intraventricular hemorrhage and complicated fungal meningoencephalitis 2 weeks postlaminectomy. This case reminds us that a prolonged history of back pain accompanied with peripheral neuropathy in diabetic patients should raise the suspicion of Aspergillus epidural abscess. Prompt aggressive diagnostic testing and management is needed to improve the likelihood of a good outcome of these patients.

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

PubMed

Kalra, Sanjay; Atkin, Stephen; Cervera, Antonio; Das, Ashok Kumar; Demir, Ozgur; Demir, Tevfik; Fariduddin, Md; Vo, Khoa Tuan; Ku, Bon Jeong; Kumar, Ajay; Latif, Zafar A; Malek, Rachid; Matawaran, Bien J; Mehta, Roopa; Tran, Nam Quang; Panelo, Araceli; Ruder, Sundeep; Saldana, Joel Rodriquez; Shaikh, Khalid A; Shakya, Amit; Shrestha, Dina; Unnikrishnan, A G

2018-05-23

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

Inhibition of α-glucosidase and hypoglycemic effect of stilbenes from the Amazonian plant Deguelia rufescens var. urucu (Ducke) A. M. G. Azevedo (Leguminosae).

PubMed

Pereira, Aline C; Arruda, Mara S; da Silva, Ewerton A; da Silva, Milton N; Lemos, Virgínia S; Cortes, Steyner F

2012-01-01

The control of blood glucose levels is critical in the treatment of diabetes mellitus. α-Glucosidase inhibitors are of great importance in reducing hyperglycemia, and plants have provided many of these agents. The present study aimed at investigating the effect of two stilbenes, lonchocarpene and 3,5-dimethoxy-4'-O-prenyl-trans-stilbene (DPS), isolated from the Amazonian plant Deguelia rufescens var. urucu, on α-glucosidase activity and on mice postprandial hyperglycemia. Lonchocarpene and DPS inhibited α-glucosidase in vitro, with pIC(50) values of 5.68 ± 0.12 and 5.73 ± 0.08, respectively. In addition, when given orally, DPS produced a significant reduction of hyperglycemia induced by an oral tolerance test, while lonchocarpene did not. Data suggest that DPS may have a potential use as an antidiabetic drug. © Georg Thieme Verlag KG Stuttgart · New York.

Antimicrobial activity and phytochemical characterization of Carya illinoensis.

PubMed

Bottari, Nathieli Bianchin; Lopes, Leonardo Quintana Soares; Pizzuti, Kauana; Filippi Dos Santos Alves, Camilla; Corrêa, Marcos Saldanha; Bolzan, Leandro Perger; Zago, Adriana; de Almeida Vaucher, Rodrigo; Boligon, Aline Augusti; Giongo, Janice Luehring; Baldissera, Matheus Dellaméa; Santos, Roberto Christ Vianna

2017-03-01

Carya illinoensis is a widespread species, belonging to the Juglandaceae family, commonly known as Pecan. Popularly, the leaves have been used in the treatment of smoking as a hypoglycemic, cleansing, astringent, keratolytic, antioxidant, and antimicrobial agent. The following research aimed to identify for the first time the phytochemical compounds present in the leaves of C. illinoensis and carry out the determination of antimicrobial activity of aqueous and ethanolic extracts. The antimicrobial activity was tested against 20 microorganisms by determining the minimum inhibitory concentration (MIC). Phenolic acids (gallic acid and ellagic acid), flavonoids (rutin), and tannins (catechins and epicatechins) were identified by HPLC-DAD and may be partially responsible for the antimicrobial activity against Gram-positive, Gram-negative, and yeast. The results showed MIC values between 25 mg/mL and 0.78 mg/mL. The extracts were also able to inhibit the production of germ tubes by Candida albicans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ficus carica L. (Moraceae): Phytochemistry, Traditional Uses and Biological Activities.

PubMed

Mawa, Shukranul; Husain, Khairana; Jantan, Ibrahim

2013-01-01

This paper describes the botanical features of Ficus carica L. (Moraceae), its wide variety of chemical constituents, its use in traditional medicine as remedies for many health problems, and its biological activities. The plant has been used traditionally to treat various ailments such as gastric problems, inflammation, and cancer. Phytochemical studies on the leaves and fruits of the plant have shown that they are rich in phenolics, organic acids, and volatile compounds. However, there is little information on the phytochemicals present in the stem and root. Reports on the biological activities of the plant are mainly on its crude extracts which have been proven to possess many biological activities. Some of the most interesting therapeutic effects include anticancer, hepatoprotective, hypoglycemic, hypolipidemic, and antimicrobial activities. Thus, studies related to identification of the bioactive compounds and correlating them to their biological activities are very useful for further research to explore the potential of F. carica as a source of therapeutic agents.

[Control of type 2 diabetes mellitus in Spain today: identification of the main obstacles in daily clinical practice].

PubMed

Torres, Irene Vinagre; Donlo, Ignacio Conget

2013-09-01

Type 2 diabetes mellitus (DM2) is a highly prevalent chronic disease with major social and healthcare repercussions due to the development of acute and chronic complications. The care of patients with DM2 represents between 6.3% and 7.4% of the budget of the Spanish national health service and is mainly centered on hospital admissions and hypoglycemic agents, leading to an annual expenditure of 1.290 € to 1.476 € per patient. The attainment of glycemic targets remains complex and inadequate, despite new drugs for the treatment of DM2, the available scientific evidence, and national and international guidelines. The main causes proposed for failure to achieve these targets in DM2 are clinical inertia (found in 40% of physicians in Spain treating patients with HbA1c > 7%), poor treatment adherence, the problems inherent to the health system, and the natural history of the disease. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Garlic as an anti-diabetic agent: recent progress and patent reviews.

PubMed

Padiya, Raju; Banerjee, Sanjay K

2013-08-01

This article reviews recent literature on the usage and relevance of garlic and its bioactive components in controlling diabetes and diabetes-associated pathologies; and also updates recent patents on the subject. Antidiabetic effect of garlic is well documented even in ancient medical literature. Garlic and its active ingredients have been extensively studied for their antidiabetic efficacies in either experimentally induced or genetic animal models of diabetes. Human studies are also available where hypoglycemic effect of garlic was reported. The beneficial effects of garlic are mainly attributed to the presence of volatile sulfur compounds like alliin, allicin, diallyl disulfide, diallyl trisulfide, diallyl sulfide, S-allyl cysteine, ajoene and allyl mercaptan. Garlic and garlic extracts have been shown to be effective in reducing insulin resistance. Therefore, considering the importance of garlic in controlling diabetic complications, several preparations and food processes containing garlic have been patented. This review discusses some of the recent progresses made in this field and consolidates the results.

Resolution of electroconvulsive therapy refractory major depressive disorder with unintentional hypoglycemic seizure: a case report.

PubMed

Rosenblat, Joshua D; Devarajan, Sivakumaran

2013-09-01

We report a 74-year-old white woman with type 1 diabetes and major depressive disorder refractory to multiple medications who received 15 electroconvulsive therapy treatments with minimal improvement. After an accidental hypoglycemic seizure, the patient's symptoms completely resolved. In conclusion, the present case reveals an instance where electroconvulsive therapy-induced seizures appeared to be minimally effective, whereas a single accidental hypoglycemia-induced seizure was incredibly effective for the resolutions of depressive symptoms. Although this case presents a single efficacious use of accidental insulin coma therapy, the applicability is limited because of the known risks of insulin coma therapy.

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats

PubMed Central

Sathya, S.; Kokilavani, R.; Gurusamy, K.

2008-01-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level. PMID:22557305

Hypoglycemic effect of Opuntia streptacantha Lemaire in NIDDM.

PubMed

Frati-Munari, A C; Gordillo, B E; Altamirano, P; Ariza, C R

1988-01-01

To assess the hypoglycemic effect of the nopal Opuntia streptacantha Lemaire (O. streptacantha Lem.), three groups of patients with non-insulin-dependent diabetes mellitus (NIDDM) were studied. Group one (16 patients) ingested 500 g of broiled nopal stems. Group 2 (10 patients) received only 400 ml of water as a control test. Three tests were performed on group 3 (6 patients): one with nopal, a second with water, and a third with ingestion of 500 g broiled squash. Serum glucose and insulin levels were measured at 0, 60, 120, and 180 min. After the intake of O. streptacantha Lem., serum glucose and serum insulin levels decreased significantly in groups 1 and 3, whereas no similar changes were noticed in group 2. The mean reduction of glucose reached 17.6 +/- 2.2% of basal values at 180 min in group 1 and 16.2 +/- 1.8% in group 3; the reduction of serum insulin at 180 min reached 50.2 +/- 8.0% in group 1 and 40.3 +/- 12.4% in group 3. This study shows that the stems of O. streptacantha Lem. cause a hypoglycemic effect in patients with NIDDM. The mechanism of this effect is unknown, but an increased insulin sensitivity is suggested.

Vindogentianine, a hypoglycemic alkaloid from Catharanthus roseus (L.) G. Don (Apocynaceae).

PubMed

Tiong, Soon Huat; Looi, Chung Yeng; Arya, Aditya; Wong, Won Fen; Hazni, Hazrina; Mustafa, Mohd Rais; Awang, Khalijah

2015-04-01

Vindogentianine, a new indole alkaloid together with six known alkaloids, vindoline, vindolidine, vindolicine, vindolinine, perivine and serpentine were isolated from leaf extract (DA) of Catharanthus roseus (L.) G. Don. Their structures were elucidated by spectroscopic methods; NMR, MS, UV and IR. Vindogentianine is a dimer containing a vindoline moiety coupled to a gentianine moiety. After 24h incubation, vindogentianine exhibited no cytotoxic effect in C2C12 mouse myoblast and β-TC6 mouse pancreatic cells (IC50>50μg/mL). Real-time cell proliferation monitoring also indicated vindogentianine had little or no effect on C2C12 mouse myoblast cell growth at the highest dose tested (200μg/mL), without inducing cell death. Vindogentianine exhibited potential hypoglycemic activity in β-TC6 and C2C12 cells by inducing higher glucose uptake and significant in vitro PTP-1B inhibition. However, in vitro α-amylase and α-glucosidase inhibition assay showed low inhibition under treatment of vindogentianine. This suggests that hypoglycemic activity of vindogentianine may be due to the enhancement of glucose uptake and PTP-1B inhibition, implying its therapeutic potential against type 2 diabetes. Copyright © 2015 Elsevier B.V. All rights reserved.

Antioxidant and hypoglycemic effects of Diospyros lotus fruit fermented with Microbacterium flavum and Lactobacillus plantarum.

PubMed

Zhang, Zhi-Peng; Ma, Jun; He, Yuan-Yuan; Lu, Jun; Ren, Di-Feng

2018-06-01

Diospyros lotus, a member of the Ebenaceae family, has long been used as a traditional sedative in China. In this study, the antioxidant and hypoglycemic effects of non-fermented and microorganism-fermented D. lotus were explored. The total phenolic and vitamin C contents of microorganism-fermented D. lotus for 24-72 h were less than those of non-fermented. High-performance liquid chromatography showed that the tannic, catechinic, and ellagic acid contents increased significantly upon fermentation for 24 h. D. lotus fermented with Microbacterium flavum for 24 h exhibited the highest DPPH radical scavenging activity (IC 50  = 4.18 μg mL -1 ), and the highest ABTS radical scavenging activity was exhibited at 72 h of fermentation (IC 50  = 29.18 μg mL -1 ). The anti-α-glucosidase activity of fermented D. lotus was higher (2.06-4.73-fold) than that of non-fermented one. Thus, fermented D. lotus is a useful source of natural antioxidants, and a valuable food, exhibiting antioxidant and hypoglycemic properties. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

In vitro studies on the hypoglycemic potential of Ficus racemosa stem bark.

PubMed

Ahmed, Faiyaz; Urooj, Asna

2010-02-01

Medicinal plants have been reported to play an important role in modulating glycemic responses and have preventive and therapeutic implications. Several mechanisms have been proposed for the antidiabetic effect of medicinal plants such as inhibition of carbohydrate-metabolizing enzymes, manipulation of glucose transporters, beta-cell regeneration and enhancing insulin-releasing activity. The present investigation evaluated the possible mechanism of action through which Ficus racemosa stem bark (Moraceae) exerts its hypoglycemic effect using suitable in vitro techniques. Ficus racemosa bark (FRB) exhibited significantly higher (P < or = 0.01) glucose-binding capacity than wheat bran (WB) and acarbose (ACB) consequently showed significantly higher (P < or = 0.01) retardation of glucose diffusion compared to WB and ACB. In case of amylolysis kinetics the liberation of glucose was greatly inhibited by FRB, as reflected by a significantly lower (P < or = 0.01) glucose diffusion rate in the system containing FRB compared to the control and acarbose. Furthermore, FRB significantly increased (P < or = 0.01) the rate of glucose transport across the yeast cell membrane and also in isolated rat hemi-diaphragm. The findings indicate F. racemosa bark to possess strong hypoglycemic effect and hence can be utilized as an adjunct in the management of diabetes mellitus.

Comparison quality of life patients treated with insulin and oral hypoglycemic drugs

NASA Astrophysics Data System (ADS)

Harahap, A. W.; Nasution, M. S.

2018-03-01

Diabetes mellitus (DM) is a group of chronic metabolic diseases with characteristic hyperglycemia that occurs due to abnormalities in insulin secretion, insulin action or both. Improved quality of life is one of the goals of DM management. This study aims to compare thequality of life in40 patients with type 2 diabetes using insulin therapy and 40 patients using oral hypoglycemic drugs in H. Adam Malik Hospital year 2015. This study is an observational study with cross-sectionalstudy designand consecutive sampling method. Evaluation of the patient’s quality of life taken through interviews and questionnaires using the Short Form-36 questionnaire consistingof8 domains of quality of life. Statistical analysis using unpaired t-test and Mann-Whitney test. Results of the quality of life-based on patient characteristics showed significant differences in education factor (p=0.005) and employment factor (p=0.001). Quality of life-based on therapy showed significant differences in domain role of physical (p=0.005) and domain role of emotional (p=0.038).The quality of life of patients with type 2 diabetes using insulin better than using hypoglycemic drug significantly in domain role of physical and domain role of emotions.

Hypoglycemic and Hypolipidemic Effects of the Cracked-Cap Medicinal Mushroom Phellinus rimosus (Higher Basidiomycetes) in Streptozotocin-Induced Diabetic Rats.

PubMed

Rony, Kuttikkadan A; Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K

2015-01-01

Phellinus rimosus is a parasitic host specific polypore mushroom with profound antioxidant, antihepatotoxic, anti-inflammatory, antitumor, and antimutagenic activities. This study investigated the hypoglycemic and hypolipidemic activities of the wood-inhabiting polypore mushroom Ph. Rimosus in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by single intraperitoneal injection of STZ (45 mg/kg) to Wistar rats. The effects of 30 days treatment with Ph. Rimosus (50 and 250 mg/ kg) and glibenclamide (0.65 mg/kg) on blood glucose level, serum insulin, serum lipid profile, liver glycogen, liver function enzymes, and non-enzymic and enzymic antioxidants activities in pancreas, liver, and kidney were evaluated in STZ-induced diabetic rats. Oral administration of Ph. Rimosus extract exhibited a significant reduction in blood glucose, triacylglycerol, total cholesterol, LDL-cholesterol, and liver function enzymes, and increased serum insulin, liver glycogen, and HDL-cholesterol levels in STZ-induced diabetic rats. Furthermore, Ph. Rimosus treatment increased antioxidant status in pancreas, liver, and kidney tissues with concomitant decreases in levels of thiobarbituric acid- reactive substances. Results of this study indicated that Ph. Rimosus possessed significant hypoglycemic and hypolipidemic activities and this effect may be related to its insulinogenic and antioxidant effect.

The effects of corn silk on glycaemic metabolism.

PubMed

Guo, Jianyou; Liu, Tongjun; Han, Linna; Liu, Yongmei

2009-11-23

Corn silk contains proteins, vitamins, carbohydrates, Ca, K, Mg and Na salts, fixed and volatile oils, steroids such as sitosterol and stigmasterol, alkaloids, saponins, tannins, and flavonoids. Base on folk remedies, corn silk has been used as an oral antidiabetic agent in China for decades. However, the hypoglycemic activity of it has not yet been understood in terms of modern pharmacological concepts. The purpose of this study is to investigate the effects of corn silk on glycaemic metabolism. Alloxan and adrenalin induced hyperglycemic mice were used in the study. The effects of corn silk on blood glucose, glycohemoglobin (HbA1c), insulin secretion, damaged pancreatic beta-cells, hepatic glycogen and gluconeogenesis in hyperglycemic mice were studied respectively. After the mice were orally administered with corn silk extract, the blood glucose and the HbA1c were significantly decreased in alloxan-induced hyperglycemic mice (p < 0.05, p < 0.01, respectively), while the level of insulin secretionn was markedly elevated in alloxa-induced hyperglycemic mice (p < 0.05). The alloxan-damaged pancreatic beta-cells of the mice were partly recovered gradually after the mice were administered with corn silk extract 15 days later. Also, the body weight of the alloxan-induced hyperglycemic mice was increased gradually. However, ascension of blood glucose induced by adrenalin and gluconeogenesis induced by L-alanine were not inhibited by corn silk extract treatment (p > 0.05). Although corn silk extract increased the level of hepatic glycogen in the alloxan-induced hyperglycemic mice, there was no significant difference between them and that of the control group(p > 0.05). Corn silk extract markedly reduced hyperglycemia in alloxan-induced diabetic mice. The action of corn silk extract on glycaemic metabolism is not via increasing glycogen and inhibiting gluconeogenesis but through increasing insulin level as well as recovering the injured beta-cells. The results suggest that corn silk extract may be used as a hypoglycemic food or medicine for hyperglycemic people in terms of this modern pharmacological study.

Sub-antimicrobial Doxycycline for Periodontitis Reduces Hemoglobin A1c in Subjects with Type 2 Diabetes: a Pilot Study

PubMed Central

Engebretson, Steven P.; Hey-Hadavi, Judith

2011-01-01

In vitro and animal studies suggest a possible role for the tetracycline class of drugs in the inhibition of non-enzymatic protein glycation. We conducted a 3-month, randomized placebo-controlled pilot clinical trial of conventional sub-gingival debridement, (periodontal therapy) combined with either a three month regimen of sub-antimicrobial-dose doxycycline (SDD), a two week regimen of antimicrobial-dose doxycycline (ADD), or placebo in 45 patients with long-standing type 2 diabetes (mean duration 9 years) and untreated chronic periodontitis. Subjects were taking stable doses of oral hypoglycemic medications and/or insulin. Treatment response was assessed by measuring hemoglobin A1c (HbA1c),plasma glucose, and clinical periodontal disease measures. At one-month and three-month follow-up, clinical measures of periodontitis were decreased in all groups(data to be presented elsewhere). At three months, mean HbA1c levels in the SDD group were reduced 0.9% unitsfrom 7.2% units ± 2.2(±SD), to 6.3% units ±1.1, which represents a 12.5% improvement. In contrast, there was no significant change in HbA1c in the ADD (7.5%± 2.0 to 7.8%± 2.1) or placebo (8.5%± 2.0 to 8.5%± 2.6) groups. Mean HbA1c change from baseline was significantly greater in the SDD group compared with the ADD group (p=0.04) but not placebo (p=0.22). Moreover, a larger proportion of subjects in the SDD group experienced improvement (p<0.05) compared to the ADD or placebo groups. Mean plasma glucose levels were not significantly different between or within the groups. The results of this pilot study suggest that the treatment of periodontitis with sub-gingival debridement and 3-months of daily sub-antimicrobial-dose doxycycline may decrease HbA1c in patients with type 2 diabetes taking normally prescribed hypoglycemic agents. PMID:21782948

Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats.

PubMed

Wainstein, Julio; Ganz, Tali; Boaz, Mona; Bar Dayan, Yosefa; Dolev, Eran; Kerem, Zohar; Madar, Zecharia

2012-07-01

Olive tree (Olea europaea L.) leaves have been widely used in traditional remedies in European and Mediterranean countries as extracts, herbal teas, and powder. They contain several potentially bioactive compounds that may have hypoglycemic properties. To examine the efficacy of 500 mg oral olive leaf extract taken once daily in tablet form versus matching placebo in improving glucose homeostasis in adults with type 2 diabetes (T2DM). In this controlled clinical trial, 79 adults with T2DM were randomized to treatment with 500 mg olive leaf extract tablet taken orally once daily or matching placebo. The study duration was 14 weeks. Measures of glucose homeostasis including Hba1c and plasma insulin were measured and compared by treatment assignment. In a series of animal models, normal, streptozotocin (STZ) diabetic, and sand rats were used in the inverted sac model to determine the mechanism through which olive leaf extract affected starch digestion and absorption. In the randomized clinical trial, the subjects treated with olive leaf extract exhibited significantly lower HbA1c and fasting plasma insulin levels; however, postprandial plasma insulin levels did not differ significantly by treatment group. In the animal models, normal and STZ diabetic rats exhibited significantly reduced starch digestion and absorption after treatment with olive leaf extract compared with intestine without olive leaf treatment. Reduced digestion and absorption was observed in both the mucosal and serosal sides of the intestine. Though reduced, the decline in starch digestion and absorption did not reach statistical significance in the sand rats. Olive leaf extract is associated with improved glucose homeostasis in humans. Animal models indicate that this may be facilitated through the reduction of starch digestion and absorption. Olive leaf extract may represent an effective adjunct therapy that normalizes glucose homeostasis in individuals with diabetes.

Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats.

PubMed

Aloulou, Ahmed; Hamden, Khaled; Elloumi, Dhouha; Ali, Madiha Bou; Hargafi, Khaoula; Jaouadi, Bassem; Ayadi, Fatma; Elfeki, Abdelfattah; Ammar, Emna

2012-05-16

Diabetes has become a serious health problem and a major risk factor associated with troublesome health complications, such as metabolism disorders and liver-kidney dysfunctions. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study aimed to investigate and compare the hypoglycemic and antilipidemic effects of kombucha and black tea, two natural drinks commonly consumed around the world, in surviving diabetic rats. Alloxan diabetic rats were orally supplied with kombucha and black tea at a dose of 5 mL/kg body weight per day for 30 days, fasted overnight, and sacrificed on the 31st day of the experiment. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglcerides, urea, creatinine, transaminases, transpeptidase, lipase, and amylase activities. Their pancreases were isolated and processed to measure lipase and α-amylase activities and to perform histological analysis. The findings revealed that, compared to black tea, kombucha tea was a better inhibitor of α-amylase and lipase activities in the plasma and pancreas and a better suppressor of increased blood glucose levels. Interestingly, kombucha was noted to induce a marked delay in the absorption of LDL-cholesterol and triglycerides and a significant increase in HDL-cholesterol. Histological analyses also showed that it exerted an ameliorative action on the pancreases and efficiently protected the liver-kidney functions of diabetic rats, evidenced by significant decreases in aspartate transaminase, alanine transaminase, and gamma-glytamyl transpeptidase activities in the plasma, as well as in the creatinine and urea contents. The findings revealed that kombucha tea administration induced attractive curative effects on diabetic rats, particularly in terms of liver-kidney functions. Kombucha tea can, therefore, be considered as a potential strong candidate for future application as a functional supplement for the treatment and prevention of diabetes.

Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats

PubMed Central

2012-01-01

Background Diabetes has become a serious health problem and a major risk factor associated with troublesome health complications, such as metabolism disorders and liver-kidney dysfunctions. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study aimed to investigate and compare the hypoglycemic and antilipidemic effects of kombucha and black tea, two natural drinks commonly consumed around the world, in surviving diabetic rats. Methods Alloxan diabetic rats were orally supplied with kombucha and black tea at a dose of 5 mL/kg body weight per day for 30 days, fasted overnight, and sacrificed on the 31st day of the experiment. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglcerides, urea, creatinine, transaminases, transpeptidase, lipase, and amylase activities. Their pancreases were isolated and processed to measure lipase and α-amylase activities and to perform histological analysis. Results The findings revealed that, compared to black tea, kombucha tea was a better inhibitor of α-amylase and lipase activities in the plasma and pancreas and a better suppressor of increased blood glucose levels. Interestingly, kombucha was noted to induce a marked delay in the absorption of LDL-cholesterol and triglycerides and a significant increase in HDL-cholesterol. Histological analyses also showed that it exerted an ameliorative action on the pancreases and efficiently protected the liver-kidney functions of diabetic rats, evidenced by significant decreases in aspartate transaminase, alanine transaminase, and gamma-glytamyl transpeptidase activities in the plasma, as well as in the creatinine and urea contents. Conclusions The findings revealed that kombucha tea administration induced attractive curative effects on diabetic rats, particularly in terms of liver-kidney functions. Kombucha tea can, therefore, be considered as a potential strong candidate for future application as a functional supplement for the treatment and prevention of diabetes. PMID:22591682

Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity

PubMed Central

Nahar, Laizuman; Nasrin, Fatema; Zahan, Ronok; Haque, Anamul; Haque, Ekramul; Mosaddik, Ashik

2014-01-01

Background: Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. Objective: The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). Materials and Methods: Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. Results: There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. Conclusion: These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress. PMID:24761124

Clinical experience with repaglinide in patients with non-insulin-dependent diabetes mellitus.

PubMed

Shapiro, Menachem S; Abrams, Zvi; Lieberman, Nicky

2005-02-01

Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone. To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study. The study group comprised 688 patients, aged 26-95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n = 132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide (group 2, n = 302); and c) lifestyle modification alone (drug-naive) (group 3, n = 254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4-8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia. The fasting blood sugar level of the entire cohort dropped from 191 +/- 2.4 to 155 +/- 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 +/- 0.1 to 7.7 +/- 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 +/- 0.22% (P < 0.0001), 1.14 +/- 0.24% (P < 0.0001), and 1.51 +/- 0.31% (P = 0.0137). Weight dropped from 81 +/- 0.7 to 80.2 +/- 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 +/- 0.4 to 2.4 +/- 0.4 (P < 0.001). No serious adverse reactions occurred during the study. Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.

[INERTIA study: Clinical inertia in non-insulinized patients on oral hypoglycemic treatment. A study in Spanish primary and specialty care settings].

PubMed

González-Clemente, José Miguel; Font, Beatriu; Lahoz, Raquel; Llauradó, Gemma; Gambús, Gemma

2014-06-06

To study clinical inertia in the management of oral hypoglycemic agents (OHA) in non-insulin treated patients with type 2 diabetes mellitus (T2DM) in Spain. Epidemiological, cross-sectional, retrospective (2 years), multicenter study. Clinical inertia was measured as the total number of patients without OHA treatment intensification divided by the total number of patients with inadequate HbA1c values (≥7%), multiplied by 100. Total clinical inertia (TCI) was the absence of OHA treatment intensification in all visits with a HbA1c≥7% values in the previous 2 years; partial clinical inertia (PCI) occurred when this absence only occurred in some of these visits. We assessed OHA treatment compliance with the Morisky-Green test. We included 2,971 patients, 1,416 adequately controlled (HbA1c<7%) and 1,555 inadequately controlled (HbA1c≥7%). PCI prevalence was 52.5%(95% confidence interval [95% CI] 52.4-52.6%) while TCI prevalence was 12.8% (95% CI 12.2-13.8%). PCI was lower in patients adequately controlled as compared with those inadequately controlled (31.4% vs. 71.8%; P<.001). PCI was associated with sedentary lifestyle, hypertension and higher prevalence of micro and macrovascular complications. Only 38.0% of patients were compliant with the OHA treatment, being this percentage even lower in subjects with ICP. Two variables were independently associated with ICP: female sex (odds ratio [OR] 1.43; 95% CI 1.09-1.86%) and a shorter duration of DM2 (OR 0.98; 95% CI 0.95-0.99). One out of 2 patients with T2DM and treated with OHA without insulin suffer from PCI. Only 4 out of 10 patients are compliant with OHA treatment. Female sex and a shorter duration of T2DM are independently associated with PCI. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Impact of stress-induced diabetes on outcomes in severely burned children.

PubMed

Finnerty, Celeste C; Ali, Arham; McLean, Josef; Benjamin, Nicole; Clayton, Robert P; Andersen, Clark R; Mlcak, Ronald P; Suman, Oscar E; Meyer, Walter; Herndon, David N

2014-04-01

Post-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60 and 110 mg/dL. Because of frequent hypoglycemic episodes, a less-stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80 and 160 mg/dL after elevations >180 mg/dL. We randomized pediatric patients with massive burns into 2 groups, patients receiving sliding scale insulin to lower blood glucose levels (n = 145) and those receiving no insulin (n = 98), to determine the differences in morbidity and mortality. Patients 0 to 18 years old with burns covering ≥ 30% of the total body surface area and not randomized to receive anabolic agents were included in this study. End points included glucose levels, infections, resting energy expenditure, lean body mass, bone mineral content, fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes. Maximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent, with older children requiring more insulin (p < 0.05). Daily maximum and daily minimum, but not 6 am, glucose levels were significantly different based on treatment group (p < 0.05). Insulin significantly increased resting energy expenditure and improved bone mineral content (p < 0.05). Each additional wound infection increased incidence of hyperglycemia (p = 0.004). There was no mortality in patients not receiving insulin, only in patients who received insulin (p < 0.004). Muscle strength was increased in patients receiving insulin (p < 0.05). Burn-induced hyperglycemia develops in a subset of severely burned children. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted bone mineral content and muscle strength, but increased resting energy expenditure, hypoglycemic episodes, and mortality. New glucose-lowering strategies might be needed. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Metabolic surgery and intestinal gene expression: Digestive tract and diabetes evolution considerations

PubMed Central

Rodrigues, Marcos Ricardo da Silva; Santo, Marco Aurelio; Favero, Giovani Marino; Vieira, Elaine Cristina; Artoni, Roberto Ferreira; Nogaroto, Viviane; de Moura, Egberto Gaspar; Lisboa, Patricia; Milleo, Fabio Quirillo

2015-01-01

AIM: To investigate the effects of bariatric surgery on metabolic parameters, incretin hormone secretion, and duodenal and ileal mucosal gene expression. METHODS: Nine patients with type 2 diabetes mellitus (T2DM), chronic serum hyperglycemia for more than 2 years, and a body mass index (BMI) of 30-35 kg/m2 underwent metabolic surgery sleeve gastrectomy with transit bipartition between May 2011 and December 2011. Blood samples were collected pre and 3, 6 and 12 mo postsurgery. Duodenal and ileal mucosa samples were collected pre- and 3 mo postsurgery. Pre- and postoperative blood samples were collected in the fasting state before ingestion of a standard meal (520 kcal) and again 30, 60, 90, and 120 min after the meal to determine hemoglobin A1c (HbA1c) levels and the lipid profile, which consisted of triglyceride and total cholesterol levels. Intestinal gene expression of p53 and transforming growth factor (TGF)-β was analyzed using quantitative reverse-transcription PCR. Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were quantified using the enzyme-linked immunoassay method and analyzed pre- and postoperatively. Student’s t test or repeated measurements analysis of variance with Bonferroni corrections were performed as appropriate. RESULTS: BMI values decreased by 15.7% within the initial 3 mo after surgery (31.29 ± 0.73 vs 26.398 ± 0.68, P < 0.05) and then stabilized at 22% at 6 mo postoperative, resulting in similar values 12 mo postoperatively (20-25 kg/m2). All of the patients experienced improved T2DM, with 7 patients (78%) achieving complete remission (HbA1c < 6.5%), and 2 patients (22%) achieving improved diabetes (HbA1c < 7.0% with or without the use of oral hypoglycemic agents). At 3 mo postoperatively, fasting plasma glucose had also decreased (59%) (269.55 ± 18.24 mg/dL vs 100.77 ± 3.13 mg/dL, P < 0.05) with no further significant changes at 6 or 12 mo postoperatively. In the first month postoperatively, there was a complete withdrawal of hypoglycemic medications in all patients, who were taking at least 2 hypoglycemic drugs preoperatively. GLP-1 levels significantly increased after surgery (149.96 ± 31.25 vs 220.23 ± 27.55) (P < 0.05), while GIP levels decreased but not significantly. p53 gene expression significantly increased in the duodenal mucosa (P < 0.05, 2.06 fold) whereas the tumor growth factor-β gene expression significantly increased (P < 0.05, 2.52 fold) in the ileal mucosa after surgery. CONCLUSION: Metabolic surgery ameliorated diabetes in all of the patients, accompanied by increased anti-proliferative intestinal gene expression in non-excluded segments of the intestine. PMID:26078577

Metforminium Decavanadate as a Potential Metallopharmaceutical Drug for the Treatment of Diabetes Mellitus.

PubMed

Treviño, Samuel; Velázquez-Vázquez, Denisse; Sánchez-Lara, Eduardo; Diaz-Fonseca, Alfonso; Flores-Hernandez, José Ángel; Pérez-Benítez, Aarón; Brambila-Colombres, Eduardo; González-Vergara, Enrique

2016-01-01

New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM) and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca), a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatments with 3.7 μg (2.5 μM)/300 g/twice a week for DM2 and 7.18 μg (4.8 μM)/300 g/twice a week for DM1 of MetfDeca, respectively, were administered. The resulting pharmacological data showed nontoxicological effects on liver and kidney. At the same time, MetfDeca showed an improvement of carbohydrates and lipids in tissues and serum. MetfDeca treatment was better than the monotherapies with metformin for DM2 and insulin for DM1. Additionally, MetfDeca showed a protective effect on pancreatic beta cells of DM1 rats, suggesting a possible regeneration of these cells, since they recovered their insulin levels. Therefore, MetfDeca could be considered not only as an insulin-mimetic agent, but also as an insulin-enhancing agent. Efforts to elucidate the mechanism of action of this compound are now in progress.

Metforminium Decavanadate as a Potential Metallopharmaceutical Drug for the Treatment of Diabetes Mellitus

PubMed Central

Treviño, Samuel; Velázquez-Vázquez, Denisse; Sánchez-Lara, Eduardo; Diaz-Fonseca, Alfonso; Flores-Hernandez, José Ángel; Pérez-Benítez, Aarón; Brambila-Colombres, Eduardo; González-Vergara, Enrique

2016-01-01

New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM) and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca), a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatments with 3.7 μg (2.5 μM)/300 g/twice a week for DM2 and 7.18 μg (4.8 μM)/300 g/twice a week for DM1 of MetfDeca, respectively, were administered. The resulting pharmacological data showed nontoxicological effects on liver and kidney. At the same time, MetfDeca showed an improvement of carbohydrates and lipids in tissues and serum. MetfDeca treatment was better than the monotherapies with metformin for DM2 and insulin for DM1. Additionally, MetfDeca showed a protective effect on pancreatic beta cells of DM1 rats, suggesting a possible regeneration of these cells, since they recovered their insulin levels. Therefore, MetfDeca could be considered not only as an insulin-mimetic agent, but also as an insulin-enhancing agent. Efforts to elucidate the mechanism of action of this compound are now in progress. PMID:27119007

Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

PubMed Central

Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

2014-01-01

The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy. PMID:25400436

The treatment of diabetes mellitus of patients with chronic liver disease.

PubMed

García-Compeán, Diego; González-González, José A; Lavalle-González, Fernando J; González-Moreno, Emmanuel I; Maldonado-Garza, Héctor J; Villarreal-Pérez, Jesús Zacarías

2015-01-01

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.

[Sodium-glucose co-transporter-2 inhibitors: from the bark of apple trees and familial renal glycosuria to the treatment of type 2 diabetes mellitus].

PubMed

Mauricio, Dídac

2013-09-01

The therapeutic armamentarium for the treatment of hyperglycemia in type 2 diabetes mellitus is still inadequate. We are currently witnessing the introduction of a new mode of hypoglycemic treatment through induction of glycosuria to decrease the availability of the metabolic substrate, i.e. glucose. Clinical trials have shown that sodium-glucose co-transporter-2 (SGLT2) inhibitors are as efficacious as other oral hypoglycemic drugs. This article discusses the basic features of this new treatment concept and the efficacy and safety of this new drug group. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Natural products with hypoglycemic, hypotensive, hypocholesterolemic, antiatherosclerotic and antithrombotic activities.

PubMed

Wang, H X; Ng, T B

1999-01-01

This article reviews compounds of botanical origin which are capable of lowering plasma levels of glucose and cholesterol and blood pressure, as well as compounds inhibiting atherosclerosis and thrombosis. Hypoglycemic natural products comprise flavonoids, xanthones, triterpenoids, alkaloids, glycosides, alkyldisulfides, aminobutyric acid derivatives, guanidine, polysaccharides and peptides. Hypotensive compounds include flavonoids, diterpenes, alkaloids, glycosides, polysaccharides and proteins. Among natural products with hypocholesterolemic activity are beta-carotene, lycopene, cycloartenol, beta-sitosterol, sitostanol, saponin, soybean protein, indoles, dietary fiber, propionate, mevinolin (beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor) and polysaccharides. Heparins, flavonoids, tocotrienols, beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors (statins), garlic compounds and fungal proteases exert antithrombotic action. Statins and garlic compounds also possess antiatherosclerotic activity.

In Vivo Hypoglycemic Effect of Kigelia africana (Lam): Studies With Alloxan-Induced Diabetic Mice.

PubMed

Njogu, Stephen M; Arika, Wycliffe M; Machocho, Alex K; Ngeranwa, Joseph J N; Njagi, Eliud N M

2018-01-01

The claims by the traditional herbal medicine practitioners that Kigelia africana has bioactivity against several diseases, including diabetes mellitus, were investigated in this study. Type I diabetes mellitus was induced in mice by intraperitoneal administration of alloxan monohydrate followed by treatment with the therapeutic doses of the aqueous and ethyl acetate leaf extract of K africana to the experimentally diabetic mice. The treatment effects were compared with the normal control, diabetic control, and diabetic control rats treated with a standard antidiabetic drugs (insulin administered intraperitoneally at 1 IU/kg body weight in 0.1 mL physiological saline or glibenclamide administered orally at 3 mg/kg body weight in 0.1 mL physiological saline). Phytochemical composition of the leaf extract was assessed using standard procedures and mineral elements assessed using atomic absorption spectrophotometry and total reflection X-ray fluorescence system. Oral and intraperitoneal administration of the aqueous and ethyl acetate leaf extract caused a statistically significant dose-independent reduction in plasma glucose level in alloxan-induced diabetic mice. The observed hypoglycemic activity of this plant extract could be attributed to the observed phytochemicals and trace elements, which have been associated with exhibiting antidiabetic properties. Therefore, the data appear to support the hypoglycemic effects of K africana validating its folkloric usage.

The association between fasting hypoglycemia and methylated mercaptopurine metabolites in children with acute lymphoblastic leukemia.

PubMed

Melachuri, Samyuktha; Gandrud, Laura; Bostrom, Bruce

2014-06-01

Symptomatic fasting hypoglycemia has been reported as an unusual side effect in patients with acute lymphoblastic leukemia (ALL) on maintenance therapy. We evaluated the relation of the red cell 6-mercaptopurine (6-MP) metabolite 6-methyl-mercaptopurine (6MMP) with hypoglycemia. We retrospectively reviewed charts of three patients with ALL and symptomatic hypoglycemia while fasting who were noted to have high levels of 6MMP. All patients had an empiric trial of switching from evening to morning 6-MP administration, and two patients were subsequently switched to twice daily dosing. Patients also received complex carbohydrates at bedtime. Switching 6-MP from evening to morning administration reduced 6MMP levels yet preserved adequate levels of the active metabolite red cell 6-thioguanine nucleotide (6TGN). All patients had decreased hypoglycemic events when changed from evening to morning dosing. Two patients showed a rebound in 6MMP levels with return of hypoglycemic symptoms. Both were then switched to twice daily 6-MP dosing with one having a decrease in 6MMP and hypoglycemic symptoms. High levels of 6MMP are associated with symptomatic hypoglycemia which may be mitigated by switching to morning or twice daily 6-MP dose administration. © 2014 Wiley Periodicals, Inc.

Matrix tablets for sustained release of repaglinide: Preparation, pharmacokinetics and hypoglycemic activity in beagle dogs.

PubMed

He, Wei; Wu, Mengmeng; Huang, Shiqing; Yin, Lifang

2015-01-15

Repaglinide (RG) is an efficient antihyperglycemic drug; however, due to its short half-life, patients are required to take the marketed products several times a day, which compromises the therapeutic effects. The present study was conducted to develop a hydrophilic sustained release matrix tablet for RG with the aims of prolonging its action time, reducing the required administration times and side effects and improving patient adherence. The matrix tablets were fabricated by a direct compression method, the optimized formulation for which was obtained by screening the factors that affected the drug release. Moreover, studies of the pharmacokinetics and hypoglycemic activity as measured by glucose assay kits were performed in dogs. Sustained drug releases profiles over 10h and a reduced influence of medium pHs on release were achieved with the optimized formulation; moreover, the in vivo performance of extended release formulation was also examined, and better absorption, a one-fold decrease in Cmax, a two-fold increase of Tmax and a prolonged hypoglycemic effect compared to the marketed product were observed. In conclusion, sustained RG release and prolonged action were observed with present matrix tablets, which therefore provide a promising formulation for T2D patients who require long-term treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

[Conversional and endoscopic procedures following bariatric surgery].

PubMed

Zorron, R; Bothe, C; Junghans, T; Pratschke, J; Benzing, C; Krenzien, F

2016-10-01

The Roux-en-Y gastric bypass (RYGB) is the therapy of choice in bariatric surgery. Sleeve gastrectomy and gastric banding are showing higher rates of treatment failure, reducing obesity-associated morbidity and body weight insufficiently. Moreover, gastroesophageal reflux disease (GERD) can occur refractory to medication. Therefore, a laparoscopic conversion to RYGB can be reasonable as long as specific conditions are fulfilled.Endoscopic procedures are currently being applied to revise bariatric procedures. Therapy failure following RYGB occurs in up to 20 % of cases. Transoral outlet reduction is the minimally invasive method of choice to reduce gastrojejunal anastomosis of the alimentary limb. The diameter of a gastric sleeve can be unwantedly enlarged as well; that can be reduced by placement of a longitudinal full-thickness suture.Severe hypoglycemic episodes can be present in patients following RYGB. Hypoglycemic episodes have to be diagnosed first and can be treated conventionally. Alternatively, a laparoscopic approach according to Branco-Zorron can be used for non-responders. Hypoglycemic episodes can thus be prevented and body weight reduction can be assured.Conversional and endoscopic procedures can be used in patients with treatment failure following bariatric surgery. Note that non-invasive approaches should have been applied intensively before a revisional procedure is performed.

Acute and chronic hypoglycemic effect of Ibervillea sonorae root extracts-II.

PubMed

Alarcon-Aguilar, F J; Calzada-Bermejo, F; Hernandez-Galicia, E; Ruiz-Angeles, C; Roman-Ramos, R

2005-03-21

Ibervillea sonorae's root, or "wareque" (Cucurbitaceae), is widely used in Mexican traditional medicine for the control of diabetes mellitus. In the present study, the hypoglycemic effects produced by the acute and chronic administration of various extracts of Ibervillea sonorae were investigated. Both the traditional preparation (aqueous decoction) and the raw extract (juice) from the root resulted in significant reductions of glycemia in healthy mice after intraperitoneal administration at a dose of 600 mg/kg. Additionally, ground dried root was used to obtain a dichloromethane (DCM) extract and a methanol (MeOH) extract. The DCM extract induced a clear reduction of glycemia in healthy (P < 0.05) and in alloxan-diabetic mice. The intraperitoneally administered DCM extract caused a severe hypoglycemia that produced lethality in all the treated animals when doses of 300 and 600 mg/kg body weight were used. Since the DCM extract showed a marked hypoglycemic activity, it was administered daily per os to alloxan diabetic rats, employing corn oil and tolbutamide as controls. After 41 days of DCM extract administration at a dose of 300 mg/kg/day, diabetic rats showed improvement in glycemia, body weight, triglycerides, and GPT in comparison with the diabetic control group. Total cholesterol, GOT, and uric acid blood levels were not affected.

Ancient Records and Modern Research on the Mechanisms of Chinese Herbal Medicines in the Treatment of Diabetes Mellitus

PubMed Central

Zhang, Hai-ming; Liang, Feng-xia

2015-01-01

Over the past decades, Chinese herbal medicines (CHM) have been extensively and intensively studied through from both clinical and experimental perspectives and CHM have been proved to be effective in the treatment of diabetes mellitus (DM). This study, by searching ancient records and modern research papers, reviewed CHM in terms of their clinical application and principal mechanism in the treatment of DM. We summarized the use of CHM mentioned in 54 famous ancient materia medica monographs and searched papers on the hypoglycemic effect of several representative CHM. Main mechanisms and limitations of CHM and further research direction for DM were discussed. On the basis of the study, we were led to conclude that TCM, as a main form of complementary and alternative medicine (CAM), was well recorded in ancient literatures and has less adverse effects as shown by modern studies. The mechanisms of CHM treatment of DM are complex, multilink, and multitarget, so we should find main hypoglycemic mechanism through doing research on CHM monomer active constituents. Many CHM monomer constituents possess noteworthy hypoglycemic effects. Therefore, developing a novel natural product for DM and its complications is of much significance. It is strongly significant to pay close attention to CHM for treatment of DM and its complications. PMID:25815039

Cerebral glycogen in humans following acute and recurrent hypoglycemia: Implications on a role in hypoglycemia unawareness.

PubMed

Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Khowaja, Ameer; Kubisiak, Kristine; Eberly, Lynn E; Seaquist, Elizabeth R

2017-08-01

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1- 13 C]glucose intravenously over 80+ h while maintaining euglycemia. 13 C-glycogen levels in the occipital lobe were measured by 13 C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13 C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.

Hypoglycemic activities of A- and B-type procyanidin oligomer-rich extracts from different Cinnamon barks.

PubMed

Lu, Zhaolian; Jia, Qi; Wang, Rui; Wu, Ximin; Wu, Yingchun; Huang, Caiguo; Li, Yiming

2011-02-15

Procyanidin oligomers in Cinnamon are thought to be responsible for the biological activity in the treatment of diabetes mellitus (DM). To clarify types of procyanidin oligomers in different Cinnamon species and investigate their different effects, the present study investigated procyanidin oligomers in polyphenolic oligomer-rich extracts of three Cinnamon samples by LC-MS methods, and their hypoglycemic activities were detected in vivo and in vitro. The results showed that two of the three samples from Cinnamomum cassia were rich in B-type procyanidin oligomers, and the other sample was rich in A-type procyanidin oligomers. The Cinnamon extracts were administered at doses of 200 and 300 mg/kg body wt. in high-fat diet-fed and low-dose streptozotocin (STZ)-induced diabetic mice for 14 days. The results showed that blood glucose concentrations were significantly decreased in all Cinnamon extract groups compared with the control group (p<0.05). Administration of the Cinnamon extracts significantly increased the consumption of extracellular glucose in insulin-resistant HepG2 cells and normal HepG2 cells compared with the control group. These results suggest that both A- and B-type procyanidin oligomers in different Cinnamon species have hypoglycemic activities and may improve insulin sensitivity in type 2 DM. Copyright © 2010 Elsevier GmbH. All rights reserved.

Blood Glucose Reduction by Diabetic Drugs with Minimal Hypoglycemia Risk for Cardiovascular Outcomes: Evidence from Meta-regression Analysis of Randomized Controlled Trials.

PubMed

Huang, Chi-Jung; Wang, Wei-Ting; Sung, Shih-Hsien; Chen, Chen-Huan; Lip, Gregory Yh; Cheng, Hao-Min; Chiang, Chern-En

2018-05-02

To investigate the effects of blood glucose control with antihyperglycemic agents with minimal hypoglycemia risk on cardiovascular outcomes in patients with type 2 diabetes (T2D). Randomized controlled trials (RCTs) comparing the relative efficacy and safety of antidiabetic drugs with less hypoglycemia risk were comprehensively searched in MEDLINE, Embase, and the Cochrane Library up to January 27, 2018. Mixed-effects meta-regression analysis was conducted to explore the relationship between haemoglobin A1c (HbA1c) reduction and the risk of major adverse cardiovascular events (MACE), myocardial infarction, stroke, cardiovascular death, all-cause death, and hospitalization for heart failure. Ten RCTs comprising 92400 participants with T2D were included and provided information on 9773 MACE during a median follow-up of 2.6 years. The mean HbA1c concentration was 0.42% lower (median, 0.27-0.86%) for participants given antihyperglycemic agents than those given placebo. The meta-regression analysis demonstrated that HbA1c reduction was significantly associated with a decreased risk of MACE (β value, -0.39 to -0.55; P<0.02) even after adjusting for each of the following possible confounding factors including age, sex, baseline HbA1c, duration of follow-up, difference in achieved systolic blood pressure, difference in achieved body weight, or risk difference in hypoglycemia. Lowering HbA1c by 1% conferred a significant risk reduction of 30% (95% CI, 17-40%) for MACE. By contrast, the meta-regression analysis for trials using conventional agents failed to demonstrate a significant relationship between achieved HbA1c difference and MACE risk (P>0.74). Compared with placebo, newer T2D agents with less hypoglycemic hazard significantly reduced the risk of MACE. The MACE reduction seems to be associated with HbA1c reduction in a linear relationship. This article is protected by copyright. All rights reserved.

Indonesia Cohort of IO HAT Study to Evaluate Diabetes Management, Control, and Complications in Retrospective and Prospective Periods Among Insulin-Treated Patients with Type 1 and Type 2 Diabetes.

PubMed

Rudijanto, Achmad; Saraswati, Made R; Yunir, Em; Kumala, Poppy; Puteri, Happy Hs; Mandang, Veny Vv

2018-01-01

hypoglycemia is a major adverse event of insulin therapy for diabetes mellitus patients. The study was conducted to evaluate the incidence of hypoglycemia among insulin treated patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) in the Indonesian cohort. this Indonesian cohort study consisted of retrospective and prospective evaluation of hypoglycemic episodes, using International Operations Hypoglycemia Assessment Tool (IO HAT) in 374 patients with diabetes (T1DM; n=17 or T2DM; n=357). The patients of ≥18 years of age and treated with insulin for >12 months were selected for this study (ClinicalTrials.gov number: NCT02306681). a total of 374 patients were enrolled in this study and completed SAQ1. All patients with T1DM (17 [100%]), and 347 (97.2%) patients with T2DM completed SAQ2. Almost all the patients in the 4-week prospective period reported at least one hypoglycemic event (T1DM 100%, T2DM 99.4%) and the incidence rate of any hypoglycemia was 67.5 events per patient-year (PPY) and 25.7 events PPY for T1DM and T2DM patients, respectively. Among patients with T1DM and T2DM, 5.9% and 36.4%, respectively, did not know what hypoglycemia was at baseline, also high proportion of patients had impaired hypoglycemic awareness in the study (82.4% and 62.7%, respectively). overall, high proportion of patients reported hypoglycemic events in the prospective period indicating under reporting during the retrospective period due to recall bias. Therefore, there is a need for patient education program to improve the awareness of hypoglycemia in diabetes patient in Indonesia.

Uncovering undetected hypoglycemic events

PubMed Central

Unger, Jeff

2012-01-01

Hypoglycemia is the rate-limiting factor that often prevents patients with diabetes from safely and effectively achieving their glycemic goals. Recent studies have reported that severe hypoglycemia is associated with a significant increase in the adjusted risks of major macrovascular events, major microvascular events, and mortality. Minor hypoglycemic episodes can also have serious implications for patient health, psychological well being, and adherence to treatment regimens. Hypoglycemic events can impact the health economics of the patient, their employer, and third-party payers. Insulin treatment is a key predictor of hypoglycemia, with one large population-based study reporting an overall prevalence of 7.1% (type 1 diabetes mellitus) and 7.3% (type 2 diabetes mellitus) in insulin-treated patients, compared with 0.8% in patients with type 2 diabetes treated with an oral sulfonylurea. Patients with type 1 diabetes typically experience symptomatic hypoglycemia on average twice weekly and severe hypoglycemia once annually. The progressive loss of islet cell function in patients with type 2 diabetes results in a higher risk of both symptomatic and unrecognized hypoglycemia over time. Patients with diabetes who become hypoglycemic are also more susceptible to developing defective counter-regulation, also known as hypoglycemia awareness autonomic failure, which is life-threatening and must be aggressively addressed. In patients unable to recognize hypoglycemia symptoms, frequent home monitoring or use of continuous glucose sensors are critical. Primary care physicians play a key role in the prevention and management of hypoglycemia in patients with diabetes, particularly in those requiring intensive insulin therapy, yet physicians are often unaware of the multitude of consequences of hypoglycemia or how to deal with them. Careful monitoring, adherence to guidelines, and use of optimal treatment combinations are all important steps toward improving care in patients with diabetes. The most important goals are for primary care physicians to recognize that every patient treated with antihyperglycemic medications is at risk of iatrogenic hypoglycemia and to ask patients about hypoglycemia at every visit. PMID:22563248

Multivariate Prediction Equations for HbA1c Lowering, Weight Change, and Hypoglycemic Events Associated with Insulin Rescue Medication in Type 2 Diabetes Mellitus: Informing Economic Modeling.

PubMed

Willis, Michael; Asseburg, Christian; Nilsson, Andreas; Johnsson, Kristina; Kartman, Bernt

2017-03-01

Type 2 diabetes mellitus (T2DM) is chronic and progressive and the cost-effectiveness of new treatment interventions must be established over long time horizons. Given the limited durability of drugs, assumptions regarding downstream rescue medication can drive results. Especially for insulin, for which treatment effects and adverse events are known to depend on patient characteristics, this can be problematic for health economic evaluation involving modeling. To estimate parsimonious multivariate equations of treatment effects and hypoglycemic event risks for use in parameterizing insulin rescue therapy in model-based cost-effectiveness analysis. Clinical evidence for insulin use in T2DM was identified in PubMed and from published reviews and meta-analyses. Study and patient characteristics and treatment effects and adverse event rates were extracted and the data used to estimate parsimonious treatment effect and hypoglycemic event risk equations using multivariate regression analysis. Data from 91 studies featuring 171 usable study arms were identified, mostly for premix and basal insulin types. Multivariate prediction equations for glycated hemoglobin A 1c lowering and weight change were estimated separately for insulin-naive and insulin-experienced patients. Goodness of fit (R 2 ) for both outcomes were generally good, ranging from 0.44 to 0.84. Multivariate prediction equations for symptomatic, nocturnal, and severe hypoglycemic events were also estimated, though considerable heterogeneity in definitions limits their usefulness. Parsimonious and robust multivariate prediction equations were estimated for glycated hemoglobin A 1c and weight change, separately for insulin-naive and insulin-experienced patients. Using these in economic simulation modeling in T2DM can improve realism and flexibility in modeling insulin rescue medication. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol

PubMed Central

Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed AS

2016-01-01

Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17–99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of −2.24 to −15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities for resveratrol delivery. PMID:26792979

Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol.

PubMed

Balata, Gehan F; Essa, Ebtessam A; Shamardl, Hanan A; Zaidan, Samira H; Abourehab, Mohammed As

2016-01-01

Resveratrol is a nonflavonoid polyphenolic compound which has a broad range of desirable biological actions which include antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and antitumor activities. However, there is concern that the bioavailability of resveratrol may limit some of its clinical utility. So, the aim of this study was to enhance the dissolution rate and oral hypoglycemic and hypolipidemic effect of resveratrol. This was achieved using self-emulsifying drug delivery system. The solubility of resveratrol was determined in various oils, surfactants, and cosurfactants. Phase diagram was plotted to identify the efficient self-emulsification regions using olive oil, Tween 80, and propylene glycol. The prepared self-emulsifying drug delivery system formulations were tested for thermodynamic stability, emulsification efficiency, droplet size, zeta potential, and in vitro drug release. Self-emulsification time averaged 17-99 seconds without precipitation and the mean droplet sizes ranged from 285 to 823 nm with overall zeta potential of -2.24 to -15.4 mv. All formulations improved drug dissolution in relation to unprocessed drug with a trend of decreased dissolution parameters with increasing oil content. The optimized formula, F19, with dissolution efficiency of 94% compared to only 42% of pure drug was used to study the in vivo hypoglycemic and hypolipidemic effects of resveratrol in diabetic-induced albino rats and comparing these effects with that of pure resveratrol in different doses. Treatment with the optimized formula, F19, at 10 mg/kg had significant hypoglycemic and hypolipidemic effects in diabetic-induced albino rats which were nearly similar to the high dose (20 mg/kg) of unprocessed resveratrol. From the study, it was concluded that formulation F19 has good emulsification property with uniform globule size, satisfactory in vitro drug release profile, and significant in vivo hypoglycemic effects which identify future opportunities for resveratrol delivery.

A glucose model based on support vector regression for the prediction of hypoglycemic events under free-living conditions.

PubMed

Georga, Eleni I; Protopappas, Vasilios C; Ardigò, Diego; Polyzos, Demosthenes; Fotiadis, Dimitrios I

2013-08-01

The prevention of hypoglycemic events is of paramount importance in the daily management of insulin-treated diabetes. The use of short-term prediction algorithms of the subcutaneous (s.c.) glucose concentration may contribute significantly toward this direction. The literature suggests that, although the recent glucose profile is a prominent predictor of hypoglycemia, the overall patient's context greatly impacts its accurate estimation. The objective of this study is to evaluate the performance of a support vector for regression (SVR) s.c. glucose method on hypoglycemia prediction. We extend our SVR model to predict separately the nocturnal events during sleep and the non-nocturnal (i.e., diurnal) ones over 30-min and 60-min horizons using information on recent glucose profile, meals, insulin intake, and physical activities for a hypoglycemic threshold of 70 mg/dL. We also introduce herein additional variables accounting for recurrent nocturnal hypoglycemia due to antecedent hypoglycemia, exercise, and sleep. SVR predictions are compared with those from two other machine learning techniques. The method is assessed on a dataset of 15 patients with type 1 diabetes under free-living conditions. Nocturnal hypoglycemic events are predicted with 94% sensitivity for both horizons and with time lags of 5.43 min and 4.57 min, respectively. As concerns the diurnal events, when physical activities are not considered, the sensitivity is 92% and 96% for a 30-min and 60-min horizon, respectively, with both time lags being less than 5 min. However, when such information is introduced, the diurnal sensitivity decreases by 8% and 3%, respectively. Both nocturnal and diurnal predictions show a high (>90%) precision. Results suggest that hypoglycemia prediction using SVR can be accurate and performs better in most diurnal and nocturnal cases compared with other techniques. It is advised that the problem of hypoglycemia prediction should be handled differently for nocturnal and diurnal periods as regards input variables and interpretation of results.

Accuracy evaluation of a new real-time continuous glucose monitoring algorithm in hypoglycemia.

PubMed

Mahmoudi, Zeinab; Jensen, Morten Hasselstrøm; Dencker Johansen, Mette; Christensen, Toke Folke; Tarnow, Lise; Christiansen, Jens Sandahl; Hejlesen, Ole

2014-10-01

The purpose of this study was to evaluate the performance of a new continuous glucose monitoring (CGM) calibration algorithm and to compare it with the Guardian(®) REAL-Time (RT) (Medtronic Diabetes, Northridge, CA) calibration algorithm in hypoglycemia. CGM data were obtained from 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. Data were obtained in two separate sessions using the Guardian RT CGM device. Data from the same CGM sensor were calibrated by two different algorithms: the Guardian RT algorithm and a new calibration algorithm. The accuracy of the two algorithms was compared using four performance metrics. The median (mean) of absolute relative deviation in the whole range of plasma glucose was 20.2% (32.1%) for the Guardian RT calibration and 17.4% (25.9%) for the new calibration algorithm. The mean (SD) sample-based sensitivity for the hypoglycemic threshold of 70 mg/dL was 31% (33%) for the Guardian RT algorithm and 70% (33%) for the new algorithm. The mean (SD) sample-based specificity at the same hypoglycemic threshold was 95% (8%) for the Guardian RT algorithm and 90% (16%) for the new calibration algorithm. The sensitivity of the event-based hypoglycemia detection for the hypoglycemic threshold of 70 mg/dL was 61% for the Guardian RT calibration and 89% for the new calibration algorithm. Application of the new calibration caused one false-positive instance for the event-based hypoglycemia detection, whereas the Guardian RT caused no false-positive instances. The overestimation of plasma glucose by CGM was corrected from 33.2 mg/dL in the Guardian RT algorithm to 21.9 mg/dL in the new calibration algorithm. The results suggest that the new algorithm may reduce the inaccuracy of Guardian RT CGM system within the hypoglycemic range; however, data from a larger number of patients are required to compare the clinical reliability of the two algorithms.

Budget impact of continuous subcutaneous insulin infusion therapy in patients with type 1 diabetes who experience severe recurrent hypoglycemic episodes in Spain.

PubMed

Giménez, Marga; Elías, Isabel; Álvarez, María; Quirós, Carmen; Conget, Ignacio

Hypoglycemia is one of the most common complications to achieve a good metabolic control, and has been listed by several scientific associations as a common indication to start treatment with continuous subcutaneous insulin infusion (CSII). Use of CSII is still residual in Spain as compared to neighbouring countries, and cost of acquisition cost is one of the main reasons. This study estimates the budget impact of treatment with CSII, as compared to multiple daily insulin injections, of patients with type 1 diabetes mellitus who experience recurrent severe hypoglycemia episodes from the National Healthcare System perspective. Budget impact was based on a retrospective, observational study evaluating the efficacy of CSII in patients with type 1 diabetes mellitus conducted at Hospital Clínic i Universitari in Barcelona, where one of the main indications for switching to CSII were recurrent severe hypoglycemia episodes. The mean number of annual episodes was 1.33 in the two years prior to CSII start and 0.08 in the last two years of follow up (p=0.003). Costs of treatment and major hypoglycemic events over a four-year period were considered. Costs were taken from different Spanish data sources and expressed in € of 2016. Treatment with CSII increased costs by €9,509 per patient as compared to multiple daily insulin injections (€11,902-€2,393). Cost associated to severe hypoglycemic events decreased by €19,330 per patient treated with CSIII (€1,371-€20,701). Results suggest mean total savings of €9,821 per patient during the four-year study period. The higher costs associated to CSII therapy may be totally offset by the severe hypoglycemic events prevented. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes? A Narrative Review.

PubMed

Costello, Rebecca B; Dwyer, Johanna T; Saldanha, Leila; Bailey, Regan L; Merkel, Joyce; Wambogo, Edwina

2016-11-01

Cinnamon (Cinnamomum sp) has been suggested to help patients with type 2 diabetes mellitus (T2DM) achieve better glycemic control, although conclusions from meta-analyses are mixed. To evaluate whether the use of cinnamon dietary supplements by adults with T2DM had clinically meaningful effects on glycemic control, as measured by changes in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c), a comprehensive PubMed literature search was performed. Eleven randomized controlled trials were identified that met our inclusion criteria that enrolled 694 adults with T2DM receiving hypoglycemic medications or not. In 10 of the studies, participants continued to take their hypoglycemic medications during the cinnamon intervention period. Studies ranged from 4 to 16 weeks in duration; seven studies were double-blind. Cinnamon doses ranged from 120 to 6,000 mg/day. The species of cinnamon used varied: seven used Cinnamomum cassia or Cinnamomum aromaticum, one used Cinnamomum zeylanicum, and three did not disclose the species. Because of the heterogeneity of the studies, a meta-analysis was not conducted. All 11 of the studies reported some reductions in FPG during the cinnamon intervention, and of the studies measuring HbA1c very modest decreases were also apparent with cinnamon, whereas changes in the placebo groups were minimal. However, only four studies achieved the American Diabetes Association treatment goals (FPG <7.2 mmol/L [130 mg/dL] and/or HbAlc <7.0). We conclude that cinnamon supplements added to standard hypoglycemic medications and other lifestyle therapies had modest effects on FPG and HbA1c. Until larger and more rigorous studies are available, registered dietitian nutritionists and other health care professionals should recommend that patients continue to follow existing recommendations of authoritative bodies for diet, lifestyle changes, and hypoglycemic drugs. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes – A Narrative Review?

PubMed Central

Costello, Rebecca B.; Dwyer, Johanna T.; Saldanha, Leila; Bailey, Regan L.; Merkel, Joyce; Wambogo, Edwina

2016-01-01

Cinnamon (Cinnamomum sp.) has been suggested to help patients with type 2 diabetes mellitus (T2DM) achieve better glycemic control although conclusions from meta-analyses are mixed. To evaluate whether the use of cinnamon dietary supplements by adults with T2DM had clinically meaningful effects on glycemic control, as measured by changes in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c), a comprehensive PubMed literature search was performed. Eleven RCTs were identified meeting our inclusion criteria that enrolled 694 adults with T2DM receiving hypoglycemic medications or not. In 10 of the studies participants continued to take their hypoglycemic medications during the cinnamon intervention period. Studies ranged from 4 to 16 weeks in duration; seven studies were double-blinded. Cinnamon doses ranged from 120 to 6000 mg/d. The species of cinnamon used varied; 7 used C. cassia/C. aromaticum; 1 used C. zeylanicum, and 3 did not disclose it. Because of the heterogenity of the studies, a metaanalysis was not conducted. All 11 of the studies reported some reductions in FPG during the cinnamon intervention, and of the studies measuring HbA1c very modest decreases were also apparent with cinnamon, while changes in the placebo groups were minimal. However, only four studies achieved the American Diabetes Association treatment goals (FPG <7.2 mmol/L or 130 mg/dL and/or HbAlc <7.0). We conclude that cinnamon supplements added to standard hypoglycemic medications and other lifestyle therapies had modest effects on FPG and HbA1c. Until larger and more rigorous studies are available, dietitians and other healthcare professionals should recommend that patients continue to follow existing recommendations of authoritative bodies for diet, lifestyle changes, and hypoglycemic drugs. PMID:27618575

Reduced risk of hypoglycemia with once-daily glargine versus twice-daily NPH and number needed to harm with NPH to demonstrate the risk of one additional hypoglycemic event in type 2 diabetes: Evidence from a long-term controlled trial

PubMed Central

Rosenstock, Julio; Fonseca, Vivian; Schinzel, Stefan; Dain, Marie-Paule; Mullins, Peter; Riddle, Matthew

2016-01-01

Aims This analysis evaluated HbA1c-adjusted hypoglycemia risk with glargine versus neutral protamine Hagedorn (NPH) over a 5-year study in patients with Type 2 diabetes mellitus (T2DM). Clinical significance was assessed using number needed to harm (NNH) to demonstrate the risk of one additional patient experiencing at least one hypoglycemic event. Methods Individual patient-level data for symptomatic documented hypoglycemia and HbA1c values from a 5-year randomized study comparing once-daily glargine (n = 513) with twice-daily NPH (n = 504) were analyzed. Symptomatic hypoglycemia was categorized according to concurrent self-monitoring blood glucose levels and need for assistance. Hypoglycemic events per patient-year as a function of HbA1c were fitted by negative binomial regression using treatment and HbA1c at endpoint as independent variables. An estimate of NNH was derived from logistic regression models. Results The cumulative number of symptomatic hypoglycemia events was consistently lower with glargine compared with NPH over 5 years. Compared with twice-daily NPH, once-daily glargine treatment resulted in significantly lower adjusted odds ratios (OR) for all daytime hypoglycemia (OR 0.74; p = 0.030) and any severe event (OR 0.64; p = 0.035), representing a 26% and 36% reduction in the odds of daytime and severe hypoglycemia, respectively. Our model predicts that, if 25 patients were treated with NPH instead of glargine, then one additional patient would experience at least one severe hypoglycemic event. Conclusions This analysis of long-term insulin treatment confirms findings from short-term studies and demonstrates that glargine provides sustained, clinically meaningful reductions in risk of hypoglycemia compared with NPH in patients with T2DM. PMID:24856612

Quantification of Toxins in Soapberry (Sapindaceae) Arils: Hypoglycin A and Methylenecyclopropylglycine

PubMed Central

Isenberg, Samantha L.; Carter, Melissa D.; Hayes, Shelby R.; Graham, Leigh Ann; Johnson, Darryl; Mathews, Thomas P.; Harden, Leslie A.; Takeoka, Gary R.; Thomas, Jerry D.; Pirkle, James L.; Johnson, Rudolph C.

2016-01-01

Methylenecyclopropylglycine (MCPG) and hypoglycin A (HGA) are naturally-occurring amino acids found in some soapberry fruits. Fatalities have been reported worldwide as a result of HGA ingestion, and exposure to MCPG has been implicated recently in the Asian outbreaks of hypoglycemic encephalopathy. In response to an outbreak linked to soapberry ingestion, the authors developed the first method to simultaneously quantify MCPG and HGA in soapberry fruits from 1 to 10,000 ppm of both toxins in dried fruit aril. Further, this is the first report of HGA in litchi and longan arils. This method is presented to specifically address the laboratory needs of public health investigators in the hypoglycemic encephalitis outbreaks linked to soapberry fruit ingestion. PMID:27367968

Quantification of Toxins in Soapberry (Sapindaceae) Arils: Hypoglycin A and Methylenecyclopropylglycine.

PubMed

Isenberg, Samantha L; Carter, Melissa D; Hayes, Shelby R; Graham, Leigh Ann; Johnson, Darryl; Mathews, Thomas P; Harden, Leslie A; Takeoka, Gary R; Thomas, Jerry D; Pirkle, James L; Johnson, Rudolph C

2016-07-13

Methylenecyclopropylglycine (MCPG) and hypoglycin A (HGA) are naturally occurring amino acids found in some soapberry fruits. Fatalities have been reported worldwide as a result of HGA ingestion, and exposure to MCPG has been implicated recently in the Asian outbreaks of hypoglycemic encephalopathy. In response to an outbreak linked to soapberry ingestion, the authors developed the first method to simultaneously quantify MCPG and HGA in soapberry fruits from 1 to 10 000 ppm of both toxins in dried fruit aril. Further, this is the first report of HGA in litchi, longan, and mamoncillo arils. This method is presented to specifically address the laboratory needs of public-health investigators in the hypoglycemic encephalitis outbreaks linked to soapberry fruit ingestion.

In vitro antioxidant and hypoglycemic activities of Ethiopian spice blend Berbere.

PubMed

Loizzo, Monica R; Di Lecce, Giuseppe; Boselli, Emanuele; Bonesi, Marco; Menichini, Federica; Menichini, Francesco; Frega, Natale Giuseppe

2011-11-01

The metal chelating activity, antioxidant properties, and the effect on carbohydrate-hydrolyzing enzymes of Ethiopian spice blend Berbere have been investigated. Berbere contains a total amount of phenols corresponding to 71.3 mg chlorogenic acid equivalent per gram of extract and a total flavonoid content of 32.5 mg quercetin equivalent per gram of extract. An increase of the resistance towards forced oxidation was obtained when Berbere was added to sunflower oil. In order to evaluate the bioactivity of the non-polar constituents, an n-hexane extract was obtained from Berbere. The gas chromatography-mass spectrometry analysis revealed the presence of 19 fatty acids constituents (98.1% of the total oil content). Among them, linoleic acid was the major component (72.0% of the total lipids). The ethanolic extract had the highest ferric-reducing ability power (35.4 μM Fe(II)/g) and DPPH scavenging activity with a concentration giving 50% inhibition (IC(50)) value of 34.8 μg/ml. Moreover, this extract exhibited good hypoglycemic activity against α-amylase (IC(50) = 78.3 μg/ml). In conclusion, Ethiopian spice blend Berbere showed promising antioxidant and hypoglycemic activity via the inhibition of carbohydrate digestive enzymes. These activities may be of interest from functional point of view and for the revalorization of the spice blend in gastronomy also outside the African country.

Hypoglycemic effects of Acacia nilotica in type II diabetes: a research proposal.

PubMed

Roozbeh, Nasibeh; Darvish, Leili; Abdi, Fatemeh

2017-07-26

Diabetes mellitus is a common metabolic disorder throughout the world which can negatively affect the function of various body organs. Due to their availability and few side effects, herbal medicines have been proposed as suitable alternatives in the management of diabetes. Previous studies have confirmed the anti diabetic properties of Acacia nilotica. The hypoglycemic effects of this plant have been attributed to its role in stimulating the islets of Langerhans to produce more insulin. The present paper describes a systematic review protocol for the assessment of the hypoglycemic effects of A. nilotica. Randomized and non-randomized placebo-controlled clinical trials, performed during 1999-2016 will be included. The outcomes will be measured through FBS, GCT, GTT, and OGTT in all of studies and in addition to these tests, will be measured 2HPP and HbA1c level in human study. Well-known databases will be searched for selected key terms A. nilotica, type II diabetes and hypoglycemia. The quality assessment of the selected papers will be evaluated based on SYRCLE and Cochrane Risk of Bias Tool. We believe that our findings will provide details about difficulties researchers face during the design of protocols or implementation of scientific studies. Ultimately, the publication of our findings will facilitate the development of effective treatment strategies to promote the health of people with type II DM. PROSPERO registration CRD42016053141.

Clinically significant cognitive impairment in older adults with type 1 diabetes.

PubMed

Chaytor, Naomi S; Barbosa-Leiker, Celestina; Ryan, Christopher M; Germine, Laura T; Hirsch, Irl B; Weinstock, Ruth S

2018-04-14

Little is known about cognition in older adults with type 1 diabetes. The aim of this study was to identify correlates of clinically significant cognitive impairment. Neuropsychological, diabetes-related and glycemic (HbA1c, Continuous Glucose Monitoring; CGM) data were collected from 201 older adults (≥60 years) with longstanding type 1 diabetes. Clinically significant cognitive impairment (≥2 cognitive tests ≥1.5 SD below normative data) occurred in 48% of the sample. After controlling for age, gender, education and diabetes duration, we found that hypoglycemia unawareness, recent severe hypoglycemic events, any microvascular complication, higher HbA1c and CGM average nocturnal glucose were all associated with increased odds of clinically significant cognitive impairment (ORs = 1.01-2.61), while CGM nocturnal % time below 60 mg/dL was associated with a decreased odds of cognitive impairment (OR = 0.94). Diabetes duration, diagnosis age, daytime CGM, and lifetime severe hypoglycemic events were not related to cognitive impairment status. Clinically significant cognitive impairment was common in older adults with type 1 diabetes. Diabetes-related correlates of cognitive impairment were identified, including hypoglycemia unawareness, recent severe hypoglycemic events, and CGM variables. Longitudinal research is needed to determine if these variables predict cognitive decline and if their modification alters outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Maintaining euglycemia prevents insulin-induced Fos expression in brain autonomic regulatory circuits.

PubMed

Ao, Yan; Wu, Shuying; Go, Vay Liang W; Toy, Natalie; Yang, Hong

2005-08-01

Insulin-induced hypoglycemia activates neurons in hypothalamic and brain medullary nuclei involved in central autonomic regulation. We investigated whether these central neuronal activations relates to a deficiency of glucose supply. Three groups of non-fasted, conscious rats received intravenous (iv) saline infusion (control), a hyperinsulinemic/hypoglycemic clamp, or a hyperinsulinemic/euglycemic clamp for 120 minutes and then the brains were collected for Fos immunohistochemistry. The number of Fos positive cells significantly increased in the paraventricular nucleus of the hypothalamus (PVN, 191 +/- 63 versus 66 +/- 18), pontine locus coeruleus (LC, 53 +/- 19 versus 5 +/- 2), brain medullary dorsal motor nucleus of the vagus (DMV, 26 +/- 4 versus 1 +/- 0), and nucleus tractus solitarii (NTS, 38 +/- 3 versus 10 +/- 35) in rats with hyperinsulinemic/hypoglycemic clamp compared with the controls. Maintaining blood glucose levels within physiological range by hyperinsulinemic/euglycemic clamp prevented insulin infusion-induced Fos expression in the PVN, DMV, and NTS. The numbers of Fos positive cells in these nuclei were significantly lower (-87%, -75%, and -51%, respectively) than that in the hypoglycemic rats. These results indicate that neuronal activation in hypothalamic and medullary autonomic regulatory nuclei induced by insulin administration is caused by hypoglycemia rather than a direct action of insulin. In addition, certain neurons in the medullary DMV and NTS respond to declines in glucose levels within physiological range.

Hypolipidemic and hypoglycemic activities of a oleanolic acid derivative from Malva parviflora on streptozotocin-induced diabetic mice.

PubMed

Gutiérrez, Rosa Martha Pérez

2017-05-01

One new oleanolic acid derivative, 2α,3β,23α,29α tetrahydroxyolean-12(13)-en-28-oic acid (1) was isolated from the aerial parts of Malva parviflora. Their structure was characterized by spectroscopic methods. The hypolipidemic and hypoglycemic activities of 1 was analyzed in in streptozotocin (STZ)-nicotinamide-induced type 2 diabetes in mice (MD) and type 1 diabetes in streptozotocin-induced diabetic mice (SD). Triterpene was administered orally at doses of 20 mg/kg for 4 weeks. Organ weight, body weight, glucose, fasting insulin, cholesterol-related lipid profile parameters, glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP), glucokinase, hexokinase, glucose-6-phosphatase activities and glycogen in liver were measured after 4 weeks of treatment. The results indicated that 1 regulate glucose metabolism, lipid profile, lipid peroxidation, increased body weight, glucokinase and hexokinase activities inhibited triglycerides, total cholesterol, low density lipoproteins level, SGOT, SGPT, SALP, glycogen in liver and glucose-6-phosphatase. In addition, improvement of insulin resistance and protective effect for pancreatic β-cells, also 1 may changes the expression of pro-inflammatory cytokine (IL-6 and TNF-α levels) and enzymes (PAL2, COX-2, and LOX). The results suggest that 1 has hypolipidemic and hypoglycemic, anti-inflammatory, activities, improve insulin resistance and hepatic enzymes in streptozotocin-induced diabetic mice.

[The results of the application of the pre-formed physical factors and neuroprotective therapy for the rehabilitative treatment of the patients with diabetic retinopathy].

PubMed

Nazarova, G A; Konchugova, T V; Iurova, O V; Turova, E A; Rassulova, M A; Sichinava, N V; Morozova, N E

2013-01-01

To evaluate the effectiveness of the neuroprotective agent used to treat the patients presenting with non-proliferative diabetic retinopathy. The study included 114 patients (228 eyes) at the age varying from 42 to 70 who presented with diabetes mellitus and non-proliferative diabetic retinopathy. Three groups were formed depending on the mode of treatment. The patients in main group underwent endonasal electrophoresis of 0.1% semax preparation. Patients of the comparison group were treated with intranasal instillations of semax and those of the control group received only standard hypoglycemic therapy and treatment with Doxy-Hem. The patients of the first two groups showed positive dynamics of the studied functional characteristics (visual, perimetric, and electrophysiological ones). The most pronounced and long-standing (up to 12 months) positive effect on the visual function was documented in the main group. The results of the present study give reason to recommend the inclusion of endonasal electrophoresis in the combined rehabilitation treatment of the patients presenting with diabetes mellitus and non-proliferative diabetic retinopathy.

Anti-hyperglycemic action of apigenin-6-C-β-fucopyranoside from Averrhoa carambola.

PubMed

Cazarolli, Luisa Helena; Kappel, Virgínia Demarchi; Pereira, Danielle Fontana; Moresco, Henrique Hunger; Brighente, Inês Maria Costa; Pizzolatti, Moacir Geraldo; Silva, Fátima Regina Mena Barreto

2012-10-01

A stimulatory effect of apigenin-6-C-β-fucopyranoside (1) on glucose uptake was observed when rat soleus muscle was incubated with 1, 10 and 100 μM of this flavonoid glycoside. The presence of specific insulin signaling inhibitors, such as wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and HNMPA(AM)₃, an insulin receptor tyrosine kinase activity inhibitor showed that apigenin-6-C-β-fucopyranoside triggers different metabolic pathways in skeletal muscle. The oral administration of crude extract, fractions and isolated flavonoids (apigenin-6-C-β-fucopyranoside (1) and apigenin-6-C-(2″-O-α-rhamnopyranosyl)-β-fucopyranoside (2)) from Averrhoa carambola leaves exhibited a potential hypoglycemic activity in hyperglycemic normal rats. Additionally, both flavonoids significantly increased the muscle and liver glycogen content after an acute treatment. The results indicate that A. carambola can be regarded as a potent antihyperglycemic agent with insulin secretagogue and insulin mimetic properties. Copyright © 2012 Elsevier B.V. All rights reserved.

Early morphological and functional changes in pancreas following necrosectomy for acute severe necrotizing pancreatitis.

PubMed

Bavare, Charudatta; Prabhu, Ramkrishna; Supe, Avinash

2004-01-01

Morphological and functional changes in the pancreas after surgical pancreatic necrosectomy have not been studied extensively. To study morphological changes in the pancreas, and exocrine and endocrine pancreatic function following pancreatic necrosectomy. Eighteen adult patients surviving at least one month after pancreatic necrosectomy for acute necrotizing pancreatitis were followed up. Contrast-enhanced computed tomography was done every six months. Stool fat was estimated at 3-month intervals, and need for and response to enzyme supplements were recorded. Blood sugar was measured every fortnight; in patients with hyperglycemia, need for oral hypoglycemic agents or insulin was recorded. Additional pancreatic imaging was done in some cases. Six weeks after surgery, nine of 18 patients had exocrine insufficiency. Thirteen patients developed endocrine insufficiency, including 5 who also had exocrine insufficiency. At the end of the study, 13 patients had endocrine insufficiency and 2 had exocrine insufficiency. Pancreatic size was subnormal in all patients at the end of six months. Pancreatography in three cases did not reveal any ductal abnormality. Necrotizing pancreatitis affects pancreatic exocrine or endocrine function in more than half the patients.

SGLT2 inhibitors: a novel choice for the combination therapy in diabetic kidney disease.

PubMed

Zou, Honghong; Zhou, Baoqin; Xu, Gaosi

2017-05-16

Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc. Simultaneous use of SGLT-2 inhibitors and renin-angiotensin-aldosterone system (RAAS) blockers are novel strategies to slow the progression of DKD via reducing inflammatory and fibrotic markers induced by hyperglycaemia more than either drug alone. The available population and animal based studies have described SGLT2 inhibitors plus RAAS blockers. The present review was to systematically review the potential renal benefits of SGLT2 inhibitors combined with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, mineralocorticoid receptor antagonists, and especially the angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.

Discovery of orally active hepatoselective glucokinase activators for treatment of Type II Diabetes Mellitus.

PubMed

Xu, Jiayi; Lin, Songnian; Myers, Robert W; Trujillo, Maria E; Pachanski, Michele J; Malkani, Sunita; Chen, Hsuan-Shen; Chen, Zhesheng; Campbell, Brian; Eiermann, George J; Elowe, Nadine; Farrer, Brian T; Feng, Wen; Fu, Qinghong; Kats-Kagan, Roman; Kavana, Michael; McMasters, Daniel R; Mitra, Kaushik; Tong, Xinchun; Xu, Libo; Zhang, Fengqi; Zhang, Rui; Addona, George H; Berger, Joel P; Zhang, Bei; Parmee, Emma R

2017-05-01

Systemically acting glucokinase activators (GKA) have been demonstrated in clinical trials to effectively lower blood glucose in patients with type II diabetes. However, mechanism-based hypoglycemia is a major adverse effect that limits the therapeutic potential of these agents. We hypothesized that the predominant mechanism leading to hypoglycemia is GKA-induced excessive insulin secretion from pancreatic β-cells at (sub-)euglycemic levels. We further hypothesized that restricting GK activation to hepatocytes would maintain glucose-lowering efficacy while significantly reducing hypoglycemic risk. Here we report the discovery of a novel series of carboxylic acid substituted GKAs based on pyridine-2-carboxamide. These GKAs exhibit preferential distribution to the liver versus the pancreas in mice. SAR studies led to the identification of a potent and orally active hepatoselective GKA, compound 6. GKA 6 demonstrated robust glucose lowering efficacy in high fat diet-fed mice at doses ⩾10mpk, with ⩾70-fold liver:pancreas distribution, minimal effects on plasma insulin levels, and significantly reduced risk of hypoglycemia. Copyright © 2016. Published by Elsevier Ltd.

Phytochemical composition and metabolic performance-enhancing activity of dietary berries traditionally used by Native North Americans.

PubMed

Burns Kraft, Tristan F; Dey, Moul; Rogers, Randy B; Ribnicky, David M; Gipp, David M; Cefalu, William T; Raskin, Ilya; Lila, Mary Ann

2008-02-13

Four wild berry species, Amelanchier alnifolia, Viburnum trilobum, Prunus virginiana, and Shepherdia argentea, all integral to the traditional subsistence diet of Native American tribal communities, were evaluated to elucidate phytochemical composition and bioactive properties related to performance and human health. Biological activity was screened using a range of bioassays that assessed the potential for these little-known dietary berries to affect diabetic microvascular complications, hyperglycemia, pro-inflammatory gene expression, and metabolic syndrome symptoms. Nonpolar constituents from berries, including carotenoids, were potent inhibitors of aldose reductase (an enzyme involved in the etiology of diabetic microvascular complications), whereas the polar constituents, mainly phenolic acids, anthocyanins, and proanthocyanidins, were hypoglycemic agents and strong inhibitors of IL-1beta and COX-2 gene expression. Berry samples also showed the ability to modulate lipid metabolism and energy expenditure in a manner consistent with improving metabolic syndrome. The results demonstrate that these berries traditionally consumed by tribal cultures contain a rich array of phytochemicals that have the capacity to promote health and protect against chronic diseases, such as diabetes.

Phytochemical Composition and Metabolic Performance Enhancing Activity of Dietary Berries Traditionally Used by Native North Americans

PubMed Central

Burns Kraft, Tristan F.; Dey, Moul; Rogers, Randy B.; Ribnicky, David M.; Gipp, David M.; Cefalu, William T.; Raskin, Ilya; Lila, Mary Ann

2009-01-01

Four wild berry species, Amelanchier alnifolia, Viburnum trilobum, Prunus virginiana, and Shepherdia argentea, all integral to the traditional subsistence diet of Native American tribal communities, were evaluated to elucidate phytochemical composition and bioactive properties related to performance and human health. Biological activity was screened using a range of bioassays that assessed the potential for these little-known dietary berries to affect diabetic microvascular complications, hyperglycemia, pro-inflammatory gene expression, and metabolic syndrome symptoms. Non-polar constituents from berries, including carotenoids, were potent inhibitors of aldose reductase (an enzyme involved in the etiology of diabetic microvascular complications) whereas the polar constituents, mainly phenolic acids, anthocyanins, and proanthocyanidins, were hypoglycemic agents and strong inhibitors of IL-1β and COX-2 gene expression. Berry samples also showed the ability to modulate lipid metabolism and energy expenditure in a manner consistent with improving metabolic syndrome. The results demonstrate that these berries traditionally consumed by tribal cultures contain a rich array of phytochemicals that have the capacity to promote health and protect against chronic diseases, such as diabetes. PMID:18211018

[Dapagliflozin: Beyond glycemic control in the treatment of type 2 diabetes mellitus].

PubMed

Sanz-Serra, Pol; Pedro-Botet, Juan; Flores-Le Roux, Juana A; Benaiges, David; Chillarón, Juan J

2015-01-01

Patients with type 2 diabetes mellitus (T2DM) have a high or very high cardiovascular risk. The clinical practice guidelines focus on the need to achieve optimal glycemic control, and strategies for a multifactorial therapeutic approach have shown significant cardiovascular benefits in these patients. Inhibitors of sodium-glucose co-transporter 2 (SGLT-2) are a new class of orally administered drugs in the treatment of T2DM, which act by inhibiting reabsorption of glucose in the renal proximal tubule with consequent glycosuric effect and lowering of blood glucose. Dapagliflozin, SGLT-2 inhibitor marketed in Europe and Australia, has been shown to achieve glycosylated hemoglobin reductions similar to other oral agents, as well as beneficial effects on major comorbidities associated with T2DM. Therefore, it is considered of interest to review the clinical efficacy of this new oral hypoglycemic on glycemic control, risk of hypoglycemia, and its impact on body weight, blood pressure, lipid profile and renal function. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Characterization of Momordica charantia L. polysaccharide and its protective effect on pancreatic cells injury in STZ-induced diabetic mice.

PubMed

Zhang, Cong; Chen, Hongman; Bai, Weiqi

2018-04-10

A polysaccharide with a molecular weight of 13,029Da was isolated from Momordica charantia (MCP) fruit and purified by ion-exchange and size-exclusion chromatography. The isolated polysaccharide MCPIIa contained L-Rha, D-GalA, D-Gal, D-Xyl, L-Ara in a molar ratio of 12:3.05:19.89:5.95:56. IR spectrum and NMR studies indicated that the MCPIIa sugar units were linked, via β-glycosidic bonds, to a large number of arabinofuranose, glucuronic acid, and xylopyranosyl residues. In addition, the hypoglycemic effect of MCPIIa was investigated in streptozotocin (STZ)-induced diabetic mice. After STZ-induction, MCPIIa (100, 200, or 300mg/kg body weight) was administered orally, once daily, for 28days. Glycemia in STZ-diabetogenic mice was significantly reduced, and compared with diabetes mellitus (DM) mice, serum insulin concentration increased significantly, following MCPIIa administration. Transmission electron microscopy showed an alleviation of STZ-lesions in pancreatic tissue from mice treated with MCPIIa. These results indicate that MCPIIa may be useful as an anti-diabetic agent. Copyright © 2018 Elsevier B.V. All rights reserved.

Insulin Management Strategies for Exercise in Diabetes.

PubMed

Zaharieva, Dessi P; Riddell, Michael C

2017-10-01

There is no question that regular exercise can be beneficial and lead to improvements in overall cardiovascular health. However, for patients with diabetes, exercise can also lead to challenges in maintaining blood glucose balance, particularly if patients are prescribed insulin or certain oral hypoglycemic agents. Hypoglycemia is the most common adverse event associated with exercise and insulin therapy, and the fear of hypoglycemia is also the greatest barrier to exercise for many patients. With the appropriate insulin dose adjustments and, in some cases, carbohydrate supplementation, blood glucose levels can be better managed during exercise and in recovery. In general, insulin strategies that help facilitate weight loss with regular exercise and recommendations around exercise adjustments to prevent hypoglycemia and hyperglycemia are often not discussed with patients because the recommendations can be complex and may differ from one individual to the next. This is a review of the current published literature on insulin dose adjustments and starting-point strategies for patients with diabetes in preparation for safe exercise. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association.

PubMed

Kim, Hyun Jin; Park, Seok O; Ko, Seung Hyun; Rhee, Sang Youl; Hur, Kyu Yeon; Kim, Nan Hee; Moon, Min Kyong; Lee, Byung Wan; Kim, Jin Hwa; Choi, Kyung Mook

2017-12-01

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA. Copyright © 2017 Korean Diabetes Association.

In-silico analysis of gymnemagenin from Gymnema sylvestre (Retz.) R.Br. with targets related to diabetes.

PubMed

Rathore, Poonam K; Arathy, V; Attimarad, Vijaylaxmi S; Kumar, Pramod; Roy, Subarna

2016-02-21

Diabetes is a metabolic disorder characterized by higher than normal glucose in the blood. Most oral hypoglycemic drugs available in market produce adverse side effects which have resulted in continued search for new therapeutic agents with little or no side effects. Herbal drugs are considered relatively safer alternatives and Gymnema sylvestre is one of the most well established natural remedy for diabetes and is traded worldwide under several brands. In the present study an attempt has been made to use in silico techniques to understand and predict the drug likeliness of gymnemagenin, one of the key constituents of G. sylvestre against 15 proteins having key role in carbohydrate metabolism. Gymnemagenin was found to dock well with crystallographic structures of 7 of the 15 selected targets and was found even better than the two known clinically used antidiabetic compounds, repaglinide and sitagliptin taken in the study for comparison. Gymnemagenin therefore can be considered further for development into a potent anti-diabetic drug. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of maternal obesity on pregnancy outcomes of women with gestational diabetes controlled with diet only, glyburide, or insulin.

PubMed

Joy, Saju; Roman, Ashley; Istwan, Niki; Rhea, Debbie; Desch, Cheryl; Stanziano, Gary; Saltzman, Daniel

2012-09-01

To examine the effect of obesity on maternal and neonatal outcomes in women diagnosed with gestational diabetes mellitus (GDM) and managed with diet only, glyburide, or insulin. Women with singleton gestations enrolled for outpatient services diagnosed with GDM and without history of pregnancy-related hypertension at enrollment or in a prior pregnancy were identified in a database. Women with GDM controlled by diet only (n = 3918), glyburide (n = 873), or insulin without prior exposure to oral hypoglycemic agents (n = 2229) were included. Pregnancy outcomes were compared for obese versus nonobese women within each treatment group and also compared across treatment groups within the obese and nonobese populations. Within each treatment group, obesity was associated with higher rates of cesarean delivery, pregnancy-related hypertension, macrosomia, and hyperbilirubinemia (all p < 0.05). Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in women receiving glyburide. Obesity adversely affects pregnancy outcome in women with GDM. Higher rates of pregnancy-related hypertension and hyperbilirubinemia were observed in pregnant women receiving glyburide. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Herbal therapy: A review of emerging pharmacological tools in the management of diabetes mellitus in Africa

PubMed Central

Kibiti, Cromwell Mwiti; Afolayan, Anthony Jide

2015-01-01

Background: Diabetes mellitus is a chronic physiological glucose metabolic disorder. It has affected millions of people all over the world thereby having a significant impact on quality of life. The management of diabetes includes both nonpharmacological and conventional interventions. Drawbacks in conventional therapy have led to seeking alternative therapy in herbal medicine. Therefore, the need to review, elucidate and classify their mode of action in therapy for diabetes disease arises. Materials and Methods: Comprehensive literature reports were used to review all conventional agents and herbal therapy used in the management of diabetes. An online database search was conducted for medicinal plants of African origin that have been investigated for their antidiabetic therapeutic potentials. Results: The results showed that of the documented sixty five plants used, fourteen inhibit intestinal absorption of glucose, three exhibit insulin-mimetic properties, seventeen stimulate insulin secretion from pancreatic beta cells, twelve enhance peripheral glucose uptake, one promotes regeneration of beta-cell of islets of Langerhans, thirteen ameliorate oxidative stress and twenty induces hypoglycemic effect (mode of action is still obscure). Thirteen of these plants have a duplicate mode of actions while one of them has three modes of actions. These agents have a similar mechanism of action as the conventional drugs. Conclusion: In conclusion, antidiabetic activities of these plants are well established; however, the molecular modulation remains unknown. It is envisaged that the use of herbal therapy will promote good health and improve the status of diabetic patients. PMID:26664014

Insulin therapy at onset of type 2 diabetes mellitus--a new concept.

PubMed

Sahay, B K

2011-04-01

In this study, insulin therapy was initiated at onset of disease in patients whose fasting blood glucose was more than 250 mg/dl. All enrolled subjects were treated with human premixed insulin (30/70) administered subcutaneously twice daily before breakfast and before dinner. A total of 113 subjects entered the study fulfilling the inclusion criteria. Good glycaemic control was achieved in a few days. The dosage requirement of insulin came down gradually after control was achieved as manifest by hypoglycaemia--leading to withdrawal of insulin. Some of them were managed with diet and exercise alone. Others required small doses of oral antidiabetic agents (OAD). There were no cases of secondary failure to OADs. Ten cases are on average duration of follow-up of 10 years. Two cases are under good control with diet and exercise alone, seven on treatment with oral hypoglycemic agents and one of them requiring insulin to maintain HbAlc below 7%. Thus insulin therapy at onset provides an opportunity to correct all the underlying pathogenic mechanisms, i.e., glucotoxicity, lipotoxicity and prevents beta cell apoptosis and suppresses inflammation, leading to beta cell protection. Such timely intervention provides long term benefits, laying the foundation for the concept of beta cell preservation rather that only replacing beta cell function. Hence we propose that all patients with type 2 diabetes should be offered insulin therapy at the onset of their diabetes for a period of 2-4 weeks.

Inhibition of α-glucosidase by polysaccharides from the fruit hull of Camellia oleifera Abel.

PubMed

Zhang, Sheng; Li, Xiang-Zhou

2015-01-22

We isolated and purified polysaccharides from the Camellia oleifera Abel. fruit hull and studied its hypoglycemic potential. Our results revealed six polysaccharides (CFPA-1-5 & CFPB) from the aqueous extract from the defatted C. oleifera fruit hull. Purified polysaccharides (purity >90%) were investigated for the inhibition of α-glucosidase activity in vitro. Two polysaccharides, CFPB and CFPA-3 were present in high concentration in the fruit hull and showed a dose-dependent inhibition of α-glucosidase activity, with IC50 concentrations of 11.80 and 10.95 μg/mL, respectively. This result suggests that polysaccharides (CFP) extracted from the fruit hull of C. oleifera may have potential as functional foods with featuring a hypoglycemic effect. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antidiabetic, antioxidant and anti inflammatory properties of water and n-butanol soluble extracts from Saharian Anvillea radiata in high-fat-diet fed mice.

PubMed

Kandouli, Chouaib; Cassien, Mathieu; Mercier, Anne; Delehedde, Caroline; Ricquebourg, Emilie; Stocker, Pierre; Mekaouche, Mourad; Leulmi, Zineb; Mechakra, Aicha; Thétiot-Laurent, Sophie; Culcasi, Marcel; Pietri, Sylvia

2017-07-31

According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties. Six extracts (water soluble and organic) from aerial parts of the plant were analyzed phytochemically (total phenolic and flavonoid content) and screened for in vitro superoxide (by chemiluminescence) and hydroxyl radical (by electron paramagnetic resonance spin-trapping) scavenging, antioxidant (DPPH, TRAP and ORAC assays), xanthine oxidase, metal chelating, α-amylase and α-glucosidase inhibitory property, and protective effects on copper-induced lipoprotein oxidation. Then selected hydroalcoholic and aqueous extracts were assessed for toxicity in normal human lung fibroblasts and A549 cancer cells using FMCA and MTT assays. Two water-soluble extracts having the best overall properties were assessed for their (i) protective effect at 1-15µg/mL on metabolic activity of rat insulinoma-derived INS-1 cells exposed to hyperglycemic medium, and (ii) acute hypoglycemic effect on 16-weeks HFD-induced diabetic mice. Then diabetic mice were administered HFD supplemented by extracts (up to 150mg/kg/day) for 12 additional weeks using standard diet as control and the antidiabetic drug, metformin (150mg/kg), as positive control. Then the antidiabetic, anti-inflammatory and antioxidant activity of extracts were determined. Of the highly efficient polyphenolics-enriched hydroalcoholic and ethyl acetate extracts, the lyophilized aqueous (AQL) and butanol extracts were not toxic in cells (≤ 400µg/mL) or when given orally in normal mice (≤ 2000mg/kg), exerted a dose-dependent hypoglycemic action in diabetic mice, which was maximal at the dose of 150mg/kg. Upon administering this dose for 12 weeks, both extracts significantly ameliorated body weight control capacity, recovery of plasma glucose and insulin level, reduced oxidative stress in blood, myocardial and skeletal muscles, and improved hyperlipidemic and inflammatory status. Moreover, diabetes-related complications were optimally ameliorated by oral therapy based on halved doses (75mg/kg) of a mixture of AQL and metformin. Current investigation supports the traditional medicinal usage of Anvillea radiata and suggests that both readily accessible and low-cost bio-extracts have the potency to develop an antihyperglycemic, antihyperlipidemic and protective agent against beta-cells and muscle dysfunction at doses compatible with the common practices of indigenous people for the management of metabolic disorders. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

What Is Hypoglycemia?

MedlinePlus

... a severe hypoglycemic reaction. The body's most important fuel is glucose, a type of sugar. When you ... the body's cells, where it's used as a fuel. Someone with diabetes who takes too much insulin ...

77 FR 75492 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

... Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of final disposition. SUMMARY: FMCSA announces... severe hypoglycemic reactions resulting in loss of consciousness or seizure, requiring the assistance of...

Efficacy and safety comparison of add-on therapy with liraglutide, saxagliptin and vildagliptin, all in combination with current conventional oral hypoglycemic agents therapy in poorly controlled Chinese type 2 diabetes.

PubMed

Li, C-J; Yu, Q; Yu, P; Zhang, Q-M; Ding, M; Liu, X-J; Yu, D-M

2014-09-01

To compare the efficacy and safety of adding liraglutide, saxagliptin and vildagliptin to current therapy in Chinese type 2 diabetes subjects with poor glycemic control.A 24-week, randomized, open-label, parallel clinical trial was performed. A total 178 patients completed the trial who had been randomly assigned to add-on once daily liraglutide (1.2 mg/day injected subcutaneously), to saxagliptin (5 mg once daily) or to vildagliptin (50 mg twice daily). Glycosylated hemoglobin (HbA1c) values, fasting and postprandial blood glucose (FBG and P2BG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated.Over the 24-week treatment period, greater lowering of mean of HbA1c was achieved with 1.2 mg liraglutide (-1.50%, 95% CI [-1.67, -1.34]) than with saxagliptin (-1.23%, 95% CI [-1.36, -1.11]) and vildagliptin (-1.25%, 95% CI [-1.37, -1.13]). There was no significant between-group difference of percentages of subjects who reached a target HbA1c<7.0%, but significantly more subjects with liraglutide achieved HbA1c≤6.5% compared with saxagliptin and vildagliptin. The mean reduction of FBG value from baseline was 2.23 mmol/L with liraglutide, much greater than 1.83 mmol/L with saxagliptin (p=0.013), but similar to 2.03 mmol/L with -vildaglitpin group. As to the P2BG value, greater reductions was found with liraglutide (-4.80 mmol/L) than -3.56 mmol/L with saxagliptin (p=0.000) and -3.57 mmol/L with vildagliptin (p=0.000). Moreover, greater mean reductions of body weight and BMI with liraglutide (-6.0 kg and -2.1 kg/m(2)) were achieved than with saxagliptin and vildagliptin (both p<0.001), whereas no significant difference was found between saxagliptin and vildagliptin group. The incidence of hypoglycemia was recorded low and similar in each treatment group. Nausea was more common with liraglutide (27%) than with saxagliptin (3.2%) and vildagliptin (5.2%), but no significant between-group difference was reported in other AEs.Adding liraglutide demonstrated superiority to saxagliptin and vildagliptin for reductions of HbA1c and weight loss in Chinese subjects with T2DM who had inadequate glycemic control with conventional oral hypoglycemic agents. These findings support the add-on of liraglutide could offer notable advantages over DPP-4 inhibitors in both efficacy and safety. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

76 FR 37882 - Qualification of Drivers; Exemption Applications; Diabetes Mellitus

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

... Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of final disposition. SUMMARY: FMCSA announces... hypoglycemic reactions resulting in loss of consciousness or seizure requiring the assistance of another person...

Cost-effectiveness of G5 Mobile continuous glucose monitoring device compared to self-monitoring of blood glucose alone for people with type 1 diabetes from the Canadian societal perspective.

PubMed

Chaugule, Shraddha; Graham, Claudia

2017-11-01

To evaluate the cost-effectiveness of real-time continuous glucose monitoring (CGM) compared to self-monitoring of blood glucose (SMBG) alone in people with type 1 diabetes (T1DM) using multiple daily injections (MDI) from the Canadian societal perspective. The IMS CORE Diabetes Model (v.9.0) was used to assess the long-term (50 years) cost-effectiveness of real-time CGM (G5 Mobile CGM System; Dexcom, Inc., San Diego, CA) compared with SMBG alone for a cohort of adults with poorly-controlled T1DM. Treatment effects and baseline characteristics of patients were derived from the DIAMOND randomized controlled clinical trial; all other assumptions and costs were sourced from published research. The accuracy and clinical effectiveness of G5 Mobile CGM is the same as the G4 Platinum CGM used in the DIAMOND randomized clinical trial. Base case assumptions included (a) baseline HbA1c of 8.6%, (b) change in HbA1c of -1.0% for CGM users vs -0.4% for SMBG users, and (c) disutilities of -0.0142 for non-severe hypoglycemic events (NSHEs) and severe hypoglycemic events (SHEs) not requiring medical intervention, and -0.047 for SHEs requiring medical resources. Treatment costs and outcomes were discounted at 1.5% per year. The incremental cost-effectiveness ratio for the base case G5 Mobile CGM vs SMBG was $33,789 CAD/quality-adjusted life-year (QALY). Sensitivity analyses showed that base case results were most sensitive to changes in percentage reduction in hypoglycemic events and disutilities associated with hypoglycemic events. The base case results were minimally impacted by changes in baseline HbA1c level, incorporation of indirect costs, changes in the discount rate, and baseline utility of patients. The results of this analysis demonstrate that G5 Mobile CGM is cost-effective within the population of adults with T1DM using MDI, assuming a Canadian willingness-to-pay threshold of $50,000 CAD per QALY.

Changes in HbA1c, insulin dose and incidence of hypoglycemia in patients with type 1 diabetes after switching to insulin degludec in an outpatient setting: an observational study.

PubMed

Landstedt-Hallin, Lena

2015-08-01

Insulin degludec, a basal insulin with an ultra-long duration of action, became available in Sweden from July 2013. The diabetes team at Danderyd Hospital decided to perform a clinical follow-up of patients with type 1 diabetes switching to insulin degludec to evaluate its clinical performance, using a simple form and available measures, thereby indirectly assessing cost-effectiveness. This was a prospective, open-label, single-arm, observational, clinical follow-up from August 2013 to February 2015 of consecutive patients who switched to insulin degludec according to predefined indications (i.e., currently administering basal insulin twice daily, unacceptable HbA1c, repeated hypoglycemic events and/or unstable glucose, difficulty with fixed-time administration) in conjunction with professional judgment and patient wishes. Information about HbA1c, insulin dose and frequency of hypoglycemia (self-reported by patient recall) was collected at baseline and repeated after 4-6 months. In February 2015, data were available on 357 patients. Median time to follow-up was 20 weeks. Mean (SD) HbA1c decreased from 68.9 (15.7) to 65.8 (14.3) mmol/mol, p < 0.0001, and this improvement was achieved despite less insulin. Median reduction of the total insulin dose (basal + prandial) was 12% (interquartile range [IQR] -20% to -3%). The mean (SD) number of self-reported hypoglycemic events in the previous 4 weeks decreased from 8.2 (8.9) to 6.4 (7.6) events, p < 0.0001, and nocturnal hypoglycemic events were reduced from 1.6 (2.9) to 0.7 (2.0) events, p < 0.0001. Due to improvement in glycemic control, reduction of hypoglycemic events and reduction of insulin dose, we concluded that insulin degludec was clinically useful and economically justifiable for our patients with type 1 diabetes. Not every patient may benefit to the same degree after switching to insulin degludec. Controlled studies are needed to confirm these benefits in a larger sample of real-world patients.

Long-Term Home Study on Nocturnal Hypoglycemic Alarms Using a New Fully Implantable Continuous Glucose Monitoring System in Type 1 Diabetes.

PubMed

Wang, Xiaolin; Ioacara, Sorin; DeHennis, Andrew

2015-11-01

This study analyzed the overall nocturnal performance during home use of a long-term subcutaneous implantable continuous glucose monitoring (CGM) sensor. In this study, 12 subjects with type 1 diabetes mellitus (T1DM) (mean±SD age, 37±8 years; mean±SD disease duration, 11±6 years) were implanted with an investigational continuous glucose sensor in the upper arm for up to 90 days. All subjects received full access to real-time glucose display and user programmable hypo- and hyperglycemic alarms. Subjects calibrated the sensors with a self-monitoring of blood glucose (SMBG) meter and continued to rely on their regular SMBG measurements for their diabetes management. Accuracy of the sensors during the home-use study was calculated using SMBG as the reference. The nocturnal sensor attenuation (NSA) concept was tested. Sensitivity and specificity of the nocturnal hypoglycemic alarm were calculated. Mean±SD glucose sensor life span was 87±7 days. The mean±SE absolute relative difference over the range of 40-400 mg/dL for the sensors in this home-use study was 12.3±0.7% using SMBG as the reference. The hypoglycemia alarms were set to be triggered when the glucose level went below 70 mg/dL. Percentage of nights with hypoglycemic alarms triggered for at least 10 min was 13.6%. Recovery into euglycemia within 30 min from the timestamp of the immediate confirmatory SMBG testing was obtained in 74% of all episodes (n=20). The implanted continuous glucose sensor showed a hypoglycemia detection sensitivity and specificity of 77% and 96%, respectively. The NSA-associated high negative rate of change of at least -4 mg/dL/min was not encountered during night use of the system. This home-use study of a fully implantable, long-term continuous glucose sensor shows excellent performance in nocturnal hypoglycemia detection in T1DM patients. The apparent lack of NSA affecting the implanted sensor and the high specificity of the hypoglycemic alarm expedite the recovery from nighttime hypoglycemia.

Molecular structure and spectroscopic investigations combined with hypoglycemic/anticancer and docking studies of a new barbituric acid derivative

NASA Astrophysics Data System (ADS)

Barakat, Assem; Soliman, Saied M.; Elshaier, Yaseen A. M. M.; Ali, M.; Al-Majid, Abdullah Mohammed; Ghabbour, Hazem A.

2017-04-01

The one-pot synthesis reaction of barbituric acid derivative, 1,3-cyclohexandione, and 4-fluorobenzaldehyde in water mediated by NHEt2 as base afforded 4 with excellent yield. The synthesized compound was characterized by spectrophotometric tools as well as X-ray single crystal diffraction technique. The stability of the nine possible isomers of the synthesized compound was studied using the B3LYP method and 6-31G(d,p) basis set. The electronic and spectroscopic properties of the most stable isomer were predicted. The UV-Vis absorption spectrum displayed two bands at 203 and 257 nm in the solvent chloroform. The latter was calculated at 235.6 nm (f = 0.1995) in the gas phase due to H-2→L (42%) and H-1→L+2 (14%) excitations. In solution, using chloroform as a solvent, a slight bathochromic shift to 237.6 nm with an increase in the absorption intensity (f = 0.2898) was predicted. The molecular orbital energy level diagram of this transition band was characterized mainly by π-π* transitions. The 13C and 1H NMR chemical shifts correlated well with the experimental data. The correlations had higher correlation coefficients (R2) when solvent effects were considered. The atomic charges were calculated using natural population analysis and the charged regions were presented using a molecular electrostatic potential (MEP) map. The synthesized compound was examined as a hypoglycemic agent via inhibition of α-glucosidase and β-glucuronidase enzymes. Its inhibitory activity against α-glucosidase was 10 times greater than the inhibitory activity of the standard drug acarbose (IC50 77.9 ± 0.3 μM and 840 ± 1.73 μM, respectively). Moreover, the target compound was evaluated for anticancer activity against MCF-7, H460, 3T3, and Hela cell lines. It demonstrated inhibitory activity against the MCF-7 and H460 cell lines with IC50 5.80 ± 0.12 and 19.6 ± 0.5 μM, respectively, in comparison to doxorubicin. The docking study was performed using the OpenEye program.

Medicinal flowers. III. Marigold. (1): hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and new oleanane-type triterpene oligoglycosides, calendasaponins A, B, C, and D, from Egyptian Calendula officinalis.

PubMed

Yoshikawa, M; Murakami, T; Kishi, A; Kageura, T; Matsuda, H

2001-07-01

The methanolic extract and its 1-butanol-soluble fraction from the flowers of Calendula officinalis were found to show a hypoglycemic effect, inhibitory activity of gastric emptying, and gastroprotective effect. From the 1-butanol-soluble fraction, four new triterpene oligoglycosides, calendasaponins A, B, C, and D, were isolated, together with eight known saponins, seven known flavonol glycosides, and a known sesquiterpene glucoside. Their structures were elucidated on the basis of chemical and physicochemical evidence. The principal saponin constituents, glycosides A, B, C, D, and F, exhibited potent inhibitory effects on an increase in serum glucose levels in glucose-loaded rats, gastric emptying in mice, and ethanol- and indomethacin-induced gastric lesions in rats. Some structure-activity relationships are discussed.

Conditional VHL Gene Deletion Causes Hypoglycemic Death Associated with Disproportionately Increased Glucose Uptake by Hepatocytes through an Upregulated IGF-I Receptor

PubMed Central

Kurabayashi, Atsushi; Kakinuma, Yoshihiko; Morita, Taku; Inoue, Keiji; Sato, Takayuki; Furihata, Mutsuo

2013-01-01

Our conditional VHL knockout (VHL-KO) mice, having VHL gene deletion induced by tamoxifen, developed severe hypoglycemia associated with disproportionately increased storage of PAS-positive substances in the liver and resulted in the death of these mice. This hypoglycemic state was neither due to impaired insulin secretion nor insulin receptor hypersensitivity. By focusing on insulin-like growth factor I (IGF-I), which has a similar effect on glucose metabolism as the insulin receptor, we demonstrated that IGF-I receptor (IGF-IR) protein expression in the liver was upregulated in VHL-KO mice compared to that in the mice without VHL deletion, as was the expression of glucose transporter (GLUT) 1. The interaction of the receptor for activated C kinase (RACK) 1, which predominantly binds to VHL, was enhanced in VHL-KO livers with IGF-IR, because VHL deletion increased free RACK1 and facilitated the IGF-IR-RACKI interaction. An IGF-IR antagonist retarded hypoglycemic progression and sustained an euglycemic state. These IGF-IR antagonist effects on restoring blood glucose levels also attenuated PAS-positive substance storage in the liver. Because the effect of IGF-I on HIF-1α protein synthesis is mediated by IGF-IR, our results indicated that VHL inactivation accelerated hepatic glucose storage through the upregulation of IGF-IR and GLUT1 and that IGF-IR was a key regulator in VHL-deficient hepatocytes. PMID:23874892

A Review of the Hypoglycemic Effects of Five Commonly Used Herbal Food Supplements

PubMed Central

Deng, Ruitang

2013-01-01

Hyperglycemia is a pathological condition associated with prediabetes and diabetes. The incidence of prediabetes and diabetes is increasing and imposes great burden on healthcare worldwide. Patients with prediabetes and diabetes have significantly increased risk for cardiovascular diseases and other complications. Currently, management of hyperglycemia includes pharmacological interventions, physical exercise, and change of life style and diet. Food supplements have increasingly become attractive alternatives to prevent or treat hyperglycemia, especially for subjects with mild hyperglycemia. This review summarized current patents and patent applications with relevant literature on five commonly used food supplements with claims of hypoglycemic effects, including emblica officinalis (gooseberry), fenugreek, green tea, momordica charantia (bitter melon) and cinnamon. The data from human clinical studies did not support a recommendation for all five supplements to manage hyperglycemia. Fenugreek and composite supplements containing emblica officinalis showed the most consistency in lowering fasting blood sugar (FBS) or glycated hemoglobin (HbA1c) levels in diabetic patients. The hypoglycemic effects of cinnamon and momordica charantia were demonstrated in most of the trials with some exceptions. However, green tea exhibited limited benefits in reducing FBS or HbA1c levels and should not be recommended for managing hyperglycemia. Certain limitations are noticed in a considerable number of clinical studies including small sample size, poor experimental design and considerable variations in participant population, preparation format, daily dose, and treatment duration. Future studies with more defined participants, standardized preparation and dose, and improved trial design and size are warranted. PMID:22329631

Repetitive and profound insulin-induced hypoglycemia results in brain damage in newborn rats: an approach to establish an animal model of brain injury induced by neonatal hypoglycemia.

PubMed

Zhou, Dong; Qian, Jing; Liu, Chun-Xi; Chang, Hong; Sun, Ruo-Peng

2008-10-01

The human neonate is at a higher risk for hypoglycemia-induced neuronal injury than other pediatric and adult patients. Repetitive and profound neonatal hypoglycemia can result in severe neurologic sequelae, of which the mechanisms was not elucidated by hitherto. Moreover, no reliable animal model of brain injury induced by neonatal hypoglycemia is available in order to carry out more research. Therefore, we tried to induce neonatal hypoglycemia in newborn rats by fasting and insulin injection, and then examined the neuronal degeneration after repetitive hypoglycemic insults by Fluoro-Jade B (FJB) staining. Experimental animals were randomly divided into four groups: insulin-treated rats with short hypoglycemia, insulin-treated rats with prolonged hypoglycemia, fasted rats, and control rats. Insulin injection and fasting both could induce consistent hypoglycemia in newborn rats. But from FJB staining results, only in insulin-treated rats with prolonged hypoglycemia could extensive neurodegeneration be detected. We can conclude that FJB staining is a useful method of marking neuronal degeneration in neonatal rats following hypoglycemic brain damage. Repetitive and profound neonatal hypoglycemia can result in extensive neurodegeneration, and it seems that neurons of the cortex, dentate gyrus of the hippocampus, the thalamus, and the hypothalamus are more vulnerable to hypoglycemic insult in newborn rats. Repetitive and profound insulin-induced hypoglycemia in newborn rats can establish a reliable animal model of brain injury resulting from neonatal hypoglycemia.

Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study.

PubMed

Maury, Eric; Vitry, Paola; Galbois, Arnauld; Ait-Oufella, Hafid; Baudel, Jean-Luc; Guidet, Bertrand; Offenstadt, Georges

2012-06-14

We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device. We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin]. Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71-48.8; p < 0.001). The administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.

[Continuous glucose monitoring with type 1 diabetes mellitus].

PubMed

López-Siguero, J P; García Arias, M J; del Pino de la Fuente, A; Moreno Molina, J A

2003-03-01

Appropriate metabolic control of children with type 1 diabetes mellitus (DM) is based on frequent measurements of capillary glycemia. However, this method offers only partial information on fluctuations in glycemia during the day, while episodes of postprandial hyperglycemia and hypoglycemia, mainly nocturnal, go unnoticed. To analyze pre- and postprandial blood glucose levels, as well as the presence and duration of hypoglycemic episodes in diabetic children aged more than 8 years old with more than one year of disease duration. Seventeen patients of both sexes (mean age: 12 years old) with type 1 DM were monitored with the continuous glucose monitoring system (CGMS) during working days. Maximum values of pre- and postprandial glucose (1-3 hours after breakfast, lunch and dinner) were registered. Data were downloaded with a Com-station. The mean duration of sensor-wearing was 2.97 days. Pre- and postprandial values were high: mean preprandial values were between 144.9 and 160.5 mg % and mean postprandial values were between 230.4 and 248.8 mg %. The mean number of hypoglycemic episodes detected with the sensor was 4.9 compared with 1.8 detected with the glucometer (p < 0.05). Episodes of mainly nocturnal asymptomatic hypoglycemia were detected with a mean duration of 145 minutes during the night and 75 minutes during the day. The use of continuous subcutaneous glucose monitoring demonstrates that glycemic objectives are not achieved by conventional insulin therapy. It also shows that there are a high number of hypoglycemic episodes, most of which are asymptomatic.

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect.

PubMed

Yin, Juntao; Hou, Yantao; Yin, Yuyun; Song, Xiaoyong

2017-01-01

Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action.

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

PubMed Central

Yin, Juntao; Hou, Yantao; Yin, Yuyun; Song, Xiaoyong

2017-01-01

Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action. PMID:29263662

Effects of Gymnema sylvestre extract on the pharmacokinetics and pharmacodynamics of glimepiride in streptozotocin induced diabetic rats.

PubMed

Kamble, Bhagyashree; Gupta, Ankur; Moothedath, Ismail; Khatal, Laxman; Janrao, Shirish; Jadhav, Amol; Duraiswamy, B

2016-02-05

Gymnema sylvestre, important Indian traditional herbal medicine has been used for diabetes from several years and marketed as single or multi-herb formulations globally. People are consuming G. sylvestre along with conventional hypoglycemic drugs. Therefore, there is need of evidence based assessment of risk versus benefits when G. sylvestre co-administered with conventional oral hypoglycemic drugs. In present investigation, pharmacodynamics and pharmacokinetic interactions with oral hypoglycemic drug, glimepiride (GLM) was studied in streptozotocin (STZ) induced diabetic rats. A specific and rapid HPLC-ESI-MS/MS method was established for simultaneous quantification of GLM and gymnemagenin (GMG) in rat plasma. Pharmacokinetic and pharmacodynamic interaction studies were carried out in STZ induced diabetic rats after concomitant administration of 400 mg/kg of G. sylvestre extract and 0.8 mg/kg of GLM for 28 days. The developed HPLC-ESI-MS/MS method was rapid, specific, and precise. Con-comitant oral administration of G. sylvestre extract (400 mg/kg) and GLM (0.8 mg/kg) in diabetic rats for 28 days showed beneficial pharmacodynamic interactions whereas no major alterations in the pharmacokinetics parameters of GLM and GMG were observed. This interaction demonstrated in animal model implies that significant clinical outcome might occur during concomitant administration of G. sylvestre extract and GLM especially in diabetic patients and warrants further studies in the same set up. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the hypoglycemic and hypolipidemic effects of an ethylacetate fraction of Artocarpus heterophyllus (jak) leaves in streptozotocin-induced diabetic rats

PubMed Central

Chackrewarthy, S.; Thabrew, M. I.; Weerasuriya, M. K. B.; Jayasekera, S.

2010-01-01

Aqueous extracts of mature leaves of Artocarpus heterophyllus (jak) are used by traditional medical practitioners in Sri Lanka and India for the treatment of diabetes. This study was conducted to investigate the hypoglycemic and hypolipidemic effects of an ethylacetate (EA) fraction of the mature leaves of A. heterophyllus in a streptozotocin (STZ) induced diabetic rat model. In normoglycemic rats, administration of a single dose (20 mg/kg) of the EA fraction resulted in a significant (P < 0.05) reduction in the fasting blood glucose concentration and a significant improvement in glucose tolerance (P < 0.05), compared to the controls. In STZ-induced diabetic rats, chronic administration of the EA fraction of A. heterophyllus leaves daily for 5 weeks resulted in a significant lowering of serum glucose, cholesterol and triglyceride (TG) levels. Compared to control diabetic rats, the extract-treated rats had 39% less serum glucose, 23% lower serum total cholesterol and 40% lower serum TG levels and 11% higher body weight at the end of the fifth week. The percentage reductions in the serum parameters mediated by the test fraction were comparable with those produced by glibenclamide (0.6 mg/kg), the reference drug used in this study. It can be concluded that the EA fraction of A. heterophyllus leaves contains one or more hypoglycemic and hypolipidemic principles which have the potential to be developed further for the treatment of diabetes specifically associated with a hyperlipidemic state. PMID:20931077

Evaluation of the hypoglycemic and hypolipidemic effects of an ethylacetate fraction of Artocarpus heterophyllus (jak) leaves in streptozotocin-induced diabetic rats.

PubMed

Chackrewarthy, S; Thabrew, M I; Weerasuriya, M K B; Jayasekera, S

2010-07-01

Aqueous extracts of mature leaves of Artocarpus heterophyllus (jak) are used by traditional medical practitioners in Sri Lanka and India for the treatment of diabetes. This study was conducted to investigate the hypoglycemic and hypolipidemic effects of an ethylacetate (EA) fraction of the mature leaves of A. heterophyllus in a streptozotocin (STZ) induced diabetic rat model. In normoglycemic rats, administration of a single dose (20 mg/kg) of the EA fraction resulted in a significant (P < 0.05) reduction in the fasting blood glucose concentration and a significant improvement in glucose tolerance (P < 0.05), compared to the controls. In STZ-induced diabetic rats, chronic administration of the EA fraction of A. heterophyllus leaves daily for 5 weeks resulted in a significant lowering of serum glucose, cholesterol and triglyceride (TG) levels. Compared to control diabetic rats, the extract-treated rats had 39% less serum glucose, 23% lower serum total cholesterol and 40% lower serum TG levels and 11% higher body weight at the end of the fifth week. The percentage reductions in the serum parameters mediated by the test fraction were comparable with those produced by glibenclamide (0.6 mg/kg), the reference drug used in this study. It can be concluded that the EA fraction of A. heterophyllus leaves contains one or more hypoglycemic and hypolipidemic principles which have the potential to be developed further for the treatment of diabetes specifically associated with a hyperlipidemic state.

Antidiabetic effect of polyphenolic extracts from selected edible plants as α-amylase, α -glucosidase and PTP1B inhibitors, and β pancreatic cells cytoprotective agents - a comparative study.

PubMed

Zakłos-Szyda, Małgorzata; Majewska, Iwona; Redzynia, Małgorzata; Koziołkiewicz, Maria

2015-01-01

Type 2 diabetes mellitus, which is usually a result of wrong dietary habits and reduced physical activity, represents 85-95% of all diabetes cases and among other diet related diseases is the major cause of deaths. The disease is characterized mainly by hyperglycemia, which is associated with attenuated insulin sensitivity or beta cells dysfunction caused by multiple stimuli, including oxidative stress and loss of insulin secretion. Since polyphenols possess multiple biological activities and constitute an important part of the human diet, they have recently emerged as critical phytochemicals in type 2 diabetes prevention and treatment. Their hypoglycemic action results from their antioxidative effect involved in recovering of altered antioxidant defenses and restoring insulin secreting machinery in pancreatic cells, or abilities to inhibit the activity of carbohydrates hydrolyzing enzymes (α-amylase and α-glucosidase) or protein tyrosine phosphatase 1B (PTP1B), which is known as the major negative regulator in insulin signaling. This study investigates the total phenolic content (Folin-Ciocalteu and HPLC methods) and antioxidant capacity (ABTS) of 20 polyphenolic extracts obtained from selected edible plants, which were screened in terms of α -amylase, α - glucosidase and protein tyrosine phosphatase 1B inhibitors or protective agents against oxidative stress induced by tertbutylhydroperoxide (t-BOOH) in βTC3 pancreatic beta cells used as a model target for antidiabetes drugs. The study concludes that Chaenomeles japonica, Oenothera paradoxa and Viburnum opulus may be promising natural sources for active compounds with antidiabetic properties.

Oxidative stress in normal hematopoietic stem cells and leukemia.

PubMed

Samimi, Azin; Kalantari, Heybatullah; Lorestani, Marzieh Zeinvand; Shirzad, Reza; Saki, Najmaldin

2018-04-01

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000-2017) of English-language literature using the terms 'oxidative stress,' 'reactive oxygen species,' 'hematopoietic stem cell,' and 'leukemia.' The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long-term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject. © 2018 APMIS. Published by John Wiley & Sons Ltd.

Effects of D-phenylalanine-derivative hypoglycemic agent A-4166 on pancreatic alpha- and beta-cells: comparative study with glibenclamide.

PubMed

Hirose, H; Maruyama, H; Seto, Y; Ito, K; Fujita, T; Dan, K; Kanda, N; Saruta, T; Kato, R

1995-03-01

We have reported that N-[(trans-4-isopropyl-cyclohexyl)-carbonyl]-D-phenylalanine (A-4166) stimulates insulin secretion in animal studies. To further elucidate the mechanisms underlying the actions of this agent, we investigated the effects of A-4166 on insulin and glucagon secretion with or without diazoxide, an ATP-sensitive potassium channel opener, using isolated perfused rat pancreas preparations, and compared the results with those of glibenclamide. Both 30 mumol/l A-4166 and 3 mumol/l glibenclamide significantly stimulated insulin secretion and reduced glucagon secretion to similar levels at a glucose concentration of 5.6 mmol/l (p < 0.01 for both vs. basal levels). After infusion of A-4166 was stopped, insulin levels promptly returned to the basal values, while insulin levels increased further even after discontinuation of glibenclamide. Furthermore, 100 mumol/l diazoxide significantly inhibited the insulin-stimulatory effects of both 30 mumol/l A-4166 and 3 mumol/l glibenclamide (p < 0.05 and p < 0.01, respectively). However, the effects of diazoxide on glucagon secretion differed between the two groups; 30 mumol/l A-4166 produced a transient increase in glucagon secretion (p < 0.05 vs. basal levels) but 3 mumol/l glibenclamide suppressed glucagon secretion further (p < 0.01 vs. without diazoxide) with concomitant administration of 100 mumol/l diazoxide. These findings suggest that A-4166 directly stimulates insulin secretion, at least in part, through mechanisms resembling those of sulfonylurea, but exerts different effect on glucagon secretion in isolated perfused rat pancreas.

Advancing Medication Safety: Establishing a National Action Plan for Adverse Drug Event Prevention.

PubMed

Harris, Yael; Hu, Dale J; Lee, Christine; Mistry, Mishale; York, Andrew; Johnson, Tisha K

2015-08-01

Adverse drug events (ADEs) are important contributors to preventable morbidity and mortality, comprising one third of all hospital adverse events. In response to growing evidence detailing the high prevalence of ADEs, particularly among vulnerable older adults, Congress requested that the Secretary of the Department of Health and Human Services (HHS) convene a Federal Interagency Steering Committee to establish a National Action Plan to focus on ADE prevention. In August 2014, the Office of Disease Prevention and Health Promotion released the final version of the National Action Plan for Adverse Drug Event Prevention. The Action Plan directly supports the goals of the HHS Strategic Plan and the Patient Protection and Affordable Care Act by providing guidance on tracking and preventing ADEs, as well as describing evidence-based tools and resources to enhance medication safety. ADE ACTION PLAN CONTENT: The Federal Interagency Steering Committee focused the Action Plan on ADEs that are clinically significant, account for the greatest number of measurable harms as identified by using existing surveillance tools, and are largely preventable. As such, the decision was made to target three medication classes: anticoagulants, diabetes agents (insulin and oral hypoglycemic agents), and opioids. The Action Plan is organized around four key areas: surveillance; evidence-based prevention; payment, policy incentives, and oversight; and research opportunities to advance medication safety. One measure of the ADE Action Plan's success will be the wider dissemination of information and educational resources to providers and patients (or consumers) regarding the risks associated with medications. Future Action Plan iterations are likely to consider other high-priority medication classes and update the recommendations.

Embolization as an Alternative Treatment of Insulinoma in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peppa, Melpomeni, E-mail: molypepa@otenet.g; Brountzos, Elias; Economopoulos, Nicolaos

2009-07-15

Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and tomore » prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.« less

Antimicrobial and hypoglycemic activities of novel N-Mannich bases derived from 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thiones.

PubMed

Al-Abdullah, Ebtehal S; Al-Tuwaijri, Hanaa M; Hassan, Hanan M; Haiba, Mogedda E; Habib, Elsayed E; El-Emam, Ali A

2014-12-11

The reaction of 5-(1-adamantyl)-4-ethyl or allyl-1,2,4-triazoline-3-thione with formaldehyde solution and various 1-substituted piperazines yielded the corresponding N-Mannich bases. The newly synthesized N-Mannich bases were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Six compounds showed potent antibacterial activity against one or more of the tested microorganisms, while two compounds exhibited moderate activity against the tested Gram-positive bacteria. None of the newly synthesized compounds were proved to possess marked activity against Candida albicans. The oral hypoglycemic activity of six compounds was determined in streptozotocin (STZ)-induced diabetic rats. Four compounds produced significant strong dose-dependent reduction of serum glucose levels, compared to gliclazide at 10 mg/kg dose level (potency ratio > 75%).

Hypoglycemic and antihyperglycemic effect of Semecarpus anacardium Linn in normal and streptozotocin-induced diabetic rats.

PubMed

Arul, B; Kothai, R; Christina, A J M

2004-12-01

The effect of ethanolic extract of dried nuts of Semecarpus anacardium on blood glucose was investigated in both normal (hypoglycemic) and streptozotocin-induced diabetic (antihyperglycemic) rats. The blood glucose levels were measured at 0, 1, 2 and 3 h after the treatment. The ethanolic extract of S. anacardium (100 mg/kg) reduced the blood glucose of normal rats from 85.83 +/- 1.55 to 65.83 +/- 2.20 mg/dl, 3 h after oral administration of the extract (p < 0.05). It also significantly lowered blood glucose levels in streptozotocin-induced diabetic rats from 335.33 +/- 4.90 to 132.17 +/- 4.49 mg/dl, 3 h after oral administration of the extract (p < 0.05). The antihyperglycemic activity of S. anacardium was compared with tolbutamide, a sulfonyl urea derivative used in diabetes mellitus. 2004 Prous Science

Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of a polysaccharide from the cultural mycelium of Cordyceps sinensis.

PubMed

Kiho, T; Hui, J; Yamane, A; Ukai, S

1993-12-01

Crude polysaccharides were obtained from a hot-water extract and alkaline extracts of the cultural mycelium of Cordyceps sinensis. They showed significant activity in normal mice and streptozotocin-induced diabetic mice as a result of intraperitoneal (i.p.) injection. A crude polysaccharide (CS-OHEP) obtained from 5% sodium hydroxide extract slightly lowered the plasma glucose level in normal mice by oral (p.o.) administration. A neutral polysaccharide (CS-F30) exhibited higher hypoglycemic activity than its crude polysaccharide (CS-OHEP), exhibited by i.p. injection, and it significantly lowered the glucose level by p.o. administration (50 mg/kg). However, it hardly affected the plasma insulin level in normal mice. CS-F30 ([alpha]D + 21 degrees in water) is composed of galactose, glucose and mannose (molar percent, 62:28:10), and its molecular weight is about 45000.

Drug–drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats

PubMed Central

Sultanpur, CM; Satyanarayana, S; Reddy, NS; Kumar, KE; Kumar, S

2010-01-01

Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug–drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD –POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution. PMID:21264118

Novel Use of Glucagon in a Closed-Loop System for Prevention of Hypoglycemia in Type 1 Diabetes

PubMed Central

Castle, Jessica R.; Engle, Julia M.; Youssef, Joseph El; Massoud, Ryan G.; Yuen, Kevin C.J.; Kagan, Ryland; Ward, W. Kenneth

2010-01-01

OBJECTIVE To minimize hypoglycemia in subjects with type 1 diabetes by automated glucagon delivery in a closed-loop insulin delivery system. RESEARCH DESIGN AND METHODS Adult subjects with type 1 diabetes underwent one closed-loop study with insulin plus placebo and one study with insulin plus glucagon, given at times of impending hypoglycemia. Seven subjects received glucagon using high-gain parameters, and six subjects received glucagon in a more prolonged manner using low-gain parameters. Blood glucose levels were measured every 10 min and insulin and glucagon infusions were adjusted every 5 min. All subjects received a portion of their usual premeal insulin after meal announcement. RESULTS Automated glucagon plus insulin delivery, compared with placebo plus insulin, significantly reduced time spent in the hypoglycemic range (15 ± 6 vs. 40 ± 10 min/day, P = 0.04). Compared with placebo, high-gain glucagon delivery reduced the frequency of hypoglycemic events (1.0 ± 0.6 vs. 2.1 ± 0.6 events/day, P = 0.01) and the need for carbohydrate treatment (1.4 ± 0.8 vs. 4.0 ± 1.4 treatments/day, P = 0.01). Glucagon given with low-gain parameters did not significantly reduce hypoglycemic event frequency (P = NS) but did reduce frequency of carbohydrate treatment (P = 0.05). CONCLUSIONS During closed-loop treatment in subjects with type 1 diabetes, high-gain pulses of glucagon decreased the frequency of hypoglycemia. Larger and longer-term studies will be required to assess the effect of ongoing glucagon treatment on overall glycemic control. PMID:20332355

Pancreatic protective and hypoglycemic effects of Vitex agnus-castus L. fruit hydroalcoholic extract in D-galactose-induced aging mouse model

PubMed Central

Ahangarpour, Akram; Oroojan, Ali Akbar; Khorsandi, Layasadat; Najimi, Seyedeh Asma

2017-01-01

D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus-castus (VAC) has potential pancreatic protective effect. Hence, this study was designed to evaluate the hypoglycemic and pancreas protective effects of VAC hydroalcoholic extract in D-galactose-induced aging female mice. In the present experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice (weighing 30–35 g) were divided into 6 groups of control, VAC hydroalcoholic extract, D-galactose, D-galactose + VAC hydroalcoholic extract, aged, aged + VAC hydroalcoholic extract. The aged model was prepared by subcutaneous injection of D-galactose for 45 days and, VAC hydroalcoholic extract was gavaged twice a day in the last 7 days. 24 h after the last drug and extract administrations, serum samples and pancreatic tissues were removed to evaluate experimental and histological determinations. Serum glucose level decreased in VAC, D-galactose and, aged-treated groups compared to the control (P < 0.05). Insulin level increased in VAC and decreased in D-galactose and aged VAC-treated mice compared to the control (P < 0.05). Homeostasis model assessment-estimated insulin resistance (HOMA-IR) increased in D-galactose, aging, and VAC hydroalcoholic extract groups (P < 0.05) and, administration of VAC hydroalcoholic extract improved HOMA-IR in D-galactose and aging treated animals. Despite the size of pancreatic islets decreased in aged and D-galactose groups, VAC administration recovered it. Present data showed that VAC hydroalcoholic extract has hypoglycemic and pancreatic protective effects in natural aged and aging model mice. PMID:28515766

Pancreatic protective and hypoglycemic effects of Vitex agnus-castus L. fruit hydroalcoholic extract in D-galactose-induced aging mouse model.

PubMed

Ahangarpour, Akram; Oroojan, Ali Akbar; Khorsandi, Layasadat; Najimi, Seyedeh Asma

2017-04-01

D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus-castus (VAC) has potential pancreatic protective effect. Hence, this study was designed to evaluate the hypoglycemic and pancreas protective effects of VAC hydroalcoholic extract in D-galactose-induced aging female mice. In the present experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice (weighing 30-35 g) were divided into 6 groups of control, VAC hydroalcoholic extract, D-galactose, D-galactose + VAC hydroalcoholic extract, aged, aged + VAC hydroalcoholic extract. The aged model was prepared by subcutaneous injection of D-galactose for 45 days and, VAC hydroalcoholic extract was gavaged twice a day in the last 7 days. 24 h after the last drug and extract administrations, serum samples and pancreatic tissues were removed to evaluate experimental and histological determinations. Serum glucose level decreased in VAC, D-galactose and, aged-treated groups compared to the control ( P < 0.05). Insulin level increased in VAC and decreased in D-galactose and aged VAC-treated mice compared to the control ( P < 0.05). Homeostasis model assessment-estimated insulin resistance (HOMA-IR) increased in D-galactose, aging, and VAC hydroalcoholic extract groups ( P < 0.05) and, administration of VAC hydroalcoholic extract improved HOMA-IR in D-galactose and aging treated animals. Despite the size of pancreatic islets decreased in aged and D-galactose groups, VAC administration recovered it. Present data showed that VAC hydroalcoholic extract has hypoglycemic and pancreatic protective effects in natural aged and aging model mice.

Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway.

PubMed

Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

2016-12-09

Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na⁺-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C ) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway

PubMed Central

Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

2016-01-01

Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na+-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway. PMID:27941667

Continuous Glucose Monitoring in Newborn Infants

PubMed Central

Thomas, Felicity; Signal, Mathew; Harris, Deborah L.; Weston, Philip J.; Harding, Jane E.; Shaw, Geoffrey M.

2014-01-01

Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data. PMID:24876618

Biochemical Evaluation of the Hypoglycemic Effects of Extract and Fraction of Cassia fistula Linn. in Alloxan-induced Diabetic Rats

PubMed Central

Jarald, E. E.; Joshi, S. B.; Jain, D. C.; Edwin, S.

2013-01-01

Various extracts of flowers of Cassia fistula Linn (Leguminosae) such as petroleum ether (60-80°), chloroform, acetone, ethanol, aqueous, and crude aqueous extracts and two fractions of ethanol extract were tested for antihyperglycemic activity in glucose-overloaded hyperglycemic rats. The effective antihyperglycemic extracts and fraction were tested for their hypoglycemic activity at two dose levels, 200 and 400 mg/kg, respectively. To confirm their utility in higher models, the effective extracts and fraction of C. fistula were subjected to antidiabetic study in an alloxan-induced diabetic model at two dose levels, 200 and 400 mg/kg, respectively. Biochemical parameters like glucose, urea, creatinine, serum cholesterol, serum triglyceride, high-density lipoprotein, low-density lipoprotein, hemoglobin, and glycosylated hemoglobin were also assessed in experimental animals. The petroleum ether and ethanol extracts of C. fistula and the water-soluble fraction of ethanol extract were found to exhibit significant antihyperglycemic activity. The extracts, at the given doses, did not produce hypoglycemia in fasted normal rats, and the fraction exhibited weak hypoglycemic effect after 2 h of the treatment. Treatment of diabetic rats with ethanol extract and water-soluble fraction of this plant restored the elevated biochemical parameters significantly (P<0.05) to the normal level. No activity was found in the petroleum ether extract of the plant. Comparatively, the water-soluble fraction of ethanol extract was found to be more effective than the ethanol extract, and the activity was comparable with that of the standard, glibenclamide (5 mg/kg). PMID:24302797

Safety and efficacy of an intensive insulin protocol in a burn-trauma intensive care unit.

PubMed

Cochran, Amalia; Davis, Lynn; Morris, Stephen E; Saffle, Jeffrey R

2008-01-01

Aggressive glycemic management in critically ill patients with acute burn injury or life-threatening soft-tissue infections has not been thoroughly evaluated. An intensive insulin protocol with target glucose values of less than 120 mg/dl was implemented in October 2005 in our regional Burn-Trauma intensive care unit. We reviewed our initial experience with this protocol to evaluate the safety and efficacy of aggressive glycemic control in these patient groups. Patients were placed on the intensive insulin protocol based upon the need for glycemic management during their hospitalization for burn or soft-tissue disease. Patient information prospectively collected while on protocol included all measured blood glucose values, total daily insulin use, and incidence of hypoglycemic episodes, defined as serum glucose <60 mg/dl. Thirty patients (17 burns, 13 soft-tissue infections) were placed on the intensive insulin protocol during the first 16 months of use. The mean daily blood glucose level for burn patients was 115.9 mg/dl and for soft-tissue disease patients was 119.5 mg/dl. There was a 5% incidence of hypoglycemic episodes per protocol day. All hypoglycemic episodes were treated by holding the insulin infusion, and no episode had known adverse effects. Hyperglycemia in critically ill patients with burns and extensive soft-tissue disease can be effectively managed with an insulin protocol that targets blood glucose values of less than 120 mg/dl with minimal incidence of hypoglycemia. A multicenter prospective randomized trial would provide the ideal forum for evaluating clinical outcome benefits of using an intensive insulin protocol.

New Approach for the Development of Improved Traditional Medicine: Case of a Preparation of an Oral Hypoglycemic Medicine from Laportea ovalifolia (Schumach. & Thonn.) Chew. (Urticaceae).

PubMed

Tsabang, Nolé; Kadjob, Stella; Mballa, Rose N; Yedjou, Clement G; Nnanga, Nga; Donfagsiteli, Néhémie T; Tchinda, Alembert T; Agbor, Gabriel A; Ntsama, Claudine; Tchounwou, Paul B

2015-08-01

A majority of Africans rely on traditional medicine as the primary form of health care. Yet most traditional medicine products have a short shelf life, especially for water-based formulations such as macerations, infusions and decoctions. Indeed, many of these water extracts become unfit for human consumption after five to seven days of conservation either because of the degradation or toxicity of active components, and/or the growth of pathogenic organisms. The purpose of this study was to describe and apply a new approach for the development of an improved traditional medicine (ITM) that is cheap, very efficient, not toxic, and easy to produce, and that can be conserved for a longer time without a significant loss of activity. Hence, Laportea ovalifolia was selected from an ethnobotanical prospection in all regions of Cameroon, and was used to prepare an oral hypoglycemic product. This preparation required 9 steps focused on the characterization of the plant species, and the standardization of the ethnopharmacological preparation by a multidisciplinary team of scientists with expertise in botany, ecology, pharmacognosy and pharmacology. Resultantly, four galenic formulations of hypoglycemic medications were produced. A relationship between these four formulations was described as follow: One spoon of oral suspension (10 ml)=one sachet of powder=2 tablets=3 capsules. Hence, our research provides new insight into a drug discovery approach that could alleviate the major problems affecting traditional medicine and enhance its effectiveness in addressing health care in developing and undeveloped countries.

Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats.

PubMed

Erejuwa, O O; Sulaiman, S A; Wahab, M S; Sirajudeen, K N S; Salleh, M S Md; Gurtu, S

2010-09-01

Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas. Copyright 2010 Elsevier Masson SAS. All rights reserved.

History of diabetes mellitus.

PubMed

Ahmed, Awad M

2002-04-01

Clinical features similar to diabetes mellitus were described 3000 years ago by the ancient Egyptians. The term "diabetes" was first coined by Araetus of Cappodocia (81-133AD). Later, the word mellitus (honey sweet) was added by Thomas Willis (Britain) in 1675 after rediscovering the sweetness of urine and blood of patients (first noticed by the ancient Indians). It was only in 1776 that Dobson (Britain) firstly confirmed the presence of excess sugar in urine and blood as a cause of their sweetness. In modern time, the history of diabetes coincided with the emergence of experimental medicine. An important milestone in the history of diabetes is the establishment of the role of the liver in glycogenesis, and the concept that diabetes is due to excess glucose production Claude Bernard (France) in 1857. The role of the pancreas in pathogenesis of diabetes was discovered by Mering and Minkowski (Austria) 1889. Later, this discovery constituted the basis of insulin isolation and clinical use by Banting and Best (Canada) in 1921. Trials to prepare an orally administrated hypoglycemic agent ended successfully by first marketing of tolbutamide and carbutamide in 1955. This report will also discuss the history of dietary management and acute and chronic complications of diabetes.

Vildagliptin, a DPP4 inhibitor, alleviates diabetes-associated cognitive deficits by decreasing the levels of apoptosis-related proteins in the rat hippocampus.

PubMed

Zhang, Dan-Dan; Shi, Nan; Fang, Hui; Ma, Liang; Wu, Wei-Ping; Zhang, Ya-Zhong; Tian, Jin-Li; Tian, Luo-Bing; Kang, Kang; Chen, Si

2018-06-01

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3β signaling pathway.

SGLT2-I in the Hospital Setting: Diabetic Ketoacidosis and Other Benefits and Concerns.

PubMed

Levine, Joshua A; Karam, Susan L; Aleppo, Grazia

2017-07-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents. They are increasingly being prescribed in the outpatient diabetic population. In this review, we examine the risks and benefits of continuation and initiation of SGLT2 inhibitors in the inpatient setting. There are currently no published data regarding safety and efficacy of SGLT2 inhibitor use in the hospital. Outpatient data suggests that SGLT2 inhibitors have low hypoglycemic risk. They also decrease systolic blood pressure and can prevent cardiovascular death. The EMPA-REG study also showed a decrease in admissions for acute decompensated heart failure. There have been increasing cases of diabetic ketoacidosis, and specifically the euglycemic manifestation, associated with SGLT2 inhibitors use. We present two cases of inpatient SGLT2 inhibitor use, one of continuation of outpatient therapy and one of new initiation of therapy. We then discuss potential risks and methods to mitigate these as well as benefits of these medications in the inpatient setting. We cautiously suggest the use of SGLT2 inhibitors in the hospital. However, these must be used judiciously and the practitioner must be aware of euglycemic diabetic ketoacidosis and its risk factors in this population.

Pattern of pharmaceutical retailing of anti-diabetic products in Ibadan, Nigeria.

PubMed

Famuyiwa, O O

1991-01-01

Twenty-four pharmacists in the city of Ibadan were surveyed through a self-administered structured questionnaire as to the extent of their involvement in the pharmaceutical retailing of antidiabetic products and their cost. Oral hypoglycemic agents especially, chlorpropamide (Diabenese) and glibenclamide (Daonil) were the most readily available drugs being obtainable from 21 (87.5%) pharmacies. Insulin was stocked regularly by only 14 (58.3%) of the pharmacists and insulin syringes and needles could be obtained from only 10 (41.6%) of the pharmacies. Among materials for urine testing, clinistix strip was the most readily available and fully one-third of the pharmacies did not stock any such material. The prices of all the products were disturbingly high and between 1983 and 1986 when retail prices were re-assessed, the cost of some materials had escalated by as much as 400%. Scarcity of antidiabetic products and their high cost pose serious challenges for those involved in the care of diabetic patients in Nigeria. Some suggestions have been made as to what steps both the government and the pharmaceutical industry can take in ensuring the availability of these life sustaining products for the increasingly large Nigerian diabetic population.

Self-management support for insulin therapy in type 2 diabetes.

PubMed

Funnell, Martha M; Kruger, Davida F; Spencer, Mary

2004-01-01

The purpose of this article is to describe the self-management support that can be provided by diabetes educators for type 2 diabetes patients who are transitioning from therapy with oral hypoglycemic agents to insulin. The role of the diabetes educator in patient education and self-management support during all aspects of insulin therapy is discussed. Phases during which support may be especially important include the decision-making process, initiation, and maintenance. Although some patients make the decision fairly easily, the introduction of insulin therapy is likely to raise many issues and questions for many type 2 diabetes patients. The more reluctant patients may experience psychological insulin resistance, a syndrome where insulin therapy is viewed as a threat or failure, which can affect health professionals as well. The diabetes educator can provide support and approaches to help diminish this resistance and make the transition to insulin therapy easier and more effective for patients with type 2 diabetes. Education and ongoing self-management support are needed for informed decision making and the initiation and maintenance of insulin therapy. Therefore, diabetes educators have a critical role to play during both the decision-making process and the safe transition to insulin therapy.

Natural products used for diabetes.

PubMed

Shapiro, Karen; Gong, William C

2002-01-01

To review the efficacy and safety of natural products commonly used for diabetes. English and Spanish-language journals retrieved through a MEDLINE search of articles published between 1960 and December 2001 using these index terms: Opuntia, karela, gymnema, tecoma, alpha lipoic acid, thioctic acid, ginseng, panaxans, and diabetes. Natural products have long been used in traditional systems of medicine for diabetes. Products in common use include nopal (prickly pear cactus), fenu-greek, karela (bitter melon), gymnema, ginseng, tronadora, chromium, and alpha-lipoic acid. The popularity of these products varies among people of different ethnicities. Nopal is the most commonly used herbal hypoglycemic among persons of Mexican descent. Karela is more commonly used by persons from Asian countries. Some of these agents have gained universal appeal. For a select number of products, studies have revealed single or multiple mechanisms of action. For several of these, high soluble fiber content is a contributing factor. Based on the available evidence, several natural products in common use can lower blood glucose in patients with diabetes. Commonly used natural products often have a long history of traditional use, and pharmacists who have a stronger understanding of these products are better positioned to counsel patients on their appropriate use.

Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent.

PubMed

Navarrete-Vázquez, Gabriel; Alaniz-Palacios, Alfredo; Hidalgo-Figueroa, Sergio; González-Acevedo, Cristina; Ávila-Villarreal, Gabriela; Estrada-Soto, Samuel; Webster, Scott P; Medina-Franco, José L; López-Vallejo, Fabian; Guerrero-Álvarez, Jorge; Tlahuext, Hugo

2013-06-01

A tetrazole isosteric analogue of clofibric acid (1) was prepared using a short synthetic route and was characterized by elemental analysis, NMR ((1)H, (13)C) spectroscopy, and single-crystal X-ray diffraction. The in vitro inhibitory activity of 1 against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was evaluated, showing a moderate inhibitory enzyme activity (51.17% of inhibition at 10 μM), being more active than clofibrate and clofibric acid. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus rat model. The results indicated a significant decrease of plasma glucose levels, during the 7h post-administration. Additionally, we performed a molecular docking of 1 into the ligand binding pocket of one subunit of human 11β-HSD1. In this model, compound 1 binds into the catalytic site of 11β-HSD1 in two different orientations. Both of them, show important short contacts with the catalytic residues Ser 170, Tyr 183, Asp 259 and also with the nicotinamide ring of NADP(+). Copyright © 2013 Elsevier Ltd. All rights reserved.

Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes.

PubMed

Nakahara, Takeshi; Mitoma, Chikage; Hashimoto-Hachiya, Akiko; Takahara, Masakazu; Tsuji, Gaku; Uchi, Hiroshi; Yan, Xianghong; Hachisuka, Junichi; Chiba, Takahito; Esaki, Hitokazu; Kido-Nakahara, Makiko; Furue, Masutaka

2015-10-01

Opuntia ficus-indica (OFI) is a cactus species widely used as an anti-inflammatory, antilipidemic, and hypoglycemic agent. It has been shown that OFI extract (OFIE) inhibits oxidative stress in animal models of diabetes and hepatic disease; however, its antioxidant mechanism remains largely unknown. In this study, we demonstrated that OFIE exhibited potent antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and the downstream antioxidant enzyme quinone oxidoreductase 1 (NQO1), which inhibited the generation of reactive oxygen species in keratinocytes challenged with tumor necrosis factor α or benzo[α]pyrene. The antioxidant capacity of OFIE was canceled in NRF2 knockdown keratinocytes. OFIE exerted this NRF2-NQO1 upregulation through activation of the aryl hydrocarbon receptor (AHR). Moreover, the ligation of AHR by OFIE upregulated the expression of epidermal barrier proteins: filaggrin and loricrin. OFIE also prevented TH2 cytokine-mediated downregulation of filaggrin and loricrin expression in an AHR-dependent manner because it was canceled in AHR knockdown keratinocytes. Antioxidant OFIE is a potent activator of AHR-NRF2-NQO1 signaling and may be beneficial in treating barrier-disrupted skin disorders.

Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro.

PubMed

Broadhurst, C L; Polansky, M M; Anderson, R A

2000-03-01

To evaluate the possible effects on insulin function, 49 herb, spice, and medicinal plant extracts were tested in the insulin-dependent utilization of glucose using a rat epididymal adipocyte assay. Cinnamon was the most bioactive product followed by witch hazel, green and black teas, allspice, bay leaves, nutmeg, cloves, mushrooms, and brewer's yeast. The glucose oxidation enhancing bioactivity was lost from cinnamon, tea, witch hazel, cloves, bay leaf and allspice by poly(vinylpyrrolidone) (PVP) treatment, indicating that the active phytochemicals are likely to be phenolic in nature. The activity of sage, mushrooms, and brewers's yeast was not removed by PVP. Some products such as Korean ginseng, flaxseed meal, and basil have been reported to be effective antidiabetic agents; however, they were only marginally active in our assay. Our technique measures direct stimulation of cellular glucose metabolism, so it may be that the active phytochemicals in these plants improve glucose metabolism via other mechanisms or that this in vitro screening is not a reliable predictor of hypoglycemic effects in vivo for some products. In summary, the positive effects of specific plant extracts on insulin activity suggest a possible role of these plants in improving glucose and insulin metabolism.

Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria

PubMed Central

Jauregui, Alexandra; Mintz, Daniel H; Mundel, Peter; Fornoni, Alessia

2010-01-01

Purpose of review In diabetic nephropathy (DN), insulin resistance and hyperinsulinemia correlate with the development of albuminuria. The possibility that altered insulin signaling in glomerular cells and particularly podocytes contributes to the development of DN will be discussed. Recent findings While normal podocytes uptake glucose in response to insulin, diabetic podocytes become insulin resistant in experimental DN prior to the development of significant albuminuria. Both clinical and experimental data suggest that insulin sensitizers may be renoprotective independently of their systemic effects on the metabolic control of diabetes. Summary We will review the clinical and experimental evidence that altered insulin signaling correlates with the development of DN in both type 1 and type 2 diabetes, and that insulin sensitizers may be superior to other hypoglycemic agents in the prevention of DN. We will then review potential mechanisms by which altered podocyte insulin signaling may contribute to the development of DN. Understanding the role of podocyte in glucose metabolism is important because it may lead to the discovery of novel pathogenetic mechanisms of DN, it may affect current strategies for prevention and treatment of DN, and it may allow for the identification of novel therapeutic targets. PMID:19724224

An unusual case of adolescent type 2 diabetes mellitus: Prader–Willi syndrome

PubMed Central

Basheer, Riyas; Jalal, Muhammed Jasim Abdul; Gomez, Ramesh

2016-01-01

Prader–Willi syndrome (PWS) is a complex genetic disorder, characterized by neonatal hypotonia, developmental delay, short stature, childhood obesity, hypogonadism, and characteristic facial features. Here we report a 21-year-old male who presented with uncontrolled glycemic status. He was diagnosed to have diabetes mellitus at the age of 15 with osmotic symptoms – polyuria, polydipsia, and polyphagia. In the early period, after diagnosis, his blood sugars were reasonably controlled with oral hypoglycemic agents. However, a year back, he was switched onto insulin therapy due to secondary OHA failure. On examination, his body mass index was 36 kg/m2. He had bilateral gynecomastia, decreased biparietal diameter, almond shaped eyes with esotropia. He had hypogonadism and also had mild cognitive impairment. He did not have any proximal myopathy or other focal neurological deficits. Hormonal evaluation showed low testosterone and inappropriately normal fluorescence in situ hybridization suggestive of central hypogonadism. With fetal and neonatal hypotonia, delayed developmental milestones, hypogonadism, and early onset diabetes, he fulfilled the clinical criteria for the diagnosis of PWS. Multidisciplinary approach of clinicians together with family and social support are essential to bring out the optimal outcome for such syndromic cases. PMID:27453871

A Clinical Practice Guideline to Guide a System Approach to Diabetes Care in Hong Kong

PubMed Central

2017-01-01

The Hospital Authority of Hong Kong is a statutory body that manages all the public medical care institutions in Hong Kong. There are currently around 400,000 diabetic patients under its care at 17 hospitals (providing secondary care for 40%) and 73 General Outpatient Clinics (providing primary care for 60%). The patient population has been growing at 6% to 8% per year over the past 5 years, estimated to include over 95% of all diagnosed patients in Hong Kong. In order to provide equitable and a minimal level of care within resources and local system factors constraints, a Clinical Practice Guideline on the management of type 2 diabetes mellitus was drawn in 2013 to guide a system approach to providing diabetes care. There is an algorithm for the use of various hypoglycemic agents. An organizational drug formulary governs that less expansive options have to be used first. A number of clinical care and patient empowerment programs have been set up to support structured and systematic diabetes care. With such a system approach, there have been overall improvements in diabetes care with the percentage of patients with glycosylated hemoglobin <7% rising from 40% in 2010 to 52% in 2015. PMID:28447435

Chemical and Biological Aspects of Extracts from Medicinal Plants with Antidiabetic Effects

PubMed Central

Gushiken, Lucas F.; Beserra, Fernando P.; Rozza, Ariane L.; Bérgamo, Patrícia L.; Bérgamo, Danilo A.; Pellizzon, Claudia H.

2016-01-01

Diabetes mellitus is a chronic disease and a leading cause of death in western countries. Despite advancements in the clinical management of the disease, it is not possible to control the late complications of diabetes. The main characteristic feature of diabetes is hyperglycemia, which reflects the deterioration in the use of glucose due to a faulty or poor response to insulin secretion. Alloxan and streptozotocin (STZ) are the chemical tools that are most commonly used to study the disease in rodents. Many plant species have been used in ethnopharmacology or to treat experimentally symptoms of this disease. When evaluated pharmacologically, most of the plants employed as antidiabetic substances have been shown to exhibit hypoglycemic and antihyperglycemic activities, and to contain chemical constituents that may be used as new antidiabetic agents. There are many substances extracted from plants that offer antidiabetic potential, whereas others may result in hypoglycemia as a side effect due to their toxicity, particularly their hepatotoxicity. In this article we present an updated overview of the studies on extracts from medicinal plants, relating the mechanisms of action by which these substances act and the natural principles of antidiabetic activity. PMID:28012277

Hibiscus sabdariffa leaf polyphenolic extract induces human melanoma cell death, apoptosis, and autophagy.

PubMed

Chiu, Chun-Tang; Hsuan, Shu-Wen; Lin, Hui-Hsuan; Hsu, Cheng-Chin; Chou, Fen-Pi; Chen, Jing-Hsien

2015-03-01

Melanoma is the least common but most fatal form of skin cancer. Previous studies have indicated that an aqueous extract of Hibiscus sabdariffa leaves possess hypoglycemic, hypolipidemic, and antioxidant effects. In this study, we want to investigate the anticancer activity of Hibiscus leaf polyphenolic (HLP) extract in melanoma cells. First, HLP was exhibited to be rich in epicatechin gallate (ECG) and other polyphenols. Apoptotic and autophagic activities of HLP and ECG were further evaluated by DAPI stain, cell-cycle analysis, and acidic vascular organelle (AVO) stain. Our results revealed that both HLP and ECG induced the caspases cleavages, Bcl-2 family proteins regulation, and Fas/FasL activation in A375 cells. In addition, we also revealed that the cells presented AVO-positive after HLP treatments. HLP could increase the expressions of autophagy-related proteins autophagy-related gene 5 (ATG5), Beclin1, and light chain 3-II (LC3-II), and induce autophagic cell death in A375 cells. These data indicated that the anticancer effect of HLP, partly contributed by ECG, in A375 cells. HLP potentially could be developed as an antimelanoma agent. © 2015 Institute of Food Technologists®

Vildagliptin, a DPP4 inhibitor, alleviates diabetes-associated cognitive deficits by decreasing the levels of apoptosis-related proteins in the rat hippocampus

PubMed Central

Zhang, Dan-Dan; Shi, Nan; Fang, Hui; Ma, Liang; Wu, Wei-Ping; Zhang, Ya-Zhong; Tian, Jin-Li; Tian, Luo-Bing; Kang, Kang; Chen, Si

2018-01-01

Cognitive impairment is a prevalent but underestimated complication of diabetes, which can cause spatial memory and learning deficits. In the present study, a streptozotocin-induced type 2 diabetic rat model was employed to investigate the effects of vildagliptin, a new oral hypoglycemic agent that acts by inhibiting dipeptidyl peptidase-4, on diabetes-associated cognitive impairments, as well as the molecular mechanisms involved. The present findings demonstrated that vildagliptin treatment prevented memory impairment and decreased the apoptosis of hippocampal neurons. It also attenuated the abnormal expression of caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein in the diabetic model. Vildagliptin treatment also reversed diabetes-induced decreases in phosphorylated (p)-protein kinase B (Akt) and p-glycogen synthase kinase 3β (GSK3β), brain-derived neurotrophic factor and nerve growth factor expression levels. The results indicated that the administration of vildagliptin exerts a protective effect against cognitive deficits by decreasing the expression of apoptosis-related proteins in the hippocampus and that this protective effect was mediated via the Akt/GSK3β signaling pathway.

21 CFR 310.517 - Labeling for oral hypoglycemic drugs of the sulfonylurea class.

Code of Federal Regulations, 2012 CFR

2012-04-01

... cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on... vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who...

21 CFR 310.517 - Labeling for oral hypoglycemic drugs of the sulfonylurea class.

Code of Federal Regulations, 2013 CFR

2013-04-01

... cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on... vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who...

21 CFR 310.517 - Labeling for oral hypoglycemic drugs of the sulfonylurea class.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on... vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who...

21 CFR 310.517 - Labeling for oral hypoglycemic drugs of the sulfonylurea class.

Code of Federal Regulations, 2011 CFR

2011-04-01

... cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on... vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who...

21 CFR 310.517 - Labeling for oral hypoglycemic drugs of the sulfonylurea class.

Code of Federal Regulations, 2010 CFR

2010-04-01

... cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on... vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who...

Evaluation of extraction protocols for anti-diabetic phytochemical substances from medicinal plants.

PubMed

Okoduwa, Stanley Irobekhian Reuben; Umar, Ismaila A; James, Dorcas B; Inuwa, Hajara M; Habila, James D

2016-12-15

To examine the efficacy of three extraction techniques: Soxhlet-extraction (SE), cold-maceration (CM) and microwave-assisted-extraction (MAE) using 80% methanol as solvent. The study was performed on each of 50 g of Vernonia amygdalina (VA) and Occimum gratissimum (OG) leaves respectively. The percentage yield, duration of extraction, volume of solvent used, qualitative and quantitative phytoconstituents present was compared. The biological activities (hypoglycemic effect) were investigated using albino wistar rat model of diabetes mellitus ( n = 36) with a combined dose (1:1) of the two plants leaf extracts (250 mg/kg b.w.) from the three methods. The extracts were administered orally, once daily for 21 d. In this report, the percentage VA extract yield from MAE was highest (20.9% ± 1.05%) within 39 min using 250 mL of solvent, when compared to the CM (14.35% ± 0.28%) within 4320 min using 900 mL of solvent and SE (15.75% ± 0.71%) within 265 min using 500 mL of solvent. The percentage differences in OG extract yield between: MAE vs SE was 41.05%; MAE vs CM was 46.81% and SE vs CM was 9.77%. The qualitative chemical analysis of the two plants showed no difference in the various phytoconstituents tested, but differs quantitatively in the amount of the individual phytoconstituents, as MAE had significantly high yield ( P > 0.05) on phenolics, saponins and tannins. SE technique gave significantly high yield ( P > 0.05) on alkaloid, while CM gave significant high yield on flavonoids. The extracts from CM exhibited a significantly ( P > 0.05) better hypoglycemic activity within the first 14-d of treatment (43.3% ± 3.62%) when compared to MAE (36.5% ± 0.08%) and SE methods (33.3% ± 1.60%). However, the percentage hypoglycemic activity, 21 d post-treatment with 250 mg/kg b.w. extract from MAE was 72.6% ± 1.03% and it was more comparable to 10 mg/kg b.w. glibenclamide treated group (75.0% ± 0.73%), unlike the SE (69.5% ± 0.71%) and CM (69.1% ± 1.03%). CM technique produces extract with better hypoglycemic activity, whereas; MAE is a better option for high yield of phytoconstituents using less solvent within a short time.

Evaluation of extraction protocols for anti-diabetic phytochemical substances from medicinal plants

PubMed Central

Okoduwa, Stanley Irobekhian Reuben; Umar, Ismaila A; James, Dorcas B; Inuwa, Hajara M; Habila, James D

2016-01-01

AIM To examine the efficacy of three extraction techniques: Soxhlet-extraction (SE), cold-maceration (CM) and microwave-assisted-extraction (MAE) using 80% methanol as solvent. METHODS The study was performed on each of 50 g of Vernonia amygdalina (VA) and Occimum gratissimum (OG) leaves respectively. The percentage yield, duration of extraction, volume of solvent used, qualitative and quantitative phytoconstituents present was compared. The biological activities (hypoglycemic effect) were investigated using albino wistar rat model of diabetes mellitus (n = 36) with a combined dose (1:1) of the two plants leaf extracts (250 mg/kg b.w.) from the three methods. The extracts were administered orally, once daily for 21 d. RESULTS In this report, the percentage VA extract yield from MAE was highest (20.9% ± 1.05%) within 39 min using 250 mL of solvent, when compared to the CM (14.35% ± 0.28%) within 4320 min using 900 mL of solvent and SE (15.75% ± 0.71%) within 265 min using 500 mL of solvent. The percentage differences in OG extract yield between: MAE vs SE was 41.05%; MAE vs CM was 46.81% and SE vs CM was 9.77%. The qualitative chemical analysis of the two plants showed no difference in the various phytoconstituents tested, but differs quantitatively in the amount of the individual phytoconstituents, as MAE had significantly high yield (P > 0.05) on phenolics, saponins and tannins. SE technique gave significantly high yield (P > 0.05) on alkaloid, while CM gave significant high yield on flavonoids. The extracts from CM exhibited a significantly (P > 0.05) better hypoglycemic activity within the first 14-d of treatment (43.3% ± 3.62%) when compared to MAE (36.5% ± 0.08%) and SE methods (33.3% ± 1.60%). However, the percentage hypoglycemic activity, 21 d post-treatment with 250 mg/kg b.w. extract from MAE was 72.6% ± 1.03% and it was more comparable to 10 mg/kg b.w. glibenclamide treated group (75.0% ± 0.73%), unlike the SE (69.5% ± 0.71%) and CM (69.1% ± 1.03%). CONCLUSION CM technique produces extract with better hypoglycemic activity, whereas; MAE is a better option for high yield of phytoconstituents using less solvent within a short time. PMID:28031778

Ventromedial Hypothalamic Nitric Oxide Production Is Necessary for Hypoglycemia Detection and Counterregulation

PubMed Central

Fioramonti, Xavier; Marsollier, Nicolas; Song, Zhentao; Fakira, Kurt A.; Patel, Reema M.; Brown, Stacey; Duparc, Thibaut; Pica-Mendez, Arnaldo; Sanders, Nicole M.; Knauf, Claude; Valet, Philippe; McCrimmon, Rory J.; Beuve, Annie; Magnan, Christophe; Routh, Vanessa H.

2010-01-01

OBJECTIVE The response of ventromedial hypothalamic (VMH) glucose-inhibited neurons to decreased glucose is impaired under conditions where the counterregulatory response (CRR) to hypoglycemia is impaired (e.g., recurrent hypoglycemia). This suggests a role for glucose-inhibited neurons in the CRR. We recently showed that decreased glucose increases nitric oxide (NO) production in cultured VMH glucose-inhibited neurons. These in vitro data led us to hypothesize that NO release from VMH glucose-inhibited neurons is critical for the CRR. RESEARCH DESIGN AND METHODS The CRR was evaluated in rats and mice in response to acute insulin-induced hypoglycemia and hypoglycemic clamps after modulation of brain NO signaling. The glucose sensitivity of ventromedial nucleus glucose-inhibited neurons was also assessed. RESULTS Hypoglycemia increased hypothalamic constitutive NO synthase (NOS) activity and neuronal NOS (nNOS) but not endothelial NOS (eNOS) phosphorylation in rats. Intracerebroventricular and VMH injection of the nonselective NOS inhibitor NG-monomethyl-l-arginine (l-NMMA) slowed the recovery to euglycemia after hypoglycemia. VMH l-NMMA injection also increased the glucose infusion rate (GIR) and decreased epinephrine secretion during hyperinsulinemic/hypoglycemic clamp in rats. The GIR required to maintain the hypoglycemic plateau was higher in nNOS knockout than wild-type or eNOS knockout mice. Finally, VMH glucose-inhibited neurons were virtually absent in nNOS knockout mice. CONCLUSIONS We conclude that VMH NO production is necessary for glucose sensing in glucose-inhibited neurons and full generation of the CRR to hypoglycemia. These data suggest that potentiating NO signaling may improve the defective CRR resulting from recurrent hypoglycemia in patients using intensive insulin therapy. PMID:19934009

Change in hexose distribution volume and fractional utilization of ( sup 18 F)-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, E.T.; Cooper, M.; Chen, C.T.

1990-02-01

We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-minmore » period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi (18F)-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM.« less

Hindbrain lactate regulates preoptic gonadotropin-releasing hormone (GnRH) neuron GnRH-I protein but not AMPK responses to hypoglycemia in the steroid-primed ovariectomized female rat.

PubMed

Shrestha, P K; Briski, K P

2015-07-09

Steroid positive-feedback activation of the gonadotropin-releasing hormone (GnRH)-pituitary luteinizing hormone (LH) neuroendocrine axis propagates the pre ovulatory LH surge, a crucial component of female reproduction. Our work shows that this key event is restrained by inhibitory metabolic input from hindbrain A2 noradrenergic neurons. GnRH neurons express the ultra-sensitive energy sensor adenosine 5'-monophosphate-activated protein kinase (AMPK); here, we investigated the hypothesis that GnRH nerve cell AMPK and peptide neurotransmitter responses to insulin-induced hypoglycemia are controlled by hindbrain lack of the oxidizable glycolytic end-product L-lactate. Data show that hypoglycemic inhibition of LH release in steroid-primed ovariectomized female rats was reversed by coincident caudal hindbrain lactate infusion. Western blot analyses of laser-microdissected A2 neurons demonstrate hypoglycemic augmentation [Fos, estrogen receptor-beta (ER-β), phosphoAMPK (pAMPK)] and inhibition (dopamine-beta-hydroxylase, GLUT3, MCT2) of protein expression in these cells, responses that were normalized by insulin plus lactate treatment. Hypoglycemia diminished rostral preoptic GnRH nerve cell GnRH-I protein and pAMPK content; the former, but not the latter response was reversed by lactate. Results implicate caudal hindbrain lactoprivic signaling in hypoglycemia-induced suppression of the LH surge, demonstrating that lactate repletion of that site reverses decrements in A2 catecholamine biosynthetic enzyme and GnRH neuropeptide precursor protein expression. Lack of effect of lactate on hypoglycemic patterns of GnRH AMPK activity suggests that this sensor is uninvolved in metabolic-inhibition of positive-feedback-stimulated hypophysiotropic signaling to pituitary gonadotropes. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Empowerment-Based Diabetes Self-Management Education to Maintain Glycemic Targets During Ramadan Fasting in People With Diabetes Who Are on Conventional Insulin: A Feasibility Study

PubMed Central

Sahmoud, Sahar I.; Abdelsalam, Mona M.; Eichorst, Barbara

2017-01-01

Objective. This study aims to assess the feasibility of promoting safe Ramadan fasting through diabetes self-management education (DSME) and to determine the effect of such education on hypoglycemic episodes. Design and methods. This prospective study included subjects attending Ramadan reinforcement sessions for participants in the Educational Program for People with Diabetes (EPPWD) at the Ain-Shams University Diabetes Center in Cairo, Egypt. The DSME sessions started 2–3 weeks before Ramadan and included one experimental fasting day during the first week and one during the second week. Participants’ A1C and serum fructosamine levels were measured before and after Ramadan, and they completed weekly self-monitoring of blood glucose (SMBG) logs. Results. Among 21 participants who were intending to fast for Ramadan, 14 completed the program. Their mean A1C was 6.7 ± 1.6%, and SMBG results showed a statistically nonsignificant difference in mean blood glucose levels before and after Ramadan (123.84 ± 39.96 and 123.84 ± 25.92 mg/dL, respectively; P >0.05). Serum fructosamine after Ramadan declined by 10% from pre-Ramadan levels. The mean number of hypoglycemic events before Ramadan was 3 ± 1.04, which declined to 1.4 ± 0.5 during Ramadan. Differences between group 1 (those without hypoglycemia, n = 8) and group 2 (those with hypoglycemia, n = 6) were nonsignificant for all variables, including A1C. Conclusion. Ramadan fasting is feasible for people with diabetes who are on a multiple daily injection insulin regimen and participate in the EPPWD. The number of hypoglycemic events per month declined with the attainment of DSME. PMID:28270713

Impact of recurrent hypoglycemic stress on hindbrain A2 nerve cell energy metabolism and catecholamine biosynthesis: modulation by estradiol.

PubMed

Tamrakar, Pratistha; Briski, Karen P

2017-01-01

It is unclear if habituation of hindbrain A2 metabolo‑sensory neurons to recurrent insulin-induced hypoglycemia (RIIH) correlates with estradiol-dependent adjustments in energy metabolism that favor positive energy balance. Laser-microdissected A2 cells from estradiolor oil-implanted ovariectomized female rats were analyzed by Western blot to assess effects of three prior daily insulin injections on basal and hypoglycemic patterns of catecholamine biosynthetic enzyme dopamine-beta-hydroxylase (DβH) and rate-limiting energy pathway enzyme protein expression. Precedent hypoglycemia respectively decreased or increased baseline DβH expression in estradiol- (E) vs. oil (O)-treated rats; this protein profile was further suppressed or augmented in those animals at 2 hr after re-induction of hypoglycemia. These data suggest that estradiol may curtail A2 noradrenergic‑controlled functions both in the midst of and between hypoglycemic bouts. Results also show that prior hypoglycemia exposure upregulated A2 neuron glycolytic enzyme protein levels when E was present, and exerted differential effects on basal and hypoglycemia-associated respiratory chain and fatty acid synthetic pathway enzyme expression. E may thus accordingly amplify glycolysis-derived metabolites/energy, coupled with reduced reliance on oxidative phosphorylation, and activate the fatty acid synthetic pathway during RIIH. E may also be of benefit by preventing maladaptive reductions in A2 neuron Krebs cycle/electron transport enzyme expression during re-exposure to hypoglycemia. Augmentation of negative energy balance during this recurring metabolic stress in the absence of E is a likely impetus for augmented vs. decreased A2 signaling of energy imbalance by DβH in O vs. E rats during RIIH.

Evaluation of the influence of blood glucose level on oral candidal colonization in complete denture wearers with Type-II Diabetes Mellitus: An in vivo Study.

PubMed

Ganapathy, Dhanraj Muthuveera; Joseph, Sajeesh; Ariga, Padma; Selvaraj, Anand

2013-01-01

Candidal colonization in complete denture wearers is a commonly encountered condition that worsens in the presence of untreated Diabetes Mellitus. The aim of this study was to evaluate the correlation between oral candidiasis in denture-bearing mucosa and elevated blood glucose levels in complete denture wearers and to evaluate the effect of oral hypoglycemic drug therapy in controlling oral candidal colonization in denture-bearing mucosa of complete denture wearers with Type II Diabetes Mellitus. This prospective observational study involved the participation of 15 complete denture wearers with Type II Diabetes Mellitus. The sample collection was made prior and after oral hypoglycaemic drug intervention, by swabbing the rugal surfaces of palatal mucosa, cultured and the density of the candidal colony formed was analyzed and interpreted as colony forming units (CFU) per mL. The candidal samples CFU and corresponding pre- and post-prandial blood glucose levels were estimated, analyzed and compared using Karl Pearson correlation analysis and paired t-test (α = 0.05). The Karl Pearson correlation analysis showed that there was a positive correlation between the blood glucose levels (PPS and FBS) and the candidal colonization (CFU) (P < 0.05). The mean values of all the variables were analyzed using the paired t-test. There was significant reduction in the mean values of blood glucose levels (P < 0.001) and the mean values of the CFU (P < 0.001) following oral hypoglycemic drug therapy. Positive correlation was observed between oral candidiasis in complete denture-bearing mucosa and elevated blood glucose levels and oral hypoglycemic drug therapy has a positive effect in controlling oral candidal colonization in complete denture wearers with Type II Diabetes Mellitus.

Cost-effectiveness of sensor-augmented pump therapy versus standard insulin pump therapy in patients with type 1 diabetes in Denmark.

PubMed

Roze, S; de Portu, S; Smith-Palmer, J; Delbaere, A; Valentine, W; Ridderstråle, M

2017-06-01

The use of continuous subcutaneous insulin infusion (CSII) in type 1 diabetes (T1D) has increased in recent years. Sensor-augmented pump therapy (SAP) with low glucose suspend (LGS) (allowing temporary suspension of insulin delivery if blood glucose level falls below a pre-defined threshold level) provides additional benefits over CSII alone, but is associated with higher acquisition costs. Therefore, a cost-effectiveness analysis of SAP+LGS versus CSII in patients with T1D was performed. Analyses were performed using the CORE Diabetes Model in two different patient cohorts in Denmark, one with hyperglycemia at baseline and one with increased risk for hypoglycemic events. Clinical input data were sourced from published literature. The analysis was performed over a lifetime time horizon from a societal perspective. Future costs and clinical outcomes were discounted at 3% per annum. In patients who were hyperglycemic at baseline the use of SAP+LGS versus CSII resulted in improved quality-adjusted life expectancy (12.44 versus 10.99 quality-adjusted life years [QALYs]) but higher mean lifetime costs (DKK 2,027,316 versus DKK 1,801,293) leading to an incremental cost-effectiveness ratio (ICER) of DKK 156,082 per QALY gained. For patients at increased risk for hypoglycemic events the ICER for SAP+LGS versus CSII was DKK 89,868 per QALY gained. The ICER for SAP+LGS versus CSII falls below commonly cited willingness-to-pay thresholds. Therefore, in Denmark, the use of SAP+LGS is likely to be considered cost-effective relative to CSII for patients with T1D who are either hyperglycemic, despite CSII use, or who experience frequent severe hypoglycemic events. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences in self-monitored, blood glucose test strip utilization by therapy for type 2 diabetes mellitus.

PubMed

Tavares, Ruben; Duclos, Marc; Brabant, Marie-Josée; Checchin, Daniella; Bosnic, Nevzeta; Turvey, Katherine; Terres, Jorge Alfonso Ross

2016-06-01

To determine whether blood glucose test strip (BGTS) utilization in patients with type 2 diabetes (T2D) is associated with the type of diabetes therapy, classified according to hypoglycemic risk. A retrospective, longitudinal (2006-2012) study of Canadian private drug plans (PDP) and Ontario Public Drug Programs (OPDP) prescription claims was conducted. Analyses were restricted to patients with T2D with or without a claim for BGTS. Daily BGTS utilization (TS/patient/day) was evaluated by diabetes therapy classified by hypoglycemic risk. Multivariate analyses were conducted to identify determinants of BGTS utilization. The T2D cohort comprised 5,759,591 observations from 1,949,129 claimants. Mean BGTS utilization was 0.84 TS/patient/day and differed between PDP and OPDP (0.66 vs. 1.00). Daily utilization was greatest in patients receiving therapy associated with a pre-defined high risk of hypoglycemia [insulin: basal + bolus (2.16), premixed (1.65), basal (1.16), other insulin regimens (2.13), and sulfonylureas (0.74)] versus non-sulfonylurea non-insulin-based regimens (0.52). For non-insulin therapy, BGTS utilization was greater for patients on multiple non-insulin therapies versus monotherapy (0.74 vs. 0.53 TS/patient/day). In multivariate analyses, drivers for BGTS utilization included insulin use, previous BGTS use, and female gender. Previous diabetes therapy and duration of therapy were negatively correlated with BGTS utilization. BGTS utilization varies depending on the type of therapy used to treat T2D according to hypoglycemic risk. Decision making regarding BGTS needs to account for robust analyses of current utilization and its value in those settings, including in patients not receiving diabetes therapy and the prevalence of circumstances conducive to more intensive monitoring.

HypoDE: Research Design and Methods of a Randomized Controlled Study Evaluating the Impact of Real-Time CGM Usage on the Frequency of CGM Glucose Values <55 mg/dl in Patients With Type 1 Diabetes and Problematic Hypoglycemia Treated With Multiple Daily Injections.

PubMed

Heinemann, Lutz; Deiss, Dorothee; Hermanns, Norbert; Graham, Claudia; Kaltheuner, Matthias; Liebl, Andreas; Price, David

2015-05-01

Systems for continuous glucose monitoring (CGM) have been available for a number of years, and numerous clinical studies have been performed with them. Interestingly, in many of these studies patients with an increased risk of hypoglycemic events were excluded. In addition, in most studies subjects were using a pump for insulin delivery. Therefore our knowledge about the benefit of CGM in patients employing multiple daily injections (MDI) of insulin is limited, especially when it comes to a reduction in the risk of low glucose events in high-risk individuals. We are planning to run a 26-week randomized controlled study in Germany (HypoDE, Hypoglycemia in Deutschland) that is focused on evaluating if such a reduction can be observed in patients on MDI with an increased risk of low glucose events. In all, 160 patients will participate in the study, randomized into the intervention group and control group. Ideally one would study if the frequency of severe hypoglycemic events is different between both groups. However, this would require such a large sample size and study duration, so for pragmatic reasons we will use low glucose levels <55 mg/dl (measured by CGM) for at least 20 minutes as a risk marker for severe hypoglycemic events. The results from the HypoDE study shall help determine the advantage of using CGM in subjects with type 1 diabetes with an increased risk of low glucose events treated with MDI. © 2015 Diabetes Technology Society.

The effects of abnormalities of glucose homeostasis on the expression and binding of muscarinic receptors in cerebral cortex of rats.

PubMed

Sherin, Antony; Peeyush, Kumar T; Naijil, George; Nandhu, Mohan Sobhana; Jayanarayanan, Sadanandan; Jes, Paul; Paulose, Cheramadathikudiyil Skaria

2011-01-25

Glucose homeostasis in humans is an important factor for the functioning of nervous system. Both hypo and hyperglycemia contributes to neuronal functional deficit. In the present study, effect of insulin induced hypoglycemia and streptozotocin induced diabetes on muscarinic receptor binding, cholinergic enzymes; AChE, ChAT expression and GLUT3 in the cerebral cortex of experimental rats were analysed. Total muscarinic, muscarinic M(1) receptor showed a significant decrease and muscarinic M(3) receptor subtype showed a significant increased binding in the cerebral cortex of hypoglycemic rats compared to diabetic and control. Real-Time PCR analysis of muscarinic M(1), M(3) receptor subtypes confirmed the receptor binding studies. Immunohistochemistry of muscarinic M(1), M(3) receptors using specific antibodies were also carried out. AChE and GLUT3 expression up regulated and ChAT expression down regulated in hypoglycemic rats compared to diabetic and control rats. Our results showed that hypo/hyperglycemia caused impaired glucose transport in neuronal cells as shown by altered expression of GLUT3. Increased AChE and decreased ChAT expression is suggested to alter cortical acetylcholine metabolism in experimental rats along with altered muscarinic receptor binding in hypo/hyperglycemic rats, impair cholinergic transmission, which subsequently lead to cholinergic dysfunction thereby causing learning and memory deficits. We observed a prominent cholinergic functional disturbance in hypoglycemic condition than in hyperglycemia. Hypoglycemia exacerbated the neurochemical changes in cerebral cortex induced by hyperglycemia. These findings have implications for both therapy and identification of causes contributing to neuronal dysfunction in diabetes. Copyright © 2010 Elsevier B.V. All rights reserved.

Patients' with type 2 diabetes willingness to pay for insulin therapy and clinical outcomes

PubMed Central

Feher, Michael D; Brazier, John; Schaper, Nicolaas; Vega-Hernandez, Gabriela; Bøgelund, Mette

2016-01-01

Objectives This study assessed patient preferences, using willingness to pay as a method to measure different treatment characteristics or attributes associated with injectable insulin therapy in patients with type 2 diabetes. Research design and methods Adults with type 2 diabetes in 12 countries, diagnosed >6 months prior and receiving insulin for >3 months, were recruited through a representative online panel. Data were collected via online questionnaire and analyzed using a standard choice model for discrete choice experiment. Results A total of 3758 patients from North America (n=646), South America (n=1537), and Europe (n=1575) completed the study. Mean glycated hemoglobin (HbA1c) levels in North America, South America, and Europe were 63 mmol/mol (7.9%), 75 mmol/mol (9.0%), and 64 mmol/mol (8.0%), respectively. In the three regions, monthly willingness to pay was US$116, US$74, and US$92, respectively, for a 1%-point decrease in HbA1c; US$99, US$80, and US$104 for one less major hypoglycemic event per year; and US$64, US$37 and US$60 for a 3 kg weight decrease. To avoid preinjection preparation of insulin, the respective values were US$47, US$18, and US$37, and US$25, US$25, and US$24 for one less injection per day. Among respondents on basal-only insulin who had previously tried a more intensive regimen, reasons for switching back included difficulty in handling multiple injections and risk of hypoglycemic events. Conclusions Reducing HbA1c, frequency of major hypoglycemic events and weight decrease were the highest valued outcomes in each region. The administrative burden of injections was also considered important. PMID:27158518

Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.

PubMed

Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G

2015-10-01

Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

PubMed Central

Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S; Nora, Mário; Gonçalves, Gil; Albrechtsen, Nicolai Wewer; Hartmann, Bolette; Holst, Jens Juul

2015-01-01

Summary Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were normal but octreotide scintigraphy showed a single focus of abnormal radiotracer uptake at the site of the nodule. There were no other clinical signs of hormone secreting pNET and gastrointestinal hormone measurements were not performed. The patient underwent surgical enucleation with complete remission of the hypoglycemic episodes. Histopathology revealed a well-differentiated neuroendocrine carcinoma with low-grade malignancy with positive chromogranin A and glucagon immunostaining. An extract of the resected tumor contained a high concentration of glucagon (26.707 pmol/g tissue), in addition to traces of GLP1 (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach to the post-bariatric surgery hypoglycemia patient. Learning points pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric surgery. PMID:26266036

Welltang - A smart phone-based diabetes management application - Improves blood glucose control in Chinese people with diabetes.

PubMed

Zhou, Weibin; Chen, Min; Yuan, Jingyun; Sun, Yan

2016-06-01

The primary objective was to evaluate the impact of the smart phone-based diabetes management application, Welltang, on glycated hemoglobin (HbA1c). The second objective was to measure whether Welltang improves blood glucose, low-density lipoprotein cholesterol, weight, blood pressure, hypoglycemic events, satisfaction of patients to use Welltang, diabetes knowledge of patients, and self-care behaviors. One hundred evenly randomized subjects with diabetes, aged 18-74years, were recruited from the outpatient Department of Endocrinology for a 3-month study. The Welltang intervention group received training for the use of Welltang, while the control group received their usual standard of care. HbA1c, blood glucose, low-density lipoprotein cholesterol, weight, blood pressure, hypoglycemic events, satisfaction of patients to use Welltang, diabetes knowledge of patients, and self-care behaviors were measured. Patient data were analyzed using independent t test and paired sample test using SPSS version 12. The average decrease in HbA1c was 1.95% (21mmol/mol) in the intervention group and 0.79% (8mmol/mol) in the control group (P<0.001). Measures of self-monitored blood glucose, diabetes knowledge, and self-care behaviors improved in patients in the intervention group. Eighty four percent of patients in the intervention group were satisfied with the use of Welltang. Differences in hypoglycemic events, low-density lipoprotein cholesterol, weight, and blood pressure were not statistically significant. Diabetes patients using the Welltang application achieved statistically significant improvements in HbA1c, blood glucose, satisfaction of patients to use of Welltang, diabetes knowledge, and self-care behaviors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Understanding the economic burden of nonsevere nocturnal hypoglycemic events: impact on work productivity, disease management, and resource utilization.

PubMed

Brod, Meryl; Wolden, Michael; Christensen, Torsten; Bushnell, Donald M

2013-12-01

Nonsevere hypoglycemic events are common and may occur in one-third of persons with diabetes as often as several times a week. This study's objective was to examine the economic burden of nonsevere nocturnal hypoglycemic events (NSNHEs). A 20-minute Web-based survey, with items derived from the literature, expert input, and patient interviews, assessing the impact of NSNHEs was administered in nine countries to 18 years and older patients with self-reported diabetes having an NSNHE in the past month. A total of 20,212 persons were screened, with 2,108 respondents meeting criteria and included in the analysis sample. The cost of lost work productivity per NSNHE was estimated to be between $10.21 (Germany) and $28.13 (the United Kingdom), representing 3.3 to 7.5 hours of lost work time per event. A reduction in work productivity (presenteeism) was also reported. Compared with respondents' usual blood sugar monitoring practice, on average, 3.6 ± 6.6 extra tests were conducted in the week following the event at a cost of approximately $87.1 per year. Additional costs were also incurred for doctor visits as well as medical care required because of falls or injuries incurred during the NSNHE for an annual cost of $2,111.3 per person per year. When taking into consideration the multiple impacts of NSNHEs for the total sample and the frequency that these events occur, the resulting total annual economic burden was $288,000 or $127 per person per event. NSNHEs have serious consequences for patients. Greater attention to treatments that reduce NSNHEs can have a major impact on reducing the economic burden of diabetes. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

The efficacy of black cumin seed (Nigella sativa) oil and hypoglycemic drug combination to reduce HbA1c level in patients with metabolic syndrome risk

NASA Astrophysics Data System (ADS)

Rachman, P. N. R.; Akrom; Darmawan, E.

2017-11-01

Metabolic syndrome is a conditions caused by metabolic abnormalities include central obesity, atherogenic dyslipidemia, hypertension, and insulin resistance. HbA1c examination is required to study the long-term glycemic status and to prevent diabetic complications of metabolic syndrome. The purpose of this study is to determine the efficacy of black cumin seed (Nigella sativa) oil and hypoglycemic drug combination to reduce HbA1c level in patients with metabolic syndrome risk. This research performed using an experimental randomized single - blind controlled trial design. A total of 99 outpatients at the Jetis I Public Health Center, Yogyakarta, Indonesia with metabolic syndrome risk were divided into three groups: The control group received placebo and two treatment groups received black seed oil orally at dose of 1.5 mL/day and 3 mL/day, respectively, for 20 days. The clinical conditions such as blood pressure, pulse rate, BMI, blood glucose serum and HbA1c levels were examined on day 0 and 21. The results obtained were analyzed with one-way ANOVA test. The mean of HbA1c levels of all groups before treatment was higher than the normal values and there was no significant difference in HbA1c value on day 0. Administration of 1.5 and 3 mL/day of black seed oil for 20 days decreased (p<0.05) HbA1c levels. It can be concluded that administration of black cumin seed oil and hypoglycemic drug combination for 20 days in patients at risk of metabolic syndrome may reduce to HbA1c levels.

Physician nutrition and cognition during work hours: effect of a nutrition based intervention.

PubMed

Lemaire, Jane B; Wallace, Jean E; Dinsmore, Kelly; Lewin, Adriane M; Ghali, William A; Roberts, Delia

2010-08-17

Physicians are often unable to eat and drink properly during their work day. Nutrition has been linked to cognition. We aimed to examine the effect of a nutrition based intervention, that of scheduled nutrition breaks during the work day, upon physician cognition, glucose, and hypoglycemic symptoms. A volunteer sample of twenty staff physicians from a large urban teaching hospital were recruited from the doctors' lounge. During both the baseline and the intervention day, we measured subjects' cognitive function, capillary blood glucose, "hypoglycemic" nutrition-related symptoms, fluid and nutrient intake, level of physical activity, weight, and urinary output. Cognition scores as measured by a composite score of speed and accuracy (Tput statistic) were superior on the intervention day on simple (220 vs. 209, p = 0.01) and complex (92 vs. 85, p < 0.001) reaction time tests. Group mean glucose was 0.3 mmol/L lower (p = 0.03) and less variable (coefficient of variation 12.2% vs. 18.0%) on the intervention day. Although not statistically significant, there was also a trend toward the reporting of fewer hypoglycemic type symptoms. There was higher nutrient intake on intervention versus baseline days as measured by mean caloric intake (1345 vs. 935 kilocalories, p = 0.008), and improved hydration as measured by mean change in body mass (+352 vs. -364 grams, p < 0.001). Our study provides evidence in support of adequate workplace nutrition as a contributor to improved physician cognition, adding to the body of research suggesting that physician wellness may ultimately benefit not only the physicians themselves but also their patients and the health care systems in which they work.

Continuous glucose monitoring in newborn infants: how do errors in calibration measurements affect detected hypoglycemia?

PubMed

Thomas, Felicity; Signal, Mathew; Harris, Deborah L; Weston, Philip J; Harding, Jane E; Shaw, Geoffrey M; Chase, J Geoffrey

2014-05-01

Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data. © 2014 Diabetes Technology Society.

A Human Glucagon-Like Peptide-1-albumin Recombinant Protein with Prolonged Hypoglycemic Effect Provides Efficient and Beneficial Control of Glucose Metabolism in Diabetic Mice.

PubMed

Li, Caina; Yang, Miaomiao; Hou, Guojiang; Liu, Shuainan; Huan, Yi; Yu, Dongan; Sun, Sujuan; Liu, Quan; Yan, Shousheng; Shen, Zhufang

2017-09-01

GW002 is a recombinant protein engineered by fusing the C-terminal region of human glucagon-like peptide-1 (GLP-1) to the N-terminal region of human serum albumin (HSA) with a peptide linker. This study aims to evaluate its anti-diabetic effects both in vitro and in vivo. The GLP-1 receptor-dependent luciferase reporter plasmid was transiently transfected in NIT-1 cells to calculate the half-maximal concentration (EC 50 ) for GLP-1 receptor activation, and normal ICR mice and diabetic KKAy mice were acutely injected with GW002 (1, 3, 9 mg/kg) subcutaneously to evaluate the hypoglycemic action, while the diabetic KKAy and db/db mice were treated with GW002 once daily for 7 weeks to evaluate the effects on glucose metabolism. The results showed that GW002 activated GLP-1 receptor in NIT-1 cells with higher EC 50 versus exendin-4 (46.7 vs. 7.89 nM), and single subcutaneous injection of GW002 at doses of 1, 3 and 9 mg/kg efficiently restrained the glycemia variation after oral glucose loading in ICR mice for at least 4 d, as well as reducing the non-fasting blood glucose in KKAy mice for about 2 d, while repeated injections of GW002 significantly improved abnormal glycaemia, hemoglobin (Hb)A1c levels, oral glucose intolerance and β-cell function in diabetic db/db mice. These results suggested that GW002 showed prolonged hypoglycemic action by activating its cognate receptor and provided efficient control of glucose metabolism. Thus GW002 may be a potential treatment for the management of type 2 diabetes.

Ultrasonic extraction of polysaccharides from Laminaria japonica and their antioxidative and glycosidase inhibitory activities

NASA Astrophysics Data System (ADS)

Wan, Peng; Yang, Xiaoman; Cai, Bingna; Chen, Hua; Sun, Huili; Chen, Deke; Pan, Jianyu

2015-08-01

In the present study, ultrasonic extraction technique (UET) is used to improve the yield of polysaccharides from Laminaria japonica (LJPs). And their antioxidative as well as glycosidase inhibitory activities are investigated. Box-Behnken design (BBD) combined with response surface methodology (RSM) is applied to optimize ultrasonic extraction for polysaccharides. The optimized conditions are obtained as extraction time at 54 min, ultrasonic power at 1050 W, extraction temperature at 80°C and ratio of material to solvent at 1:50 (g mL-1). Under these optimal ultrasonic extraction conditions, an actual experimental yield (5.75% ± 0.3%) is close to the predicted result (5.67%) with no significant difference ( P > 0.05). Vitro antioxidative and glycosidase inhibitory activities tests indicate that the crude polysaccharides (LJP) and two major ethanol precipitated fractions (LJP1 and LJP2) are in a concentration-dependent manner. LJP2 (30%-60% ethanol precipitated polysaccharides) possesses the strongest α-glucosidase inhibitory activity and moderate scavenging activity against hydroxyl radicals (66.09% ± 2.19%, 3.0 mg mL-1). Also, the inhibitory activity against α-glucosidase (59.08% ± 3.79%, 5.0 mg mL-1) is close to that of acarbose (63.99% ± 3.27%, 5.0 mg mL-1). LJP1 (30% ethanol precipitated polysaccharides) exhibits the strongest scavenging activity against hydroxyl radicals (99.80% ± 0.00%, 3.0 mg mL-1) and moderate α-glucosidase inhibitory activity (47.76% ± 1.92%, 5.0 mg mL-1). LJP shows the most remarkable DPPH scavenging activity (66.20% ± 0.11%, 5.0 mg mL-1) but weakest α-glucosidase inhibitory activity (37.77% ± 1.30%, 5.0 mg mL-1). However, all these LJPs exert weak inhibitory effects against α-amylase. These results show that UET is an effective method for extracting bioactive polysaccharides from seaweed materials. LJP1 and LJP2 can be developed as a potential ingredient in hypoglycemic agents or functional food for the management of diabetes. This study provides scientific evidence and advances in the preparation technology and a hypoglycemic activities evaluation method for seaweed polysaccharides, especially glycosidase inhibition in combination with an antioxidative activity evaluation method.

Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

PubMed Central

Lukashevich, Valentina; Schweizer, Anja; Foley, James E; Dickinson, Sheila; Groop, Per-Henrik; Kothny, Wolfgang

2013-01-01

Background The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2) and longstanding type 2 diabetes not adequately controlled with insulin therapy, which is a difficult-to-treat population, with limited therapeutic options and a high susceptibility to hypoglycemia. Methods This was a post hoc subanalysis of data obtained during a previously described randomized, double-blind, parallel-group, 24-week study comparing the efficacy and safety of vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m2, 100 randomized to vildagliptin, 78 randomized to placebo), all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent) for longstanding type 2 diabetes (mean approximately 19 years). Results With vildagliptin in combination with insulin, the adjusted mean change (AMΔ) in HbA1c from baseline (7.7% ± 0.1%) was −0.9% ± 0.4% and the between-treatment difference (vildagliptin – placebo) was −0.6% ± 0.2% (P < 0.001). The percentage of patients achieving endpoint HbA1c < 7.0% was significantly higher with vildagliptin than placebo (45.2% versus 22.8%, P = 0.008). When added to insulin, vildagliptin and placebo had comparable hypoglycemic profiles and did not cause weight gain. Both treatments were similarly well tolerated, with comparable incidences of adverse events, serious adverse events, and deaths. Conclusion When added to insulin therapy in patients with severe renal impairment and longstanding type 2 diabetes, vildagliptin 50 mg once daily was efficacious, eliciting HbA1c reductions consistent with those previously reported for a patient population with much more recent onset of type 2 diabetes and normal renal function, and had a hypoglycemic profile comparable with placebo. Accordingly, vildagliptin is a suitable treatment option for patients with advanced type 2 diabetes and impaired renal function who require insulin therapy and present a serious therapeutic challenge in clinical practice. PMID:23378769

New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2).

PubMed

Yki-Järvinen, Hannele; Bergenstal, Richard; Ziemen, Monika; Wardecki, Marek; Muehlen-Bartmer, Isabel; Boelle, Emmanuelle; Riddle, Matthew C

2014-12-01

To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes using basal insulin (≥42 units/day) plus oral antihyperglycemic drugs (OADs). EDITION 2 was a multicenter, open-label, two-arm study. Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point was change in HbA1c. The main secondary end point was percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemic events from week 9 to month 6. Randomized participants (n = 811) had a mean (SD) HbA₁c of 8.24% (0.82) and BMI of 34.8 kg/m(2) (6.4). Glycemic control improved similarly with both basal insulins; least squares mean (SD) reduction from baseline was -0.57% (0.09) for Gla-300 and -0.56% (0.09) for Gla-100 (mean difference -0.01% [95% CI -0.14 to 0.12]), with 10% higher dose of Gla-300. Less nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 (relative risk 0.77 [95% CI 0.61-0.99]; P = 0.038) and during the first 8 weeks. Fewer nocturnal and any time (24 h) hypoglycemic events were reported during the entire 6-month period. Weight gain was lower with Gla-300 than with Gla-100 (P = 0.015). No between-treatment differences in safety parameters were identified. Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Comparison of Glycemic Excursion in Patients with New Onset Type 2 Diabetes Mellitus before and after Treatment with Repaglinide.

PubMed

Hezarkhani, Sharabeh; Bonakdaran, Shokufeh; Rajabian, Reza; Shahini, Najmeh; Marjani, Abdoljalal

2013-01-01

Due to industrialization and sedentary life, incidence of type 2 diabetes (DM2) is increasing seriously. Repaglinide is a glucose reducing agent that predominantly reduces post-prandial glucose. Continuous glucose monitoring system (CGMS) monitors blood glucose excursions over a 3-day period. CGMS can be used as a therapeutic and diagnostic instrument in diabetics. There are not enough studies about using CGMS in DM2. The aim of this study was to determine the blood glucose excursions in patients with new onset of DM2. 10 patients with new onset of DM2 were entered to this study. As the first therapeutic management, patients received diabetic diet and moderate exercise for 3-weeks, if they did not achieve blood glucose goal (Fasting blood glucoser (FBG) <120mg/dl, 2-hour postprandial blood glucose (2hpp) <180mg/dl), were considered to undergo 3-days CGMS at baseline and after 4-weeks on Repaglinide (0.5mg three times before meals). Mean excursions of blood glucose were not different at the onset and at the end of treatment (6±4.05 VS 7.6±5.2 episodes, P=0.49). There were also no significant differences between mean duration of hypoglycemic episodes (zero VS 5.1±14.1 hours, P =0.28) and hyperglycemic episodes before and after therapy (7.6±5.2 VS 5.7±4.1, P=0.42), but mean hyperglycemia duration was significantly reduced at the end of therapy (21±26.17 VS 57.7±35.3, P=0.001). Patients experienced a mean of 0.3±0.67 episodes of hypoglycemia after therapy showed no significant difference before it (P =0.19). Mean FBG (with CGMS) was significantly lower after therapy than before it (142.9±54.31 VS 222.9±82.6, P <0.001). This study showed the usefulness of CGMS not only as a diagnostic but also as an educational and therapeutic tool that in combination with Repaglinide (with the lowest effective dose and duration) can significantly reduce FBG and glycemic excursions in DM2 patients and hypoglycemic events are low.

Food and Insulin Effect on QT/QTC Interval of ECG

ClinicalTrials.gov

2014-08-19

Effects of Different Meals on the QT/QTc Interval; Insulin and Oral Hypoglycemic [Antidiabetic] Drugs Causing Adverse Effects in Therapeutic Use; C-Peptide Effects on the QT/QTc Interval; Moxifloxacin ECG Profile in Fed and Fasted State; Japanese vs. Caucasian TQT Comparison

14 CFR 67.313 - General medical condition.

Code of Federal Regulations, 2014 CFR

2014-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.213 - General medical condition.

Code of Federal Regulations, 2012 CFR

2012-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.313 - General medical condition.

Code of Federal Regulations, 2012 CFR

2012-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.313 - General medical condition.

Code of Federal Regulations, 2011 CFR

2011-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.113 - General medical condition.

Code of Federal Regulations, 2012 CFR

2012-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.113 - General medical condition.

Code of Federal Regulations, 2014 CFR

2014-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.113 - General medical condition.

Code of Federal Regulations, 2011 CFR

2011-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.213 - General medical condition.

Code of Federal Regulations, 2014 CFR

2014-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.113 - General medical condition.

Code of Federal Regulations, 2013 CFR

2013-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.313 - General medical condition.

Code of Federal Regulations, 2013 CFR

2013-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.213 - General medical condition.

Code of Federal Regulations, 2013 CFR

2013-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

14 CFR 67.213 - General medical condition.

Code of Federal Regulations, 2011 CFR

2011-01-01

... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other hypoglycemic drug for control. (b) No other organic, functional, or structural disease, defect, or limitation that the Federal Air Surgeon, based on the case history and appropriate, qualified medical judgment...

Glucagon Kits: Are Your Patients Prepared for a Hypoglycemic Emergency

DTIC Science & Technology

2016-06-03

of about $120,000,000. 1 The American Diabetes Association (ADA) recommends people with diabetes have an immediate source of glucose to treat mild or...severe diabetic hypoglycemia with glucagon: An underutilized therapeutic approach. Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy. 20

The Pharmacological Potential of Mushrooms

PubMed Central

2005-01-01

This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly. PMID:16136207

Insulin-like plant proteins as potential innovative drugs to treat diabetes-The Moringa oleifera case study.

PubMed

Paula, P C; Oliveira, J T A; Sousa, D O B; Alves, B G T; Carvalho, A F U; Franco, O L; Vasconcelos, I M

2017-10-25

Various plant species have long been used in traditional medicine worldwide to treat diabetes. Among the plant-based compounds with hypoglycemic properties, studies on insulin-like proteins isolated from leaves, fruits and seeds are rarely reported in the relevant literature. Our research group has been investigating the presence of insulin-like proteins in Moringa oleifera, a plant species native to India, and we have obtained a leaf protein isolate and semi-purified derived fractions, as well as a seed coat protein fraction (Mo-SC), with hypoglycemic activity in chemically induced diabetic mice that have increased tolerance to orally administered glucose. Equally importantly, Mo-SC possesses insulin-like antigenic epitopes. In this context, the present review aims to highlight that prospection of insulin-like proteins in plants is of the utmost importance both for finding new drugs for the treatment of diabetes and for shedding light on the mechanisms involved in diabetes. Copyright © 2016 Elsevier B.V. All rights reserved.

PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs

PubMed Central

Conaldi, Pier Giulio

2016-01-01

Neuroblastoma (NB) is the most common and aggressive pediatric cancer, characterized by a remarkable phenotypic diversity and high malignancy. The heterogeneous clinical behavior, ranging from spontaneous remission to fatal metastatic disease, is attributable to NB biology and genetics. Despite major advances in therapies, NB is still associated with a high morbidity and mortality. Thus, novel diagnostic, prognostic, and therapeutic approaches are required, mainly to improve treatment outcomes of high-risk NB patients. Among neuroepithelial cancers, NB is the most studied tumor as far as PPAR ligands are concerned. PPAR ligands are endowed with antitumoral effects, mainly acting on cancer stem cells, and constitute a possible add-on therapy to antiblastic drugs, in particular for NB with unfavourable prognosis. While discussing clinical background, this review will provide a synopsis of the major studies about PPAR expression in NB, focusing on the potential beneficial effects of hypoglycemic drugs, thiazolidinediones and metformin, to reduce the occurrence of relapses as well as tumor regrowth in NB patients. PMID:27799938

PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs.

PubMed

Vella, Serena; Conaldi, Pier Giulio; Florio, Tullio; Pagano, Aldo

2016-01-01

Neuroblastoma (NB) is the most common and aggressive pediatric cancer, characterized by a remarkable phenotypic diversity and high malignancy. The heterogeneous clinical behavior, ranging from spontaneous remission to fatal metastatic disease, is attributable to NB biology and genetics. Despite major advances in therapies, NB is still associated with a high morbidity and mortality. Thus, novel diagnostic, prognostic, and therapeutic approaches are required, mainly to improve treatment outcomes of high-risk NB patients. Among neuroepithelial cancers, NB is the most studied tumor as far as PPAR ligands are concerned. PPAR ligands are endowed with antitumoral effects, mainly acting on cancer stem cells, and constitute a possible add-on therapy to antiblastic drugs, in particular for NB with unfavourable prognosis. While discussing clinical background, this review will provide a synopsis of the major studies about PPAR expression in NB, focusing on the potential beneficial effects of hypoglycemic drugs, thiazolidinediones and metformin, to reduce the occurrence of relapses as well as tumor regrowth in NB patients.

Biochemical analysis of Cassia fistula aqueous extract and phytochemically synthesized gold nanoparticles as hypoglycemic treatment for diabetes mellitus

PubMed Central

Daisy, P; Saipriya, K

2012-01-01

Cassia fistula stem bark was used for the preparation of aqueous extract and synthesis of gold nanoparticles to evaluate the hypoglycemic effects of the plant. The synthesized gold nanoparticles were characterized by ultraviolet-visible spectroscopy for their absorbance pattern, Fourier transform infrared spectroscopy to identify possible functional groups, and scanning electron microscopy to determine the size of the nanoparticles. The present investigation reports the efficacy of the gold nanoparticles as promising in the treatment of hyperglycemia. Body weight, serum glucose concentrations, liver function tests, kidney function tests, and lipid profile were analyzed. A significantly larger decrease in serum biochemistry parameters and an increase in body weight, total protein levels, and high-density lipoprotein were observed in rats with streptozotocin-induced diabetes treated with gold nanoparticles than in the ones treated with the aqueous extract. The results of this study confirm that C. fistula gold nanoparticles have promising antidiabetic properties. PMID:22419867

Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice.

PubMed

Xu, Xin; Shan, Bin; Liao, Cai-Hu; Xie, Jian-Hua; Wen, Ping-Wei; Shi, Jia-Yi

2015-11-01

A water-soluble polysaccharide (MCP) was isolated from the fruits of Momordica charantia L., and the hypoglycemic effects of MCP were investigated in both normal healthy and alloxan-induced diabetic mice. MCP was orally administered once a day after 3 days of alloxan-induction at 100, 200 and 300mg/kg body weight for 28 day. Results showed that fasting blood glucose level (BGL) was significantly decreased, whereas the glucose tolerance was marked improvement in alloxan-induced diabetic mice, and loss in body weight was also prevented in diabetic mice compared to the diabetic control group. The dosage of 300mg/kg body weight exhibited the best effects. In addition, MCP did not exhibit any toxic symptoms in the limited toxicity evaluation in mice. The results suggest that MCP possess significantly dose-dependent anti-diabetic activity on alloxan-induced diabetic mice. Hence, MCP can be incorporated as a supplement in health-care food, drugs and/or combined with other hypoglycemic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Hypoglycemic and hypolipidemic effects of Lactobacillus fermentum, fruit extracts of Syzygium cumini and Momordica charantia on diabetes induced mice.

PubMed

Yousaf, Sehar; Hussain, Abid; Rehman, Shafiqur; Aslam, Muhammad Shahbaz; Abbas, Zaigham

2016-09-01

A lot of treatment strategies available for diabetes but its complications are still a medical problem around the globe. It demands to find out some alternative therapeutic measures. In order to investigate the anti-diabetic potential of probiotics and natural extracts, this study was designed. Accordingly, a local source of yogurt probiotic strain Lactobacillus fermentum was isolated and characterized that showed its probiotic properties. Besides this, natural extracts of plants fruits like java plum (Syzygium cumini) and bitter gourd (M. charantia) were made. Lactobacillus fermentum and the extracts were administered individually as well as in combination to diabetes induced mice. Different parameters like body weight, blood glucose level and lipid profile including total cholesterol, HDL & LDL were analyzed before and after treatment. The results showed that Lactobacillus fermentum and natural extracts have hypoglycemic as well hypolipidemic activity against diabetic mice. This study can further investigated to screen potential compounds from these extracts to control the glucose and the lipid levels in diabetic patients.

Molecular diversity and hypoglycemic polypeptide-P content of Momordica charantia in different accessions and different seasons.

PubMed

Tian, Miao; Zeng, Xiang-Qing; Song, Huan-Lei; Hu, Shan-Xin; Wang, Fu-Jun; Zhao, Jian; Hu, Zhi-Bi

2015-04-01

Momordica charantia (MC) has been used for treating diabetes mellitus from ancient times in Asia, Africa and South America. There are many MC accessions in local markets. Polypeptide-P as a main hypoglycemic component in MC was first studied in this experiment to illustrate the different contents in MC of different accessions and different harvesting times. Nineteen MC accessions collected from different regions were clustered into three groups using random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) molecular markers. Content of polypeptide-P in the tested MC accessions was detected by western blot (WB) method. The WB results revealed that polypeptide-P was detected in MC accessions harvested in June and July but not in September and October. Furthermore, Polypeptide-P content corresponded well with the MC accessions. Our results suggest that the MC accessions and the harvesting times or the weather during harvest play significant roles in high content of polypeptide-P. © 2014 Society of Chemical Industry.

Hypoglycemic and antioxidant potential of coconut water in experimental diabetes.

PubMed

Preetha, P P; Devi, V Girija; Rajamohan, T

2012-07-01

Coconut water is a natural nutritious beverage that contains several biologically active compounds. The present study aims to evaluate the hypoglycemic and antioxidant effects of mature coconut water (MCW) on alloxan-induced diabetes in experimental rats. The experimental animals were divided into four groups - normal control, normal rats treated with MCW, diabetic control and diabetic rats treated with MCW. The blood glucose, plasma insulin, hemoglobin, glycated hemoglobin, activities of the various antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase) and lipid peroxidation markers (malondialdehyde, hydroperoxides and conjugated dienes) were evaluated in all the groups. The results indicate that the diabetic animals treated with MCW had decreased blood glucose levels and reduced oxidative stress induced by alloxan, which was evident from the increased activities of the antioxidant enzymes and the decreased levels of the lipid peroxidation products. The overall results indicate that MCW significantly attenuated hyperglycemia and oxidative stress in alloxan-induced diabetic rats, indicating the therapeutic potential of MCW.

Food insecurity and medication adherence in low-income older Medicare beneficiaries with type 2 diabetes.

PubMed

Sattler, Elisabeth Lilian Pia; Lee, Jung Sun; Bhargava, Vibha

2014-01-01

Little is known about diabetes management among low-income older Americans. This study used statewide self-administered survey and Medicare claims data to examine the relationships of food insecurity and medication (re)fill adherence in a sample of Medicare Part D beneficiaries with type 2 diabetes in need of food assistance in Georgia in 2008 (n = 243, mean age 74.2 ± 7.8 years, 27.2% African American, 77.4% female). (Re)fill adherence to oral hypoglycemics was measured as Proportion of Days Covered. Food insecurity was assessed using a six-item validated standard measure. About 54% of the sample were food insecure. About 28% of the diabetic sample did not (re)fill any diabetes medication and over 80% had at least one diabetes complication. Food insecure participants showed comparable (re)fill adherence to food secure participants. However, 57% of food insecure participants were nonadherent to oral hypoglycemics. Underlying basic needs must be addressed to improve diabetes management in this population.

Antibacterial and Hypoglycemic Diterpenoids from Salvia chamaedryoides.

PubMed

Bisio, Angela; De Mieri, Maria; Milella, Luigi; Schito, Anna M; Parricchi, Anita; Russo, Daniela; Alfei, Silvana; Lapillo, Margherita; Tuccinardi, Tiziano; Hamburger, Matthias; De Tommasi, Nunziatina

2017-02-24

A surface extract of the aerial parts of Salvia chamaedryoides afforded 13 diterpenes (1-13), with seven compounds (1, 3, 4, 7-9, 12) described for the first time. The structures of the new compounds were established using 1D and 2D NMR spectroscopic methods, HRESIMS, and ECD data. The potential hypoglycemic effects of the crude extract, fractions, and pure compounds from S. chamaedryoides were investigated by inhibition of α-glucosidase and α-amylase enzymes. The extract and its fractions showed a moderate dose-dependent inhibition; the pure compounds exhibited differential inhibitory activity against these two enzymes. Molecular modeling studies were also performed to suggest the interaction mode of compound 3 in the α-glucosidase enzyme active site. The antimicrobial activity of the purified compounds was investigated against 26 clinical pathogens. No activity was detected for the Gram-negative species tested nor on Candida albicans and C. glabrata, while variable susceptibilities were observed using Gram-positive staphylococcal and enterococcal species.

In vitro hypoglycemic effects of hot water extract from Auricularia polytricha (wood ear mushroom).

PubMed

Wu, Ni-Jung; Chiou, Fu-Jing; Weng, Yih-Ming; Yu, Zer-Ran; Wang, Be-Jen

2014-06-01

Viscous dietary fibers were shown to alleviate postprandial blood glucose. Auricularia polytricha (wood ear mushroom, WEM) contains rich amount fibers and water extract WEM was highly viscous. This study aimed to investigate whether WEM extract exhibited hypoglycemic effect in vitro. The effects of WEM extract on glucose adsorption, glucose diffusion, starch digestion and α-amylase activity were examined and compared to those of two high soluble fibers, psyllium and oat fiber and one insoluble fiber, cellulose. Our results showed that WEM extract and psyllium possessed similar ability to adsorb glucose which may thus decrease the level of dialysis glucose. The decrease of dialysis rate is dose-dependent. WEM extract can also suppress the activity of α-amylase which may thus inhibit the digestion of polysaccharides. Since WEM extract exhibited the ability to adsorb glucose and to suppress the activity of α-amylase; it might contribute a beneficial effect on postprandial levels of blood sugar.

Diabetes Drug Prescription Pattern and Awareness Among Health Care Providers in Sub-Himalayan Region of India: A Population Based Study.

PubMed

Mokta, Jatinder; Mokta, Kiran; Ranjan, Asha; Joshi, Ivan; Garg, Mahak

2017-05-01

To determine the pattern of diabetic drug prescription and awareness about diabetes among primary health providers in the rural areas of Himachal Pradesh situated in the western Himalayas at an elevation range from 350 meters (1,148ft) to 6900 meters (22,966ft) above sea level. Study was conducted in 20 rural areas of Himachal Pradesh, located 50 to 400 Km from state capital, at 2200 to 10,000 feet altitude. Non-pregnant diabetic adults were surveyed through 31 diabetic camps. Detailed history, weight, height, waist circumference, body mass index recorded. Fasting or random blood glucose, glycated hemoglobin, lipid profile measured and blood pressure recorded. 894 diabetic patients were included in the study (59.83% male) with the mean age of 52.94±6.78 years. Two in three patients were on oral hypoglycemic agents (OHAs), and one in three on alternative approaches for diabetes control. Among OHAs, sulphonylureas (SU) were the most commonly prescribed oral agents in 76.09% of patients followed by metformin in 23.87%. Glibenclamide was the most commonly prescribed SU in 44.60%. Amlodipine and atenolol was the commonest anti-hypertensive drug prescribed in 77.85% either in combination or as individual drug. Only 10.59% were on lipid lowering therapy. For primary care providers glycemic target was the mainstay of diabetes treatment with little emphasis on blood pressure control and no emphasis on lipid reduction. Sulphonylureas were the commonest anti-diabetic drug prescribed by the primary care providers followed by metformin. Insulin was prescribed to 2.23% only. Combination of amlodipine and atenolol was the commonest anti-hypertensive drugs prescribed and only 10% of patients were prescribed statin.

Methicillin-resistant Staphylococcus aureus nasal carriage and infection among patients with diabetic foot ulcer.

PubMed

Lin, Shin-Yi; Lin, Nai-Yu; Huang, Yu-Yao; Hsieh, Chi-Chun; Huang, Yhu-Chering

2018-06-04

To evaluate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage in patients with diabetic foot ulcer (DFU) in Taiwan, and to assess the concordance between colonizing and clinical MRSA isolates from the patients. A total of 354 nasal specimens were collected from 112 to 242 diabetic patients with and without foot ulcer, respectively. MRSA clinical isolates from DFU wound cultures were collected for comparison. Nasal carriage rate of S. aureus and MRSA was similar between diabetic patients with and without foot ulcer (15.2% vs. 16.9% for S. aureus and 5.4% vs. 1.7% for MRSA). Nasal S. aureus colonization was an independent predictor for wound S. aureus infection (Odds ratio [OR]: 5.33, 95% confidence interval [CI]: 1.61-17.59), so did nasal MRSA colonization (OR: 19.09, 95% CI: 2.12-171.91). The levels of glycated hemoglobin, and the usage with immunosuppressant agent were associated with S. aureus nasal colonization while oral hypoglycemic agent usage a protective factor. Sequence type 59/staphylococcal chromosome cassette mec IV or V, the local endemic community-associated clone, accounted for 42% and 70% of the clinical and colonizing isolates, respectively. Six of 10 patients with paired colonizing and clinical isolates, either MRSA or methicillin-sensitive S. aureus, had a genetically identical strain from a single patient. Less than one-fifth of patients with DFU have nasal S. aureus, including MRSA, colonization; however, the colonization is significantly associated with S. aureus diabetic foot infection. Screening for S. aureus colonizing status in DFU patients might have a potential clinical implication. Copyright © 2018. Published by Elsevier B.V.

Emerging links between type 2 diabetes and Alzheimer’s disease

PubMed Central

Sridhar, Gumpeny R; Lakshmi, Gumpeny; Nagamani, Gumpeny

2015-01-01

Type 2 diabetes mellitus and Alzheimer’s disease are both associated with increasing age, and each increases the risk of development of the other. Epidemiological, clinical, biochemical and imaging studies have shown that elevated glucose levels and diabetes are associated with cognitive dysfunction, the most prevalent cause of which is Alzheimer’s disease. Cross sectional studies have clearly shown such an association, whereas longitudinal studies are equivocal, reflecting the many complex ways in which the two interact. Despite the dichotomy, common risk and etiological factors (obesity, dyslipidemia, insulin resistance, and sedentary habits) are recognized; correction of these by lifestyle changes and pharmacological agents can be expected to prevent or retard the progression of both diseases. Common pathogenic factors in both conditions span a broad sweep including chronic hyperglycemia per se, hyperinsulinemia, insulin resistance, acute hypoglycemic episodes, especially in the elderly, microvascular disease, fibrillar deposits (in brain in Alzheimer’s disease and in pancreas in type 2 diabetes), altered insulin processing, inflammation, obesity, dyslipidemia, altered levels of insulin like growth factor and occurrence of variant forms of the protein butyrylcholinesterase. Of interest not only do lifestyle measures have a protective effect against the development of cognitive impairment due to Alzheimer’s disease, but so do some of the pharmacological agents used in the treatment of diabetes such as insulin (especially when delivered intranasally), metformin, peroxisome proliferator-activated receptors γ agonists, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes must be recognized as a risk for development of Alzheimer’s disease; clinicians must ensure preventive care be given to control and postpone both conditions, and to identify cognitive impairment early to manage it appropriately. PMID:26069723

A Cohort Study of Thiazolidinediones and Fractures in Older Adults with Diabetes

PubMed Central

Solomon, Daniel H.; Cadarette, Suzanne M.; Choudhry, Niteesh K.; Canning, Claire; Levin, Raisa; Stürmer, Til

2009-01-01

Context: Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-γ and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. Objective: The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. Design: We conducted a cohort study. Participants: Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. Main Outcome: We measured the incidence of fracture within the cohort. Results: Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98–1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94–1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. Conclusions: As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin. PMID:19470635

Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

PubMed

Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

2016-06-01

Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties.

PubMed

Ma, Lingman; Qian, Lifen; Ying, Qidi; Zhang, Yan; Zhou, Changlin; Wu, Guanzhong

2017-01-15

Here, we investigated whether I 4 , which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE -/- mice were fed a Western diet and simultaneously administered I 4 , glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I 4 . The data indicated that I 4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I 4 , at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1β, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I 4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I 4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I 4 exerts potent inhibitory effects on atherosclerosis onset and development. Copyright © 2016. Published by Elsevier Ireland Ltd.

Outbreak of acute hypoglycemic encephalopathy associated with litchi consumption, Muzaffarpur, India, 2014

USDA-ARS?s Scientific Manuscript database

Background: Seasonal outbreaks of an acute neurologic illness with high mortality among young children occur annually in Muzaffarpur, Bihar, the largest litchi (lychee) fruit cultivation region in India. A wide range of infectious and non-infectious etiologies, including an association with litchi...

Detection of methylenecyclopropylglycine (MCPG) and hypoglycin A in litchi fruit (abstract)

USDA-ARS?s Scientific Manuscript database

Introduction Methylenecyclopropylalanine (hypoglycin A), an unusual amino acid, is known to occur in the fruit of Blighia sapida Koenig. Known as ackee fruit, this member of the family Sapindaceae (soapberry family) is associated with a hypoglycemic malady, and Jamaican vomiting sickness. Another f...

Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial.

PubMed

Ly, Trang T; Nicholas, Jennifer A; Retterath, Adam; Lim, Ee Mun; Davis, Elizabeth A; Jones, Timothy W

2013-09-25

Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events. To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy. A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia. Patients were randomized to insulin pump only or automated insulin suspension for 6 months. The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique. Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P <.001). There was no change in glycated hemoglobin in either group: mean, 7.4 (95% CI, 7.2-7.6) to 7.4 (95% CI, 7.2-7.7) in the pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes. anzctr.org.au Identifier: ACTRN12610000024044.

Threshold-based insulin-pump interruption for reduction of hypoglycemia.

PubMed

Bergenstal, Richard M; Klonoff, David C; Garg, Satish K; Bode, Bruce W; Meredith, Melissa; Slover, Robert H; Ahmann, Andrew J; Welsh, John B; Lee, Scott W; Kaufman, Francine R

2013-07-18

The threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia. We randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values. A total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insulin-pump therapy (control group, 126 patients). The changes in glycated hemoglobin values were similar in the two groups. The mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold-suspend group than in the control group (980 ± 1200 mg per deciliter [54.4 ± 66.6 mmol per liter] × minutes vs. 1568 ± 1995 mg per deciliter [87.0 ± 110.7 mmol per liter] × minutes, P<0.001). Nocturnal hypoglycemic events occurred 31.8% less frequently in the threshold-suspend group than in the control group (1.5 ± 1.0 vs. 2.2 ± 1.3 per patient-week, P<0.001). The percentages of nocturnal sensor glucose values of less than 50 mg per deciliter (2.8 mmol per liter), 50 to less than 60 mg per deciliter (3.3 mmol per liter), and 60 to less than 70 mg per deciliter (3.9 mmol per liter) were significantly reduced in the threshold-suspend group (P<0.001 for each range). After 1438 instances at night in which the pump was stopped for 2 hours, the mean sensor glucose value was 92.6 ± 40.7 mg per deciliter (5.1 ± 2.3 mmol per liter). Four patients (all in the control group) had a severe hypoglycemic event; no patients had diabetic ketoacidosis. This study showed that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values. (Funded by Medtronic MiniMed; ASPIRE ClinicalTrials.gov number, NCT01497938.).

Postoperative Hypoglycemia Is Associated With Worse Outcomes After Cardiac Operations.

PubMed

Johnston, Lily E; Kirby, Jennifer L; Downs, Emily A; LaPar, Damien J; Ghanta, Ravi K; Ailawadi, Gorav; Kozower, Benjamin D; Kron, Irving L; McCall, Anthony L; Isbell, James M

2017-02-01

Hypoglycemia is a known risk of intensive postoperative glucose control in patients undergoing cardiac operations. However, neither the consequences of hypoglycemia relative to hyperglycemia, nor the possible interaction effects, have been well described. We examined the effects of postoperative hypoglycemia, hyperglycemia, and their interaction on short-term morbidity and mortality. Single-institution Society of Thoracic Surgeons (STS) database patient records from 2010 to 2014 were merged with clinical data, including blood glucose values measured in the intensive care unit (ICU). Exclusion criteria included fewer than three glucose measurements and absence of an STS predicted risk of morbidity or mortality score. Primary outcomes were operative mortality and composite major morbidity (permanent stroke, renal failure, prolonged ventilation, pneumonia, or myocardial infarction). Secondary outcomes included ICU and postoperative length of stay. Hypoglycemia was defined as below 70 mg/dL, and hyperglycemia as above 180 mg/dL. Simple and multivariable regression models were used to evaluate the outcomes. A total of 2,285 patient records met the selection criteria for analysis. The mean postoperative glucose level was 140.8 ± 18.8 mg/dL. Overall, 21.4% of patients experienced a hypoglycemic episode (n = 488), and 1.05% (n = 24) had a severe hypoglycemic episode (<40 mg/dL). The unadjusted odds ratio (UOR) for operative mortality for patients with any hypoglycemic episode compared with those without was 5.47 (95% confidence interval [CI] 3.14 to 9.54), and the UOR for major morbidity was 4.66 (95% CI 3.55 to 6.11). After adjustment for predicted risk of morbidity or mortality and other significant covariates, the adjusted odds (AOR) of operative mortality were significant for patients with any hypoglycemia (AOR 4.88, 95% CI 2.67 to 8.92) and patients with both events (AOR 8.29, 95% CI 1.83 to 37.5) but not hyperglycemia alone (AOR 1.62, 95% CI 0.56 to 4.69). The AOR of major morbidity for patients with both hypoglycemic and hyperglycemic events was 14.3 (95% CI 6.50 to 31.4). Postoperative hypoglycemia is associated with both mortality and major morbidity after cardiac operations. The combination of both hyperglycemia and hypoglycemia represents a substantial increase in risk. Although it remains unclear whether hypoglycemia is a cause, an early warning sign, or a result of adverse events, this study suggests that hypoglycemia may be an important event in the postoperative period after cardiac operations. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

ERIC Educational Resources Information Center

Rovet, Joanne F.; And Others

1988-01-01

Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

AMPK activation by pterostilbene contributes to suppression of hepatic gluconeogenic gene expression and glucose production in H4IIE cells

USDA-ARS?s Scientific Manuscript database

Pterostilbene, a bioactive component of blueberries and grapes, shows structural similarity to resveratrol, and exhibits antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, and cholesterol lowering effects. This study examined potential mechanisms that may contribute to its lipid- and glucose...

Abdominal lipectomy and mesh repair of midline periumbilical hernia after bariatric surgery: how to spare the umbilicus.

PubMed

Iannelli, Antonio; Bafghi, Abdi; Negri, Chiara; Gugenheim, J

2007-09-01

Abdominal lipectomy is becoming an increasingly common surgical procedure in patients with esthetic deformities resulting from massive weight loss induced by bariatric surgery. Sometimes a midline incisional hernia coexists with the pendulus abdomen. Herein presented is a technique to perform a retromuscular mesh repair of the incisional hernia while sparing the umbilicus. The abdominal lipectomy with concomitant retro-muscular mesh repair of a midline incisional hernia is done sparing the vascular supply of the umbilicus on one side only. 5 consecutive women with pendulus abdomen resulting from bariatric surgery-induced massive weight loss and concomitant midline incisional hernia underwent abdominal lipectomy and incisional hernia mesh repair. Mean BMI was 28.6 kg/m2 (range 26-35), one patient was a smoker, and another had type 2 diabetes requiring oral hypoglycemic agents. Two patients had had a previous incisional hernia repair with intraperitoneal mesh. One patient had partial necrosis of the umbilicus and another experienced necrosis of only the epidermis that recovered fully. The umbilicus can be safely spared during abdominal lipectomy with concomitant midline incisional hernia mesh repair. Recurrent incisional hernia and common risk factors for wound healing such as diabetes and obesity increase the risk of umbilical necrosis.

Effects of Silymarin on Diabetes Mellitus Complications: A Review.

PubMed

Stolf, Aline Maria; Cardoso, Cibele Campos; Acco, Alexandra

2017-03-01

Diabetes mellitus is a common metabolic disorder that is caused by a deficit in the production of (type 1) or response to (type 2) insulin. Diabetes mellitus is characterized by a state of chronic hyperglycemia and such symptoms as weight loss, thirst, polyuria, and blurred vision. These disturbances represent one of the major causes of morbidity and mortality nowadays, despite available treatments, such as insulin, insulin secretagogues, insulin sensitizers, and oral hypoglycemic agents. However, many efforts have been made to discover new drugs for diabetes treatment, including medicinal plant extracts. Silymarin is a powder extract of the seeds from Silybum marianum, a plant from the Asteraceae family. The major active ingredients include four isomers: silybin, isosilybin, silychristin, and silydianin. Silymarin is indicated for the treatment of hepatic disorders, such as cirrhosis, chronic hepatitis, and gallstones. Moreover, several studies of other pathologies, including diabetes, sepsis, osteoporosis, arthritis, hypercholesterolemia, cancer, viral infections, and Alzheimer's and Parkinson's diseases, have tested the effects of silymarin and reported promising results. This article reviews data from clinical, in vivo, and in vitro studies on the use of silymarin, with a focus on the complications of diabetes, including nephropathy, neuropathy, healing delays, oxidative stress, hepatotoxicity, and cardiomyopathy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Foeniculum vulgare Mill: A Review of Its Botany, Phytochemistry, Pharmacology, Contemporary Application, and Toxicology

PubMed Central

Patel, Vainav V.; Bandivdekar, Atmaram H.

2014-01-01

Foeniculum vulgare Mill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology of Foeniculum vulgare. It also compiles available scientific evidence for the ethnobotanical claims and to identify gaps required to be filled by future research. Findings based on their traditional uses and scientific evaluation indicates that Foeniculum vulgare remains to be the most widely used herbal plant. It has been used for more than forty types of disorders. Phytochemical studies have shown the presence of numerous valuable compounds, such as volatile compounds, flavonoids, phenolic compounds, fatty acids, and amino acids. Compiled data indicate their efficacy in several in vitro and in vivo pharmacological properties such as antimicrobial, antiviral, anti-inflammatory, antimutagenic, antinociceptive, antipyretic, antispasmodic, antithrombotic, apoptotic, cardiovascular, chemomodulatory, antitumor, hepatoprotective, hypoglycemic, hypolipidemic, and memory enhancing property. Foeniculum vulgare has emerged as a good source of traditional medicine and it provides a noteworthy basis in pharmaceutical biology for the development/formulation of new drugs and future clinical uses. PMID:25162032

Subjects with impaired fasting glucose: evolution in a period of 6 years.

PubMed

Leiva, E; Mujica, V; Orrego, R; Wehinger, S; Soto, A; Icaza, G; Vásquez, M; Díaz, L; Andrews, M; Arredondo, M

2014-01-01

To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients.

Evaluation of Asteraceae herbal extracts in the management of diabetes and obesity. Contribution of caffeoylquinic acids on the inhibition of digestive enzymes activity and formation of advanced glycation end-products (in vitro).

PubMed

Spínola, Vítor; Castilho, Paula C

2017-11-01

The study was performed to assess, for the first time, the in vitro anti-diabetic potential of ten Asteraceae plant extracts to inhibit the activity of digestive enzymes (α-amylase, α-, β-glucosidases and lipase) responsible for hydrolysis/digestion of sugar and lipids. Prevention of advanced glycation end-products (AGEs) formation was evaluated in bovine serum albumin/ribose glycation reaction model. The phytochemical profiles and caffeoylquinic acids (CQAs) contents were determined for the methanolic extract of each plant. Analyzed plant extracts exhibited significant inhibitory activity against key digestive enzymes linked to type II diabetes and obesity. A strong inhibition was observed for glucosidases and mild activity towards amylase and lipase (compared to reference compounds). Moreover, some extracts exhibited potent ability to prevent formation of AGEs, implicated in some diabetic complications. Caffeoylquinic acids were dominant in all plant extracts and findings demonstrate that these compounds are the most relevant hypoglycemic and anti-glycation agents. From the obtained results, Argyranthemum pinnatifidum, Helichrysum melaleucum, and Phagnalon lowei are good candidates for further development of phyto-pharmaceutical preparations as complementary therapy for diabetes and obesity control. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-assembling bubble carriers for oral protein delivery.

PubMed

Chuang, Er-Yuan; Lin, Kun-Ju; Lin, Po-Yen; Chen, Hsin-Lung; Wey, Shiaw-Pyng; Mi, Fwu-Long; Hsiao, Hsu-Chan; Chen, Chiung-Tong; Sung, Hsing-Wen

2015-09-01

Successful oral delivery of therapeutic proteins such as insulin can greatly improve the quality of life of patients. This study develops a bubble carrier system by loading diethylene triamine pentaacetic acid (DTPA) dianhydride, a foaming agent (sodium bicarbonate; SBC), a surfactant (sodium dodecyl sulfate; SDS), and a protein drug (insulin) in an enteric-coated gelatin capsule. Following oral administration to diabetic rats, the intestinal fluid that has passed through the gelatin capsule saturates the mixture; concomitantly, DTPA dianhydride produces an acidic environment, while SBC decomposes to form CO2 bubbles at acidic pH. The gas bubbles grow among the surfactant molecules (SDS) owing to the expansion of the generated CO2. The walls of the CO2 bubbles consist of a self-assembled film of water that is in nanoscale and may serve as a colloidal carrier to transport insulin and DTPA. The grown gas bubbles continue to expand until they bump into the wall and burst, releasing their transported insulin, DTPA, and SDS into the mucosal layer. The released DTPA and SDS function as protease inhibitors to protect the insulin molecules as well as absorption enhancers to augment their epithelial permeability and eventual absorption into systemic circulation, exerting their hypoglycemic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Solid lipid nanoparticles for pulmonary delivery of insulin.

PubMed

Liu, Jie; Gong, Tao; Fu, Hualin; Wang, Changguang; Wang, Xiuli; Chen, Qian; Zhang, Qin; He, Qin; Zhang, Zhirong

2008-05-22

Growing attention has been given to the potential of pulmonary route as an alternative for non-invasive systemic delivery of therapeutic agents. In this study, novel nebulizer-compatible solid lipid nanoparticles (SLNs) for pulmonary drug delivery of insulin were developed by reverse micelle-double emulsion method. The influences of the amount of sodium cholate (SC) and soybean phosphatidylcholine (SPC) on the deposition properties of the nanoparticles were investigated. Under optimal conditions, the entrapment delivery (ED), respirable fraction (RF) and nebulization efficiency (NE) of SLNs could reach 96.53, 82.11 and 63.28%, respectively, and Ins-SLNs remained stable during nebulization. Fasting plasma glucose level was reduced to 39.41% and insulin level was increased to approximately 170 microIU/ml 4h after pulmonary administration of 20 IU/kg Ins-SLNs. A pharmacological bioavailability of 24.33% and a relative bioavailability of 22.33% were obtained using subcutaneous injection as a reference. Incorporating fluorescent-labelled insulin into SLNs, we found that the SLNs were effectively and homogeneously distributed in the lung alveoli. These findings suggested that SLNs could be used as a potential carrier for pulmonary delivery of insulin by improving both in vitro and in vivo stability as well as prolonging hypoglycemic effect, which inevitably resulted in enhanced bioavailability.

Antimycobacterial and Antibacterial Activity of Allium sativum Bulbs

PubMed Central

Viswanathan, V.; Phadatare, A. G.; Mukne, Alka

2014-01-01

Tuberculosis is one of the major public health problems faced globally. Resistance of Mycobacterium tuberculosis to antitubercular agents has called for an urgent need to investigate newer drugs to combat tuberculosis. Garlic (Allium sativum) is an edible plant which has generated a lot of curiosity throughout human history as a medicinal plant. Garlic contains sulfur compounds like allicin, ajoene, allylmethyltrisulfide, diallyltrisulfide, diallyldisulphide and others which exhibit various biological properties like antimicrobial, anticancer, antioxidant, immunomodulatory, antiinflammatory, hypoglycemic, and cardiovascular effects. According to various traditional systems of medicine, garlic is one of the established remedies for tuberculosis. The objective of the current study was to investigate in vitro antimycobacterial activity as well as anti-bacterial activity of various extracts rich in specific phytoconstituents from garlic. Preparation of garlic extracts was done based on the chemistry of the constituents and their stability. The estimation of in vitro antimycobacterial activity of different garlic extracts was done using Resazurin microtire plate assay technique whereas activity of garlic oil was evaluated by colony count method. The antibacterial activity of extracts and oil was estimated by zone of inhibition method. Extracts of garlic rich in allicin and ajoene showed appreciable antimycobacterial activity as compared to standard drugs. Garlic oil demonstrated significant antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus. PMID:25035540

Mass spectrometric analysis of pharmaceutical adulterants in products labeled as botanical dietary supplements or herbal remedies: a review.

PubMed

Vaclavik, Lukas; Krynitsky, Alexander J; Rader, Jeanne I

2014-11-01

The increased availability and use of botanical dietary supplements and herbal remedies among consumers has been accompanied by an increased frequency of adulteration of these products with synthetic pharmaceuticals. Unscrupulous producers may add drugs and analogues of various classes, such as phosphodiesterase type 5 (PDE-5) inhibitors, weight loss, hypoglycemic, antihypertensive and anti-inflammatory agents, or anabolic steroids, to develop or intensify biological effects of dietary supplements or herbal remedies. The presence of such adulterated products in the marketplace is a worldwide problem and their consumption poses health risks to consumers. Analytical methods that allow rapid and reliable testing of dietary supplements for the presence of synthetic drugs are needed to address such fraudulent practices. Mass spectrometry (MS) and hyphenated techniques such as liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have become primary tools in this endeavor. The present review critically assesses the role and summarizes the applications of MS in the analysis of pharmaceutical adulterants in botanical dietary supplements and herbal remedies. The uses of MS techniques in detection, confirmation, and quantification of known pharmaceutical adulterants as well as in screening for and structure elucidation of unexpected adulterants and novel designer drugs are discussed.

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

PubMed

Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

2015-01-01

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

FT-IR, Laser-Raman spectra and computational analysis of 5-Methyl-3-phenylisoxazole-4-carboxylic acid.

PubMed

Sert, Yusuf; Mahendra, M; Keskinoğlu, S; Chandra; Srikantamurthy, N; Umesha, K B; Çırak, Ç

2015-03-15

In this study the experimental and theoretical vibrational frequencies of a newly synthesized anti-tumor, antiviral, hypoglycemic, antifungal and anti-HIV agent namely, 5-Methyl-3-phenylisoxazole-4-carboxylic acid has been investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths, bond angles and torsion angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr and DFT/M06-2X: highly parametrized, empirical exchange correlation function) with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data and results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated by using the same theoretical calculations. Copyright © 2014 Elsevier B.V. All rights reserved.

FT-IR, Laser-Raman spectra and computational analysis of 5-Methyl-3-phenylisoxazole-4-carboxylic acid

NASA Astrophysics Data System (ADS)

Sert, Yusuf; Mahendra, M.; Keskinoğlu, S.; Chandra; Srikantamurthy, N.; Umesha, K. B.; Çırak, Ç.

2015-03-01

In this study the experimental and theoretical vibrational frequencies of a newly synthesized anti-tumor, antiviral, hypoglycemic, antifungal and anti-HIV agent namely, 5-Methyl-3-phenylisoxazole-4-carboxylic acid has been investigated. The experimental FT-IR (4000-400 cm-1) and Laser-Raman spectra (4000-100 cm-1) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths, bond angles and torsion angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr and DFT/M06-2X: highly parametrized, empirical exchange correlation function) with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data and results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated by using the same theoretical calculations.

Acute hypoglycemia causes depressive-like behaviors in mice.

PubMed

Park, Min Jung; Yoo, Samuel W; Choe, Brian S; Dantzer, Robert; Freund, Gregory G

2012-02-01

Reports in humans advocate a link between hypoglycemia and altered mood. Such observations, however, have not been mechanistically explored. Here we examined depressive-like behaviors in mice resulting from acute hypoglycemia. Mice were fasted for 12 hours and then administered intraperitoneal insulin to induce a blood glucose nadir of 50 mg/dL at 0.75 hour after injection that by 2 hours postinjection had returned to normal. The behaviors of locomotion, forced swim, saccharin preference, and novel object recognition were subsequently examined. Mice made hypoglycemic showed depressive-like behaviors 24 hours after resolution of hypoglycemia as evidenced by increased immobility in the forced swim test (FST) and reduced saccharin preference. Movement and memory were not impacted by hypoglycemia 24 hours after its resolution. By 48 hours posthypoglycemia, depressive-like behaviors resolved. In contrast, neither peripheral insulin administration without resultant hypoglycemia nor intracerebroventricular insulin administration altered performance in the FST. The antidepressants fluoxetine and desipramine prevented hypoglycemia-induced immobility in the FST, as did the antiadrenergic agents phentolamine, metoprolol, and butoxamine. Epinephrine and norepinephrine administration caused increased immobility in the FST at 24 hours postadministration that subsequently resolved by 48 hours. These data indicate that, in mice, acute hypoglycemia through adrenergic pathways caused depressive-like behaviors that exist well beyond the resolution of hypoglycemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Hypoglycemic effect of Lupinus mutabilis in healthy volunteers and subjects with dysglycemia.

PubMed

Fornasini, M; Castro, J; Villacrés, E; Narváez, L; Villamar, M P; Baldeón, M E

2012-01-01

Metabolic syndrome and type-2 diabetes are increasing health problems that negatively affect health care systems worldwide. There is a constant urge to develop new therapies with better effects, lower side effects at lower prices to treat these diseases. Lupinus species and their derivates are good candidates to be used as hypoglycaemic agents. A phase II clinical trial was conducted to assess the role of raw Lupinus mutabilis on blood glucose and insulin in normoglycemic and dysglycemic subjects. Results show that consumption of L. mutabilis by normal weight healthy young individuals did not change importantly blood glucose and insulin levels. On the other hand, consumption of similar doses of lupinus by dysglycemic individuals (fasting glucose > 100 mg/dL) decreased significantly blood glucose. Lupinus effects were greater in those subjects with higher basal glucose levels. Glucose lowering effects of lupinus were not observed after soy intake that was used as control. A statistically significant reduction in insulin levels was also observed in the lupinus group compared with the soy group after 60 minutes of treatment. Furthermore, only treatment with lupinus improved insulin resistance in dysglycemic subjects. These data demonstrate that lupinus consumption could be a feasible and low cost alternative to treat chronic hyperglycemic diseases.

[Evaluation and perioperative management of patients with diabetes mellitus. A challenge for the anesthesiologist].

PubMed

Pontes, João Paulo Jordão; Mendes, Florentino Fernandes; Vasconcelos, Mateus Meira; Batista, Nubia Rodrigues

Diabetes mellitus (DM) is characterized by alteration in carbohydrate metabolism, leading to hyperglycemia and increased perioperative morbidity and mortality. It evolves with diverse and progressive physiological changes, and the anesthetic management requires attention regarding this disease interference in multiple organ systems and their respective complications. Patient's history, physical examination, and complementary exams are important in the preoperative management, particularly glycosylated hemoglobin (HbA1c), which has a strong predictive value for complications associated with diabetes. The goal of surgical planning is to reduce the fasting time and maintain the patient's routine. Patients with Type 1 DM must receive insulin (even during the preoperative fast) to meet the basal physiological demands and avoid ketoacidosis. Whereas patients with Type 2 DM treated with multiple injectable and/or oral drugs are susceptible to develop a hyperglycemic hyperosmolar state (HHS). Therefore, the management of hypoglycemic agents and different types of insulin is fundamental, as well as determining the surgical schedule and, consequently, the number of lost meals for dose adjustment and drug suspension. Current evidence suggests the safe target to maintain glycemic control in surgical patients, but does not conclude whether it should be obtained with either moderate or severe glycemic control. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Chemical profile, radical scavenging and cytotoxic activity of yellow gentian leaves (Genitaneae luteaefolium) grown in northern regions of Montenegro.

PubMed

Balijagić, Jasmina; Janković, Teodora; Zdunić, Gordana; Bosković, Jelena; Savikin, Katarina; Godevac, Dejan; Stanojković, Tatjana; Jovancević, Miodrag; Menković, Nebojsa

2012-11-01

LC-ESI-MS and HPLC were used for the identification of the constituents from G. lutea leaves collected at different localities, as well as for quantification of the main compounds. Seven secoiridoids, five C-glucoflavones and three xanthones, were identified. Swertiamarin derivatives, namely eustomorusside (2), eustomoside (3) and septemfidoside (5), were detected in G. lutea for the first time. Concentrations of five constituents (swertiamarin, gentiopicrin, isovitexin, mangiferin and isogentisin) were determined. The relationship between concentrations of y-pyrones and altitude was observed with statistically significant correlation (r = 0.94). The extracts were also evaluated for their content of total phenolics, and antiradical and cytotoxic activities. The total phenolics content ranged from 7.7 to 12.7 mg GAE/g, and the IC50 values for DPPH radical scavenging activity varied between 0.45 to 2.02 mg/mL. The leaf extract exhibited moderate cytotoxic effects toward HeLa cells with an IC50 value of 41.1 microg/mL, while gentiopicrin, mangiferin and isogentisin exerted strong activity against HeLa cells, with IC50 values ranging from 5.7 to 8.8 microg/mL. The results confirm the traditional usage of G. lutea leaves and also suggest their possible utilization as hepatoprotective, hypoglycemic and anti-inflammatory agents.

Women are less likely than men to achieve optimal glycemic control after 1 year of treatment: A multi-level analysis of a Korean primary care cohort.

PubMed

Choe, Seung-Ah; Kim, Joo Yeong; Ro, Young Sun; Cho, Sung-Il

2018-01-01

We investigated differences in the achievement of glycemic control among newly diagnosed type-2 diabetes patients according to gender using a multi-clinic retrospective cohort study. Optimal glycemic control was defined as hemoglobin A1c (HbA1c) of less than 6.5% after 1 year of diabetes management. A generalized linear mixed model, which controlled for the fixed effects of baseline characteristics and prescribed oral hypoglycemic agent (OHA), was used to calculate the probability of achieving the target HbA1c. The study included 2,253 newly diagnosed type-2 diabetes patients who completed 1 year of diabetic management, including OHA, in the 36 participating primary clinics. Within the study population, the women had an older average age, were less likely to smoke or drink alcohol, and showed lower levels of fasting blood glucose and HbA1c at the time of diagnosis. There were no significant differences by sex in prescribed OHA or median number of visits. After 1 year of diabetes management, 38.9% of women and 40.6% of men achieved the target HbA1c-a small but significant difference. This suggests that type-2 diabetes is managed less well in women than in men.

An open label study on the supplementation of Gymnema sylvestre in type 2 diabetics.

PubMed

Kumar, Smriti Nanda; Mani, Uliyar Vitaldas; Mani, Indirani

2010-09-01

Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycemia, and associated with long-term damage and dysfunction of various organs. Management of diabetes is therefore vital and involves maintaining euglycemia as much as possible by reducing blood glucose and by increasing insulin sensitivity and peripheral glucose uptake. Ayurveda has promoted the management of diabetes by regulating carbohydrate metabolism using several medicinal herbs, one of which is Gymnema sylvestre (GS). GS has been used in parts of India as a hypoglycemic agent and the results have been encouraging. Accordingly, we planned a quasi-experimental study to investigate the efficacy of the herb among type 2 diabetics. Patients enrolled from free-living population were purposively assigned to experimental or control groups, based on their willingness to participate in the study. The experimental group was supplemented with 500 mg of the herb per day for a period of 3 months, and the efficacy of the herb was assessed through a battery of clinical and biochemical tests. Supplementation of the diet with GS reduced polyphagia, fatigue, blood glucose (fasting and post-prandial), and glycated hemoglobin and there was a favorable shift in lipid profiles and in other clinico-biochemical tests. These findings suggest a beneficial effect of GS in the management of diabetes mellitus.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coronado-Gonzalez, Jose Antonio; Razo, Luz Maria del; Garcia-Vargas, Gonzalo

Inorganic arsenic exposure in drinking water has been recently related to diabetes mellitus. To evaluate this relationship the authors conducted in 2003, a case-control study in an arseniasis-endemic region from Coahuila, a northern state of Mexico with a high incidence of diabetes. The present analysis includes 200 cases and 200 controls. Cases were obtained from a previous cross-sectional study conducted in that region. Diagnosis of diabetes was established following the American Diabetes Association criteria, with two fasting glucose values {>=}126 mg/100 ml ({>=}7.0 mmol/l) or a history of diabetes treated with insulin or oral hypoglycemic agents. The next subject studied,more » subsequent to the identification of a case in the cross-sectional study was taken as control. Inorganic arsenic exposure was measured through total arsenic concentrations in urine, measured by hydride-generation atomic absorption spectrophotometry. Subjects with intermediate total arsenic concentration in urine (63.5-104 {mu}g/g creatinine) had two-fold higher risk of having diabetes (odds ratio=2.16; 95% confidence interval: 1.23, 3.79), but the risk was almost three times greater in subjects with higher concentrations of total arsenic in urine (odds ratio=2.84; 95% confidence interval: 1.64, 4.92). This data provides additional evidence that inorganic arsenic exposure may be diabetogenic.« less

Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion.

PubMed

Liu, Yanqun; Tang, Guanghui; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

2014-09-05

Current studies demonstrated that metformin is not only a hypoglycemic drug, but also a neuro-protective agent. However, the effect of metformin during ischemic brain injury is unclear. The aim of the present study is to explore the effect of metformin during ischemic brain injury. Adult male CD1 mice underwent 90min transient middle cerebral artery occlusion. Metformin (200mg/kg) was given at the time of reperfusion daily until sacrifice. Results showed that metformin treatment significantly reduced ischemia-induced brain atrophy volume compared to the control (p<0.05). Immunostaining results showed that the microvessel density in the peri-focal region of metformin treated mice was greatly increased compared to the control (p<0.05). Similarly, the numbers of BrdU+/DCX+ and nestin+ cells in the subventricular zone were increased in metformin treated mice compared to the control (p<0.05). Furthermore, we demonstrated that metformin treatment activated AMPK signaling pathway and promoted eNOS phosphorylation. Thus, we concluded that metformin promoted focal angiogenesis and neurogenesis and attenuated ischemia-induced brain injury in mice after middle cerebral artery occlusion, suggesting that metformin is a potential new drug for ischemic stroke therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Children with Diabetes: Perceptions of Supports for Self- Management at School.

ERIC Educational Resources Information Center

Nabors, Laura; Lehmkuhl, Heather; Christos, Nicole; Andreone, Teresa L.

2003-01-01

Surveyed and interviewed children and adolescents with diabetes regarding the types of support they needed at school. Children felt supported at school and offered many ideas about how teachers, nurses, and friends could provide support. They reported needing additional support to cope with hypoglycemic episodes. Results suggest that improved…

Psychological Factors in Diabetes Mellitus. A Review of the Literature with Emphasis on Adolescence.

ERIC Educational Resources Information Center

Greydanus, Donald E.; Hofmann, Adele D.

1979-01-01

Emphasis is given to the major role that emotional components play in the development and maintenance of the teenage diabetic with frequent ketoacidotic or hypoglycemic episodes. The integration of adolescent developmental issues into physician treatment plans is stressed. Journal availability: Medical Association, 535 N. Dearborn Street, Chicago,…

Purification and characterisation of a hypoglycemic peptide from Momordica Charantia L. Var. abbreviata Ser.

PubMed

Yuan, Xiaoqing; Gu, Xiaohong; Tang, Jian

2008-11-15

A water-soluble peptide MC2-1-5 from Momordica charantia L. Var. Abbreviata Ser., with hypoglycemic effect, was purified by ultrafiltration, gel filtration chromatography and reverse-phase high performance liquid chromatography (RP-HPLC). The infrared (IR) spectra showed characteristic absorption peaks and the molecular mass of MC2-1-5 was found to be 3405.5174Da by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The sequence of its first 10 N-terminal amino acids was GHPYYSIKKS as determined by a protein sequencer. MC2-1-5 reduced the blood glucose level in alloxan-induced diabetic mice by 61.70% and 69.18% at 2 and 4h, respectively, after oral administration at a dose of 2mg/kg. The oral glucose tolerance test (OGTT) showed MC2-1-5 produced a reduction of 25.50%, 39.62% and 41.74% in blood glucose level after 1, 2 and 3h, respectively, of oral administration compared with a diabetic control. Copyright © 2008 Elsevier Ltd. All rights reserved.

A bioactive sesquiterpene from Bixa orellana.

PubMed

Raga, Dennis D; Espiritu, Rafael A; Shen, Chien-Chang; Ragasa, Consolacion Y

2011-01-01

A dichloromethane extract of the air-dried leaves of Bixa orellana afforded ishwarane 1, phytol 2, polyprenol 3, and a mixture of stigmasterol 4a and sitosterol 4b by silica gel chromatography. The structure of 1 was elucidated by extensive 1D and 2D NMR spectroscopy. Compound 1 at three doses (25, 50, and 100 mg/kg BW) was tested for prophylactic, gastrointestinal motility, analgesic, hypoglycemic, and antimicrobial potentials. Results of the prophylactic assay demonstrated the anti-toxic property of 1 at 100 mg/kg BW. A 50 mg/kg BW dose of 1 resulted in a more propulsive movement of the gastrointestinal tract (88.38 ± 13.59%) compared to the negative control (78.47 ± 10.61%). Tail flick and acetic acid writhing tests indicated that 100 mg/kg BW 1 had minimal analgesic activity. Compound 1 demonstrated no hypoglycemic potential on the animals tested. Compound 1 exhibited moderate antifungal activity against C. albicans, low activity against T. mentagrophytes, and low antibacterial activity against E. coli, S. aureus, and P. aeruginosa. It was inactive against B. subtilis and A. niger.

beta. -Receptor-mediated increase in cerebral blood flow during hypoglycemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hollinger, B.R.; Bryan, R.M.

1987-10-01

The authors tested the hypothesis that {beta}-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin; normoglycemic control rates were given saline. Propranolol was administered to some control and some hypoglycemic rats to block the {beta}-adrenergic receptors. Regional CBF was measured using 4-(N-methyl-{sup 14}C)iodoantipyrine. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied frommore » {approximately}60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. They conclude that {beta}-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia.« less

Search for Compounds with Hypoglycemic Activity in the Series of 1-[2-(1H-Tetrazol-5-yl)-R1-phenyl]-3-R2-phenyl(ethyl)ureas and R1-Tetrazolo[1,5-c]quinazolin-5(6H)-ones

PubMed Central

Antypenko, Oleksii M.; Kovalenko, Sergiy I.; Zhernova, Galina O.

2016-01-01

Methods of 1-[2-(1H-tetrazol-5-yl)-R1-phenyl]-3-R2-phenyl(ethyl)ureas and R1-tetrazolo[1,5-c]quinazolin-5(6H)-ones synthesis were designed. IR, LC-MS, 1H NMR, and elemental analysis data evaluated the structure and purity of the obtained compounds. Different products, depending on the reaction conditions, were distinguished and discussed. The preliminary hypoglycemic activity of 36 synthesized compounds was revealed. Docking studies to 11β-hydroxysteroid dehydrogenase 1, γ-peroxisome proliferator-activated receptor, and dipeptidyl peptidase-4 were conducted. Eight of these substances were further tested on glucocorticoid-induced insulin resistance models, namely glucose tolerance, oral rapid insulin, and adrenalin tests. One of the most active compounds turned out to be tetrazolo[1,5-c]quinazolin-5(6H)-one 3.1, exceeding the reference drugs Metformin (50 and 200 mg/kg) and Gliclazide (50 mg/kg). PMID:27222601

Neonatal hypoglycemia.

PubMed

Straussman, Sharon; Levitsky, Lynne L

2010-02-01

Hypoglycemia in the newborn may be associated with both acute decompensation and long-term neuronal loss. Studies of the cause of hypoglycemic brain damage and the relationship of hypoglycemia to disorders associated with hyperinsulinism have aided in our understanding of this common clinical finding. A recent consensus workshop concluded that there has been little progress toward a precise numerical definition of neonatal hypoglycemia. Nonetheless, newer brain imaging modalities have provided insight into the relationship between neuronal energy deficiency and central nervous system damage. Laboratory studies have begun to reveal the mechanism of hypoglycemic damage. In addition, there is new information about hyperinsulinemic hypoglycemia of genetic, environmental, and iatrogenic origin. The quantitative definition of hypoglycemia in the newborn remains elusive because it is a surrogate marker for central nervous system energy deficiency. Nonetheless, the recognition that hyperinsulinemic hypoglycemia, which produces profound central nervous system energy deficiency, is most likely to lead to long-term central nervous system damage, has altered management of children with hypoglycemia. In addition, imaging studies on neonates and laboratory evaluation in animal models have provided insight into the mechanism of neuronal damage.

Prolonged hypoglycemia after a suicidal ingestion of repaglinide with unexpected slow plasma elimination.

PubMed

Elling, Roland; Spehl, Marco Simon; Wohlfarth, Ariane; Auwaerter, Volker; Hermanns-Clausen, Maren

2016-01-01

Repaglinide is a short-acting insulin secretagogue with high interindividual variability in pharmacokinetics due to genetic polymorphisms. Little is known about repaglinide overdoses, both with respect to pharmacokinetics and appropriate management. Given its short serum half-life of less than 1 h, hypoglycemic effects of repaglinide are expected to cease within a few hours post-ingestion. A 15-year-old girl ingested 10.5 mg of repaglinide in a suicide attempt. Few hours later, she developed a strong food craving, nausea, abdominal pain, and a headache. The lowest recorded serum glucose was 44 mg/dl (2.4 mmol/l) 14 h post-ingestion. Using liquid chromatography-mass spectrometry, we detected repaglinide serum levels of 5.3, 2.6, and 1.0 ng/ml at 14, 20, and 26 h post-ingestion, respectively. This case illustrates that in the context of overdose, repaglinide can lead to prolonged hypoglycemia. We therefore recommend glucose monitoring and observation for 24 h in all patients who remain hypoglycemic or show symptoms of hypoglycemia for an unusually long period of time.

Severe lactic acidosis and acute renal failure following ingestion of metformin and kerosene oil: a case report.

PubMed

Rathnapala, Amila; Matthias, Thushara; Jayasinghe, Saroj

2012-01-17

Kerosene is a freely accessible hydrocarbon used in Sri Lankan (and other Asian) households for cooking and for lighting lamps. Kerosene poisoning is rarely reported among adults and its toxicological effects are not well known. Metformin is a commonly used oral hypoglycemic drug and its overdose leads primarily to lactic acidosis. Combined poisoning of metformin and kerosene and their interactions have not been reported. An 18-year-old, previously healthy, unmarried Sinhalese woman was referred following ingestion of 17.5 g of metformin and approximately 200 mL of kerosene oil in a suicide attempt. She had vomiting, burning epigastric pain, and a hypoglycemic seizure (capillary blood glucose of 42 mg/dL). Subsequently, she developed severe lactic acidosis followed by acute renal insufficiency, was treated with sodium bicarbonate, and underwent intermittent hemodialysis with bicarbonate. She recovered completely. This report proposes possible interactions that occur between metformin and kerosene that augment toxicity when the two are ingested together. It also stresses the importance of early treatment with intermittent hemodialysis in severe lactic acidosis with maintenance of blood glucose.

[Management of hyperglycemic crises and severe hypoglycemia in the emergency department].

PubMed

Miyake, Yasufumi

2014-02-01

The morbidity of hyperglycemic crises and acute hypoglycemic attacks in patients with diabetes mellitus has been increasing for the past several decades. One of the reasons for this is the increase in the number of patients with diabetes. The increased proportion of aging and isolation in society is another reason. The author has discussed patients with these complaints: their epidemiology, pathophysiology, and management in the emergency department. Hyperglycemic crises include diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic syndrome (HHS), and lactic acidosis (LA). Younger patients with type 1 diabetes suffer from DKA; inappropriate insulin therapy or infection is usually the trigger. Older patients with type 2 diabetes are at risk of HHS in the course of sepsis or in the perioperative period. The treatment of both types of patients is common. Sufficient amount of intravenous extracellular fluid and constant infusion of insulin are essential. The development of LA is not associated with the use of metformin, but with the severity of the pre-existing disease. Early recognition and aggressive treatment is vital to improving the prognosis of hyperglycemic emergencies and severe hypoglycemic episodes.

Edible Flowers: A Rich Source of Phytochemicals with Antioxidant and Hypoglycemic Properties.

PubMed

Loizzo, Monica Rosa; Pugliese, Alessandro; Bonesi, Marco; Tenuta, Maria Concetta; Menichini, Francesco; Xiao, Jianbo; Tundis, Rosa

2016-03-30

Edible flowers are receiving renewed interest as rich sources of bioactive compounds. Ethanol extracts of eight edible flowers were phytochemically characterized and investigated for their bioactivity. Rutin, quercetin, luteolin, kaempferol, and myricetin were selected as standards and quantified by HPLC. The fatty acid profile was analyzed by GC and GC-MS. Antioxidant properties were evaluated by using different in vitro tests. The hypoglycemic effects were investigated via the inhibition of α-amylase and α-glucosidase. Sambucus nigra exhibited the highest radical-scavenging activity (IC50 of 1.4 μg/mL), followed by Hedysarum coronarium (IC50 of 1.6 μg/mL). Both species contained high quercetin and rutin contents. S. nigra extract exerted the highest activity in preventing lipid oxidation. Malva sylvestris extract inhibited both α-amylase and α-glucosidase with IC50 values of 7.8 and 11.3 μg/mL, respectively. These findings support the consumption of edible flowers as functional foods and their use as sources of natural antioxidants by the food industry.

[Functional saponins in tea flower (flower buds of Camellia sinensis): gastroprotective and hypoglycemic effects of floratheasaponins and qualitative and quantitative analysis using HPLC].

PubMed

Yoshikawa, Masayuki; Wang, Tao; Sugimoto, Sachiko; Nakamura, Seikou; Nagatomo, Akifumi; Matsuda, Hisashi; Harima, Shoichi

2008-01-01

As a part of our characterization studies on the bioactive saponin constituents of tea flowers (Camellia sinensis, flower buds), the methanolic extract and 1-butanol-soluble portion (the saponin fraction) from the flower buds were found to exhibit potent inhibitory effects on ethanol- and indomethacin-induced gastric mucosal lesions in rats and on serum glucose elevation in sucrose-loaded rats. Among the constituents of the 1-butanol-soluble portion, floratheasaponins A, B, and C showed gastroprotective and hypoglycemic activities. Furthermore, we have developed qualitative and quantitative methods using HPLC for the principle saponins, floratheasaponins A-F, in tea flowers, which were previously found to show antiallergic and antiobesity effects. Using those methods, the saponin composition of Indian tea flowers were found to be similar to those of Chinese (Anhui) but not of Japanese tea flowers. On the other hand, it was found that the floratheasaponin contents in tea flowers varied markedly during the blooming period, and they were abundant at half-bloom. Additionally, the contents of caffeine in the tea flowers were examined using HPLC.

Sexual lifestyle among young adults with type 1 diabetes.

PubMed

Pinhas-Hamiel, Orit; Tisch, Efrat; Levek, Noa; Ben-David, Rachel Frumkin; Graf-Bar-El, Chana; Yaron, Mariana; Boyko, Valentina; Lerner-Geva, Liat

2017-02-01

Sexual lifestyles including sexual activity, problems, satisfaction, and the formation and maintenance of relationships are greatly affected by physical health. Data are limited regarding the sexual lifestyle of adolescents and young adults with type 1 diabetes mellitus (T1DM). Fear of hypoglycemic episodes during sexual intercourse and intimacy issues can impact individuals with T1DM. The aim of this study was to assess sexual lifestyles of individuals with T1DM. Fifty-three patients with T1DM, 27 (51%) males, mean ± SD age 27.9 ± 8.3 years completed the Hypoglycemia Fear Survey-II and the Sex Practices and Concerns questionnaire. Thirty-seven (70%) reported they never or almost never had concerns in their sexual lifestyles that were related to their diabetes. None experienced severe hypoglycemia during sex, but 21 (40%) reported occasional mild hypoglycemic events. More than two-thirds do not take any measures to prevent hypoglycemia before sex (decreasing insulin dose, snacks, and measuring blood glucose levels). Fear of hypoglycemia during sex was reported by 18 (35%); those who reported increased fear experienced mild hypoglycemic events during sex (61.1% vs 26.5%, P = .01), were singles (94.4% vs 64.7%, P = .02), and had higher scores on the Worries subscale of the Hypoglycemia Fear Survey-II (42.8 ± 12.8 vs 34.9 ± 10.5, P = .04) compared with those who did not. Among young people with T1DM, most do not have concerns regarding sex that are related to their diabetes, and most do not take specific measures before or after sex. One-third, however, fear of hypoglycemia during sex, mostly singles and those who experienced hypoglycemia in the past. Caregivers should be aware and address these concerns. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Nocturnal continuous glucose monitoring: accuracy and reliability of hypoglycemia detection in patients with type 1 diabetes at high risk of severe hypoglycemia.

PubMed

Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik; Tarnow, Lise; Thorsteinsson, Birger

2013-05-01

A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe hypoglycemia. Seventy-two type 1 diabetes patients with recurrent severe hypoglycemia (two or more events within the last year) participated for 4 nights in blinded CGM recordings (Guardian(®) REAL-Time CGMS and Sof-Sensor(®); Medtronic MiniMed, Northridge, CA). Blood was drawn hourly from 23:00 to 07:00 h for plasma glucose (PG) measurements (gold standard). Valid data were obtained in 217 nights. The sensitivity of CGM was 65% (95% confidence interval, 53-77%) below 4 mmol/L, 40% (24-56%) below 3 mmol/L, and 17% (0-47%) below 2.2 mmol/L. PG and CGM readings correlated in the total measurement range (Spearman's ρ=0.82; P<0.001). In the normo- and hyperglycemic ranges CGM underestimated PG by 1.1 mmol/L (0.9-1.2 mmol/L) (P<0.001); in contrast, in the hypoglycemic range (PG<4 mmol/L) CGM overestimated PG levels by 1.0 mmol/L (P<0.001). The mean absolute relative differences in the hypo- (≤3.9 mmol/L), normo- (4-9.9 mmol/L), and hyperglycemic (≥10 mmol/L) ranges were 45% (37-53%), 23% (22-25%), and 20% (19-21%), respectively. Continuous glucose error grid analysis indicated a clinical accuracy of 56%, 99%, and 93% in the hypo-, normo-, and hyperglycemic ranges, respectively. The accuracy in the hypoglycemic range of nocturnal CGM data using Sof-Sensor is suboptimal in type 1 diabetes patients at high risk of severe hypoglycemia. To ensure clinical useful sensitivity in detection of nocturnal hypoglycemic episodes, an alarm threshold should not be lower than 4 mmol/L.

Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

PubMed

Kober, P M; Filkins, J P

1981-01-01

Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

Management of cardiovascular risk factors with pioglitazone combination therapies in type 2 diabetes: an observational cohort study

PubMed Central

2011-01-01

Background Type 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. The authors aimed to assess the relative effectiveness of pioglitazone (Pio), metformin (Met) and any sulfonylurea (SU) combinations in non-insulin-treated T2D patients who were failing previous hypoglycemic therapy. Methods Over a 1-year period, two multicenter, open-labeled, controlled, 1-year, prospective, observational studies evaluated patients with T2D (n = 4585) from routine clinical practice in Spain and Greece with the same protocol. Patients were eligible if they had been prescribed Pio + SU, Pio + Met or SU + Met serving as a control cohort, once they had failed with previous therapy. Anthropometric measurements, lipid and glycemic profiles, blood pressure, and the proportions of patients at microvascular and macrovascular risk were assessed. Results All study treatment combinations rendered progressive 6-month and 12-month lipid, glycemic, and blood pressure improvements. Pio combinations, especially Pio + Met, were associated with increases in HDL-cholesterol and decreases in triglycerides and in the atherogenic index of plasma. The proportion of patients at high risk decreased after 12 months in all study cohorts. Minor weight changes (gain or loss) and no treatment-related fractures occurred during the study. The safety profile was good and proved similar among treatments, except for more hypoglycemic episodes in patients receiving SU and for the occurrence of edema in patients using Pio combinations. Serious cardiovascular events were rarely reported. Conclusions In patients with T2D failing prior hypoglycemic therapies, Pio combinations with SU or Met (especially Pio + Met) improved blood lipid and glycemic profiles, decreasing the proportion of patients with a high microvascular or macrovascular risk. The combination of Pio with SU or Met may therefore be recommended for T2D second-line therapy in the routine clinical practice, particularly in patients with dyslipidemia. PMID:21314919

Artemisia dracunculus L. polyphenols complexed to soy protein show enhanced bioavailability and hypoglycemic activity in C57BL/6 mice

PubMed Central

Ribnicky, D.M.; Roopchand, D.E.; Poulev, A; Kuhn, P.; Oren, A.; Cefalu, W.T.; Raskin, I.

2014-01-01

Objective Scientifically-validated food-based interventions are a practical means of addressing the epidemic of metabolic syndrome. An ethanolic extract of Artemisia dracunculus L. (PMI-5011) containing bioactive polyphenols, such as 2′, 4′–dihydroxy-4-methoxydihydrochalcone (DMC-2), improved insulin resistance in vitro and in vivo. Plant polyphenols are concentrated and stabilized when complexed to protein-rich matrices, such as soy protein isolate (SPI), which act as effective food-based delivery vehicles. In this study we compared bioaccessibility, bioavailability and efficacy of polyphenols extracted from A. dracunculus and delivered as PMI-5011 (ethanolic extract alone), formulated with the non-food excipient Gelucire®, (5011- Gelucire), or sorbed to SPI (5011-Nutrasorb®). Materials and Methods PMI-5011, 5011-Gelucire or 5011-Nutrasorb each containing 162 μg of DMC-2 was delivered to the TNO Intestinal Model-1 (TIM-1) of the human upper gastrointestinal tract to compare the effect of delivery vehicle on DMC-2 bioaccessibility. C57BL6/J mice were orally administered 5011-Nutrasorb or PMI-5011 to compare effects of polyphenol-protein complexation on acute hypoglycemic activity and bioavailability of DMC-2 in serum. Results At 500 mg/kg, 5011-Nutrasorb and PMI-5011 had similar hypoglycemic activity in high fat diet-induced diabetes mouse model despite the fact that 5011-Nutrasorb delivered 15-times less DMC-2 (40 μg/kg vs. 600 μg/kg). This can be partially explained by 8 times greater DMC-2 absorption into serum from 5011-Nutrasorb than from PMI-5011. TIM-1 experiments confirmed higher total bioaccessibility of DMC-2 in vitro when delivered in 5011-Nutrasorb (50.2 %) or Gelucire-5011 (44.4 %) compared to PMI-5011 (27.1 %) (p = 0.08). Conclusion Complexation with soy protein makes anti-diabetic A. dracunculus polyphenols more bioavailable and bioaccessible. PMID:24985105

Heart rate informed artificial pancreas system enhances glycemic control during exercise in adolescents with T1D.

PubMed

DeBoer, Mark D; Cherñavvsky, Daniel R; Topchyan, Katarina; Kovatchev, Boris P; Francis, Gary L; Breton, Marc D

2017-11-01

To evaluate the safety and performance of using a heart rate (HR) monitor to inform an artificial pancreas (AP) system during exercise among adolescents with type 1 diabetes (T1D). In a randomized, cross-over trial, adolescents with T1D age 13 - 18 years were enrolled to receive on separate days either the unmodified UVa AP (stdAP) or an AP system connected to a portable HR monitor (AP-HR) that triggered an exercise algorithm for blood glucose (BG) control. During admissions participants underwent a structured exercise regimen. Hypoglycemic events and CGM tracings were compared between the two admissions, during exercise and for the full 24-hour period. Eighteen participants completed the trial. While number of hypoglycemic events during exercise and rest was not different between visits (0.39 AP-HR vs 0.50 stdAP), time below 70 mg dL -1 was lower on AP-HR compared to stdAP, 0.5±2.1% vs 7.4±12.5% (P = 0.028). Time with BG within 70-180 mg dL -1 was higher for the AP-HR admission vs stdAP during the exercise portion and overall (96% vs 87%, and 77% vs 74%), but these did not reach statistical significance (P = 0.075 and P = 0.366). Heart rate signals can safely and efficaciously be integrated in a wireless AP system to inform of physical activity. While exercise contributes to hypoglycemia among adolescents, even when using an AP system, informing the system of exercise via a HR monitor improved time <70 mg dL -1 . Nonetheless, it did not significantly reduce the total number of hypoglycemic events, which were low in both groups. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in Meriones shawi rats.

PubMed

Aissaoui, Abderrahmane; Zizi, Soumia; Israili, Zafar H; Lyoussi, Badiâa

2011-09-01

The use of an aqueous extract of coriander (Coriandrum sativum L.; Apiaceae, Umbelliferae) seeds (CS-extract) in Moroccan traditional treatment of diabetes remains to be experimentally validated. The study aim was to investigate potential hypoglycemic (and hypolipidemic) activity of CS-extract after a single oral dose and after daily dosing for 30 days (sub-chronic study) in normal and obese-hyperglycemic-hyperlipidemic (OHH) Meriones shawi rats. After a single oral dose of CS-extract (20mg/kg; predetermined as optimum), plasma glucose, insulin, total cholesterol (TC), and triglycerides (TG) were measured in normal and OHH rats (hypercaloric diet and forced limited physical activity); glibenclamide (GLB; 2.5mg/kg) was used as reference. In the sub-chronic study, the effect of CS-extract and GLB (at the above doses) on body weight (BW), plasma glucose, insulin, TC, LDL-cholesterol, HDL-cholesterol, TG, urea and creatinine was determined in normal and OHH rats; insulin resistance (IR as HOMA-IR), atherosclerotic and cardioprotective indices were calculated. A single dose of CS-extract or GLB suppressed hyperglycemia in OHH rats, and normo-glycemia was achieved at 6-h post-dose; there was no effect on lipids, TG or insulin, but IR decreased significantly. The hypoglycemic effect was lower in normal rats. In the sub-chronic study in OHH rats, the test substances (CS-extract>GLB) reduced plasma glucose (normoglycemia on Day 21), insulin and IR, TC, LDL-cholesterol, and TG. Atherosclerotic index decreased while cardioprotective indices increased only by CS-extract, with no effect on BW, urea or creatinine. Sub-chronic administration of CS-extract in OHH Meriones shawi rats normalized glycemia and decreased the elevated levels of insulin, IR, TC, LDL-cholesterol and TG. Since, the CS-extract decreased several components of the metabolic syndrome and decreased atherosclerotic and increased cardioprotective indices, CS-extract may have cardiovascular protective effect. The present study validates the traditional use of coriander in diabetes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Neurocognitive functioning in children diagnosed with diabetes before age 10 years.

PubMed

Kaufman, F R; Epport, K; Engilman, R; Halvorson, M

1999-01-01

Our objective was to determine scores on tests of neurocognitive functioning in children diagnosed with diabetes before age 10 years and to determine the association of age of diagnosis, duration of diabetes, subtle hypoglycemia, severe hypoglycemia, and history of hypoglycemic seizures with these neurocognitive test scores. Fifty-five of 62 eligible patients with a mean age of 7.9 +/- 1.6 years followed in our center were given the Woodcock-Johnson Psychoeducational Battery, Beery Developmental Test of Visual-Motor Integration, Finger Tapping, Grooved Pegboard, and Verbal Selective Reminding tests to evaluate the following domains: memory/attention, visual-perceptual, broad cognitive function, academic achievement, and fine motor speed/coordination. Fifteen age-matched siblings served as controls. Twenty-seven subjects were less than 5 years of age when diagnosed with diabetes, the mean age at diagnosis was 4.5 +/- 2.1 years of age, and mean diabetes duration was 2.6 +/- 2.0 years. Eighteen patients had a history of severe hypoglycemia, eight of whom had hypoglycemic seizures. The mean HbA1c was 7.8 +/- 1.1% for the year prior to testing. Our results showed that the overall mean scores for the extensive neurocognitive battery were within the normal range and were comparable to the scores of the age-matched sibling controls. Age of diagnosis and duration of diabetes did not relate to neurocognitive test results. Mean HbA1c had a negative association with some tests of memory/attention (p < 0.03-0.04) and academic achievement (p < 0.005-0.03), while number of blood glucose levels less than mg/dL had a positive association with memory/attention (p < 0.004-0.04), verbal comprehension (p < 0.03) and academic achievement (p < 0.018-0.05). There was no association of neurocognitive test scores with severe hypoglycemia, but subjects with history of hypoglycemic seizures had a decrease in scores on tests assessing memory skills (p < 0.03) including short term memory and memory for words. These data suggest that overall neurocognitive test scores were within the normal range and comparable to controls. However, specific aspects of neurocognitive functioning may be adversely affected by having had a hypoglycemic seizure, but not by episodes of severe hypoglycemia without seizure. Lower HbA1c and an increase in the number of blood glucose levels less than 70 mg/ dL (subtle hypoglycemia) which were associated with higher scores in some domains of academic achievement and memory suggests that stable glycemia may influence cognitive abilities and/or that successful diabetes management requires cognitive skills. Strategies to diminish the risk of seizures with hypoglycemia should be investigated.

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients

PubMed Central

Chen, Ying; Zhu, Ling-Ling; Zhou, Quan

2014-01-01

Background Falls among the elderly are an issue internationally and a public health problem that brings substantial economic and quality-of-life burdens to individuals and society. Falls prevention is an important measure of nursing quality and patient safety. Numerous studies have evaluated the association of medication use with fall risk in elderly patients. However, an up-to-date review has not been available to summarize the multifaceted pharmaceutical concerns in the prevention of medication-related falls. Materials and methods Relevant literature was identified by performing searches in PubMed, Web of Science, and the Cochrane Library, covering the period until February 2014. We included studies that described an association between medications and falls, and effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and pharmacological interventions on fall risk in elderly patients. The full text of each included article was critically reviewed, and data interpretation was performed. Results Fall-risk-increasing drugs (FRIDs) include central nervous system-acting agents, cough preparations, nonsteroidal anti-inflammatory drugs, anti-Alzheimer’s agents, antiplatelet agents, calcium antagonists, diuretics, α-blockers, digoxin, hypoglycemic drugs, neurotoxic chemotherapeutic agents, nasal preparations, and antiglaucoma ophthalmic preparations. The degree of medication-related fall risk was dependent on one or some of the following factors: drug pharmacokinetic/pharmacodynamic properties (eg, elimination half-life, metabolic pathway, genetic polymorphism, risk rating of medications despite belonging to the same therapeutic class) and/or characteristics of medication use (eg, number of medications and drug–drug interactions, dose strength, duration of medication use and time since stopping, medication change, prescribing appropriateness, and medication adherence). Pharmacological interventions, including withdrawal of FRIDs, pharmacist-conducted clinical medication review, and computerized drug alerts, were effective in reducing fall risk. Conclusion Based on the literature review, clear practical recommendations for clinicians to prevent falls in the elderly included making a list of FRIDs, establishing a computerized alert system for when to e-prescribe FRIDs, seeking an alternative drug with lower fall risk, withdrawing FRIDs if clinically indicated, taking pertinent cautions when the use of FRIDs cannot be avoidable, paying attention to prescribing appropriateness, simplifying the medication regimen, strengthening pharmacist-conducted clinical medication review, ensuring the label of each FRID dispensed contains a corresponding warning sign, being careful when medication change occurs, enhancing medication adherence, and mandating for periodic reassessment of potential risk associated with the patient’s medication regimen. Further studies should be conducted in this area, such as investigating whether medication reconciliation and improving medication adherence could decrease the rate of falls. PMID:24966681

Effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and relevant pharmacological interventions on fall risk in elderly patients.

PubMed

Chen, Ying; Zhu, Ling-Ling; Zhou, Quan

2014-01-01

Falls among the elderly are an issue internationally and a public health problem that brings substantial economic and quality-of-life burdens to individuals and society. Falls prevention is an important measure of nursing quality and patient safety. Numerous studies have evaluated the association of medication use with fall risk in elderly patients. However, an up-to-date review has not been available to summarize the multifaceted pharmaceutical concerns in the prevention of medication-related falls. Relevant literature was identified by performing searches in PubMed, Web of Science, and the Cochrane Library, covering the period until February 2014. We included studies that described an association between medications and falls, and effects of drug pharmacokinetic/pharmacodynamic properties, characteristics of medication use, and pharmacological interventions on fall risk in elderly patients. The full text of each included article was critically reviewed, and data interpretation was performed. Fall-risk-increasing drugs (FRIDs) include central nervous system-acting agents, cough preparations, nonsteroidal anti-inflammatory drugs, anti-Alzheimer's agents, antiplatelet agents, calcium antagonists, diuretics, α-blockers, digoxin, hypoglycemic drugs, neurotoxic chemotherapeutic agents, nasal preparations, and antiglaucoma ophthalmic preparations. The degree of medication-related fall risk was dependent on one or some of the following factors: drug pharmacokinetic/pharmacodynamic properties (eg, elimination half-life, metabolic pathway, genetic polymorphism, risk rating of medications despite belonging to the same therapeutic class) and/or characteristics of medication use (eg, number of medications and drug-drug interactions, dose strength, duration of medication use and time since stopping, medication change, prescribing appropriateness, and medication adherence). Pharmacological interventions, including withdrawal of FRIDs, pharmacist-conducted clinical medication review, and computerized drug alerts, were effective in reducing fall risk. Based on the literature review, clear practical recommendations for clinicians to prevent falls in the elderly included making a list of FRIDs, establishing a computerized alert system for when to e-prescribe FRIDs, seeking an alternative drug with lower fall risk, withdrawing FRIDs if clinically indicated, taking pertinent cautions when the use of FRIDs cannot be avoidable, paying attention to prescribing appropriateness, simplifying the medication regimen, strengthening pharmacist-conducted clinical medication review, ensuring the label of each FRID dispensed contains a corresponding warning sign, being careful when medication change occurs, enhancing medication adherence, and mandating for periodic reassessment of potential risk associated with the patient's medication regimen. Further studies should be conducted in this area, such as investigating whether medication reconciliation and improving medication adherence could decrease the rate of falls.

Improvements in the Management of Diabetic Nephropathy

PubMed Central

Dounousi, Evangelia; Duni, Anila; Leivaditis, Konstantinos; Vaios, Vasilios; Eleftheriadis, Theodoros; Liakopoulos, Vassilios

2015-01-01

The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy. PMID:26676665

Role of oral hypoglycemic agents in the management of type 2 diabetes mellitus during Ramadan

PubMed Central

Bashir, Mir Iftikhar; Pathan, Md Faruque; Raza, Syed Abbas; Ahmad, Jamal; Khan, A. K. Azad; Ishtiaq, Osama; Sahay, Rakesh K.; Sheikh, Aisha; Zargar, Abdul Hamid

2012-01-01

It is obligatory for all adult Muslims to observe fast during the holy month of Ramadan, but sick individuals including those with diabetes mellitus are exempted from the duty of fasting. Specific medical advice must be provided to individual patients concerning the potential risks they must accept if they decide to fast. Any alteration in medications deemed necessary to provide an effective and safe antidiabetic regimen should be instituted well before the start of Ramadan. Diet-controlled patients and those well controlled on insulin sensitizers have low risk of hypoglycemia and may safely fast with some modification in the timing of the doses. Newer generation sulfonylureas (gliclazide MR and glimepiride) have reasonable safety profile during Ramadan fasting and are economical options for a large number of diabetics worldwide, especially in the developing countries; older, long acting sulfonylureas like glibenclamide and chlorpropamide should be avoided during fasting. Oral DPP-IV inhibitors are important substitutes to sulfonylureas for patients with diabetes mellitus during fasting owing to their glucose-dependent mechanism of action, efficacy, and tolerability. This group of drugs causes a moderate A1c reduction, are weight neutral, and have a very low risk of hypoglycemia. Short-acting insulin secretagogues are an option in the subset of fasting diabetic patients who have predominantly post-prandial hyperglycemia. PMID:22837904

Effects of Urtica dioica supplementation on blood lipids, hepatic enzymes and nitric oxide levels in type 2 diabetic patients: A double blind, randomized clinical trial.

PubMed

Amiri Behzadi, Alidad; Kalalian-Moghaddam, Hamid; Ahmadi, Amir Hossein

2016-01-01

Oxidative stress plays an important role in the development of diabetic complications including metabolic abnormality-induced diabetic micro-vascular and macro-vascular complications. Urtica dioica L. ( U. dioica ) has been traditionally used in Iranian medicine as an herbal remedy for hypoglycemic or due to its anti-inflammatory properties. The aim of the present study was to evaluate the effects of hydro-alcoholic extract of U. dioica on blood lipids, hepatic enzymes and nitric oxide levels in patients with type 2 diabetes mellitus. 50 women with type 2 diabetes participated in this study and were randomly divided into two groups namely, control and intervention groups. Control group received placebo and intervention group received hydro-alcoholic extract of U. dioica . Before and after 8 weeks of continuous treatment, some biochemical serum levels including FPG, TG, SGPT, SGOT, HDL, LDL, SOD and NO were measured. The results indicated that after 8 weeks, in the intervention group, FPG, TG, and SGPT levels significantly decreased and HDL, NO and SOD levels significantly increased as compared to the control group. Our results encourage the use of hydro-alcoholic extract of U. dioica as an antioxidant agent for additional therapy of diabetes as hydro-alcoholic extract of U. dioica may decrease risk factors of cardiovascular incidence and other complications in patients with diabetes mellitus.