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  1. Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes.

    PubMed

    Yamagishi, Sho-ichi

    2011-04-01

    A non-enzymatic reaction between ketones or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and to the development and progression of various age-related disorders such as vascular complications of diabetes, Alzheimer's disease, cancer growth and metastasis, insulin resistance and degenerative bone disease. Under hyperglycemic and/or oxidative stress conditions, this process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions and rearrangements to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence that AGE and their receptor RAGE (receptor for AGEs) interaction elicits oxidative stress, inflammatory reactions and thrombosis, thereby being involved in vascular aging and damage. These observations suggest that the AGE-RAGE system is a novel therapeutic target for preventing diabetic vascular complications. In this paper, we review the pathophysiological role of the AGE-RAGE-oxidative stress system and its therapeutic intervention in vascular damage in diabetes. We also discuss here the potential utility of the restriction of food-derived AGEs in diabetic vascular complications.

  2. Advanced Glycation End Products (AGE) and Diabetes: Cause, Effect, or Both?

    PubMed Central

    Vlassara, Helen; Uribarri, Jaime

    2014-01-01

    Despite new and effective drug therapies, insulin resistance (IR), type 2 diabetes mellitus (T2D) and its complications remain major medical challenges. It is accepted that IR, often associated with over-nutrition and obesity, results from chronically elevated oxidant stress (OS) and chronic inflammation. Less acknowledged is that a major cause for this inflammation is excessive consumption of advanced glycation end products (AGEs) with the standard western diet. AGEs, which were largely thought as oxidative derivatives resulting from diabetic hyperglycemia, are increasingly seen as a potential risk for islet β-cell injury, peripheral IR and diabetes. Here we discuss the relationships between exogenous AGEs, chronic inflammation, IR, and T2D. We propose that under chronic exogenous oxidant AGE pressure the depletion of innate defense mechanisms is an important factor, which raises susceptibility to inflammation, IR, T2D and its complications. Finally we review evidence on dietary AGE restriction as a non-pharmacologic intervention, which effectively lowers AGEs, restores innate defenses and improves IR, thus, offering new perspectives on diabetes etiology and therapy. PMID:24292971

  3. Advanced BrainAGE in older adults with type 2 diabetes mellitus

    PubMed Central

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The “Brain Age Gap Estimation” (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2

  4. Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

    PubMed

    Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

    2016-11-01

    The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

  5. Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.

    PubMed

    Nenna, Antonio; Spadaccio, Cristiano; Lusini, Mario; Ulianich, Luca; Chello, Massimo; Nappi, Francesco

    2015-01-01

    Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

  6. Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.

    PubMed

    Illien-Jünger, Svenja; Lu, Young; Qureshi, Sheeraz A; Hecht, Andrew C; Cai, Weijing; Vlassara, Helen; Striker, Gary E; Iatridis, James C

    2015-01-01

    Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.

  7. Chronic Ingestion of Advanced Glycation End Products Induces Degenerative Spinal Changes and Hypertrophy in Aging Pre-Diabetic Mice

    PubMed Central

    Illien-Jünger, Svenja; Lu, Young; Qureshi, Sheeraz A.; Hecht, Andrew C.; Cai, Weijing; Vlassara, Helen; Striker, Gary E.; Iatridis, James C.

    2015-01-01

    Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions. PMID:25668621

  8. Diabetes in the Aged

    PubMed Central

    Grobin, Wulf

    1970-01-01

    In keeping with the already known high prevalence of diabetes among residents of the Jewish Home for the Aged, Toronto, annual screening disclosed an average incidence of 25.5% of abnormal glucose tolerance (two-hour post-glucose blood sugars above 140 mg./100 ml.) in residents not known to be diabetic. Forty-five (47%) of the 94 residents with abnormal screening values were considered subsequently to be diabetic according to our criteria. Long-term follow-up, particularly of 81 residents initially normoglycemic in 1964-5, confirmed that the natural course of glucose tolerance in this population was one of progressive deterioration. By contrast, improvement amounting to remission has been demonstrated in nine out of 20 residents several years after they had been declared diabetic, and is thought to have been induced by dietotherapy. Moderate hyperglycemia per se did not cause symptoms in these almost always keto-resistant and usually aglycosuric aged diabetics, who often claimed they felt better when hyperglycemic. Hypoglycemia was an ever present danger when anti-diabetic medication was used; it was the main reason for undertreatment. So far, data from our long-term study have not shown morbidity to be markedly increased in the diabetics, and mortality was found to be evenly distributed among diabetic and non-diabetic male residents. However, in the females there was a clear correlation between mortality rate and the diminished glucose tolerance. What may appear as overdiagnosis of diabetes in the aged is recommended in the hope that early institution of dietary treatment will delay the development of clinical diabetes and the need for anti-diabetic agents. This, in turn, would prevent iatrogenic hypoglycemia. It would also reduce the severity and frequency of spontaneous hypoglycemia which, we believe, occurs more commonly in the early phase of diabetes in the aged than is generally realized. PMID:5476778

  9. Beneficial effects of banana (Musa sp. var. elakki bale) flower and pseudostem on hyperglycemia and advanced glycation end-products (AGEs) in streptozotocin-induced diabetic rats.

    PubMed

    Bhaskar, Jamuna J; Shobha, Mysore S; Sambaiah, Kari; Salimath, Paramahans V

    2011-09-01

    Diabetes is a chronic health problem and major cause of death in most of the countries. Diet management plays an important role in controlling diabetes and its complications along with insulin and drugs. We have examined the effect of banana (Musa sp. var. elakki bale) flower and pseudostem on hyperglycemia and advanced glycation end-products (AGEs) in streptozotocin-induced diabetic rats. Our results indicated that banana flower and pseudostem have low glycemic index and have a high content of dietary fiber and antioxidants. Diabetic symptoms like hyperglycemia, polyuria, polyphagia, polydipsia, urine sugar, and body weight were ameliorated in banana flower- and pseudostem-treated rats. Increased glomerular filtration rate in the diabetic group (5.1 ± 0.22 ml/min) was decreased in banana flower-fed (2.5 ± 0.37 ml/min) and pseudostem-fed (3.0 ± 0.45 ml/min) groups and were significant at P < 0.001 and P < 0.01, respectively. Fructosamine and AGEs formed during diabetes were inhibited in treated groups when compared with the diabetic group. The diabetic group showed 11.5 ± 0.64 μg of AGEs/mg protein in kidney, whereas, in banana flower- and pseudostem-fed groups, it was reduced to 9.21 ± 0.32 and 9.29 ± 0.24 μg/mg protein, respectively, and were significant at P < 0.01. These findings suggest that banana flower and pseudostem have anti-diabetic and anti-AGEs properties and are beneficial as food supplements for diabetics.

  10. Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

    PubMed

    Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2016-04-29

    Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function.

  11. Crosstalk between advanced glycation end products (AGEs)-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications.

    PubMed

    Yamagishi, Sho-ichi; Fukami, Kei; Matsui, Takanori

    2015-01-13

    Advanced glycation end products (AGEs) consist of heterogenous group of macroprotein derivatives, which are formed by non-enzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids, and whose process has progressed at an accelerated rate under diabetes. Non-enzymatic glycation and cross-linking of protein alter its structural integrity and function, contributing to the aging of macromolecules. Furthermore, engagement of receptor for AGEs (RAGE) with AGEs elicits oxidative stress generation and subsequently evokes proliferative, inflammatory, and fibrotic reactions in a variety of cells. Indeed, accumulating evidence has suggested the active involvement of accumulation of AGEs in diabetes-associated disorders such as diabetic microangiopathy, atherosclerotic cardiovascular diseases, Alzheimer's disease and osteoporosis. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins, gut hormones secreted from the intestine in response to food intake, both of which augment glucose-induced insulin release, suppress glucagon secretion, and slow gastric emptying. Since GLP-1 and GIP are rapidly degraded and inactivated by dipeptidyl peptidase-4 (DPP-4), inhibition of DPP-4 and/or DPP-4-resistant GLP-1 analogues have been proposed as a potential target for the treatment of diabetes. Recently, DPP-4 has been shown to cleave multiple peptides, and blockade of DPP-4 could exert diverse biological actions in GLP-1- or GIP-independent manner. This article summarizes the crosstalk between AGEs-RAGE axis and DPP-4-incretin system in the development and progression of diabetes-associated disorders and its therapeutic intervention, especially focusing on diabetic vascular complications.

  12. p-Dimethylaminobenzaldehyde-reactive substances in tail tendon collagen of streptozotocin-diabetic rats: temporal relation to biomechanical properties and advanced glycation endproduct (AGE)-related fluorescence.

    PubMed

    Stefek, M; Gajdosik, A; Gajdosikova, A; Krizanova, L

    2000-11-15

    In the present work, pepsin digests of tail tendons from streptozotocin-diabetic rats were found to contain material that reacted rapidly at room temperature with p-dimethylaminobenzaldehyde (Ehrlich's reagent) to give an adduct with an absorbance spectrum characteristic of the Ehrlich chromogen of pyrrolic nature determined in ageing collagens. A significant correlation of the Ehrlich adduct with tendon mechanical strength and collagen fluorescence characteristic of advanced glycation endproducts was observed. Collagen content of the Ehrlich-positive material was found to be significantly elevated in tendons of diabetic rats compared with age-matched healthy controls. The results indicate that the p-dimethylaminobenzaldehyde-reactive pyrrole moieties may contribute to the increased cross-linking of diabetic matrix collagen. Profound inhibitory effect of aminoguanidine was observed, underlining the role of non-enzymatic mechanisms of advanced glycation in pyrrolisation and cross-linking of collagen exposed to hyperglycaemia. It is hypothesised that quantification of the p-dimethylaminobenzaldehyde-reactive material in matrix collagen may provide a tissue measure of integrated hyperglycaemia over prolonged periods of time. Further research is to assess the significance of p-dimethylaminobenzaldehyde-reactive substances in diabetic collagen tissues and to reveal their relationship to enzyme-mediated physiological pyrrolisation of ageing collagens.

  13. Inhibition of advanced glycation end products (AGEs): an implicit goal in clinical medicine for the treatment of diabetic nephropathy?

    PubMed

    Miyata, Toshio; Dan, Takashi

    2008-11-13

    Several factors are incriminated in the genesis of diabetic nephropathy (DN). To elucidate their interplays, we utilized a diabetic rat model with nephropathy (SHR/NDmcr-cp). This model is characterized by hypertension, obesity with the metabolic syndrome, diabetes with insulin resistance, and intrarenal AGE accumulation. Various therapeutic approaches were used to achieve renoprotection. Caloric restriction corrects metabolic abnormalities and protects the kidney without correcting hypertension. Anti-hypertensive agents, angiotensin II receptor blocker (ARB) and calcium channel blocker, lower blood pressure to the same extent, but only ARBs protect the kidney without changes in metabolic abnormalities. Glycemic control is better with insulin than with pioglitazone. The plasma insulin level is increased by insulin but decreased by pioglitazone which worsens the obesity. Nevertheless, pioglitazone provides renoprotection unlike insulin, perhaps as a result of the up-regulation of TGF-beta by hyperinsulinemia. Cobalt up-regulates the expression of a hypoxia-inducible factor (HIF) and its downstream genes (erythropoietin, VEGF, HO-1). It protects the kidney without correcting hypertension and metabolic abnormalities. Altogether, renoprotection is not necessarily associated with blood pressure or glycemic control. By contrast, it is almost always associated with a decreased AGE formation. AGE reduction may reflect a decreased oxidative stress as it is concomitant with a marked reduction of oxidative stress markers.

  14. AGE, RAGE, and ROS in diabetic nephropathy.

    PubMed

    Tan, Adeline L Y; Forbes, Josephine M; Cooper, Mark E

    2007-03-01

    Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Two key mechanisms implicated in the development of diabetic nephropathy include advanced glycation and oxidative stress. Advanced glycation is the irreversible attachment of reducing sugars onto amino groups of proteins to form advanced glycation end products (AGEs). AGE modification of proteins may lead to alterations in normal function by inducing cross-linking of extracellular matrices. Intracellular formation of AGEs also can cause generalized cellular dysfunction. Furthermore, AGEs can mediate their effects via specific receptors, such as the receptor for AGE (RAGE), activating diverse signal transduction cascades and downstream pathways, including generation of reactive oxygen species (ROS). Oxidative stress occurs as a result of the imbalance between ROS production and antioxidant defenses. Sources of ROS include the mitochondria, auto-oxidation of glucose, and enzymatic pathways including nicotinamide adenine dinucleotide phosphate reduced (NAD[P]H) oxidase. Beyond the current treatments to treat diabetic complications such as the optimization of blood pressure and glycemic control, it is predicted that new therapies designed to target AGEs, including AGE formation inhibitors and cross-link breakers, as well as targeting ROS using novel highly specific antioxidants, will become part of the treatment regimen for diabetic renal disease.

  15. Advanced glycation endproducts and diabetes. Beyond vascular complications.

    PubMed

    Puddu, Alessandra; Viviani, Giorgio L

    2011-06-01

    Advanced Glycation Endproducts (AGEs) are a group of heterogeneous compounds formed by the non enzymatic reactions between aldehydic group of reducing sugars with proteins, lipids or nucleic acids. Formation and accumulation of AGEs is related with the aging process and is accelerated in diabetes. Type 2 diabetes, the most common form of diabetes, is characterized by hyperglycaemia and insulin resistance associated to a progressive deterioration of beta cell function and mass. The pathogenic role of AGEs in vascular diabetic complications is widely recognised. Recently other aspects of the detrimental effects of AGEs in type 2 diabetes are emerged: AGEs interfere with the complex molecular pathway of insulin signaling, leading to insulin resistance; AGEs modify the insulin molecule, and, consequently, its function; AGEs decrease insulin secretion and insulin content. In this article we review the role of AGEs in type 2 diabetes, beyond their involvement in vascular complications.

  16. Advanced Glycation End Products and Diabetic Complications

    PubMed Central

    Singh, Varun Parkash; Bali, Anjana; Singh, Nirmal

    2014-01-01

    During long standing hyperglycaemic state in diabetes mellitus, glucose forms covalent adducts with the plasma proteins through a non-enzymatic process known as glycation. Protein glycation and formation of advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications like retinopathy, nephropathy, neuropathy, cardiomyopathy along with some other diseases such as rheumatoid arthritis, osteoporosis and aging. Glycation of proteins interferes with their normal functions by disrupting molecular conformation, altering enzymatic activity, and interfering with receptor functioning. AGEs form intra- and extracellular cross linking not only with proteins, but with some other endogenous key molecules including lipids and nucleic acids to contribute in the development of diabetic complications. Recent studies suggest that AGEs interact with plasma membrane localized receptors for AGEs (RAGE) to alter intracellular signaling, gene expression, release of pro-inflammatory molecules and free radicals. The present review discusses the glycation of plasma proteins such as albumin, fibrinogen, globulins and collagen to form different types of AGEs. Furthermore, the role of AGEs in the pathogenesis of diabetic complications including retinopathy, cataract, neuropathy, nephropathy and cardiomyopathy is also discussed. PMID:24634591

  17. DNA Advanced Glycation End Products (DNA-AGEs) Are Elevated in Urine and Tissue in an Animal Model of Type 2 Diabetes.

    PubMed

    Jaramillo, Richard; Shuck, Sarah C; Chan, Yin S; Liu, Xueli; Bates, Steven E; Lim, Punnajit P; Tamae, Daniel; Lacoste, Sandrine; O'Connor, Timothy R; Termini, John

    2017-02-20

    More precise identification and treatment monitoring of prediabetic/diabetic individuals will require additional biomarkers to complement existing diagnostic tests. Candidates include hyperglycemia-induced adducts such as advanced glycation end products (AGEs) of proteins, lipids, and DNA. The potential for DNA-AGEs as diabetic biomarkers was examined in a longitudinal study using the Lepr(db/db) animal model of metabolic syndrome. The DNA-AGE, N(2)-(1-carboxyethyl)-2'-deoxyguanosine (CEdG) was quantified by mass spectrometry using isotope dilution from the urine and tissue of hyperglycemic and normoglycemic mice. Hyperglycemic mice (fasting plasma glucose, FPG, ≥ 200 mg/dL) displayed a higher median urinary CEdG value (238.4 ± 112.8 pmol/24 h) than normoglycemic mice (16.1 ± 11.8 pmol/24 h). Logistic regression analysis revealed urinary CEdG to be an independent predictor of hyperglycemia. Urinary CEdG was positively correlated with FPG in hyperglycemic animals and with HbA1c for all mice. Average tissue-derived CEdG was also higher in hyperglycemic mice (18.4 CEdG/10(6) dG) than normoglycemic mice (4.4 CEdG/10(6) dG). Urinary CEdG was significantly elevated in Lepr(db/db) mice relative to Lepr(wt/wt), and tissue CEdG values increased in the order Lepr(wt/wt) < Lepr(wt/db) < Lepr(db/db). These data suggest that urinary CEdG measurement may provide a noninvasive quantitative index of glycemic status and augment existing biomarkers for the diagnosis and monitoring of diabetes.

  18. Advanced glycation end products and diabetic retinopathy.

    PubMed

    Milne, Ross; Brownstein, Seymour

    2013-06-01

    Retinopathy is a serious microvascular complication of diabetes and a major cause of blindness in young adults, worldwide. Early diabetic retinopathy is characterized by a loss of pericytes from retinal capillaries, the appearance of acellular capillaries and microaneurysms, and a breakdown of the blood-retinal barrier. In later stages, this can evolve into the proliferative phase in which there is neovascularization of the retina, which greatly increases the probability of vision loss. Advanced glycation end products (AGEs) which accumulate under hyperglycemic conditions are thought to play an important role in the pathogenesis of diabetic retinopathy. AGEs arise primarily by the modification of amine groups of proteins by reactive dicarbonyls such as methylglyoxal. Intracellular proteins including anti-oxidant enzymes, transcription factors and mitochondrial proteins are targets of dicarbonyl modification and this can modify their functional properties and thus compromise cellular physiology. Likewise, modification of extracellular proteins by dicarbonyls can impair cell adhesion and can generate ligands that can potentially bind to cell surface AGE receptors that activate pro-inflammatory signaling pathways. AGE inhibitors have been shown to provide protection in animal models of diabetic retinopathy and currently are being evaluated in clinical trials.

  19. Reduced dermis thickness and AGE accumulation in diabetic abdominal skin.

    PubMed

    Niu, Yiwen; Cao, Xiaozan; Song, Fei; Xie, Ting; Ji, Xiaoyun; Miao, Mingyuan; Dong, Jiaoyun; Tian, Ming; Lin, Yuan; Lu, Shuliang

    2012-09-01

    Dermatological problems in diabetes might play an important role in the spontaneous ulcers and impaired wound healing that are seen in diabetic patients. Investigation of the cause of diabetic skin disorders is critical for identifying effective treatment. The abdominal full-thickness skin tissues of 33 patients (14 nondiabetic and 19 diabetic) were analyzed. The cell viability and malondialdehyde (MDA) production of fibroblasts were measured after advanced glycosylation end product (AGE)-bovine serum albumin (BSA) exposure. Cutaneous histological observation showed reduced thickness of the diabetic abdominal dermis with morphological characteristics of obscured multilayer epithelium and shortened, thinned, and disorganized collagen fibrils with focal chronic inflammatory cell infiltration when compared with controls of the same age. Accumulation of AGEs in diabetic skin was prominent. Less hydroxyproline, higher myeloperoxidase activity, and increased MDA content were detected in diabetic skin. In vitro, the time- and dose-dependent inhibitory effects of AGE-BSA on fibroblast viability as well as the fact that AGE-BSA could promote MDA production of fibroblasts were shown. It is shown that the accumulation of AGEs in diabetic skin tissue induces an oxidative damage of fibroblasts and acts as an important contributor to the thinner diabetic abdominal dermis. The authors believe that diabetic cutaneous properties at baseline may increase the susceptibility to injury, and diabetic wounds possess atypical origin in the repair process.

  20. Reduction of advanced glycation end-product (AGE) levels in nervous tissue proteins of diabetic Lewis rats following islet transplants is related to different durations of poor metabolic control.

    PubMed

    Sensi, M; Morano, S; Morelli, S; Castaldo, P; Sagratella, E; De Rossi, M G; Andreani, D; Caltabiano, V; Vetri, M; Purrello, F; Di Mario, U

    1998-09-01

    Advanced glycation end-products (AGEs) are irreversible compounds which, by abnormally accumulating over proteins as a consequence of diabetic hyperglycaemia, can damage tissues and thus contribute to the pathogenesis of diabetic complications. This study was performed to evaluate whether restoration of euglycaemia by islet transplantation modifies AGE accumulation in central and peripheral nervous tissue proteins and, as a comparison, in proteins from a non-nervous tissue. Two groups of streptozotocin diabetic inbred Lewis rats with 4 (T1) or 8 (T2) months disease duration were grafted into the liver via the portal vein with 1200-1500 islets freshly isolated from normal Lewis rats. Transplanted rats, age-matched control and diabetic rats studied in parallel, were followed for a further 4-month period. At study conclusion, glycaemia, glycated haemoglobin and body weight were measured in all animals, and an oral glucose tolerance test (OGTT) performed in transplanted rats. AGE levels in cerebral cortex, spinal cord, sciatic nerve proteins and tail tendon collagen were measured by enzyme-linked immunosorbent assay (ELISA). Transplanted animal OGTTs were within normal limits, as were glycaemia and glycated haemoglobin. Diabetic animal AGEs were significantly higher than those of control animals. Protein AGE values were reduced in many transplanted animals compared to diabetic animals, reaching statistical significance in spinal cord (P < 0.05), sciatic nerve (P < 0.02) and tail tendon collagen (P < 0.05) of T1 animals. Thus, return to euglycaemia following islet transplantation after 4 months of diabetes with poor metabolic control reduces AGE accumulation rate in the protein fractions of the mixed and purely peripheral nervous tissues (spinal cord and sciatic nerve, respectively). However, after a double duration of bad metabolic control, a statistically significant AGE reduction has not been achieved in any of the tissues, suggesting the importance of an early

  1. Advanced glycation end products in degenerative nucleus pulposus with diabetes.

    PubMed

    Tsai, Tsung-Ting; Ho, Natalie Yi-Ju; Lin, Ying-Ting; Lai, Po-Liang; Fu, Tsai-Sheng; Niu, Chi-Chien; Chen, Lih-Huei; Chen, Wen-Jer; Pang, Jong-Hwei S

    2014-02-01

    Diabetes mellitus (DM) has been clinically proved as a risk factor of disc degeneration, and the accumulation of advanced glycation end products (AGEs) is known to be potentially involved in diabetes. The purpose of this study is to investigate the effect of AGEs in the degeneration process of diabetic nucleus pulposus (NP) in rats and humans. Diabetic NP cells from rat coccygeal discs were treated with different concentrations of AGEs (0, 50, and 100 µg/ml) for 3 days, and mRNA expressions of MMP-2 and RAGE were measured by real-time RT-PCR. In addition, conditioned medium from NP cells was used to analyze protein expression of MMP-2 activity and ERK by gelatin zymography and Western blot. These experiments were repeated using human intervertebral disc samples. The immunohistochemical expression of AGEs was significantly increased in diabetic discs. In response to AGEs, an increase of MMP-2, RAGE, and ERK at both mRNA and protein expression levels was observed in diabetic NP cells. The findings suggest that AGEs and DM are associated with disc degeneration in both species. Hyperglycemia in diabetes enhances the accumulation of AGEs in the NP and triggers disc degeneration.

  2. Recent Advances (in Diabetes Research)

    MedlinePlus

    ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  3. Diabetes and ageing-induced vascular inflammation.

    PubMed

    Assar, Mariam El; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2016-04-15

    Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly.

  4. AGE restriction in diabetes mellitus: a paradigm shift.

    PubMed

    Vlassara, Helen; Striker, Gary E

    2011-05-24

    Persistently elevated oxidative stress and inflammation precede or occur during the development of type 1 or type 2 diabetes mellitus and precipitate devastating complications. Given the rapidly increasing incidence of diabetes mellitus and obesity in the space of a few decades, new genetic mutations are unlikely to be the cause, instead pointing to environmental initiators. A hallmark of contemporary culture is a preference for thermally processed foods, replete with pro-oxidant advanced glycation endproducts (AGEs). These molecules are appetite-increasing and, thus, efficient enhancers of overnutrition (which promotes obesity) and oxidant overload (which promotes inflammation). Studies of genetic and nongenetic animal models of diabetes mellitus suggest that suppression of host defenses, under sustained pressure from food-derived AGEs, may potentially shift homeostasis towards a higher basal level of oxidative stress, inflammation and injury of both insulin-producing and insulin-responsive cells. This sequence promotes both types of diabetes mellitus. Reducing basal oxidative stress by AGE restriction in mice, without energy or nutrient change, reinstates host defenses, alleviates inflammation, prevents diabetes mellitus, vascular and renal complications and extends normal lifespan. Studies in healthy humans and in those with diabetes mellitus show that consumption of high amounts of food-related AGEs is a determinant of insulin resistance and inflammation and that AGE restriction improves both. This Review focuses on AGEs as novel initiators of oxidative stress that precedes, rather than results from, diabetes mellitus. Therapeutic gains from AGE restriction constitute a paradigm shift.

  5. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    PubMed

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-10-07

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  6. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    PubMed Central

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-01-01

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs. PMID:18840258

  7. Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats.

    PubMed

    Hou, Jun; Zheng, Dezhi; Fung, Gabriel; Deng, Haoyu; Chen, Lin; Liang, Jiali; Jiang, Yan; Hu, Yonghe

    2016-03-01

    Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1β). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM.

  8. Depression and Advanced Complications of Diabetes

    PubMed Central

    Lin, Elizabeth H.B.; Rutter, Carolyn M.; Katon, Wayne; Heckbert, Susan R.; Ciechanowski, Paul; Oliver, Malia M.; Ludman, Evette J.; Young, Bessie A.; Williams, Lisa H.; McCulloch, David K.; Von Korff, Michael

    2010-01-01

    OBJECTIVE To prospectively examine the association of depression with risks for advanced macrovascular and microvascular complications among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A longitudinal cohort of 4,623 primary care patients with type 2 diabetes was enrolled in 2000–2002 and followed through 2005–2007. Advanced microvascular complications included blindness, end-stage renal disease, amputations, and renal failure deaths. Advanced macrovascular complications included myocardial infarction, stroke, cardiovascular procedures, and deaths. Medical record review, ICD-9 diagnostic and procedural codes, and death certificate data were used to ascertain outcomes in the 5-year follow-up. Proportional hazard models analyzed the association between baseline depression and risks of adverse outcomes. RESULTS After adjustment for prior complications and demographic, clinical, and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes (hazard ratio 1.36 [95% CI 1.05–1.75]) and adverse macrovascular outcomes (1.24 [1.0–1.54]). CONCLUSIONS Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities. Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars. Further research is needed to clarify the underlying mechanisms for this association and to test interventions to reduce the risk of diabetes complications among patients with comorbid depression. PMID:19933989

  9. Advanced glycation end products and diabetic nephropathy: a comparative study using diabetic and normal rats with methylglyoxal-induced glycation.

    PubMed

    Rodrigues, Lisa; Matafome, Paulo; Crisóstomo, Joana; Santos-Silva, Daniela; Sena, Cristina; Pereira, Paulo; Seiça, Raquel

    2014-03-01

    Hyperglycemia-related advanced glycation end product (AGE) formation is a key mechanism in diabetic nephropathy. Since methylglyoxal (MG) is a potent AGE precursor, we aimed to assess the role of MG-related AGE formation in the progression of renal damages. A comparative study between Wistar (W, normal) and Goto-Kakizaki (GK, nonobese type 2 diabetic) rats was performed at 6 and 14 months old and after 14 weeks of MG administration to 6-month-old rats. Diabetic rats showed progressive structural, biochemical, and functional alterations, including AGE, albuminuria, and tissue hypoxia, which were partially mimicked by MG administration to young GK rats. Aged Wistar rats had an impairment of some parameters, whereas MG administration caused a phenotype similar to young GK rats, including oxidative stress, impaired apoptotic and angiogenic markers, and structural lesions. MG accumulation specifically impaired several of the renal disease markers progressively observed in diabetic rats, and thus, it contributes to the progression of diabetic nephropathy.

  10. [Effects of diabetes mellitus on the occurrence of age-related macular degeneration].

    PubMed

    Li, Xia; Wang, Yu-sheng

    2011-03-01

    Diabetes mellitus causing long term disturbed glucose metabolism could result in tissue injury and multiple complications. According to recent studies, diabetes mellitus might be regarded as one of the risk factors of age related macular degeneration (AMD). Diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. By studying epidemiological investigation and basic research on this subject comprehensively, it is required to review the correlation between diabetes mellitus and AMD.

  11. Postponing parenthood to advanced age

    PubMed Central

    Waldenström, Ulla

    2016-01-01

    The aim of the Postponing Parenthood project was to investigate several aspects of the delaying of childbearing phenomenon in Sweden and Norway, such as medical risks and parental experiences. Data were retrieved from the Swedish and Norwegian Medical Birth Registers and three different cohorts: the Swedish Young Adult Panel Study, the Norwegian Mother and Child Cohort, and the Swedish Women’s Experiences of Childbirth cohort. Postponing childbirth to age 35 years and later increased the risk of rare but serious pregnancy outcomes, such as stillbirth and very preterm birth. Older first-time parents were slightly more anxious during pregnancy, and childbirth overall was experienced as more difficult, compared with younger age groups. First-time mothers’ satisfaction with life decreased from about age 28 years, both when measured during pregnancy and early parenthood. Delaying parenthood to mid-30 or later was more related to lifestyle than socioeconomic factors, suggesting that much could be done in terms of informing young persons about the limitations of fertility and assisted reproductive techniques, and the risks associated with advanced parental age. PMID:27385461

  12. Diabetes and Altered Glucose Metabolism with Aging

    PubMed Central

    Kalyani, Rita Rastogi; Egan, Josephine M.

    2013-01-01

    I. Synopsis Diabetes and impaired glucose tolerance affect a substantial proportion of older adults. While the aging process can be associated with alterations in glucose metabolism, including both relative insulin resistance and islet cell dysfunction, abnormal glucose metabolism is not a necessary component of aging. Instead, older adults with diabetes and altered glucose status likely represent a vulnerable subset of the population at high-risk for complications and adverse geriatric syndromes such as accelerated muscle loss, functional disability, frailty, and early mortality. Goals for treatment of diabetes in the elderly include control of hyperglycemia, prevention and treatment of diabetic complications, avoidance of hypoglycemia and preservation of quality of life. Given the heterogeneity of the elderly population with regards to the presence of comorbidities, life expectancy, and functional status, an individualized approach to diabetes management is often appropriate. A growing area of research seeks to explore associations of dysglycemia and insulin resistance with the development of adverse outcomes in the elderly and may ultimately inform guidelines on the use of future glucose-lowering therapies in this population. PMID:23702405

  13. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications.

    PubMed

    Nagai, Ryoji; Murray, David B; Metz, Thomas O; Baynes, John W

    2012-03-01

    This article outlines evidence that advanced glycation end product (AGE) inhibitors and breakers act primarily as chelators, inhibiting metal-catalyzed oxidation reactions that catalyze AGE formation. We then present evidence that chelation is the most likely mechanism by which ACE inhibitors, angiotensin receptor blockers, and aldose reductase inhibitors inhibit AGE formation in diabetes. Finally, we note several recent studies demonstrating therapeutic benefits of chelators for diabetic cardiovascular and renal disease. We conclude that chronic, low-dose chelation therapy deserves serious consideration as a clinical tool for prevention and treatment of diabetes complications.

  14. Advanced glycation end products facilitate bacterial adherence in urinary tract infection in diabetic mice.

    PubMed

    Ozer, Ahmet; Altuntas, Cengiz Z; Izgi, Kenan; Bicer, Fuat; Hultgren, Scott J; Liu, Guiming; Daneshgari, Firouz

    2015-07-01

    Diabetic individuals have increased susceptibility to urinary tract infection (UTI), a common, painful condition. During diabetes mellitus, non-enzymatic reactions between reducing sugars and protein amine groups result in excessive production of advanced glycation end products (AGEs) that accumulate in tissues. Since bacteria adhere to cell surfaces by binding to carbohydrates, we hypothesized that adherence of bacteria to the bladder in diabetics may be enhanced by accumulation of AGEs on urothelial surface proteins. Using a murine model of UTI, we observed increased adherence of type 1 fimbriated uropathogenic Escherichia coli (UPEC) to the bladder in streptozotocin-induced diabetic female mice compared with age-matched controls, along with increased concentrations of two common AGEs in superficial urothelial cells from diabetic bladders. Several lectins with different specificities exhibited increased binding to urothelial homogenates from diabetic mice compared with controls, and two of those lectins also bound to AGEs. Furthermore, mannose-binding type 1 fimbriae isolated from UPEC bound to different AGEs, and UPEC adherence to the bladder in diabetic mice, were inhibited by pretreatment of mice with the AGE inhibitor pyridoxamine. These results strongly suggest a role for urothelial AGE accumulation in increased bacterial adherence during UTI in diabetes.

  15. The receptor for advanced glycation end products impairs collateral formation in both diabetic and non-diabetic mice.

    PubMed

    Hansen, Laura M; Gupta, Divya; Joseph, Giji; Weiss, Daiana; Taylor, W Robert

    2017-01-01

    Diabetics often have poor perfusion in their limbs as a result of peripheral artery disease and an impaired ability to generate collateral vessels. The receptor for advanced glycation end products (RAGE) is one protein that is thought to play a detrimental role in collateral development in diabetics due to increased levels of advanced glycation end products (AGE), one of its ligands, in diabetes. Thus, the aim of this study was to investigate the role of RAGE in both diabetic and non-diabetic settings in a model of collateral formation in mice. Streptozotocin was used to induce diabetes in both wild type and RAGE knockout mice. Increased levels of the AGE, N(ɛ)-(carboxymethyl) lysine (CML), were confirmed via an ELISA. A hindlimb ischemia model, in which the femoral artery is ligated, was used to drive collateral growth and reperfusion was assessed using laser Doppler perfusion imaging and histological analysis of vessels in the muscle. Both of these measurements showed impaired collateral growth in diabetic compared with wild-type mice as well as improved collateral growth in both diabetic and non-diabetic RAGE knockout mice when compared their wild-type counterparts. Distance on a freely accessed running wheel, used as a measure of perfusion recovery, showed that wild-type diabetic mice had functionally impaired recovery compared with their wild-type counterparts. Immunohistochemistry and immunoblotting showed that HMGB-1 (high-mobility group box 1), another RAGE ligand, was increased in the ischemic leg compared with the non-ischemic leg in all mice. This increase in HMGB-1 may explain improvement in animals lacking RAGE and its subsequent signaling. In conclusion, this study shows that RAGE impairs collateral growth in a diabetic setting and also in a non-diabetic setting. This demonstrates the importance of RAGE and alternate RAGE ligands in the setting of collateral vessel growth.

  16. Relationship of cytokines and AGE products in diabetic and non-diabetic patients with cataract

    PubMed Central

    Hamid, Sadaf; Gul, Anjuman; Hamid, Qamar

    2016-01-01

    Objectives Cytokines are important mediators of inflammatory and immune responses. The aim of this study was to investigate the changes in cytokines concentration (IL-6, IL-8 and TNF-α) and serum advanced glycation end products (sAGEs) in senile diabetics with or without cataract and non-diabetic patients with cataract. Methodology The study included 124 subjects (sixty or over sixty years age), distributed as four groups thirty senile diabetic patients with cataract (Group I) (16 female and 14 male), thirty senile non-diabetic patients with cataract (Group II) (15 female and 15 male), thirty three senile diabetic patients without any complication (Group III) (16 female and 17 male), thirty one apparently normal healthy individuals (Group IV) (16 female and 15 male), age, sex and weight matched with senile control subjects were investigated. Patients were selected on clinical grounds from Eye Ward Jinnah Postgraduate Medical Centre. Results Interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) levels were significantly increased (P < 0.001) in Group I and III as compared to Group II and IV. Fasting blood glucose, glycosylated hemoglobin, serum fructosamine, malondialdehyde (MDA), sAGEs, IL-6, IL-8 and TNF-α levels were significantly increased (P < 0.001) in Group I as compared to Group II and the levels were almost same in Group II and IV. There was a significant decrease in serum vitamin E and total antioxidant status (p< 0.001) in Group I and Group III as compared to Group II and Group IV. Conclusion The results of the present study thus demonstrated that levels increased in both condition but are more severe in diabetic patients with cataract that may be a predictor for cataractogenesis and the levels were almost same in Group II and IV. PMID:27833515

  17. Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications.

    PubMed

    Hartog, Jasper W L; Voors, Adriaan A; Bakker, Stephan J L; Smit, Andries J; van Veldhuisen, Dirk J

    2007-12-01

    Advanced glycation end-products (AGEs) are molecules formed during a non-enzymatic reaction between proteins and sugar residues, called the Maillard reaction. AGEs accumulate in the human body with age, and accumulation is accelerated in the presence of diabetes mellitus. In patients with diabetes, AGE accumulation is associated with the development of cardiac dysfunction. Enhanced AGE accumulation is not restricted to patients with diabetes, but can also occur in renal failure, enhanced states of oxidative stress, and by an increased intake of AGEs. Several lines of evidence suggest that AGEs are related to the development and progression of heart failure in non-diabetic patients as well. Preliminary small intervention studies with AGE cross-link breakers in heart failure patients have shown promising results. In this review, the role of AGEs in the development of heart failure and the role of AGE intervention as a possible treatment for heart failure are discussed.

  18. Childhood diabetes mellitus: recent advances & future prospects.

    PubMed

    Dejkhamron, Prapai; Menon, Ram K; Sperling, Mark A

    2007-03-01

    Diabetes mellitus (DM) is a metabolic disease characterized by absolute or relative insulin deficiency. Absolute deficiency of insulin most commonly results from an autoimmune destruction of insulin producing cells in the pancreas and in general, the term Type 1 DM (T1DM) is used to denote childhood diabetes associated with autoimmunity and absolute insulin deficiency. The term Type 2 DM (T2DM) is used to denote diabetes resulting from a relative deficiency of insulin when insulin secretion is inadequate to overcome co-existent resistance to insulin action on carbohydrate, protein or fat metabolism; T2DM is most commonly associated with the prototypic insulin resistant state of obesity. In the western hemisphere DM is one of the most prevalent chronic diseases in childhood, whereas the incidence of T1DM in developing countries is significantly less than that in the western hemisphere. Epidemiological studies indicate that there is gradual but steady increase in the incidence of both T1DM and T2DM in both developed and developing countries. This review provides an overview of the major advances in our understanding of the aetiology, pathogenesis, and clinical management of DM in children with the focus being on T1DM. Genetic predisposition, environmental causes, and emerging concepts of the pathogenesis of T1DM such as the accelerator hypothesis are discussed. The goals of treating a child with DM are to achieve normal growth and development with prevention of acute and chronic complications of DM. These goals are achieved by co-ordinated care delivered by a multidisciplinary team focusing on insulin administrations, glucose monitoring, meal planning, and screening for complications. Newer insulin analogues ("designer" insulin) and automated methods of delivery via programmable pumps have revolutionized the care of the child with diabetes. Though T1DM cannot yet be prevented, ongoing trials and strategies aimed at modulating the autoimmune response and the

  19. Vascular hypertrophy in experimental diabetes. Role of advanced glycation end products.

    PubMed Central

    Rumble, J R; Cooper, M E; Soulis, T; Cox, A; Wu, L; Youssef, S; Jasik, M; Jerums, G; Gilbert, R E

    1997-01-01

    The accelerated formation of advanced glycation end products (AGEs) and the overexpression of transforming growth factor beta (TGF-beta) have both been implicated in the pathogenesis of diabetic microvascular and macrovascular complications. Previous studies in our laboratory have demonstrated that the vascular changes in diabetes include hypertrophy of the mesenteric vasculature. To examine the role of AGEs in this process, streptozotocin-induced diabetic rats and control animals were randomized to receive aminoguanidine, an inhibitor of AGE formation, or no treatment. Animals were studied at 7 d, 3 wk, and 8 mo after induction of diabetes. When compared with control animals, diabetes was associated with an increase in mesenteric vascular weight and an increase in media wall/lumen area. By Northern analysis, TGF-beta1 gene expression was increased 100-150% (P < 0.01) and alpha1 (IV) collagen gene expression was similarly elevated to 30-110% compared to controls (P < 0.05). AGEs and extracellular matrix were present in abundance in diabetic but not in control vessels. Treatment of diabetic rats with aminoguanidine resulted in significant amelioration of the described pathological changes including overexpression of TGF-beta1 and alpha1 (IV) collagen. These data implicate the formation of AGEs in TGF-beta overexpression and tissue changes which accompany the diabetic state. PMID:9062360

  20. Advanced glycosylation end products and nutrition--a possible relation with diabetic atherosclerosis and how to prevent it.

    PubMed

    Xanthis, A; Hatzitolios, A; Koliakos, G; Tatola, V

    2007-10-01

    Advanced glycosylation end product (AGE) levels are elevated in diabetic patients and may contribute to the excessive cardiovascular disease in this population, promoting oxidant stress and chronic vascular inflammation. AGEs in people with diabetes mellitus are formed mainly by protein and lipid glucosylation in an environment of chronic hyperglycemia and also by prolonged thermal food processing (diet derived AGEs). This brief review summarizes current literature about food derived AGEs and their relationship with diabetic vascular disease and supports the importance of low AGE diet as an essential preventive or therapeutic intervention against atheromatosis progress.

  1. [Psychosocial rehabilitation in advanced age].

    PubMed

    Haag, G

    1985-02-01

    The psychosocial rehabilitation of older persons is one of the main problems in health policy. About one quarter of the over 65-year-olds face psychic problems, without, to a large extent, receiving adequate treatment and rehabilitative care. Substantial deficits exist above all in the out-patient and non-residential service sectors. In in-patient care, existing methods for psychosocial intervention (such as psychoanalysis, behavioural, client-centered, family, Gestalt, milieu, or music and dance therapy, psychodrama, reality orientation training, or resensitization techniques) are hardly ever used. This absence of applied geronto-psychology is attributable to the shortcomings of available assessment methods, multiple methodical problems of intervention research, and--above all--to insufficient staff positions for psychosocial professions in the gerontological sector. Provision of further permanent posts for psychosocial workers; development of age-specific assessment methods; interdisciplinary and systematic interventional research; the development of ambulatory, community-based services as well as intensive support for existing self-help efforts are therefore called for.

  2. Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice

    PubMed Central

    Tamarat, Radia; Silvestre, Jean-Sébastien; Huijberts, Maya; Benessiano, Joelle; Ebrahimian, Teni G.; Duriez, Micheline; Wautier, Marie-Paule; Wautier, Jean Luc; Lévy, Bernard I.

    2003-01-01

    We hypothesized that formation of advanced glycation end products (AGEs) associated with diabetes reduces matrix degradation by metalloproteinases (MMPs) and contributes to the impairment of ischemia-induced angiogenesis. Mice were treated or not with streptozotocin (40 mg/kg) and streptozotocin plus aminoguanidine (AGEs formation blocker, 50 mg/kg). After 8 weeks of treatment, hindlimb ischemia was induced by right femoral artery ligature. Plasma AGE levels were strongly elevated in diabetic mice when compared with control mice (579 ± 21 versus 47 ± 4 pmol/ml, respectively; P < 0.01). Treatment with aminoguanidine reduced AGE plasma levels when compared with untreated diabetic mice (P < 0.001). After 28 days of ischemia, ischemic/nonischemic leg angiographic score, capillary density, and laser Doppler skin-perfusion ratios were 1.4-, 1.5-, and 1.4-fold decreased in diabetic mice in reference to controls (P < 0.01). Treatment with aminoguanidine completely normalized ischemia-induced angiogenesis in diabetic mice. We next analyzed the role of proteolysis in AGE formation-induced hampered neovascularization process. After 3 days of ischemia, MMP-2 activity and MMP-3 and MMP-13 protein levels were increased in untreated and aminoguanidine-treated diabetic mice when compared with controls (P < 0.05). Despite this activation of the MMP pathway, collagenolysis was decreased in untreated diabetic mice. Conversely, treatment of diabetic mice with aminoguanidine restored collagenolysis toward levels found in control mice. In conclusion, blockade of AGE formation by aminoguanidine normalizes impaired ischemia-induced angiogenesis in diabetic mice. This effect is probably mediated by restoration of matrix degradation processes that are disturbed as a result of AGE accumulation. PMID:12805564

  3. Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice.

    PubMed

    Tamarat, Radia; Silvestre, Jean-Sébastien; Huijberts, Maya; Benessiano, Joelle; Ebrahimian, Teni G; Duriez, Micheline; Wautier, Marie-Paule; Wautier, Jean Luc; Lévy, Bernard I

    2003-07-08

    We hypothesized that formation of advanced glycation end products (AGEs) associated with diabetes reduces matrix degradation by metalloproteinases (MMPs) and contributes to the impairment of ischemia-induced angiogenesis. Mice were treated or not with streptozotocin (40 mg/kg) and streptozotocin plus aminoguanidine (AGEs formation blocker, 50 mg/kg). After 8 weeks of treatment, hindlimb ischemia was induced by right femoral artery ligature. Plasma AGE levels were strongly elevated in diabetic mice when compared with control mice (579 +/- 21 versus 47 +/- 4 pmol/ml, respectively; P < 0.01). Treatment with aminoguanidine reduced AGE plasma levels when compared with untreated diabetic mice (P < 0.001). After 28 days of ischemia, ischemic/nonischemic leg angiographic score, capillary density, and laser Doppler skin-perfusion ratios were 1.4-, 1.5-, and 1.4-fold decreased in diabetic mice in reference to controls (P < 0.01). Treatment with aminoguanidine completely normalized ischemia-induced angiogenesis in diabetic mice. We next analyzed the role of proteolysis in AGE formation-induced hampered neovascularization process. After 3 days of ischemia, MMP-2 activity and MMP-3 and MMP-13 protein levels were increased in untreated and aminoguanidine-treated diabetic mice when compared with controls (P < 0.05). Despite this activation of the MMP pathway, collagenolysis was decreased in untreated diabetic mice. Conversely, treatment of diabetic mice with aminoguanidine restored collagenolysis toward levels found in control mice. In conclusion, blockade of AGE formation by aminoguanidine normalizes impaired ischemia-induced angiogenesis in diabetic mice. This effect is probably mediated by restoration of matrix degradation processes that are disturbed as a result of AGE accumulation.

  4. Advanced Glycation End Products: A Molecular Target for Vascular Complications in Diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Nakamura, Nobutaka; Suematsu, Mika; Kaseda, Kuniyoshi; Matsui, Takanori

    2015-10-27

    A nonenzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and subsequently alters their structural integrity and function. This process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent and senescent macroprotein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence indicating that interaction of AGEs with their receptor (RAGE) elicits oxidative stress generation and as a result evokes proliferative, inflammatory, thrombotic and fibrotic reactions in a variety of cells. This evidence supports AGEs' involvement in diabetes- and aging-associated disorders such as diabetic vascular complications, cancer, Alzheimer's disease and osteoporosis. Therefore, inhibition of AGE formation could be a novel molecular target for organ protection in diabetes. This report summarizes the pathophysiological role of AGEs in vascular complications in diabetes and discusses the potential clinical utility of measurement of serum levels of AGEs for evaluating organ damage in diabetes.

  5. Human umbilical cord blood cells and diabetes mellitus: recent advances.

    PubMed

    Reddi, Alluru S; Kothari, Neil; Kuppasani, Kishore; Ende, Norman

    2015-01-01

    Stem cell therapy for patients with diabetes is an area of great interest to both scientists and clinicians. Human umbilical cord blood cells (HUCBCs) are being increasingly used as a source of stem cells for cell-based therapy for diabetes because these cells can differentiate into pancreatic islet β-cells. Administration of HUCBCs has been shown to lower blood glucose levels in diabetic animal models. The use of autologous HUCBC transfusion in type 1 diabetic children has not shown any benefit. However, "Stem Cell Educator" therapy has shown promise in long term lowering of blood glucose levels in both type 1 and type 2 diabetic patients. In this review, we will briefly discuss recent advances in HUCBC therapy in the treatment of diabetes and some of its complications.

  6. Advanced Glycation End Products Activate a Chymase-Dependent Angiotensin II Generating Pathway in Diabetic Complications

    PubMed Central

    Koka, Vijay; Wang, Wansheng; Huang, Xiao Ru; Kim-Mitsuyama, Shokei; Truong, Luan D.; Lan, Hui Y

    2006-01-01

    Background: Angiotensin II is a key mediator of diabetes-related vascular disease. It is now recognized that in addition to angiotensin converting enzyme (ACE), chymase is an important alternative angiotensin II generating enzyme in hypertension and diabetes. However, the mechanism of induction of chymase in diabetes remains unknown. Methods and Results: Here we report that chymase is upregulated in coronary and renal arteries in patients with diabetes by immunohistochemistry. Upregulation of vascular chymase is associated with deposition of advanced glycation end products (AGEs), increase in expression of the receptor for AGEs (RAGE), and activation of ERK1/2 MAP kinase. In vitro, AGEs can induce chymase expression and chymase-dependent angiotensin II generation in human vascular smooth muscle cells via the RAGE-ERK1/2 MAP kinase-dependent mechanism. This is confirmed by blockade of AGE-induced vascular chymase expression with a neutralizing RAGE antibody and an inhibitor to ERK1/2, and by overexpression of the dominant negative-ERK1/2. Compared to ACE, chymase contributes to the majority of angiotensin II production (more than 70%, p<0.01) in response to AGEs. Further more, AGE-induced Angiotensin II production is blocked by the anti-RAGE antibody and by inhibition of ERK1/2 MAP kinase activities. Conclusions: Advanced glycation end products, a hallmark of diabetes, induce chymase via the RAGE-ERK1/2 MAP kinase pathway. Chymase initiates an important alternative angiotensin II generating pathway in diabetes and may play a critical role in diabetic vascular disease. PMID:16520412

  7. Glycemia, diabetes status, and cognition in middle aged Hispanics

    PubMed Central

    Luchsinger, José A.; Cabral, Rafi; Eimicke, Joseph P.; Manly, Jennifer J.; Teresi, Jeanne

    2015-01-01

    Objective To examine the association of glycemia and diabetes status with cognition among 600 Hispanics aged 55 to 64 years from Northern Manhattan. Methods Diabetes was ascertained by history or Hemoglobin A1c (HbA1c). Normal glucose tolerance (NGT) and pre-diabetes were ascertained with HbA1c. Memory was assessed with the Selective Reminding Test (SRT). Executive abilities were assessed using the Color trails 1 and 2, and verbal fluency test. The cross-sectional association of glycemia and diabetes status with cognitive performance was examined using linear regression. Results Participants were a mean age of 59.2 ± 2.9 years old, 76.7% were women, and more than 65% had pre-diabetes or diabetes. HbA1C (β = − 0.97; p <0.001) and diabetes (β = − 2.06; p = 0.001) were related with lower SRT total recall after adjustment for demographics, education, and vascular risk factors. Pre-diabetes was associated with worse performance in color trails 2 (β = − 6.45 p = 0.022) after full adjustment. Conclusions Higher glycemia and diabetes are related to worse memory and executive abilities in late middle age, while pre-diabetes is related only to worse executive abilities. Longitudinal follow-up is needed to understand the order and progression of these deficits. PMID:26163818

  8. Recent Advances in Nanotechnology for Diabetes Treatment

    PubMed Central

    DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen

    2015-01-01

    Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to “closed-loop” insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels. “Closing the loop” between blood glucose level (BGL) measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. PMID:25641955

  9. Recent advances in nanotechnology for diabetes treatment.

    PubMed

    DiSanto, Rocco Michael; Subramanian, Vinayak; Gu, Zhen

    2015-01-01

    Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to 'closed-loop' insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels (BGLs). 'Closing the loop' between BGL measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed.

  10. Receptor for Advanced Glycation End Products (RAGE) Deficiency Attenuates the Development of Atherosclerosis in Diabetes

    PubMed Central

    Soro-Paavonen, Aino; Watson, Anna M.D.; Li, Jiaze; Paavonen, Karri; Koitka, Audrey; Calkin, Anna C.; Barit, David; Coughlan, Melinda T.; Drew, Brian G.; Lancaster, Graeme I.; Thomas, Merlin; Forbes, Josephine M.; Nawroth, Peter P.; Bierhaus, Angelika; Cooper, Mark E.; Jandeleit-Dahm, Karin A.

    2008-01-01

    OBJECTIVE—Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE−/− model of accelerated atherosclerosis. RESEARCH DESIGN AND METHODS—ApoE−/− and RAGE−/−/apoE−/− double knockout mice were rendered diabetic with streptozotocin and followed for 20 weeks, at which time plaque accumulation was assessed by en face analysis. RESULTS—Although diabetic apoE−/− mice showed increased plaque accumulation (14.9 ± 1.7%), diabetic RAGE−/−/apoE−/− mice had significantly reduced atherosclerotic plaque area (4.9 ± 0.4%) to levels not significantly different from control apoE−/− mice (4.3 ± 0.4%). These beneficial effects on the vasculature were associated with attenuation of leukocyte recruitment; decreased expression of proinflammatory mediators, including the nuclear factor-κB subunit p65, VCAM-1, and MCP-1; and reduced oxidative stress, as reflected by staining for nitrotyrosine and reduced expression of various NADPH oxidase subunits, gp91phox, p47phox, and rac-1. Both RAGE and RAGE ligands, including S100A8/A9, high mobility group box 1 (HMGB1), and the advanced glycation end product (AGE) carboxymethyllysine were increased in plaques from diabetic apoE−/− mice. Furthermore, the accumulation of AGEs and other ligands to RAGE was reduced in diabetic RAGE−/−/apoE−/− mice. CONCLUSIONS—This study provides evidence for RAGE playing a central role in the development of accelerated atherosclerosis associated with diabetes. These findings emphasize the potential utility of strategies targeting RAGE activation in the prevention and treatment of diabetic macrovascular complications. PMID:18511846

  11. Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications

    SciTech Connect

    Nagai, Rhoji; Murray, David B.; Metz, Thomas O.; Baynes, John

    2012-03-01

    Advanced glycation or glycoxidation end-products (AGE) increase in tissue proteins with age, and their rate of accumulation is increased in diabetes, nephropathy and inflammatory diseases. AGE inhibitors include a range of compounds that are proposed to act by trapping carbonyl and dicarbonyl intermediates in AGE formation. However, some among the newer generation of AGE inhibitors lack reactive functional groups that would trap reaction intermediates, indicating an alternative mechanism of action. We propose that AGE inhibitors function primarily as chelators, inhibiting metal-catalyzed oxidation reactions. The AGE-inhibitory activity of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is also consistent with their chelating activity. Finally, compounds described as AGE breakers, or their hydrolysis products, also have strong chelating activity, suggesting that these compounds also act through their chelating activity. We conclude that chelation is the common, and perhaps the primary, mechanism of action of AGE inhibitors and breakers, and that chronic, mild chelation therapy should prove useful in treatment of diabetes and age-related diseases characterized by oxidative stress, inflammation and increased chemical modification of tissue proteins by advanced glycoxidation and lipoxidation end-products.

  12. Cardiovascular KATP channels and advanced aging

    PubMed Central

    Yang, Hua-Qian; Subbotina, Ekaterina; Ramasamy, Ravichandran; Coetzee, William A.

    2016-01-01

    With advanced aging, there is a decline in innate cardiovascular function. This decline is not general in nature. Instead, specific changes occur that impact the basic cardiovascular function, which include alterations in biochemical pathways and ion channel function. This review focuses on a particular ion channel that couple the latter two processes, namely the KATP channel, which opening is promoted by alterations in intracellular energy metabolism. We show that the intrinsic properties of the KATP channel changes with advanced aging and argue that the channel can be further modulated by biochemical changes. The importance is widespread, given the ubiquitous nature of the KATP channel in the cardiovascular system where it can regulate processes as diverse as cardiac function, blood flow and protection mechanisms against superimposed stress, such as cardiac ischemia. We highlight questions that remain to be answered before the KATP channel can be considered as a viable target for therapeutic intervention. PMID:27733235

  13. [Advances in arterial hypertension and diabetes mellitus].

    PubMed

    Cordero, Alberto; Lekuona, Iñaki; Galve, Enrique; Mazón, Pilar

    2012-01-01

    In 2011, the importance of hypertension and diabetes mellitus as the two main risk factors responsible for the development of cardiovascular disease became clear, as did their significance as major public health issues. Compared with previous years, in which publication of the results of large clinical trials dominated scientific progress, in the last year, the focus has shifted to evidence that novel mechanisms associated with blood pressure, glucose metabolism and diabetes can influence cardiovascular disease. Of particular importance were clinical trials in the area of renal dysfunction, such as the SHARP and ROADMAP trials.

  14. Linagliptin blocks renal damage in type 1 diabetic rats by suppressing advanced glycation end products-receptor axis.

    PubMed

    Nakashima, S; Matsui, T; Takeuchi, M; Yamagishi, S-I

    2014-09-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We have recently found that linagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP-4) suppresses the AGE-induced oxidative stress generation and intercellular adhesion molecule-1 (ICAM-1) gene expression in endothelial cells. However, whether linagliptin could have beneficial effects on experimental diabetic nephropathy in a glucose-lowering independent manner remains unknown. To address the issue, this study examined the effects of linagliptin on renal damage in streptozotocin-induced diabetic rats. Serum levels of DPP-4 were significantly elevated in diabetic rats compared with control rats. Although linagliptin treatment for 2 weeks did not improve hyperglycemia in diabetic rats, linagliptin significantly reduced AGEs levels, RAGE gene expression, and 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress in the kidney of diabetic rats. Furthermore, linagliptin significantly reduced albuminuria, renal ICAM-1 mRNA levels, and lymphocyte infiltration into the glomeruli of diabetic rats. Our present study suggests that linagliptin could exert beneficial effects on diabetic nephropathy partly by blocking the AGE-RAGE-evoked oxidative stress generation in the kidney of streptozotocin-induced diabetic rats. Inhibition of DPP-4 by linagliptin might be a promising strategy for the treatment of diabetic nephropathy.

  15. Detection of RAGE expression and its application to diabetic wound age estimation.

    PubMed

    Ji, Xin-Yi; Chen, Yang; Ye, Guang-Hua; Dong, Miao-Wu; Lin, Ke-Zhi; Han, Jun-Ge; Feng, Xiang-Ping; Li, Xing-Biao; Yu, Lin-Sheng; Fan, Yan-Yan

    2017-01-11

    With the prevalence of diabetes, it is becoming important to analyze the diabetic wound age in forensic practice. The present study investigated the time-dependent expression of receptor for advanced glycation end products (RAGE) during diabetic wound healing in mice and its applicability to wound age determination by immunohistochemistry, double immunofluorescence, and Western blotting. After an incision was created in genetically diabetic db/db mice and control mice, mice were killed at posttraumatic intervals ranging from 6 h to 14 days, followed by the sampling of wound margin. Compared with control mice, diabetic mice showed the delayed wound healing. In control and diabetic wound specimens, RAGE immunoreactivity was observed in a small number of polymorphonuclear cells (PMNs), a number of macrophages, and fibroblasts. Morphometrically, the positive ratios of RAGE in macrophages or fibroblasts considerably increased in diabetic wounds during late repair, which exceeded 60% at 7 and 10 days post-injury. There were no control wound specimens to show a ratio of >60% in macrophages or fibroblasts. By Western blotting analysis, the ratios of RAGE to GAPDH were >1.4 in all diabetic wound samples from 7 to 10 days post-injury, which were >1.8 at 10 days after injury. By comparison, no control wound specimens indicated a ratio of >1.4. In conclusion, the expression of RAGE is upregulated and temporally distributed in macrophages and fibroblasts during diabetic wound healing, which might be closely involved in prolonged inflammation and deficient healing. Moreover, RAGE is promising as a useful marker for diabetic wound age determination.

  16. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    PubMed Central

    Kim, Junghyun; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Chan-Sik; Kim, Jin Sook

    2016-01-01

    Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs) are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE) against damage to retinal vascular cells were investigated in streptozotocin (STZ)-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling)-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs) binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells. PMID:27657123

  17. RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study

    PubMed Central

    Wang, Pin; Huang, Rong; Lu, Sen; Xia, Wenqing; Cai, Rongrong; Sun, Haixia; Wang, Shaohua

    2016-01-01

    Objective Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer’s disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cognitive impairment (MCI) among type 2 diabetes patients. Methods Of the 167 hospitalized type 2 diabetes patients recruited, 82 satisfied the diagnostic criteria for MCI, and 85 matched control individuals were classified as non-MCI. Demographic data were collected, and the soluble RAGE (sRAGE) concentrations, serum AGE-peptide (AGE-P) levels, RAGE Gly82Ser genotype and neuropsychological test results were examined. Results The MCI group exhibited a decreased sRAGE level (0.87±0.35 vs. 1.05±0.52 ng/ml, p<0.01) and an increased serum AGE-P level (3.54±1.27 vs. 2.71±1.18 U/ml, p<0.01) compared with the control group. Logistic regression analysis indicated that each unit reduction in the sRAGE concentration increased the MCI risk by 54% (OR 0.46[95% CI 0.22–0.96], p = 0.04) and that each unit increase in the AGE-P level increased the MCI risk by 72% in the type 2 diabetes patients (OR 1.72[95% CI 1.31–2.28], p<0.01). The serum sRAGE level was negatively correlated with the score on the trail making test-B (TMT-B) (r = -0.344, p = 0.002), which indicates early cognitive deficits related to diabetes. Moreover, the AGE-P level was positively correlated with multiple cognitive domains (all p<0.05). No significant differences in the neuropsychological test results or serum RAGE concentrations between the different RAGE genotypes or in the RAGE genotype frequencies between the MCI and control groups were identified (all p>0.05). Conclusions The RAGE pathway partially mediates AGE-induced MCI in diabetic patients. The serum AGE-P level may serve as a serum biomarker of MCI in these individuals, and sRAGE represents a predictor and even a potential intervention target of

  18. The receptor for advanced glycation end products (RAGE) specifically recognizes methylglyoxal-derived AGEs.

    PubMed

    Xue, Jing; Ray, Rashmi; Singer, David; Böhme, David; Burz, David S; Rai, Vivek; Hoffmann, Ralf; Shekhtman, Alexander

    2014-05-27

    Diabetes-induced hyperglycemia increases the extracellular concentration of methylglyoxal. Methylglyoxal-derived hydroimidazolones (MG-H) form advanced glycation end products (AGEs) that accumulate in the serum of diabetic patients. The binding of hydroimidozolones to the receptor for AGEs (RAGE) results in long-term complications of diabetes typified by vascular and neuronal injury. Here we show that binding of methylglyoxal-modified albumin to RAGE results in signal transduction. Chemically synthesized peptides containing hydroimidozolones bind specifically to the V domain of RAGE with nanomolar affinity. The solution structure of an MG-H1-V domain complex revealed that the hydroimidazolone moiety forms multiple contacts with a positively charged surface on the V domain. The high affinity and specificity of hydroimidozolones binding to the V domain of RAGE suggest that they are the primary AGE structures that give rise to AGEs-RAGE pathologies.

  19. Molecular mechanisms of AGE/RAGE-mediated fibrosis in the diabetic heart

    PubMed Central

    Zhao, Jia; Randive, Rushil; Stewart, James A

    2014-01-01

    Chronic hyperglycemia is one of the main characteristics of diabetes. Persistent exposure to elevated glucose levels has been recognized as one of the major causal factors of diabetic complications. In pathologies, like type 2 diabetes mellitus (T2DM), mechanical and biochemical stimuli activate profibrotic signaling cascades resulting in myocardial fibrosis and subsequent impaired cardiac performance due to ventricular stiffness. High levels of glucose nonenzymatically react with long-lived proteins, such as collagen, to form advanced glycation end products (AGEs). AGE-modified collagen increase matrix stiffness making it resistant to hydrolytic turnover, resulting in an accumulation of extracellular matrix (ECM) proteins. AGEs account for many of the diabetic cardiovascular complications through their engagement of the receptor for AGE (RAGE). AGE/RAGE activation stimulates the secretion of numerous profibrotic growth factors, promotes increased collagen deposition leading to tissue fibrosis, as well as increased RAGE expression. To date, the AGE/RAGE cascade is not fully understood. In this review, we will discuss one of the major fibrotic signaling pathways, the AGE/RAGE signaling cascade, as well as propose an alternate pathway via Rap1a that may offer insight into cardiovascular ECM remodeling in T2DM. In a series of studies, we demonstrate a role for Rap1a in the regulation of fibrosis and myofibroblast differentiation in isolated diabetic and non-diabetic fibroblasts. While these studies are still in a preliminary stage, inhibiting Rap1a protein expression appears to down-regulate the molecular switch used to activate the ζ isotype of protein kinase C thereby promote AGE/RAGE-mediated fibrosis. PMID:25512788

  20. Comparison of Age of Onset and Frequency of Diabetic Complications in the Very Elderly Patients with Type 2 Diabetes

    PubMed Central

    2016-01-01

    Background The prevalence of type 2 diabetes in elderly people has increased dramatically in the last few decades. This study was designed to clarify the clinical characteristics of type 2 diabetes in patients aged ≥80 years according to age of onset. Methods We reviewed the medical records of 289 patients aged ≥80 years with type 2 diabetes at the outpatient diabetes clinics of Kangwon National University Hospital from September 2010 to June 2014. We divided the patients into middle-age-onset diabetes (onset before 65 years of age) and elderly-onset diabetes (onset at 65+ years of age). Results There were 141 male and 148 female patients. The patients had a mean age of 83.2±2.9 years and the mean duration of diabetes was 14.3±10.4 years. One hundred and ninety-nine patients had elderly-onset diabetes. The patients with elderly-onset diabetes had a significantly lower frequency of diabetic retinopathy and nephropathy, lower serum creatinine levels, lower glycated hemoglobin (HbA1c) levels, and similar coronary revascularization and cerebral infarction rates compared to those with middle-age-onset diabetes. There was no frequency difference in coronary revascularization and cerebral infarction and HbA1c levels between three subgroups (<5, 5 to 15, and ≥15 years) of diabetes duration in elderly onset diabetes. However, both in the elderly onset diabetes and middle-age-onset diabetes, the cumulative incidence of retinopathy was increasing rapidly according to the duration of diabetes. Conclusion We report that individuals with elderly-onset diabetes have a lower frequency of diabetic retinopathy and nephropathy and similar cardiovascular complications compared to those with middle-age-onset diabetes. PMID:27586451

  1. Circulating advanced glycation peptides in streptozotocin-induced diabetic rats: evidence for preferential modification of IgG light chains.

    PubMed

    Gugliucci, A; Menini, T

    1998-01-01

    As the glycation/glycoxidation hypothesis for the genesis of diabetic complications is achieving widespread acceptance, much attention is being paid to the role of low molecular weight advanced glycation (AGE) adducts, as second generation glycating agents. We set out a study with the objective of attesting the presence of increased amounts of AGE-peptides in the circulation of streptozotocin-induced diabetic rats and to determine the nature of the plasma proteins which are main targets for advanced glycation. AGE (Ex 370/Em 440 nm) and pentosidine fluorescence (Ex 335/Em 385 nm) were significantly higher in plasma from diabetic rats after only one month of hyperglycemia as compared to controls (35 +/- 7 vs 25 +/- 2 AU, p< 0.05 and 54 +/- 14 vs 27 +/- 3 AU, p< 0.01 respectively). AGE-peptides (<10 kDa) were more than two-fold higher in diabetic animals. Immunoblots after SDS-PAGE of plasma proteins showed that AGE-IgG displayed a selective predominant increment in the same animals. When native rat IgG was incubated in the presence of AGE-peptides isolated from diabetic animals, AGE modification was already apparent after only 24 h of incubation, and was particularly important for light chains. AGE-immunoreactive light chains displayed an apparent increase in molecular weight. Aminoguanidine prevented, while copper enhanced AGE binding to IgG light chains. Our data validate the streptozotocin-induced diabetic rat as a model reproducing the presence of circulating AGE-peptides, give evidence that IgG are preferential targets for advanced glycation in plasma and suggest that this modification, mediated by AGE-peptides, can be prevented by aminoguanidine.

  2. Self–reported diabetes education among Chinese middle–aged and older adults with diabetes

    PubMed Central

    Xu, Hanzhang; Luo, Jianfeng; Wu, Bei

    2016-01-01

    Background To compare self–reported diabetes education among Chinese middle–aged and older adults with diabetes in three population groups: urban residents, migrants in urban settings, and rural residents. Methods We used data from the 2011 China Health and Retirement Longitudinal Study. The sample included 993 participants age 45 and older who reported having diabetes diagnosed from a health professional. We performed multilevel regressions performed to examine the associations between characteristics and different aspects of diabetes education received. Findings Our study shows that 20.24% of the participants received no diabetes education at all. Among those who received information, 46.82% of respondents with diabetes received weight control advice from a health care provider, 90.97% received advice on exercise, 60.37% received diet advice, 35.12% were spoken to smoking control, and only 17.89% of persons were informed of foot care. After controlling socioeconomic factors, life style, number of comorbidities and community factors, we found that compared with migrant population and rural residents, urban residents were more likely to receive diabetes education on diet. Urban residents were also more likely to obtain diabetes education and more aspects of diabetes education comparison with migrants and rural residents. Conclusions Our study suggests diabetes education is a serious concern in China, and a significant proportion of the participants did not receive advice on smoking control and foot care. Rural residents and migrants from rural areas received much less diabetes education compared with urban residents. Efforts to improve diabetes educations are urgently needed in China. PMID:27698998

  3. Diabetes technology and treatments in the paediatric age group.

    PubMed

    Shalitin, S; Peter Chase, H

    2011-02-01

    Type 1 diabetes (T1D) is one of the most common chronic childhood diseases and its incidence has doubled during the last decade. The goals of intensive management of diabetes were established in 1993 by the Diabetes Control and Complications Trial (DCCT) (1). Children with T1D and their caregivers continue to face the challenge to maintain blood glucose levels in the near-normal range. It is important to prevent sustained hyperglycaemia which is associated with long-term microvascular and macrovascular complications and to avoid recurrent episodes of hypoglycaemia or hyperglycaemia, especially in young children, which may have adverse effects on cognitive function and impede efforts to achieve the recommended glycaemic targets. Advances in the use of technology that may help maintain the metabolic control goals for young people with T1D were centred on continuous subcutaneous insulin infusion (CSII) (2-4), continuous glucose monitoring (CGM) (5-7), and combining both technologies into a closed-loop system (8-10). The dilemma in paediatrics of patient selection for insulin pump therapy was found to be most successful in those with more frequent self-monitoring of blood glucose (SMBG) and younger age prior to pump initiation (2). Similarly, those who used a dual-wave bolus probably paid closer attention to their management and had lower HbA1c levels (3). The advantage of using a pre-meal bolus to improve postprandial glucose levels was shown to offer another potential method to improve glycaemic control (4). SMBG is an important component of therapy in patients with diabetes, especially in the paediatric age group. Standard use of glucose meters for SMBG provides only intermittent single blood glucose levels, without giving the 'whole picture' of glucose variability during the 24 h, and especially during the night, when blood glucose levels are seldom measured. Therefore, the use of a device such as real-time continuous glucose monitoring (RT-CGM) that provides

  4. Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats.

    PubMed

    Li, X S; Tanz, R D; Chang, K S

    1989-08-01

    1. Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12-week diabetic rats (164 +/- 17) displayed the greatest bradycardia compared to age-matched controls (268 +/- 15; P less than 0.001), and diabetics treated with insulin (232 +/- 17; P less than 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined. 2. Hearts from 6-52 week STZ-treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10(-7) M) did not affect the resting heart rate of age-matched controls or diabetics but blocked methacholine (2.6 x 10(-6) M)-induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors. 3. At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 x 10(-6) M) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age-matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect. 4. In general, hearts from diabetic animals treated with insulin respond similarly to their agematched controls in the presence and absence of methacholine.

  5. Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats.

    PubMed

    Jagtap, A G; Patil, P B

    2010-01-01

    Cuminum cyminum is widely used as a spice in many countries. The aim of the present study was to investigate the effect of methanolic extract of seeds of C. cyminum (CC) on diabetes, oxidative stress and formation of advanced glycated end products (AGE) and obtain comparison with glibenclamide. In vitro studies indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC and glibenclamide for 28 days caused a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to diabetic control rats. Significant reduction in renal oxidative stress and AGE was observed with CC when compared to diabetic control and glibenclamide. CC and glibenclamide improved antioxidant status in kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen, collagen linked fluorescence and reduction in pepsin digestion. Treatment with CC significantly improved these parameters when compared to diabetic control and glibenclamide group. Though the antidiabetic effect of CC was comparable to glibenclamide it had better effect in controlling oxidative stress and inhibiting the AGE formation, which are implicated in the pathogenesis of diabetic microvascular complications.

  6. Vitreous advanced glycation endproducts and α-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

    PubMed Central

    Mulder, Douwe J.; Schalkwijk, Casper G.; Scheijen, Jean L.; Smit, Andries J.; Los, Leonoor I.

    2017-01-01

    Purpose Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. Methods We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 non-diabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and 5-hydro-5-methylimidazolone) and α-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. Results Mean age was 64 ± 7.6 years for T2DM patients and 63 ± 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3–7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 μmol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and α-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). Conclusions Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients. PMID:28264049

  7. A novel mouse model of advanced diabetic kidney disease.

    PubMed

    Thibodeau, Jean-Francois; Holterman, Chet E; Burger, Dylan; Read, Naomi C; Reudelhuber, Timothy L; Kennedy, Christopher R J

    2014-01-01

    Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN) such as hyperfiltration, mesangial expansion, and albuminuria yet features of late DN (hypertension, GFR decline, tubulointerstitial fibrosis) are absent or require a significant time investment for full phenotype development. Accordingly, the aim of the present study was to develop a mouse model of advanced DN with hypertension superimposed (HD mice). Mice transgenic for human renin cDNA under the control of the transthyretin promoter (TTRhRen) were employed as a model of angiotensin-dependent hypertension. Diabetes was induced in TTRhRen mice through low dose streptozotocin (HD-STZ mice) or by intercrossing with OVE26 diabetic mice (HD-OVE mice). Both HD-STZ and HD-OVE mice displayed more pronounced increases in urinary albumin levels as compared with their diabetic littermates. Additionally, HD mice displayed renal hypertrophy, advanced glomerular scarring and evidence of tubulointerstitial fibrosis. Both HD-OVE and HD-STZ mice showed evidence of GFR decline as FITC-inulin clearance was decreased compared to hyperfiltering STZ and OVE mice. Taken together our results suggest that HD mice represent a robust model of type I DN that recapitulates key features of human disease which may be significant in studying the pathogenesis of DN and in the assessment of putative therapeutics.

  8. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease

    PubMed Central

    Kalantar-Zadeh, Kamyar

    2015-01-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed. PMID:26300611

  9. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease.

    PubMed

    Goldstein-Fuchs, Jordi; Kalantar-Zadeh, Kamyar

    2015-08-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed.

  10. Prediabetes, undiagnosed diabetes, and diabetes among Mexican adults: findings from the Mexican Health and Aging Study

    PubMed Central

    Kumar, Amit; Wong, Rebeca; Ottenbacher, Kenneth J.; Al Snih, Soham

    2016-01-01

    Purpose The purpose of the study was to examine the prevalence and determinants of prediabetes, undiagnosed diabetes, and diabetes among Mexican adults from a subsample of the Mexican Health and Aging Study. Methods We examined 2012 participants from a subsample of the Mexican Health and Aging Study. Measures included sociodemographic characteristics, body mass index, central obesity, medical conditions, cholesterol, high-density lipoprotein cholesterol, hemoglobin A1c, and vitamin D. Logistic regression was performed to identify factors associated with prediabetes, undiagnosed diabetes, and self-reported diabetes. Results Prevalence of prediabetes, undiagnosed, and self-reported diabetes in this cohort was 44.2%, 18.0%, and 21.4%, respectively. Participants with high waist-hip ratio (1.61, 95% confidence interval [CI] = 1.05–2.45) and high cholesterol (1.85, 95% CI = 1.36–2.51) had higher odds of prediabetes. Overweight (1.68, 95% CI = 1.07–2.64), obesity (2.38, 95% CI = 1.41–4.02), and high waist circumference (1.60, 95% CI = 1.06–2.40) were significantly associated with higher odds of having undiagnosed diabetes. Those residing in a Mexican state with high U.S. migration had lower odds of prediabetes (0.61, 95% CI = 0.45–0.82) and undiagnosed diabetes (0.53, 95% CI = 0.41–0.70). Those engaged in regular physical activity had lower odds of undiagnosed diabetes (0.74, 95% CI = 0.57–0.97). Conclusions There is a high prevalence of prediabetes and undiagnosed diabetes among Mexican adults in this subsample. Findings suggest the need for resources to prevent, identify, and treat persons with prediabetes and undiagnosed diabetes. PMID:26872919

  11. Effect of green tea extract on advanced glycation and cross-linking of tail tendon collagen in streptozotocin induced diabetic rats.

    PubMed

    Babu, Pon Velayutham Anandh; Sabitha, Kuruvimalai Ekambaram; Shyamaladevi, Chennam Srinivasulu

    2008-01-01

    Diabetes leads to modification of collagen such as advanced glycation and cross-linking which play an important role in the pathogenesis of diabetes mellitus. We have investigated the effect of green tea on modification of collagen in streptozotocin (60 mg/kg body weight) induced diabetic rats. To investigate the therapeutic effect of green tea, treatment was begun six weeks after the onset of diabetes and green tea extract (300 mg/kg body weight) was given orally for 4 weeks. The collagen content, extent of advanced glycation, advanced glycation end products (AGE) and cross-linking of tail tendon collagen were investigated. Green tea reduced the tail tendon collagen content which increased in diabetic rats. Accelerated advanced glycation and AGE in diabetic animals, as detected by Ehrlich's-positive material and collagen linked fluorescence respectively were reduced significantly by green tea. The solubility of tail tendon collagen decreased significantly in diabetic rats indicating a remarkable increase in the cross-linking, whereas green tea increases the solubility of collagen in diabetic rats. The present study reveals that green tea is effective in reducing the modification of tail tendon collagen in diabetic rats. Thus green tea may have a therapeutic effect in the treatment of glycation induced complications of diabetes.

  12. Technology Use in Transition-Age Patients With Type 1 Diabetes

    PubMed Central

    Los, Evan; Ulrich, Jenae; Guttmann-Bauman, Ines

    2016-01-01

    Youth with chronic illnesses have the greatest risk for a decline in their health management during transition-age. Because of this demonstrated and well-known issue, research has focused on how to improve the transition of care process. Despite the increasing number of technological devices on the market and the advances in telemedicine modalities available to patients with type 1 diabetes (T1D), the utilization of technology is still suboptimal among patients of transition-age (ages 13-25). This article reviews the available resources, patterns of use in transition-age youth, and explores opportunities to advance technology use in transitioning patients with T1D from pediatric to adult care. PMID:26892506

  13. Male biological clock: a critical analysis of advanced paternal age

    PubMed Central

    Ramasamy, Ranjith; Chiba, Koji; Butler, Peter; Lamb, Dolores J.

    2016-01-01

    Extensive research defines the impact of advanced maternal age on couples’ fecundity and reproductive outcomes, but significantly less research has been focused on understanding the impact of advanced paternal age. Yet it is increasingly common for couples at advanced ages to conceive children. Limited research suggests that the importance of paternal age is significantly less than that of maternal age, but advanced age of the father is implicated in a variety of conditions affecting the offspring. This review examines three aspects of advanced paternal age: the potential problems with conception and pregnancy that couples with advanced paternal age may encounter, the concept of discussing a limit to paternal age in a clinical setting, and the risks of diseases associated with advanced paternal age. As paternal age increases, it presents no absolute barrier to conception, but it does present greater risks and complications. The current body of knowledge does not justify dissuading older men from trying to initiate a pregnancy, but the medical community must do a better job of communicating to couples the current understanding of the risks of conception with advanced paternal age. PMID:25881878

  14. Proteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation

    PubMed Central

    Kesavan, Suresh K.; Bhat, Shweta; Golegaonkar, Sandeep B.; Jagadeeshaprasad, Mashanipalya G.; Deshmukh, Arati B.; Patil, Harshal S.; Bhosale, Santosh D.; Shaikh, Mahemud L.; Thulasiram, Hirekodathakallu V.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.

    2013-01-01

    The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging. PMID:24126953

  15. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts.

    PubMed

    Li, D X; Deng, T Z; Lv, J; Ke, J

    2014-12-01

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80 ± 5.50%, P<0.01) and increased apoptosis (11.31 ± 1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  16. Treatment of diabetic retinopathy: Recent advances and unresolved challenges.

    PubMed

    Stewart, Michael W

    2016-08-25

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies.

  17. Treatment of diabetic retinopathy: Recent advances and unresolved challenges

    PubMed Central

    Stewart, Michael W

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in industrialized countries. Remarkable advances in the diagnosis and treatment of DR have been made during the past 30 years, but several important management questions and treatment deficiencies remain unanswered. The global diabetes epidemic threatens to overwhelm resources and increase the incidence of blindness, necessitating the development of innovative programs to diagnose and treat patients. The introduction and rapid adoption of intravitreal pharmacologic agents, particularly drugs that block the actions of vascular endothelial growth factor (VEGF) and corticosteroids, have changed the goal of DR treatment from stabilization of vision to improvement. Anti-VEGF injections improve visual acuity in patients with diabetic macular edema (DME) from 8-12 letters and improvements with corticosteroids are only slightly less. Unfortunately, a third of patients have an incomplete response to anti-VEGF therapy, but the best second-line therapy remains unknown. Current first-line therapy requires monthly visits and injections; longer acting therapies are needed to free up healthcare resources and improve patient compliance. VEGF suppression may be as effective as panretinal photocoagulation (PRP) for proliferative diabetic retinopathy, but more studies are needed before PRP is abandoned. For over 30 years laser was the mainstay for the treatment of DME, but recent studies question its role in the pharmacologic era. Aggressive treatment improves vision in most patients, but many still do not achieve reading and driving vision. New drugs are needed to add to gains achieved with available therapies. PMID:27625747

  18. Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.

    PubMed

    Khodeer, Dina M; Zaitone, Sawsan A; Farag, Noha E; Moustafa, Yasser M

    2016-05-01

    Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.

  19. Predictive factors for hospitalized and institutionalized care-giving of the aged patients with diabetes mellitus in Japan.

    PubMed

    Matsuzawa, Toshioki; Sakurai, Takashi; Kuranaga, Masako; Endo, Hidetoshi; Yokono, Koichi

    2011-01-21

    To identify predictive factors for hospitalized and institutionalized care-giving among a group of aged patients with diabetes mellitus in Japan, retrospective chart review was performed in 288 diabetic subjects aged 65 years or older. Independent variables, based on the chart review, were age, sex, diagnosis, diabetic control and complications. Comprehensive geriatric assessment was performed to obtain information on the functional capacity and demographic variables, including physical and mental function, and socioeconomic status. 131 diabetic patients were considered as frail elderly and characterized for their higher age, longer duration of diabetes, higher frequency of insulin use, lower cognitive function, and lower QOL, in comparison with those of non-frail patients. All non-frail diabetic patients were independently treated at their homes, while 38 subjects out of 131 frail diabetic patients were hospitalized or institutionalized. Apparent clinical features of hospitalized/institutionalized patients were higher age, higher serum creatinine, and higher prevalence of stroke episodes, advanced cognitive decline and absence of key caregiver in the family members, in comparison with those of in-home frail diabetic patients. The predicted probabilities from the multivariate logistic regression analysis in predicting hospitalized and institutionalized care-giving were as follows: Log p/(1 - p) = -19.801x1 - 54.269x2 + 721.405; where x1 = cognitive function (score), x2 = social support (score). Receiver operating characteristic curve analysis revealed a satisfactory discrimination for hospitalized and institutionalized care-giving in frail diabetic elderly with 92.9% of sensitivity and 91.4% of specificity, when the cutoff point of the model was set at 0.992. We concluded that cognitive decline and low social support are the predictive for hospital and institutional care-giving, and that demographic and mental information as well as diagnostic data should be

  20. Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy.

    PubMed

    Kumar Pasupulati, Anil; Chitra, P Swathi; Reddy, G Bhanuprakash

    2016-12-01

    Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients and a leading cause of end-stage renal disease (ESRD). Degenerative changes such as glomerular hypertrophy, hyperfiltration, widening of basement membranes, tubulointerstitial fibrosis, glomerulosclerosis and podocytopathy manifest in various degrees of proteinuria in DN. One of the key mechanisms implicated in the pathogenesis of DN is non-enzymatic glycation (NEG). NEG is the irreversible attachment of reducing sugars onto free amino groups of proteins by a series of events, which include the formation of Schiff's base and an Amadori product to yield advanced glycation end products (AGEs). AGE modification of client proteins from the extracellular matrix induces crosslinking, which is often associated with thickening of the basement membrane. AGEs activate several intracellular signaling cascades upon interaction with receptor for AGEs (RAGE), which manifest in aberrant cellular responses such as inflammation, apoptosis and autophagy, whereas other receptors such as AGE-R1, AGE-R3 and scavenger receptors also bind to AGEs and ensue endocytosis and degradation of AGEs. Elevated levels of both serum and tissue AGEs are associated with adverse renal outcome. Increased evidence supports that attenuation of AGE formation and/or inhibition of RAGE activation manifest(s) in improving renal function. This review provides insights of NEG, discusses the cellular and molecular events triggered by AGEs, which manifest in the pathogenesis of DN including renal fibrosis, podocyte epithelial-mesenchymal transition and activation of renin-angiotensin system. Therapies designed to target AGEs, such as inhibitors of AGEs formation and crosslink breakers, are discussed.

  1. Contribution of dietary advanced glycation end products (AGE) to circulating AGE: role of dietary fat.

    PubMed

    Davis, Kathleen E; Prasad, Chandan; Vijayagopal, Parakat; Juma, Shanil; Adams-Huet, Beverley; Imrhan, Victorine

    2015-12-14

    The purpose of this pilot study was to determine whether macronutrient content (low-fat v. high-fat diet) influences an indicator of advanced glycation end products (AGE), N(ε) carboxymethyl-lysine (CML), in the context of a 1-d, high-AGE diet. The effect of the diets on inflammatory markers was also assessed. A total of nineteen overweight and obese adults (nine men and ten women) without known disease were recruited to participate in a crossover challenge of a high-fat, high-AGE (HFHA) and low-fat, high-AGE (LFHA) diet. In each phase patients had fasting blood drawn, followed by consumption of a high-fat or low-fat breakfast test meal, then three postprandial blood draws at 1, 2 and 3 h after consuming the test meal. After consuming high-AGE meals for the remainder of the day, participants returned the next day for a follow-up analysis. A different pattern in the 3-h post-meal CML and soluble receptor for AGE response to the two diets was observed (P=0·01 and 0·05, respectively). No change in serum CML was observed following consumption of a LFHA breakfast (535 (25th-75th percentile 451-790) to 495 (25th-75th percentile 391-682) ng/ml; P=0·36), whereas a rise in CML occurred after the HFHA breakfast (463 (25th-75th percentile 428-664) to 578 (25th-75th percentile 474-865) ng/ml; P=0·05). High sensitivity C-reactive protein and high molecular weight adiponectin were not affected by either diet. These findings suggest that dietary CML may not be as important in influencing serum CML as other dietary factors. In addition, acute exposure to dietary CML may not influence inflammation in adults without diabetes or kidney disease. This is contrary to previous findings.

  2. AGE-breakers cleave model compounds, but do not break Maillard crosslinks in skin and tail collagen from diabetic rats.

    PubMed

    Yang, Shengzu; Litchfield, John E; Baynes, John W

    2003-04-01

    Advanced glycation end products (AGE), formed by nonenzymatic Maillard reactions between carbohydrate and protein, contribute to the increase in chemical modification and crosslinking of tissue proteins with age. Acceleration of AGE formation in collagen during hyperglycemia, with resultant effects on vascular elasticity and basement membrane permeability, is implicated in the pathogenesis of diabetic complications. AGE-breakers, such as N-phenacylthiazolium (PTB) and N-phenacyl-4,5-dimethylthiazolium (PMT) halides, have been proposed as therapeutic agents for reversing the increase in protein crosslinking in aging and diabetes. We have confirmed that these compounds, as well as the AGE-inhibitor pyridoxamine (PM), cleave the model AGE crosslink, phenylpropanedione, and have studied the effects of these compounds in reversing the increased crosslinking of skin and tail collagen isolated from diabetic rats. Crosslinking of skin collagen, measured as the half-time for solubilization of collagen by pepsin in 0.5M acetic acid, was increased approximately 5-fold in diabetic, compared to nondiabetic rats. Crosslinking of tail tendon collagen, measured as insolubility in 0.05 N acetic acid, was increased approximately 10-fold. Collagen preparations were incubated in the presence or absence of AGE-breakers or PM in phosphate buffer, pH 7.4, for 24h at 37 degrees C. These treatments did not decrease the half-time for solubilization of diabetic skin collagen by pepsin or increase the acid solubility of diabetic tail tendon collagen. We conclude that, although AGE-breakers and PM cleave model crosslinks, they do not significantly cleave AGE crosslinks formed in vivo in skin collagen of diabetic rats.

  3. Advances in management of type 1 diabetes mellitus

    PubMed Central

    Aathira, Ravindranath; Jain, Vandana

    2014-01-01

    Treatment of type 1 diabetes mellitus has always posed a challenge to balance hyperglycemia control with hypoglycemia episodes. The quest for newer therapies is continuing and this review attempts to outline the recent developments. The insulin molecule itself has got moulded into different analogues by minor changes in its structure to ensure well controlled delivery, stable half-lives and lesser side effects. Insulin delivery systems have also consistently undergone advances from subcutaneous injections to continuous infusion to trials of inhalational delivery. Continuous glucose monitoring systems are also becoming more accurate and user friendly. Smartphones have also made their entry into therapy of diabetes by integrating blood glucose levels and food intake with calculated adequate insulin required. Artificial pancreas has enabled to a certain extent to close the loop between blood glucose level and insulin delivery with devices armed with meal and exercise announcements, dual hormone delivery and pramlintide infusion. Islet, pancreas-kidney and stem cells transplants are also being attempted though complete success is still a far way off. Incorporating insulin gene and secretary apparatus is another ambitious leap to achieve insulin independence though the search for the ideal vector and target cell is still continuing. Finally to stand up to the statement, prevention is better than cure, immunological methods are being investigated to be used as vaccine to prevent the onset of diabetes mellitus. PMID:25317246

  4. Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

    PubMed

    Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

    2017-05-01

    Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue.

  5. Neurobehaviour of school age children born to diabetic mothers

    PubMed Central

    Ornoy, A; Ratzon, N; Greenbaum, C; Peretz, E; Soriano, D; Dulitzky, M

    1998-01-01

    AIM—To study the neurobehavioural effects that diabetes during pregnancy might have on children by school age.
METHODS—The neurobehavioural function of 57 school age children born to 48, well controlled diabetic mothers was compared with 57control children matched for age, birth order, and parental socioeconomic status, using several cognitive, behavioural, sensory and motor neurological tests.
RESULTS—The IQ scores of the index group children were similar to those of control children (117.7±13.4 vs 118.5±10.1). There were no differences between the groups in various sensory motor functions. However, the index group children performed less well than the controls on indices of fine and gross motor functions, as observed on the Bruininks-Oseretzky test of motor proficiency. The scores of children born to diabetic mothers were higher than controls on the Touwen and Prechtl neurological examination. They also performed worse in the Pollack tapper test which is designed to detect minor neurological deficits, inattention, and hyperactivity. The index children had higher scores on the Conners abbreviated parent-teacher questionnaire which measures hyperactivity and inattention. There was a negative correlation between the performance of the index group children on various neurodevelopmental and behavioural tests and the severity of hyperglycaemia, as assessed by blood glycosylated haemoglobin and acetonuria.
CONCLUSIONS—Diabetes during pregnancy adversely affects some fine neurological functions in children at school age, but not their cognitive scores. These effects are not correlated with the degree of glycaemic control.

 PMID:9828733

  6. The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases.

    PubMed

    Maessen, Dionne E M; Stehouwer, Coen D A; Schalkwijk, Casper G

    2015-06-01

    The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

  7. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.

    PubMed

    Kitada, Munehiro; Kume, Shinji; Takeda-Watanabe, Ai; Kanasaki, Keizo; Koya, Daisuke

    2013-02-01

    Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.

  8. Beneficial effects of metformin and irbesartan on advanced glycation end products (AGEs)-RAGE-induced proximal tubular cell injury.

    PubMed

    Ishibashi, Yuji; Matsui, Takanori; Takeuchi, Masayoshi; Yamagishi, Sho-ichi

    2012-03-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) axis contributes to diabetic nephropathy. An oral hypoglycemic agent, metformin may have a potential effect on the inhibition of glycation reactions. Further, since a pathophysiological crosstalk between renin-angiotensin system (RAS) and AGEs-RAGE axis is involved in diabetic nephropathy, it is conceivable that metformin and irbesartan additively could protect against the AGEs-RAGE-induced tubular cell injury. In this study, we addressed the issues. Metformin dose-dependently inhibited the formation of AGEs modification of bovine serum albumin (BSA). Compared with AGEs-modified BSA prepared without metformin (AGEs-MF0), those prepared in the presence of 30 mM or 100 mM metformin (AGEs-MF30 or AGEs-MF100) significantly reduced RAGE mRNA level, reactive oxygen species (ROS) generation, apoptosis, monocyte chemoattractant protein-1 and transforming growth factor-β mRNA level in tubular cells. Irbesartan further inhibited the harmful effects of AGEs-MF0 or AGEs-MF30 on tubular cells. Our present study suggests that combination therapy with metformin and irbesartan may have therapeutic potential in diabetic nephropathy; it could play a protective role against tubular injury in diabetes not only by inhibiting AGEs formation, but also by attenuating the deleterious effects of AGEs via down-regulating RAGE expression and subsequently suppressing ROS generation.

  9. Diabetes Onset at 31–45 Years of Age is Associated with an Increased Risk of Diabetic Retinopathy in Type 2 Diabetes

    PubMed Central

    Zou, Wenjun; Ni, Lisha; Lu, Qianyi; Zou, Chen; Zhao, Minjie; Xu, Xun; Chen, Haibing; Zheng, Zhi

    2016-01-01

    This hospital-based, cross-sectional study investigated the effect of age of diabetes onset on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. A total of 5,214 patients with type 2 DM who were referred to the Department of Ophthalmology at the Shanghai First People’s Hospital from 2009 to 2013 was eligible for inclusion. Diabetic retinopathy status was classified using the grading system of the Early Treatment Diabetic Retinopathy Study (ETDRS). Logistic and hierarchical regression analyses were used to identify independent variables affecting the development of DR. Upon multiple logistic regression analysis, patient age at the time of diabetes onset was significantly associated with development of DR. Further, when the risk of retinopathy was stratified by patient age at the onset of diabetes, the risk was highest in patients in whom diabetes developed at an age of 31–45 years (odds ratio [OR] 1.815 [1.139–2.892]; p = 0.012). Furthermore, when patients were divided into four groups based on the duration of diabetes, DR development was maximal at a diabetes onset age of 31–45 years within each group. A diabetes onset age of 31–45 years is an independent risk factor for DR development in Chinese type 2 DM patients. PMID:27897261

  10. Research Advances in Aging 1984-1986.

    ERIC Educational Resources Information Center

    National Inst. on Aging (DHHS/NIH), Bethesda, MD.

    The National Institute on Aging (NIA) has, for the past several years, focused attention on a wide range of clinical problems associated with aging, including falls and gait disorders, bone fractures, urinary incontinence, and hypertension. Understanding the causes of and exploring possible treatments for Alzheimer's disease has been another of…

  11. Confocal Raman study of aging process in diabetes mellitus human voluntaries

    NASA Astrophysics Data System (ADS)

    Pereira, Liliane; Téllez Soto, Claudio Alberto; dos Santos, Laurita; Ali, Syed Mohammed; Fávero, Priscila Pereira; Martin, Airton A.

    2015-06-01

    Accumulation of AGEs [Advanced Glycation End - products] occurs slowly during the human aging process. However, its formation is accelerated in the presence of diabetes mellitus. In this paper, we perform a noninvasive analysis of glycation effect on human skin by in vivo confocal Raman spectroscopy. This technique uses a laser of 785 nm as excitation source and, by the inelastic scattering of light, it is possible to obtain information about the biochemical composition of the skin. Our aim in this work was to characterize the aging process resulting from the glycation process in a group of 10 Health Elderly Women (HEW) and 10 Diabetic Elderly Women (DEW). The Raman data were collected from the dermis at a depth of 70-130 microns. Through the theory of functional density (DFT) the bands positions of hydroxyproline, proline and AGEs (pentosidine and glucosepane) were calculated by using Gaussian 0.9 software. A molecular interpretation of changes in type I collagen was performed by the changes in the vibrational modes of the proline (P) and hydroxyproline (HP). The data analysis shows that the aging effects caused by glycation of proteins degrades type I collagen differently and leads to accelerated aging process.

  12. Advanced glycation end-products induce skeletal muscle atrophy and dysfunction in diabetic mice via a RAGE-mediated, AMPK-down-regulated, Akt pathway.

    PubMed

    Chiu, Chen-Yuan; Yang, Rong-Sen; Sheu, Meei-Ling; Chan, Ding-Cheng; Yang, Ting-Hua; Tsai, Keh-Sung; Chiang, Chih-Kang; Liu, Shing-Hwa

    2016-02-01

    Diabetic myopathy, a less studied complication of diabetes, exhibits the clinical observations characterized by a less muscle mass, muscle weakness and a reduced physical functional capacity. Accumulation of advanced glycation end-products (AGEs), known to play a role in diabetic complications, has been identified in ageing human skeletal muscles. However, the role of AGEs in diabetic myopathy remains unclear. Here, we investigated the effects of AGEs on myogenic differentiation and muscle atrophy in vivo and in vitro. We also evaluated the therapeutic potential of alagebrium chloride (Ala-Cl), an inhibitor of AGEs. Muscle fibre atrophy and immunoreactivity for AGEs, Atrogin-1 (a muscle atrophy marker) and phosphorylated AMP-activated protein kinase (AMPK) expressions were markedly increased in human skeletal muscles from patients with diabetes as compared with control subjects. Moreover, in diabetic mice we found increased blood AGEs, less muscle mass, lower muscular endurance, atrophic muscle size and poor regenerative capacity, and increased levels of muscle AGE and receptor for AGE (RAGE), Atrogin-1 and phosphorylated AMPK, which could be significantly ameliorated by Ala-Cl. Furthermore, in vitro, AGEs (in a dose-dependent manner) reduced myotube diameters (myotube atrophy) and induced Atrogin-1 protein expression in myotubes differentiated from both mouse myoblasts and primary human skeletal muscle-derived progenitor cells. AGEs exerted a negative regulation of myogenesis of mouse and human myoblasts. Ala-Cl significantly inhibited the effects of AGEs on myotube atrophy and myogenesis. We further demonstrated that AGEs induced muscle atrophy/myogenesis impairment via a RAGE-mediated AMPK-down-regulation of the Akt signalling pathway. Our findings support that AGEs play an important role in diabetic myopathy, and that an inhibitor of AGEs may offer a therapeutic strategy for managing the dysfunction of muscle due to diabetes or ageing.

  13. Advanced paternal age and reproductive outcome

    PubMed Central

    Wiener-Megnazi, Zofnat; Auslender, Ron; Dirnfeld, Martha

    2012-01-01

    Women have been increasingly delaying the start of motherhood in recent decades. The same trend is seen also for men. The influence of maternal age on fertility, chromosomal anomalies, pregnancy complications, and impaired perinatal and post-natal outcome of offspring, has been thoroughly investigated, and these aspects are clinically applied during fertility and pregestational counseling. Male aging and reproductive outcome has gained relatively less attention. The purpose of this review is to evaluate updated and relevant literature on the effect of paternal age on reproductive outcome. PMID:22157982

  14. mTOR: from growth signal integration to cancer, diabetes and ageing

    PubMed Central

    Zoncu, Roberto; Sabatini, David M.; Efeyan, Alejo

    2012-01-01

    Preface In all eukaryotes, the target of rapamycin (TOR) signaling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress, and, in metazoan, growth factors. Mammalian TOR complexes 1 and 2 (mTORC1 and mTORC2) exert their actions by regulating other important kinases, such as S6K and Akt. In the last few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed its critical involvement in the onset and progression of diabetes, cancer and ageing. PMID:21157483

  15. Detection of advanced glycation end products (AGEs) on human skin by in vivo confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Martin, A. A.; Pereira, L.; Ali, S. M.; Pizzol, C. D.; Tellez, C. A.; Favero, P. P.; Santos, L.; da Silva, V. V.; Praes, C. E. O.

    2016-03-01

    The aging process involves the reduction in the production of the major components of skin tissue. During intrinsic aging and photoaging processes, in dermis of human skin, fibroblasts become senescent and have decreased activity, which produce low levels of collagen. Moreover, there is accumulation of advanced glycation end products (AGEs). AGEs have incidence in the progression of age-related diseases, principally in diabetes mellitus and in Alzheimer's diseases. AGEs causes intracellular damage and/or apoptosis leading to an increase of the free radicals, generating a crosslink with skin proteins and oxidative stress. The aim of this study is to detect AGEs markers on human skin by in vivo Confocal Raman spectroscopy. Spectra were obtained by using a Rivers Diagnostic System, 785 nm laser excitation and a CCD detector from the skin surface down to 120 μm depth. We analyzed the confocal Raman spectra of the skin dermis of 30 women volunteers divided into 3 groups: 10 volunteers with diabetes mellitus type II, 65-80 years old (DEW); 10 young healthy women, 20-33 years old (HYW); and 10 elderly healthy women, 65-80 years old (HEW). Pentosidine and glucosepane were the principally identified AGEs in the hydroxyproline and proline Raman spectral region (1000-800 cm-1), in the 1.260-1.320 cm-1 region assignable to alpha-helical amide III modes, and in the Amide I region. Pentosidine and glucosepane calculated vibrational spectra were performed through Density Functional Theory using the B3LYP functional with 3-21G basis set. Difference between the Raman spectra of diabetic elderly women and healthy young women, and between healthy elderly women and healthy young women were also obtained with the purpose of identifying AGEs Raman bands markers. AGEs peaks and collagen changes have been identified and used to quantify the glycation process in human skin.

  16. Clinical application prospect of umbilical cord-derived mesenchymal stem cells on clearance of advanced glycation end products through autophagy on diabetic wound.

    PubMed

    Han, Yanfu; Sun, Tianjun; Tao, Ran; Han, Yanqing; Liu, Jing

    2017-03-24

    Nowadays, wound healing delay due to diabetes is considered to be closely related to the accumulation of advanced glycation end products (AGEs). Although mesenchymal stem cells (MSCs) exhibit positive effects on diabetic wound healing, related mechanisms are still not fully elucidated. It has been reported that MSCs can improve the activity of autophagy in injured tissues, thereby playing an important role in wound healing. The autophagy induced by MSCs may be beneficial to diabetic wound healing via removing AGEs, which provide new ideas for clinical treatment of diabetic wounds with the potential of broad application prospects. In this study, the current research situation and application prospect of umbilical cord-derived MSCs on the clearance of AGEs in diabetic wound were reviewed.

  17. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    PubMed Central

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD. PMID:27695506

  18. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions.

    PubMed

    Das, Undurti N

    2016-10-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD.

  19. [Drivers of advanced age in traffic accidents].

    PubMed

    Bilban, Marjan

    2002-12-01

    The elderly are vulnerable and potentially unpredictable active participants in traffic who deserve special attention. Longer life expectancy entails a greater number of senior drivers, that is, persons with various health problems and difficulties accompanying old age. At the turn of the millennium, the share of population aged 65 or more in Slovenia was around 13%, and in 25 years it will be near as much as 19%. The share of drivers from this age group was 28% a year ago, and it is expected to reach about 54%. Numerous studies have shown that there are many differences in driving attitude between the young and the elderly. The young are by large active victims, and their main offense and cause of accident is speeding, while the elderly are more passive and their main offense is ignoring and enforcing the right of way. This paper focuses on the differences in the occurrence and type of injuries between the young and the elderly drivers, based on an analysis of all road accidents in Slovenia in the period between 1998-2000. Older people (over 65) caused only 4.7% of all road accidents (16.7% of all accidents involving pedestrians, 11.5% of all involving cyclists, 2.7% involving motorcyclists and 5% of all accidents involving car drivers). Of all accidents, 89.3% were without injuries, and the fatal outcome was registered in 0.4% accidents. Among the elderly (65-74 years of age), however, this share was 1%, and rising to 2.7% with the age 75 and above. By calculating the weight index, which discriminates between minor and severe injuries, and the fatal outcome, it was established that age groups 65-74 and > or = 75 cause three and five times greater damage, respectively than age groups from 18 to 54 years. With years, psychophysical changes lead to a drop in driving ability, which in turn increases the risk of road accidents. It is true that elderly people cause less traffic accidents (and also drive less) than the young, but when they are involved in an accident

  20. Predictors of Driving Outcomes in Advancing Age

    PubMed Central

    Emerson, Jamie L.; Johnson, Amy M.; Dawson, Jeffrey D.; Uc, Ergun Y.; Anderson, Steven W.

    2012-01-01

    This study aimed to develop predictive models for real-life driving outcomes in older drivers. Demographics, driving history, on-road driving errors, and performance on visual, motor, and neuropsychological test scores at baseline were assessed in 100 older drivers (ages 65–89 years [72.7]). These variables were used to predict time to driving cessation, first moving violation, or crash. Using Cox proportional hazards regression models, significant individual predictors for driving cessation were greater age and poorer scores on Near Visual Acuity, Contrast Sensitivity, Useful Field of View, Judgment of Line Orientation, Trail Making Test-Part A, Benton Visual Retention Test, Grooved Pegboard, and a composite index of overall cognitive ability. Greater weekly mileage, higher education, and “serious” on-road errors predicted moving violations. Poorer scores from Trail Making Test-Part B or Trail Making Test (B-A) and serious on-road errors predicted crashes. Multivariate models using “off-road” predictors revealed (1) age and Contrast Sensitivity as best predictors for driving cessation; (2) education, weekly mileage, and Auditory Verbal Learning Task-Recall for moving violations; and (3) education, number of crashes over the past year, Auditory Verbal Learning Task-Recall, and Trail Making Test (B-A) for crashes. Diminished visual, motor, and cognitive abilities in older drivers can be easily and noninvasively monitored with standardized off-road tests, and performances on these measures predict involvement in motor vehicle crashes and driving cessation, even in the absence of a neurological disorder. PMID:22182364

  1. Combined Anti-Inflammatory and Anti-AGE Drug Treatments Have a Protective Effect on Intervertebral Discs in Mice with Diabetes

    PubMed Central

    Illien-Junger, Svenja; Grosjean, Fabrizio; Laudier, Damien M.; Vlassara, Helen; Striker, Gary E.; Iatridis, James C.

    2013-01-01

    Objective Diabetes and low back pain are debilitating diseases and modern epidemics. Diabetes and obesity are also highly correlated with intervertebral disc (IVD) degeneration and back pain. Advanced-glycation-end-products (AGEs) increase reactive-oxygen-species (ROS) and inflammation, and are one cause for early development of diabetes mellitus. We hypothesize that diabetes results in accumulation of AGEs in spines and associated spinal pathology via increased catabolism. We present a mouse model showing that: 1) diabetes induces pathological changes to structure and composition of IVDs and vertebrae; 2) diabetes is associated with accumulation of AGEs, TNFα, and increased catabolism spinal structures; and 3) oral-treatments with a combination of anti-inflammatory and anti-AGE drugs mitigate these diabetes-induced degenerative changes to the spine. Methods Three age-matched groups of ROP-Os mice were compared: non-diabetic, diabetic (streptozotocin (STZ)-induced), or diabetic mice treated with pentosan-polysulfate (anti-inflammatory) and pyridoxamine (AGE-inhibitor). Mice were euthanized and vertebra-IVD segments were analyzed by μCT, histology and Immunohistochemistry. Results Diabetic mice exhibited several pathological changes including loss in IVD height, decreased vertebral bone mass, decreased glycosaminoglycan content and morphologically altered IVDs with focal deposition of tissues highly expressing TNFα, MMP-13 and ADAMTS-5. Accumulation of larger amounts of methylglyoxal suggested that AGE accumulation was associated with these diabetic degenerative changes. However, treatment prevented or reduced these pathological effects on vertebrae and IVD. Conclusion This is the first study to demonstrate specific degenerative changes to nucleus pulposus (NP) morphology and their association with AGE accumulation in a diabetic mouse model. Furthermore, this is the first study to demonstrate that oral-treatments can inhibit AGE-induced ROS and inflammation in

  2. Primiparity at very advanced maternal age (≥ 45 years).

    PubMed

    Glasser, Saralee; Segev-Zahav, Aliza; Fortinsky, Paige; Gedal-Beer, Debby; Schiff, Eyal; Lerner-Geva, Liat

    2011-06-30

    This study describes maternal and birth outcomes of primiparae aged ≥ 45. High rates of pregnancy complications and poor birth outcomes were found, stressing that the personal risks and ramifications to the health system should be taken into account in establishing obstetric health policy regarding primiparity at advanced maternal age.

  3. Aldose reductase (AKR1B3) regulates the accumulation of advanced glycosylation end products (AGEs) and the expression of AGE receptor (RAGE).

    PubMed

    Baba, Shahid P; Hellmann, Jason; Srivastava, Sanjay; Bhatnagar, Aruni

    2011-05-30

    Diabetes results in enhanced chemical modification of proteins by advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) precursors. These modifications have been linked to the development of several secondary diabetic complications. Our previous studies showed that aldose reductase (AR; AKR1B3) catalyzes the reduction of ALEs and AGEs precursors; however, the in vivo significance of this metabolic pathway during diabetes and obesity has not been fully assessed. Therefore we examined the role of AR in regulating ALEs and AGEs formation in murine models of diet-induced obesity and streptozotocin-induced diabetes. In comparison with wild-type (WT) and AR-null mice fed normal chow, mice fed a high-fat (HF) diet (42% kcal fat) showed increased accumulation of AGEs and protein-acrolein adducts in the plasma. AGEs and acrolein adducts were also increased in the epididymal fat of WT and AR-null mice fed a HF diet. Deletion of AR increased the accumulation of 4-hydroxy-trans-2-nonenal (HNE) protein adduct in the plasma and increased the expression of the AGE receptor (RAGE) in HF fed mice. No change in AGEs formation was observed in the kidneys of HF-fed mice. In comparison, renal tissue from AR-null mice treated with streptozotocin showed greater AGE accumulation than streptozotocin-treated WT mice. These data indicated that AR regulated the accumulation of lipid peroxidation derived aldehydes and AGEs under conditions of severe, but not mild, hyperglycemia and that deletion of AR increased RAGE-induction via mechanisms that were independent of AGEs accumulation.

  4. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation.

    PubMed

    Vistoli, G; De Maddis, D; Cipak, A; Zarkovic, N; Carini, M; Aldini, G

    2013-08-01

    Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions; (2) to elucidate the molecular basis of their biological effects; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.

  5. Activation of α7nAChR Promotes Diabetic Wound Healing by Suppressing AGE-Induced TNF-α Production.

    PubMed

    Dong, Miao-Wu; Li, Ming; Chen, Jie; Fu, Tong-Tong; Lin, Ke-Zhi; Ye, Guang-Hua; Han, Jun-Ge; Feng, Xiang-Ping; Li, Xing-Biao; Yu, Lin-Sheng; Fan, Yan-Yan

    2016-04-01

    Diabetes frequently presents accumulation of advanced glycation end products (AGEs), which might induce excessive TNF-α production from macrophages to cause impaired wound healing. Recent studies have shown that activation of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages efficiently suppressed TNF-α synthesis. The aim of this study was to investigate the accumulation of AGEs in the wounds and determine whether PNU282987, an α7nAChR agonist, can improve wound repair by inhibiting AGE-mediated TNF-α production in a streptozotocin (STZ)-induced diabetic mouse model. Animals were assigned into four groups: wounded control group, wounded diabetic group, wounded diabetic group treated intraperitoneally with PNU282987, or wounded diabetic group treated intraperitoneally with vehicle. Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound healing that was characterized by elevated accumulation of AGEs, increased TNF-α level and macrophage infiltration, and decreased fibroblast number and collagen deposition at the late stage of repair. Besides, macrophages of diabetic wounds showed expression of α7nAChR. During late repair, PNU282987 treatment of diabetic mice significantly reduced the level of TNF-α, accelerated wound healing, and elevated fibroblast number and collagen deposition. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophage cell line, were incubated with AGEs in the presence or absence of PNU282987. TNF-α production from AGE-stimulated macrophages was significantly decreased by PNU282987 in a dose-dependent manner. Furthermore, PNU282987 significantly inhibited AGE-induced nuclear factor-κB (NF-κB) activation and receptor for AGE (RAGE) expression. These results strongly suggest that activating α7nAChR can promote diabetic wound healing by suppressing AGE-induced TNF-α production, which may be closely associated with the blockage of NF-κB activation in macrophages.

  6. Screening gestational diabetes mellitus: The role of maternal age

    PubMed Central

    Kuo, Chun-Heng; Chen, Szu-Chi; Fang, Chi-Tai; Nien, Feng-Jung; Wu, En-Tzu; Lin, Shin-Yu; Chuang, Lee-Ming

    2017-01-01

    Objective Using a specific cutoff of fasting plasma glucose (FPG) to screen gestational diabetes mellitus (GDM) can reduce the use of oral glucose tolerance tests (OGTT). Since the prevalence of GDM increases with age, this screening method may not be appropriate in healthcare systems where women become pregnant at older ages. Therefore, we aimed to develop a screening algorithm for GDM that takes maternal age into consideration. Methods We included 945 pregnant women without history of GDM who received 75g OGTT to diagnose GDM in 2011. Screening algorithms using FPG with or without age were developed. Another 362 pregnant women were recruited in 2013–2015 as the validation cohort. Results Using FPG criteria alone, more GDM diagnoses were missed in women ≥35 years than in women <35 years (13.2% vs. 5.8%, p <0.001). Among GDM women ≥35 years, 63.6% had FPG <92 mg/dL (5.1 mmol/L). Use of the algorithm with an “age plus FPG” cutoff could reduce the use of OGTT (OGTT%) from 77.6% to 62.9%, while maintaining good sensitivity (from 91.9% to 90.2%) and specificity (from 100% to 100%). Similar reduction in OGTT% was found in the validation cohort (from 86.4% to 76.8%). In the simulation, if the percentage of women ≥35 years were 40% or more, the screening algorithm with an “age plus FPG” cutoff could further reduce OGTT% by 11.0%-18.8%. Conclusions A screening algorithm for GDM that takes maternal age into consideration can reduce the use of OGTT when women become pregnant at older ages. PMID:28296923

  7. Sexuality Among Middle-Aged and Older Adults With Diagnosed and Undiagnosed Diabetes

    PubMed Central

    Lindau, Stacy Tessler; Tang, Hui; Gomero, Ada; Vable, Anusha; Huang, Elbert S.; Drum, Melinda L.; Qato, Dima M.; Chin, Marshall H.

    2010-01-01

    OBJECTIVE To describe sexual activity, behavior, and problems among middle-age and older adults by diabetes status. RESEARCH DESIGN AND METHODS This was a substudy of 1,993 community-residing adults, aged 57–85 years, from a cross-sectional, nationally representative sample (N = 3,005). In-home interviews, observed medications, and A1C were used to stratify by diagnosed diabetes, undiagnosed diabetes, or no diabetes. Logistic regression was used to model associations between diabetes conditions and sexual characteristics, separately by gender. RESULTS The survey response rate was 75.5%. More than 60% of partnered individuals with diagnosed diabetes were sexually active. Women with diagnosed diabetes were less likely than men with diagnosed diabetes (adjusted odds ratio 0.28 [95% CI 0.16–0.49]) and other women (0.63 [0.45–0.87]) to be sexually active. Partnered sexual behaviors did not differ by gender or diabetes status. The prevalence of orgasm problems was similarly elevated among men with diagnosed and undiagnosed diabetes compared with that for other men, but erectile difficulties were elevated only among men with diagnosed diabetes (2.51 [1.53 to 4.14]). Women with undiagnosed diabetes were less likely to have discussed sex with a physician (11%) than women with diagnosed diabetes (19%) and men with undiagnosed (28%) or diagnosed (47%) diabetes. CONCLUSIONS Many middle-age and older adults with diabetes are sexually active and engage in sexual behaviors similarly to individuals without diabetes. Women with diabetes were more likely than men to cease all sexual activity. Older women with diabetes are as likely to have sexual problems but are significantly less likely than men to discuss them. PMID:20802158

  8. Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights

    PubMed Central

    Singh, Priyanka; Jayaramaiah, Ramesha H.; Agawane, Sachin B.; Vannuruswamy, Garikapati; Korwar, Arvind M.; Anand, Atul; Dhaygude, Vitthal S.; Shaikh, Mahemud L.; Joshi, Rakesh S.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.; Thulasiram, Hirekodathakallu V.; Giri, Ashok P.

    2016-01-01

    Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management. PMID:26739611

  9. Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights.

    PubMed

    Singh, Priyanka; Jayaramaiah, Ramesha H; Agawane, Sachin B; Vannuruswamy, Garikapati; Korwar, Arvind M; Anand, Atul; Dhaygude, Vitthal S; Shaikh, Mahemud L; Joshi, Rakesh S; Boppana, Ramanamurthy; Kulkarni, Mahesh J; Thulasiram, Hirekodathakallu V; Giri, Ashok P

    2016-01-07

    Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management.

  10. Diabetes.

    PubMed

    2014-09-23

    Essential facts Type 1 and type 2 diabetes affect 3.2 million people in the UK. Diabetes is associated with serious complications, including heart disease and stroke, which can lead to disability and premature death. It is the leading cause of preventable sight loss in people of working age in the UK. A quarter of people with diabetes will have kidney disease at some point in their lives, and the condition increases the risk of amputation. Good diabetes management has been shown to reduce the incidence of these serious complications.

  11. Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence

    PubMed Central

    Hangai, Mari; Takebe, Noriko; Honma, Hiroyuki; Sasaki, Atsumi; Chida, Ai; Nakano, Rieko; Togashi, Hirobumi; Nakagawa, Riyuki; Oda, Tomoyasu; Matsui, Mizue; Yashiro, Satoshi; Nagasawa, Kan; Kajiwara, Takashi; Takahashi, Kazuma; Takahashi, Yoshihiko; Satoh, Jo

    2016-01-01

    Aim: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes. Methods: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader. Results: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone. Conclusion: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects. PMID:26961217

  12. Baking, ageing, diabetes: a short history of the Maillard reaction.

    PubMed

    Hellwig, Michael; Henle, Thomas

    2014-09-22

    The reaction of reducing carbohydrates with amino compounds described in 1912 by Louis-Camille Maillard is responsible for the aroma, taste, and appearance of thermally processed food. The discovery that non-enzymatic conversions also occur in organisms led to intensive investigation of the pathophysiological significance of the Maillard reaction in diabetes and ageing processes. Dietary Maillard products are discussed as "glycotoxins" and thus as a nutritional risk, but also increasingly with regard to positive effects in the human body. In this Review we give an overview of the most important discoveries in Maillard research since it was first described and show that the complex reaction, even after over one hundred years, has lost none of its interdisciplinary actuality.

  13. Metformin reverts deleterious effects of advanced glycation end-products (AGEs) on osteoblastic cells.

    PubMed

    Schurman, L; McCarthy, A D; Sedlinsky, C; Gangoiti, M V; Arnol, V; Bruzzone, L; Cortizo, A M

    2008-06-01

    Advanced glycation endproducts (AGEs) are implicated in the complications of diabetes and ageing, affecting several tissues, including bone. Metformin, an insulin-sensitizer drug, reduces the risk of life-threatening macrovascular complications. We have evaluated the hypothesis that metformin can abrogate AGE-induced deleterious effects in osteoblastic cells in culture. In two osteoblast-like cell lines (UMR106 and MC3T3E1), AGE-modified albumin induced cell death, caspase-3 activity, altered intracellular oxidative stress and inhibited alkaline phosphatase activity. Metformin-treatment of osteoblastic cells prevented these AGE-induced alterations. We also assessed the expression of AGE receptors as a possible mechanism by which metformin could modulate the action of AGEs. AGEs-treatment of osteoblast-like cells enhanced RAGE protein expression, and this up-regulation was prevented in the presence of metformin. Although the precise mechanisms involved in metformin signaling are still elusive, our data implicate the AGE-RAGE interaction in the modulation of growth and differentiation of osteoblastic cells.

  14. Stimulatory effects of advanced glycation endproducts (AGEs) on fibronectin matrix assembly.

    PubMed

    Pastino, Alexandra K; Greco, Todd M; Mathias, Rommel A; Cristea, Ileana M; Schwarzbauer, Jean E

    2017-05-01

    Advanced glycation endproducts (AGEs) are a heterogeneous group of compounds that form via non-enzymatic glycation of proteins throughout our lifespan and at a higher rate in certain chronic diseases such as diabetes. AGEs contribute to the progression of fibrosis, in part by stimulating cellular pathways that affect gene expression. Long-lived ECM proteins are targets for non-enzymatic glycation but the question of whether the AGE-modified ECM leads to excess ECM accumulation and fibrosis remains unanswered. In this study, cellular changes due to AGE accretion in the ECM were investigated. Non-enzymatic glycation of proteins in a decellularized fibroblast ECM was achieved by incubating the ECM in a solution of methylglyoxal (MGO). Mass spectrometry of fibronectin (FN) isolated from the glycated matrix identified twenty-eight previously unidentified MGO-derived AGE modification sites including functional sites such as the RGD integrin-binding sequence. Mesangial cells grown on the glycated, decellularized matrix assembled increased amounts of FN matrix. Soluble AGE-modified bovine serum albumin (BSA) also stimulated FN matrix assembly and this effect was reduced by function-blocking antibodies against the receptor for AGE (RAGE). These results indicate that cells respond to AGEs by increasing matrix assembly and that RAGE is involved in this response. This raises the possibility that the accumulation of ECM during the progression of fibrosis may be enhanced by cell interactions with AGEs on a glycated ECM.

  15. The Influence of Age on the Effects of Lifestyle Modification and Metformin in Prevention of Diabetes

    PubMed Central

    Crandall, Jill; Schade, David; Ma, Yong; Fujimoto, Wilfred Y.; Barrett-Connor, Elizabeth; Fowler, Sarah; Dagogo-Jack, Sam; Andres, Reubin

    2007-01-01

    Background The incidence of type 2 diabetes increases with age. It is unknown whether interventions to prevent diabetes are as effective in elderly persons as in younger adults. Methods The Diabetes Prevention Program (DPP) demonstrated that an intensive lifestyle intervention (ILS) or metformin could prevent or delay diabetes. A predefined secondary outcome of DPP was to determine if treatment effects varied by age. Results At baseline, participants aged 60–85 years were leaner and had the best insulin sensitivity and lowest insulin secretion compared to younger age groups. Diabetes incidence rates did not differ by age in the placebo group, but ILS was more effective with increasing age (6.3, 4.9, and 3.3 cases per 100 person-years, in the 25–44, 45–59, and 60–85 year age groups, respectively; ptrend = .007). Participants aged 60–85 years had the most weight loss and metabolic equivalent (MET)-hours of physical activity. The metformin group showed a trend toward higher diabetes incidence among older participants (6.7, 7.7, and 9.3 cases per 100 person-years in the 25–44, 45–59, and 60–85 year age groups, respectively; ptrend = .07); and diabetes risk increased with age (hazard ratio [age 60–85 vs 25–44] 1.63, p .02), after adjusting for the greater weight loss in the 60–85 year age group. Conclusions Lifestyle modification was exceptionally effective in preventing diabetes in older individuals; this finding was largely explained by greater weight loss and physical activity. The limited effectiveness of metformin in older persons may reflect age-related differences in insulin action and secretion. A lifestyle modification program can be recommended for older individuals at high risk for type 2 diabetes. PMID:17077202

  16. Management and counseling of the male with advanced paternal age.

    PubMed

    Jennings, Michael O; Owen, Ryan C; Keefe, David; Kim, Edward D

    2017-02-01

    Increasing percentages of children are being born to older fathers. This has resulted in concerns about the potential adverse effects of advanced paternal age. To help clinicians counsel couples, a systemic review was performed to attempt to address questions that these couples may ask: Should routine sperm testing be performed in older males? Should preimplantation genetic diagnosis (PGD) be performed? How do providers counsel patients about risk? Should young males freeze sperm if they plan to delay paternity? Using the terms "advanced paternal age", "semen testing", "preimplantation genetic diagnosis/screening", and "cryopreservation", a comprehensive search was performed in PubMed and the Cochrane Library, and numerous international societal guidelines were reviewed. In total, 42 articles or guidelines were reviewed. There were no limits placed on the timing of the articles. Thirty articles were found to be relevant and beneficial to answering the above questions. Each question was answered separately by the supporting literature. While primary research exists to support the role of semen testing, PGD/preimplantation genetic screening, and sperm banking in males who may be affected by advancing age, comprehensive studies on the possible clinical benefit of these interventions have yet to be performed. As a result, societal guidelines have yet to incorporate distinct best-practice guidelines on advanced paternal age.

  17. Early- and advanced non-enzymatic glycation in diabetic vascular complications: the search for therapeutics.

    PubMed

    Schalkwijk, Casper G; Miyata, Toshio

    2012-04-01

    Cardiovascular disease is a common complication of diabetes and the leading cause of death among people with diabetes. Because of the huge premature morbidity and mortality associated with diabetes, prevention of vascular complications is a key issue. Although the exact mechanism by which vascular damage occurs in diabetes in not fully understood, numerous studies support the hypothesis of a causal relationship of non-enzymatic glycation with vascular complications. In this review, data which point to an important role of Amadori-modified glycated proteins and advanced glycation endproducts in vascular disease are surveyed. Because of the potential role of early- and advanced non-enzymatic glycation in vascular complications, we also described recent developments of pharmacological inhibitors that inhibit the formation of these glycated products or the biological consequences of glycation and thereby retard the development of vascular complications in diabetes.

  18. Acetoacetate promotes the formation of fluorescent advanced glycation end products (AGEs).

    PubMed

    Bohlooli, Mousa; Ghaffari-Moghaddam, Mansour; Khajeh, Mostafa; Aghashiri, Zohre; Sheibani, Nader; Moosavi-Movahedi, Ali Akbar

    2016-12-01

    Acetoacetate (AA) is an important ketone body, which produces reactive oxygen species (ROS). Advanced glycation end products (AGEs) are defined as final products of glycation process whose production is influenced by the levels of ROS. The accumulation of AGEs in the body contributes to pathogenesis of many diseases including complications of diabetes, and Alzheimer's and Parkinson's disease. Here, we evaluated the impact of AA on production of AGEs upon incubation of human serum albumin (HSA) with glucose. The effect of AA on the AGEs formation of HSA was studied under physiological conditions after incubation with glucose for 35 days. The physical techniques including circular dichroism (CD) and fluorescence spectroscopy were used to assess the impact of AA on formation and structural changes of glycated HSA (GHSA). Our results indicated that the secondary and tertiary structural changes of GHSA were increased in the presence of AA. The fluorescence intensity measurements of AGEs also showed an increase in AGEs formation. Acetoacetate has an activator effect in formation of AGEs through ROS production. The presence of AA may result in enhanced glycation in the presence of glucose and severity of complications associated with accumulation of AGEs.

  19. The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification

    PubMed Central

    2016-01-01

    AGE/RAGE signaling has been a well-studied cascade in many different disease states, particularly diabetes. Due to the complex nature of the receptor and multiple intersecting pathways, the AGE/RAGE signaling mechanism is still not well understood. The purpose of this review is to highlight key areas of AGE/RAGE mediated vascular calcification as a complication of diabetes. AGE/RAGE signaling heavily influences both cellular and systemic responses to increase bone matrix proteins through PKC, p38 MAPK, fetuin-A, TGF-β, NFκB, and ERK1/2 signaling pathways in both hyperglycemic and calcification conditions. AGE/RAGE signaling has been shown to increase oxidative stress to promote diabetes-mediated vascular calcification through activation of Nox-1 and decreased expression of SOD-1. AGE/RAGE signaling in diabetes-mediated vascular calcification was also attributed to increased oxidative stress resulting in the phenotypic switch of VSMCs to osteoblast-like cells in AGEs-induced calcification. Researchers found that pharmacological agents and certain antioxidants decreased the level of calcium deposition in AGEs-induced diabetes-mediated vascular calcification. By understanding the role the AGE/RAGE signaling cascade plays diabetes-mediated vascular calcification will allow for pharmacological intervention to decrease the severity of this diabetic complication. PMID:27547766

  20. Advanced glycation End-products (AGEs): an emerging concern for processed food industries.

    PubMed

    Sharma, Chetan; Kaur, Amarjeet; Thind, S S; Singh, Baljit; Raina, Shiveta

    2015-12-01

    The global food industry is expected to increase more than US $ 7 trillion by 2014. This rise in processed food sector shows that more and more people are diverging towards modern processed foods. As modern diets are largely heat processed, they are more prone to contain high levels of advanced glycation end products (AGEs). AGEs are a group of complex and heterogeneous compounds which are known as brown and fluorescent cross-linking substances such as pentosidine, non-fluorescent cross-linking products such as methylglyoxal-lysine dimers (MOLD), or non-fluorescent, non-cross linking adducts such as carboxymethyllysine (CML) and pyrraline (a pyrrole aldehyde). The chemistry of the AGEs formation, absorption and bioavailability and their patho-biochemistry particularly in relation to different complications like diabetes and ageing discussed. The concept of AGEs receptor - RAGE is mentioned. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Different methods of detection and quantification along with types of agents used for the treatment of AGEs are reviewed. Generally, ELISA or LC-MS methods are used for analysis of foods and body fluids, however lack of universally established method highlighted. The inhibitory effect of bioactive components on AGEs by trapping variety of chemical moieties discussed. The emerging evidence about the adverse effects of AGEs makes it necessary to investigate the different therapies to inhibit AGEs.

  1. Non-invasive screening for NAFLD and advanced fibrosis in diabetes in primary care setting by MRI and MRE

    PubMed Central

    Doycheva, Iliana; Cui, Jeffrey; Nguyen, Phirum; Costa, Eduardo A.; Hooker, Jonathan; Hofflich, Heather; Bettencourt, Ricki; Brouha, Sharon; Sirlin, Claude B.; Loomba, Rohit

    2015-01-01

    SUMMARY Background Current guidelines do not recommend screening for nonalcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. Aim We aimed to assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. Methods We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other etiology of liver disease. All patients underwent a standardized research visit, laboratory tests, MRI-PDFF, and MRE. Results Mean (± SD) age and BMI was 59.7 (±11.2) years and 30.8 (±6.5) kg/m2, respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥ 5%) and advanced fibrosis (defined as MRE ≥ 3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (p=0.028) and had higher mean BMI (p=0.0008), waist circumference (p<0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, p<0.0001). Only 26% of those with NAFLD had elevated ALT. Conclusions This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-PDFF and MRE in T2DM is feasible and may be considered after validation in a larger cohort. PMID:26369383

  2. Reproduction at an advanced maternal age and maternal health.

    PubMed

    Sauer, Mark V

    2015-05-01

    Advanced age is a risk factor for female infertility, pregnancy loss, fetal anomalies, stillbirth, and obstetric complications. These concerns are based on centuries-old observations, yet women are delaying childbearing to pursue educational and career goals in greater numbers than ever before. As a result, reproductive medicine specialists are treating more patients with age-related infertility and recurrent pregnancy loss, while obstetricians are faced with managing pregnancies often complicated by both age and comorbidities. The media portrayal of a youthful but older woman, able to schedule her reproductive needs and balance family and job, has fueled the myth that "you can have it all," rarely characterizing the perils inherent to advanced-age reproduction. Reproductive medicine specialists and obstetrician/gynecologists should promote more realistic views of the evidence-based realities of advanced maternal age pregnancy, including its high-risk nature and often compromised outcomes. Doctors should also actively educate both patients and the public that there is a real danger of childlessness if individuals choose to delay reproduction.

  3. Recent Advances in Understanding Depression in Adults with Diabetes

    PubMed Central

    Lustman, Patrick J.; Penckofer, Sue M.; Clouse, Ray E.

    2013-01-01

    The authors review the science linking depression with diabetes. Some recent heuristic research is identified that highlights progress in the field and is directing future research. Issues in the management of depression in diabetes are outlined, including interactions of depression and insulin resistance. PMID:17425915

  4. Recent Advances in Understanding Depression in Adults With Diabetes

    PubMed Central

    Lustman, Patrick J.; Penckofer, Sue M.; Clouse, Ray E.

    2013-01-01

    The authors review the science linking depression with diabetes. Some recent heuristic research is identified that highlights progress in the field and is directing future research. Issues in the management of depression in diabetes are outlined, including interactions of depression and insulin resistance. PMID:18980733

  5. The Geography of Diabetes among the General Adults Aged 35 Years and Older in Bangladesh: Recent Evidence from a Cross-Sectional Survey

    PubMed Central

    Khan, Md. Mobarak Hossain; Gruebner, Oliver; Kraemer, Alexander

    2014-01-01

    Objective To report geographical variations of sex-specific diabetes by place of residence (large cities/city corporations, small towns/other urban areas, rural areas) and region of residence (divided into seven divisions) among general adults (35+ years of age) in Bangladesh. Methods The recent cross-sectional data, extracted from the nationally representative Bangladesh Demographic and Health Survey 2011, was used. A total of 3,720 men and 3,823 women aged 35+ years, who participated in the fasting blood sugar testing, were analysed. Any person with either fasting plasma glucose level (mmol/L) ≥7.0 or taking medication for diabetes was considered as a person with diabetes. Results The prevalence of diabetes was 10.6% in men and 11.3% in women. Bivariable analyses indicated significant variations of diabetes by both geographical variables. The prevalence was highest in city corporations (men 18.0%, women 22.3%), followed by small towns (men 13.6%, women 15.2%) and rural areas (men 9.3%, women 9.5%). Regional disparities in diabetes prevalence were also remarkable, with the highest prevalence in Chittagong division and lowest prevalence in Khulna division. Multivariable logistic regression analyses provided mixed patterns of geographical disparities (depending on the adjusted variables). Some other independent risk factors for diabetes were advancing age, higher level of education and wealth, having TV (a proxy indicator of physical activity), overweight/obesity and hypertension. Conclusions Over 10% of the general adults aged 35 years and older were having diabetes. Most of the persons with diabetes were unaware of this before testing fasting plasma glucose level. Although significant disparities in diabetes prevalence by geographical variables were observed, such disparities are very much influenced by the adjusted variables. Finally, we underscore the necessities of area-specific strategies including early diagnosis and health education programmes for changing

  6. Receptor for advanced glycation end products and neuronal deficit in the fatal brain edema of diabetic ketoacidosis.

    PubMed

    Hoffman, William H; Artlett, Carol M; Zhang, Weixian; Kreipke, Christian W; Passmore, Gregory G; Rafols, Jose A; Sima, Anders A F

    2008-10-31

    Radiologic and neuropsychologic studies suggest that diabetes mellitus causes structural changes in the brain and adversely effects cognitive development. Experimental animal models of type 1 diabetes mellitus (T1DM) have advanced these findings by demonstrating duration-related neuronal and cognitive deficits in T1DM BB/Wor rats. We studied the expression of receptor for advanced glycation end products (RAGE) and neuronal densities in the brains of two patients who died as the result of clinical brain edema(BE)that developed during the treatment of severe diabetic ketoacidosis (DKA). RAGE was markedly and diffusely expressed in blood vessels, neurons, and the choroid plexus and co-localized with glial fibrillary acidic protein (GFAP) in astrocytes. Significant neuronal loss was seen in the hippocampus and frontal cortex. Astrocytosis was present and white matter was atrophied in both cases when compared to age-matched controls. Our data supports that a neuroinflammatory response occurs in the BE associated with DKA, and that even after a relatively short duration of poorly controlled T1DM, the pathogenesis of primary diabetic encephalopathy can be initiated.

  7. Litsea japonica extract inhibits neuronal apoptosis and the accumulation of advanced glycation end products in the diabetic mouse retina.

    PubMed

    Kim, Junghyun; Kim, Chan-Sik; Lee, Yun Mi; Sohn, Eunjin; Jo, Kyuhyung; Kim, Jin Sook

    2015-07-01

    The retinal accumulation of advanced glycation end products (AGEs) is a condition, which is found in diabetic retinopathy. The purpose of the present study was to investigate the protective effect of Litsea japonica extract (LJE) and to elucidate its underlying protective mechanism in model diabetic db/db mice. Male, 7 -week-old db/db mice were treated with LJE (100 or 250 mg/kg body weight) once a day orally for 12 weeks. The expression levels of AGEs and their receptor (RAGE) were subsequently assessed by immunohistochemistry. An electrophoretic mobility shift assay and southwestern histochemistry were used to detect activated nuclear factor κB (NF-κB). The immunohistochemical analysis demonstrated that LJE significantly reduced the expression levels of the AGEs and RAGE in the neural retinas of the db/db mice. LJE markedly inhibited the apoptosis of retinal ganglion cells. In addition, LJE suppressed the activation of NF-κB. These results suggested that LJE may be beneficial for the treatment of diabetes-induced retinal neurodegeneration, and the ability of LJE to attenuate retinal ganglion cell loss may be mediated by inhibition of the accumulation of AGEs.

  8. Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes.

    PubMed

    Bartáková, Vendula; Pleskačová, Anna; Kuricová, Katarína; Pácal, Lukáš; Dvořáková, Veronika; Bělobrádková, Jana; Tomandlová, Marie; Tomandl, Josef; Kaňková, Kateřina

    2016-08-01

    While the pathogenic role of dicarbonyl stress and accelerated formation of advanced glycation end products (AGEs) to glucose intolerance and to the development of diabetic complications is well established, little is known about these processes in gestational diabetes mellitus (GDM), a condition pathogenically quite similar to type 2 diabetes. The aims of the present study were (i) to determine plasma thiamine and erythrocyte thiamine diphosphate (TDP) and transketolase (TKT) activity in pregnant women with and without GDM, (ii) to assess relationships between thiamine metabolism parameters and selected clinical, biochemical and anthropometric characteristics and, finally, (iii) to analyse relationship between variability in the genes involved in the regulation of transmembrane thiamine transport (i.e. SLC19A2 and SLC19A3) and relevant parameters of thiamine metabolism. We found significantly lower plasma BMI adjusted thiamine in women with GDM (P = 0.002, Mann-Whitney) while levels of erythrocyte TDP (an active TKT cofactor) in mid-trimester were significantly higher in GDM compared to controls (P = 0.04, Mann-Whitney). However, mid-gestational TKT activity - reflecting pentose phosphate pathway activity - did not differ between the two groups (P > 0.05, Mann-Whitney). Furthermore, we ascertained significant associations of postpartum TKT activity with SNPs SLC19A2 rs6656822 and SLC19A3 rs7567984 (P = 0.03 and P = 0.007, resp., Kruskal-Wallis). Our findings of increased thiamine delivery to the cells without concomitant increase of TKT activity in women with GDM therefore indicate possible pathogenic role of thiamine mishandling in GDM. Further studies are needed to determine its contribution to maternal and/or neonatal morbidity.

  9. Age- and diabetes-induced regulation of oxidative protein modification in rat brain and peripheral tissues: consequences of treatment with antioxidant pyridoindole.

    PubMed

    Sakul, Arzu; Cumaoğlu, Ahmet; Aydin, Elif; Ari, Nuray; Dilsiz, Nihat; Karasu, Cimen

    2013-05-01

    The increased glyco- and lipo-oxidation events are considered one of the major factors in the accumulation of non-functional damaged proteins, and the antioxidants may inhibit extensive protein modification and nitrosylated protein levels, enhancing the oxidative damage at the cellular levels in aging and diabetes. Because of its central role in the pathogenesis of age-dependent and diabetes-mediated functional decline, we compared the levels of oxidatively modified protein markers, namely AGEs (Advanced Glycation End-protein adducts), 4-HNE (4-hydroxy-nonenal-histidine) and 3-NT (3-nitrotyrosine), in different tissues of young and old rats. Separately, these three oxidative stress parameters were explored in old rats subjected to experimentally induced diabetes and following a long-term treatment with a novel synthetic pyridoindole antioxidant derived from stobadine-SMe1EC2 (2-ethoxycarbonyl-8-methoxy-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indolinium dichloride). Diabetes induced by streptozotocin injection in rats aged 13-15 months, and SMe1EC2 treatment was applied during 4months to aged diabetic rats. AGEs and 4-HNE levels were significantly elevated in brain, ventricle and kidney, but not in lens and liver of aged rats when compared with young rats. Diabetes propagated ageing-induced increase in AGEs and 4-HNE in brain, ventricle and kidney, and raised significantly lens and liver AGEs and 4-HNE levels in aged rats. In aged diabetic rats, SMe1EC2 protected only the kidney against increase in AGEs, and inhibited significantly 4-HNE levels in brain, kidney, liver and lens that were observed more pronounced in lens. 3-NT was significantly increased in brain of aged rats and in kidney, lens and ventricle of aged diabetic rats, while SMe1EC2 has no protective effect on 3-NT increase. Results demonstrate that (1) the responsiveness of different tissue proteins to glyco-lipo-oxidative and nitrosative stress in the course of normal aging was miscellaneous. (2

  10. Diabetes

    MedlinePlus

    ... version of this page please turn Javascript on. Diabetes What is Diabetes? Too Much Glucose in the Blood Diabetes means ... high, causing pre-diabetes or diabetes. Types of Diabetes There are three main kinds of diabetes: type ...

  11. Recent Advances in Diagnostic Strategies for Diabetic Peripheral Neuropathy

    PubMed Central

    2016-01-01

    Diabetes is an increasing epidemic in Korea, and associated diabetic peripheral neuropathy (DPN) is its most common and disabling complication. DPN has an insidious onset and heterogeneous clinical manifestations, making it difficult to detect high-risk patients of DPN. Early diagnosis is recommended and is the key factor for a better prognosis and preventing diabetic foot ulcers, amputation, or disability. However, diagnostic tests for DPN are not clearly established because of the various pathophysiology developing from the nerve injury to clinical manifestations, differences in mechanisms according to the type of diabetes, comorbidities, and the unclear natural history of DPN. Therefore, DPN remains a challenge for physicians to screen, diagnose, follow up, and evaluate for treatment response. In this review, diagnosing DPN using various methods to assess clinical symptoms and/or signs, sensorineural impairment, and nerve conduction studies will be discussed. Clinicians should rely on established modalities and utilize current available testing as complementary to specific clinical situations. PMID:27246283

  12. Advanced glycation end products interfere with gastric smooth muscle contractile marker expression via the AGE/RAGE/NF-κB pathway.

    PubMed

    Yu, Ting; Zheng, Yongping; Wang, Yun; Xiong, Wenjie; Lin, Lin

    2017-02-01

    Excessive production of advanced glycation end products (AGE) has been implicated in the pathogenesis of diabetic complications. Smooth muscle (SM) phenotype transition is involved in diabetes-associated gastric motility dysfunction. We investigated whether AGE interfere with gastric antral SM contractile marker expression. Sixteen Sprague-Dawley rats were randomly divided into control and streptozotocin-induced diabetic groups. Sixteen weeks after streptozotocin administration, gastric antral SM strip contractility in the groups were measured. The gastric tissue expression of AGE was tested. Primary cultured gastric smooth muscle cells (SMCs) were used in complementary in vitro studies. In the presence and absence of AGE, SMCs were transfected with myocardin plasmid or treated with nuclear factor-κB (NF-κB) inhibitor or anti-RAGE antibody. Diabetic rats showed weakness of SM strip contractility and decreased expression of SM contractile marker genes (myosin heavy chains [MHC], α-actin, calponin) as compared with the control group. Gastric antral SM layer Nε-(carboxymethyl) lysine (CML) level, the major AGE compound, were increased in the diabetic rats. AGE downregulated SM contractile markers and myocardin expression in a concentration-dependent manner. Myocardin overexpression prevented these results. AGE treatment activated NF-κB in SMCs. The NF-κB inhibitor BAY 11-7082 and anti-RAGE antibody blocked the effects of AGE on myocardin downregulation. AGE may induce the development of gastric dysmotility by downregulating SM contractile proteins and myocardin expression via the AGE/RAGE/NF-κB pathway.

  13. Recent advances in exploring the genetic susceptibility to diabetic neuropathy.

    PubMed

    Politi, Cristina; Ciccacci, Cinzia; D'Amato, Cinzia; Novelli, Giuseppe; Borgiani, Paola; Spallone, Vincenza

    2016-10-01

    Diabetic polyneuropathy and cardiovascular autonomic neuropathy are common and disabling complications of diabetes. Although glycaemic control and cardiovascular risk factors are major contributory elements in its development, diabetic neuropathy recognizes a multifactorial influence and a multiplicity of pathogenetic mechanisms. Thus genetic and environmental factors may contribute to its susceptibility, each with a modest contribution, by targeting various metabolic and microvascular pathways whose alterations intervene in diabetic neuropathy pathogenesis. This review is aimed at describing major data from the available literature regarding genetic susceptibility to diabetic neuropathies. It provides an overview of the genes reported as associated with the development or progression of these complications, i.e. ACE, MTHFR, GST, GLO1, APOE, TCF7L2, VEGF, IL-4, GPX1, eNOS, ADRA2B, GFRA2, MIR146A, MIR128A. The identification of genetic susceptibility can help in both expanding the comprehension of the pathogenetic mechanisms of diabetic nerve damage and identifying biomarkers of risk prediction and response to therapeutic intervention.

  14. Skin autofluorescence relates to soluble receptor for advanced glycation end-products and albuminuria in diabetes mellitus.

    PubMed

    Skrha, J; Soupal, J; Loni Ekali, G; Prázný, M; Kalousová, M; Kvasnička, J; Landová, L; Zima, T; Skrha, J

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  15. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

    PubMed Central

    Škrha, J.; Šoupal, J.; Loni Ekali, G.; Prázný, M.; Kalousová, M.; Kvasnička, J.; Landová, L.; Zima, T.; Škrha, J.

    2013-01-01

    The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R2 = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established. PMID:23671885

  16. Advanced Glycation End Products in Extracellular Matrix Proteins Contribute to the Failure of Sensory Nerve Regeneration in Diabetes

    PubMed Central

    Duran-Jimenez, Beatriz; Dobler, Darin; Moffatt, Sarah; Rabbani, Naila; Streuli, Charles H.; Thornalley, Paul J.; Tomlinson, David R.; Gardiner, Natalie J.

    2009-01-01

    OBJECTIVE The goal of this study was to characterize glycation adducts formed in both in vivo extracellular matrix (ECM) proteins of endoneurium from streptozotocin (STZ)-induced diabetic rats and in vitro by glycation of laminin and fibronectin with methylglyoxal and glucose. We also investigated the impact of advanced glycation end product (AGE) residue content of ECM on neurite outgrowth from sensory neurons. RESEARCH DESIGN AND METHODS Glycation, oxidation, and nitration adducts of ECM proteins extracted from the endoneurium of control and STZ-induced diabetic rat sciatic nerve (3–24 weeks post-STZ) and of laminin and fibronectin that had been glycated using glucose or methylglyoxal were examined by liquid chromatography with tandem mass spectrometry. Methylglyoxal-glycated or unmodified ECM proteins were used as substrata for dissociated rat sensory neurons as in vitro models of regeneration. RESULTS STZ-induced diabetes produced a significant increase in early glycation Nε-fructosyl-lysine and AGE residue contents of endoneurial ECM. Glycation of laminin and fibronectin by methylglyoxal and glucose increased glycation adduct residue contents with methylglyoxal-derived hydroimidazolone and Nε-fructosyl-lysine, respectively, of greatest quantitative importance. Glycation of laminin caused a significant decrease in both neurotrophin-stimulated and preconditioned sensory neurite outgrowth. This decrease was prevented by aminoguanidine. Glycation of fibronectin also decreased preconditioned neurite outgrowth, which was prevented by aminoguanidine and nerve growth factor. CONCLUSIONS Early glycation and AGE residue content of endoneurial ECM proteins increase markedly in STZ-induced diabetes. Glycation of laminin and fibronectin causes a reduction in neurotrophin-stimulated neurite outgrowth and preconditioned neurite outgrowth. This may provide a mechanism for the failure of collateral sprouting and axonal regeneration in diabetic neuropathy. PMID:19720799

  17. Advanced glycation end products (AGEs) promote melanogenesis through receptor for AGEs

    PubMed Central

    Lee, Eun Jung; Kim, Ji Young; Oh, Sang Ho

    2016-01-01

    Accumulation of advanced glycation end products (AGEs) is linked with development or aggravation of many degenerative processes or disorders, including aging and atherosclerosis. AGEs production in skin cells is known to promote stiffness and loss of elasticity through their buildup in connective tissue. However, the impact of AGEs has yet to be fully explored in melanocytes. In this study, we confirmed the existence of receptor for AGE (RAGE) in melanocytes in western blot and immunofluorescence along with increased melanin production in ex vivo skin organ culture and in vitro melanocyte culture following AGEs treatment. Cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinases (ERK) 1/2 are considered as key regulatory proteins in AGEs-induced melanogenesis. In addition, blockage experiment using anti-RAGE blocking antibody has indicated that RAGE plays a pivotal role in AGE-mediated melanogenesis. Therefore, it is apparent that AGEs, known markers of aging, promote melanogenesis via RAGE. In addition, AGEs could be implicated in pigmentation associated with photoaging according to the results of increased secretion of AGEs from keratinocytes following UV irradiation. AGE-mediated melanogenesis may thus hold promise as a novel mean of altering skin pigmentation. PMID:27293210

  18. Renoprotective and lipid-lowering effects of LR compounds, novel advanced glycation end product inhibitors, in streptozotocin-induced diabetic rats.

    PubMed

    Figarola, James Lester; Scott, Steven; Loera, Sofia; Xi, Bixin; Synold, Timothy; Rahbar, Samuel

    2005-06-01

    The accelerated formation of advanced glycation/lipoxidation end products (AGEs/ALEs) has been implicated in the pathogenesis of various diabetic complications. Several natural and synthetic compounds have been proposed and advanced as inhibitors of AGE/ALE formation. We examined the effects of two new AGE/ALE inhibitors, LR-9 and LR-74, on the prevention of early renal disease and dyslipidemia in streptozotocin (STZ)-induced diabetic rats. Diabetic rats were treated with either LR-9 or LR-74 for 32 weeks. Progression of renal disease was evaluated by measurements of urinary albumin and plasma creatinine concentrations. AGE-induced chemical modification of the tail tendon collagen and levels of Nepsilon-(carboxymethyl)- and (carboxyethyl)- lysines (CML and CEL) in skin collagen were measured. AGE/ALE levels in kidneys were determined by immunohistochemistry. Plasma lipids and their lipid hydroperoxide concentrations were also determined. Treatment of either LR-9 or LR-74 significantly inhibited the increase in albuminuria, plasma creatinine, hyperlipidemia, and plasma lipid peroxidation in diabetic rats without any effects on hyperglycemia. Both compounds also reduced CML-AGE accumulation in kidney glomeruli and tubules, AGE-linked fluorescence and cross-linking of tail collagen, and levels of CML and CEL in skin collagen. These results suggest that both LR compounds can inhibit the progression of renal disease and also prevent dyslipidemia in experimental diabetes. These compounds may have an additional beneficial effect as an antioxidant against lipid peroxidation, and thus may provide alternative therapeutic options for the treatment of various diabetic macrovascular complications.

  19. Mobile patient applications within diabetes - from few and easy to advanced functionalities.

    PubMed

    Årsand, Eirik; Skrøvseth, Stein Olav; Hejlesen, Ole; Horsch, Alexander; Godtliebsen, Fred; Grøttland, Astrid; Hartvigsen, Gunnar

    2013-01-01

    Patient diaries as apps on mobile phones are becoming increasingly common, and can be a good support tool for patients who need to organize information relevant for their disease. Self-management is important to achieving diabetes treatment goals and can be a tool for lifestyle changes for patients with Type 2 diabetes. The autoimmune disease Type 1 diabetes requires a more intensive management than Type 2 - thus more advanced functionalities is desirable for users. Both simple and easy-to-use and more advanced diaries have their respective benefits, depending on the target user group and intervention. In this poster we summarize main findings and experience from more than a decade of research and development in the diabetes area. Several versions of the mobile health research platform-the Few Touch Application (FTA) are presented to illustrate the different approaches and results.

  20. Decreased cord-blood phospholipids in young age-at-onset type 1 diabetes.

    PubMed

    La Torre, Daria; Seppänen-Laakso, Tuulikki; Larsson, Helena E; Hyötyläinen, Tuulia; Ivarsson, Sten A; Lernmark, Ake; Oresic, Matej

    2013-11-01

    Children developing type 1 diabetes may have risk markers already in their umbilical cord blood. It is hypothesized that the risk for type 1 diabetes at an early age may be increased by a pathogenic pregnancy and be reflected in altered cord-blood composition. This study used metabolomics to test if the cord-blood lipidome was affected in children diagnosed with type 1 diabetes before 8 years of age. The present case-control study of 76 index children diagnosed with type 1 diabetes before 8 years of age and 76 healthy control subjects matched for HLA risk, sex, and date of birth, as well as the mother's age and gestational age, revealed that cord-blood phosphatidylcholines and phosphatidylethanolamines were significantly decreased in children diagnosed with type 1 diabetes before 4 years of age. Reduced levels of triglycerides correlated to gestational age in index and control children and to age at diagnosis only in the index children. Finally, gestational infection during the first trimester was associated with lower cord-blood total lysophosphatidylcholines in index and control children. In conclusion, metabolomics of umbilical cord blood may identify children at increased risk for type 1 diabetes. Low phospholipid levels at birth may represent key mediators of the immune system and contribute to early induction of islet autoimmunity.

  1. Meeting the Challenge of Diabetes in Ageing and Diverse Populations: A Review of the Literature from the UK

    PubMed Central

    Wilkinson, Emma; Waqar, Muhammad; Sinclair, Alan

    2016-01-01

    The impact of type 2 diabetes on ageing societies is great and populations across the globe are becoming more diverse. Complications of diabetes unequally affect particular groups in the UK older people, and people with a South Asian background are two population groups with increased risk whose numbers will grow in the future. We explored the evidence about diabetes care for older people with South Asian ethnicity to understand the contexts and mechanisms behind interventions to reduce inequalities. We used a realist approach to review the literature, mapped the main areas where relevant evidence exists, and explored the concepts and mechanisms which underpinned interventions. From this we constructed a theoretical framework for a programme of research and put forward suggestions for what our analysis might mean to providers, researchers, and policy makers. Broad themes of cultural competency; comorbidities and stratification; and access emerged as mid-level mechanisms which have individualised, culturally intelligent, and ethical care at their heart and through which inequalities can be addressed. These provide a theoretical framework for future research to advance knowledge about concordance; culturally meaningful measures of depression and cognitive impairment; and care planning in different contexts which support effective diabetes care for aging and diverse populations. PMID:27830158

  2. DNA aptamer raised against advanced glycation end products (AGEs) improves glycemic control and decreases adipocyte size in fructose-fed rats by suppressing AGE-RAGE axis.

    PubMed

    Ojima, A; Matsui, T; Nakamura, N; Higashimoto, Y; Ueda, S; Fukami, K; Okuda, S; Yamagishi, S

    2015-04-01

    Advanced glycation end products (AGEs) decrease adiponectin expression and suppress insulin signaling in cultured adipocytes through the interaction with a receptor for AGEs (RAGE) via oxidative stress generation. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. This study examined the effects of AGE-aptamer on adipocyte remodeling, AGE-RAGE-oxidative stress axis, and adiponectin expression in fructose-fed rats. Although AGE-aptamer treatment by an osmotic mini pump for 8 weeks did not affect serum insulin levels, it significantly decreased average fasting blood glucose and had a tendency to inhibit body weight gain in fructose-fed rats. Furthermore, AGE-aptamer significantly suppressed the increase in adipocyte size and prevented the elevation in AGEs, RAGE, and an oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), levels in adipose tissues of fructose-fed rats at 14-week-old, while it restored the decrease in adiponectin mRNA levels. Our present study suggests that AGE-aptamer could improve glycemic control and prevent adipocyte remodeling in fructose-fed rats partly by suppressing the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for fructose-induced metabolic derangements.

  3. Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice

    PubMed Central

    Chen, Cheng-Hsien; Chen, Tso-Hsiao; Wu, Mei-Yi; Chou, Tz-Chong; Chen, Jia-Rung; Wei, Meng-Jun; Lee, San-Liang; Hong, Li-Yu; Zheng, Cai-Mei; Chiu, I-Jen; Lin, Yuh-Feng; Hsu, Ching-Min; Hsu, Yung-Ho

    2017-01-01

    The accumulation of advanced glycation end products (AGEs) in diabetic patients induces vascular endothelial injury. Promyelocytic leukemia zinc finger protein (PLZF) is a transcription factor that can be activated by low-temperature far-infrared (FIR) irradiation to exert beneficial effects on the vascular endothelium. In the present study, we investigated the influence of FIR-induced PLZF activation on AGE-induced endothelial injury both in vitro and in vivo. FIR irradiation inhibited AGE-induced apoptosis in human umbilical vein endothelial cells (HUVECs). PLZF activation increased the expression of phosphatidylinositol-3 kinases (PI3K), which are important kinases in the autophagic signaling pathway. FIR-induced PLZF activation led to autophagy in HUVEC, which was mediated through the upregulation of PI3K. Immunofluorescence staining showed that AGEs were engulfed by HUVECs and localized to lysosomes. FIR-induced autophagy promoted AGEs degradation in HUVECs. In nicotinamide/streptozotocin-induced diabetic mice, FIR therapy reduced serum AGEs and AGEs deposition at the vascular endothelium. FIR therapy also reduced diabetes-induced inflammatory markers in the vascular endothelium and improved vascular endothelial function. These protective effects of FIR therapy were not found in PLZF-knockout mice. Our data suggest that FIR-induced PLZF activation in vascular endothelial cells protects the vascular endothelium in diabetic mice from AGE-induced injury. PMID:28071754

  4. Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways

    PubMed Central

    Suchal, Kapil; Malik, Salma; Khan, Sana Irfan; Malhotra, Rajiv Kumar; Goyal, Sameer N.; Bhatia, Jagriti; Kumari, Santosh; Ojha, Shreesh; Arya, Dharamvir Singh

    2017-01-01

    Hyperglycemia induced advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) activation is thought to involve in the development of cardiovascular disease in diabetics. Activation of AGE-RAGE axis results in the oxidative stress and inflammation. Mangiferin is found in the bark of mango tree and is known to treat diseases owing to its various biological activities. Thus, this study was designed to evaluate the effect of mangiferin in ischemia-reperfusion (IR) induced myocardial injury in diabetic rats. A single injection of STZ (70 mg/kg; i.p.) was injected to male albino Wistar rats to induce diabetes. After confirmation of diabetes, rats were administered vehicle (2 ml/kg; i.p.) and mangiferin (40 mg/kg; i.p.) for 28 days. On 28th day, left anterior descending coronary artery was ligated for 45 min and then reperfused for 60 min. Mangiferin treatment significantly improved cardiac function, restored antioxidant status, reduced inflammation, apoptosis and maintained myocardial architecture. Furthermore, mangiferin significantly inhibited the activation of AGE-RAGE axis, c-Jun N-terminal kinase (JNK) and p38 and increased the expression of extracellular regulated kinase 1/2 (ERK1/2) in the myocardium. Thus, mangiferin attenuated IR injury in diabetic rats by modulation of AGE-RAGE/MAPK pathways which further prevented oxidative stress, inflammation and apoptosis in the myocardium. PMID:28181586

  5. Oxidative stress in aging: advances in proteomic approaches.

    PubMed

    Ortuño-Sahagún, Daniel; Pallàs, Mercè; Rojas-Mayorquín, Argelia E

    2014-01-01

    Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual's Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging.

  6. Oxidative Stress in Aging: Advances in Proteomic Approaches

    PubMed Central

    Ortuño-Sahagún, Daniel; Pallàs, Mercè; Rojas-Mayorquín, Argelia E.

    2014-01-01

    Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual's Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging. PMID:24688629

  7. Soluble Receptor for Advanced Glycation End Products Improves Stromal Cell–Derived Factor-1 Activity in Model Diabetic Environments

    PubMed Central

    Olekson, Melissa Przyborowski; Faulknor, Renea A.; Hsia, Henry C.; Schmidt, Ann Marie; Berthiaume, François

    2016-01-01

    Objective: In diabetes, hyperglycemia causes the accumulation of advanced glycation end products (AGEs) that trigger reactive oxygen species (ROS) generation through binding the receptor for AGEs (RAGE). Because exogenous growth factors have had little success in enhancing chronic wound healing, we investigated whether hyperglycemia-induced AGEs interfere with cellular responses to extracellular signals. We used stromal cell–derived factor-1 (SDF-1), an angiogenic chemokine also known to promote stem cell recruitment in skin wounds. Approach: Human leukemia-60 (HL-60) cells and mouse peripheral blood mononuclear cells (PBMCs), which express the SDF-1 receptor CXCR-4, were incubated for 24 h in medium supplemented with 25 mM d-glucose. Soluble RAGE (sRAGE) was used to block RAGE activation. Response to SDF-1 was measured in cellular migration and ROS assays. A diabetic murine excisional wound model measured SDF-1 liposome and sRAGE activity in vivo. Results: Hyperglycemia led to significant accumulation of AGEs, decreased SDF-1–directed migration, and elevated baseline ROS levels; it suppressed the ROS spike normally triggered by SDF-1. sRAGE decreased the ROS baseline and restored both the SDF-1–mediated spike and cell migration. Topically applied sRAGE alone promoted healing and enhanced the effect of exogenous SDF-1 on diabetic murine wounds. Innovation: While there is interest in using growth factors to improve wound healing, this strategy is largely ineffective in diabetic wounds. We show that sRAGE may restore signaling, thus potentiating the effect of exogenously applied growth factors. Conclusion: Blocking RAGE with sRAGE restores SDF-1–mediated cellular responses in hyperglycemic environments and may potentiate the effectiveness of SDF-1 applied in vivo. PMID:28078186

  8. Complications in Advanced Diabetics in a Tertiary Care Centre: A Retrospective Registry-Based Study

    PubMed Central

    Ankush; Gomes, Edwin; Dessai, Ankush

    2016-01-01

    Introduction Diabetes is a major public health problem in our country and complications of diabetes are a major cause of morbidity and mortality. There is a need to quantify the complications in order to improve our strategies for prevention and management. Aim To measure the prevalence of complications in type 2 diabetics following up at a tertiary care centre and to study its association with the socio-demographic and clinical parameters. Materials and Methods A retrospective record based study was conducted on 3261 type 2 diabetic patients on insulin therapy, recorded in the diabetic registry maintained at Goa Medical College from Aug 2009 to May 2012. Data on anthropometric measurements, demographic characteristics, complications and other details were extracted from these records. Results Out of the 3261 patients 1025 (31.4%) had macrovascular complications and 1122 (34.4%) had at least one microvascular complication. The prevalence of peripheral vascular disease, coronary artery disease and stroke were 6.7%, 21.3% and 6.6% respectively and were significantly higher in males. The prevalence of diabetic retinopathy, nephropathy and neuropathy were 16.7%, 16.5% and 16.3% respectively with diabetic nephropathy being significantly higher in males. Trend analysis showed significant association of rising prevalence of all complications with age (p<0.05). Duration of diabetes also showed significantly positive trend for all complications (p<0.05) except stroke. Conclusion The study presents the prevalence of diabetic complications in patients reporting to a tertiary hospital in Goa. Coronary artery disease was found to be the most common complication. As age and duration of diabetes were found to be significantly associated, efforts should be made towards promoting earlier diagnosis of diabetes so as to improve management and decrease the chances of complications. PMID:27190861

  9. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression.

    PubMed

    Ishibashi, Y; Matsui, T; Takeuchi, M; Yamagishi, S

    2012-11-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in tubulointerstitial damage in diabetic nephropathy. Recently, metformin has been shown to ameliorate tubular injury both in cell culture and diabetic animal model. However, effects of metformin on AGEs-induced tubular cell apoptosis and damage remain unknown. We examined here whether and how metformin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was evaluated by DNA fragmentation and annexin V expression level. AGEs upregulated RAGE mRNA levels and subsequently increased ROS generation and intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and transforming growth factor-β gene expression in human renal proximal tubular cells, all of which were significantly blocked by the treatment of 0.01 and 0.1 mM metformin. Compound C, an inhibitor of AMP-activated protein kinase significantly blocked the effects of metformin on RAGE gene expression and ROS generation in AGEs-exposed tubular cells. Furthermore, metformin dose-dependently inhibited the AGEs-induced apoptotic cell death of tubular cells; 1 mM metformin completely suppressed the pro-apoptotic effects of AGEs in 2 different assay systems. Our present study suggests that metformin could inhibit the AGEs-induced apoptosis and inflammatory and fibrotic reactions in tubular cells probably by reducing ROS generation via suppression of RAGE expression through AMP-activated protein kinase activation. Metformin may protect against tubular cell injury in diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.

  10. Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption.

    PubMed

    Yang, Xiao; Gandhi, Chintan; Rahman, Md Mizanur; Appleford, Mark; Sun, Lian-Wen; Wang, Xiaodu

    2015-12-01

    Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Previous studies have shown controversial results regarding the role of in situ AGEs accumulation in osteoclastic resorption. To address this issue, this study cultured human osteoclast cells directly on human cadaveric bone slices from different age groups (young and elderly) to warrant its relevance to in vivo conditions. The cell culture was terminated on the 3rd, 7th, and 10th day, respectively, to assess temporal changes in the number of differentiated osteoclasts, the number and size of osteoclastic resorption pits, the amount of bone resorbed, as well as the amount of matrix AGEs released in the medium by resorption. In addition, the in situ concentration of matrix AGEs at each resorption pit was also estimated based on its AGEs autofluorescent intensity. The results indicated that (1) osteoclastic resorption activities were significantly correlated with the donor age, showing larger but shallower resorption pits on the elderly bone substrates than on the younger ones; (2) osteoclast resorption activities were not significantly dependent on the in situ AGEs concentration in bone matrix, and (3) a correlation was observed between osteoclast activities and the concentration of AGEs released by the resorption. These results suggest that osteoclasts tend to migrate away from initial anchoring sites on elderly bone substrate during resorption compared to younger bone substrates. However, such behavior is not directly related to the in situ concentration of AGEs in bone matrix at the resorption sites.

  11. Interaction between Advanced Glycation End Products Formation and Vascular Responses in Femoral and Coronary Arteries from Exercised Diabetic Rats

    PubMed Central

    Delbin, Maria A.; Davel, Ana Paula C.; Couto, Gisele Kruger; de Araújo, Gustavo G.; Rossoni, Luciana Venturini; Antunes, Edson; Zanesco, Angelina

    2012-01-01

    Background The majority of studies have investigated the effect of exercise training (TR) on vascular responses in diabetic animals (DB), but none evaluated nitric oxide (NO) and advanced glycation end products (AGEs) formation associated with oxidant and antioxidant activities in femoral and coronary arteries from trained diabetic rats. Our hypothesis was that 8-week TR would alter AGEs levels in type 1 diabetic rats ameliorating vascular responsiveness. Methodology/Principal Findings Male Wistar rats were divided into control sedentary (C/SD), sedentary diabetic (SD/DB), and trained diabetic (TR/DB). DB was induced by streptozotocin (i.p.: 60 mg/kg). TR was performed for 60 min per day, 5 days/week, during 8 weeks. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (PHE) and tromboxane analog (U46619) were obtained. The protein expressions of eNOS, receptor for AGEs (RAGE), Cu/Zn-SOD and Mn-SOD were analyzed. Tissues NO production and reactive oxygen species (ROS) generation were evaluated. Plasma nitrate/nitrite (NOx−), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and Nε-(carboxymethyl) lysine (CML, AGE biomarker). A rightward shift in the concentration-response curves to ACh was observed in femoral and coronary arteries from SD/DB that was accompanied by an increase in TBARS and CML levels. Decreased in the eNOS expression, tissues NO production and NOx− levels were associated with increased ROS generation. A positive interaction between the beneficial effect of TR on the relaxing responses to ACh and the reduction in TBARS and CML levels were observed without changing in antioxidant activities. The eNOS protein expression, tissues NO production and ROS generation were fully re-established in TR/DB, but plasma NOx− levels were partially restored. Conclusion Shear stress induced by TR fully restores the eNOS/NO pathway in both preparations from non-treated diabetic

  12. Reactive immunization suppresses advanced glycation and mitigates diabetic nephropathy.

    PubMed

    Shcheglova, Tatiana; Makker, Sudesh; Tramontano, Alfonso

    2009-05-01

    Agents that inhibit glycation end products by reducing the carbonyl load from glycation and glycoxidation are an emerging pharmacologic approach to treat complications of diabetes. We previously demonstrated that antibodies generated to the glycoprotein keyhole limpet hemocyanin (KLH) can cross-link with reactive carbonyl residues on protein conjugates. Here, we immunized streptozotocin-induced diabetic rats with KLH to assess the capacity of the elicited antibodies to intercept carbonyl residues on glycated proteins and to mitigate glycation-related pathology. Compared with diabetic rats immunized with adjuvant alone, KLH-immunized diabetic rats had decreased levels of glycated peptides in sera and demonstrated a reduction in albuminuria, proteinuria, deposition of glycation end products in the kidney, and histologic damage. In vitro, low molecular weight glycated peptides from rat serum reacted with anti-KLH antibodies at a faster rate than normal IgG and selectively modified the lambda chains. The reaction products contained peptide sequences from type I collagen alpha chain, albumin, and LDL receptor-related protein. These adduction reactions were inhibited by free KLH and by reduction of glycated peptides with borohydride. In summary, these results suggest that inherent reactivity of Ig light chains provides a natural mechanism for the removal of cytotoxic glycation products. This reactivity can be augmented by glycoprotein-specific reactive immunization, a potential biopharmaceutical approach to glycation-related pathology.

  13. A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus with disease duration.

    PubMed

    Ashraf, Jalaluddin M; Arfat, Mir Yasir; Arif, Zarina; Ahmad, Jamal; Moinuddin; Alam, Khursheed

    2015-02-01

    Nonenzymatic glycation of amino groups of DNA bases by reducing sugars can generate advanced glycation end products (AGEs). Cellular formation of AGEs under normal physiology is continuously scanned and removed by efficient system in the cells. However, excess formation and accumulation of AGEs may be cause or consequence of some human diseases. Mammalian DNA incubated with d-glucose for 28 days at 37°C showed structural changes in DNA as confirmed by UV, fluorescence, CD, melting temperature, S1 nuclease sensitivity and gel electrophoresis. Formation of DNA-AGE was confirmed by HPLC and LC-MS. Enzyme immunoassay and electrophoretic mobility shift assay of autoantibodies in type 2 diabetes patients' sera with disease duration of 5-15 years exhibited significantly high binding with DNA-AGE as compared to patients with 1-5 years of disease duration. Autoantibodies against aberrant DNA-AGE may be important in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients.

  14. [Age-related features of immunocompetent cells of human placenta associated with diabetes mellitus].

    PubMed

    Durnova, A O; Poliakova, V O; Pal'chenko, N A

    2010-01-01

    The immune-competent cells of placenta play the important role in protection of developing fetus against infectious agents; but their dysfunction can lead to development of placental insufficiency that affects health both fetus and mother. The aim of this study was the comparative analysis of presence of immune competent cells in villous chorion of mature placenta, taken from women with diabetes of different age groups. In our study we found three subpopulations of immune cells in villous chorion of mature placenta: natural killer cells (NK), B-lymphocytes and macrophages. Prevailing subpopulation are macrophages, they are detected 1,8 times more often than B-lymphocytes, and 2,3 times more often than NK. The quantity of immune competent cells in groups with diabetes of various types is different. Thus, the greatest number of macrophages was detected in group with diabetes type II of middle age (29-35 years)-- 4.62 +/- 0.93%, B-lymphocytes in group of women with diabetes type I of younger age (18-28 years)--2.50 +/- 0.30%, NK-cells in group with diabetes type I of younger age--1.98 +/- 0,42%. Analysis of received data showed the differences in expression of markers of immune cells in women of different age groups, which brings about the conclusion of various reactance of immune system of women with diabetes depending on age.

  15. Stress-strain analysis of contractility in the ileum in response to flow and ramp distension in streptozotocin-induced diabetic rats--association with advanced glycation end product formation.

    PubMed

    Zhao, Jingbo; Chen, Pengmin; Gregersen, Hans

    2015-04-13

    This study compared the ileal contractility and analyzed the association between contractility with advanced glycation end product (AGE) formation in normal and streptozotocin (STZ)-induced diabetic rats. Nine STZ-induced diabetic rats (Diabetes group) and 9 normal rats (Normal group) were used. The motility experiments were carried out on ileums in organ baths containing physiological Krebs solution. Ileal pressure and diameter changes were obtained from basic, flow-induced and ramp distension-induced contractions. The frequency and amplitude of contractions were analyzed from pressure-diameter curves. Distension-induced contraction thresholds and maximum contraction amplitude of basic and flow-induced contractions were calculated in terms of stress and strain. AGE and its receptor (RAGE) in the layers were detected by immunohistochemistry staining. The maximum stress of flow-induced contractions was lowest in the Diabetes Group (P<0.05). During ramp distension, the pressure and stress thresholds and Young's modulus to induce phasic contraction were lowest in the Diabetes Group (P<0.05 and P<0.01). AGE and RAGE expressions in the different ileum layers were highest in the Diabetes group. The contraction pressure and stress thresholds were significantly associated with AGE expression in the muscle layer and RAGE expression in mucosa epithelium and neurons. The diabetic intestine was hypersensitive to distension for contraction induction. However, the contraction force produced by smooth muscle was lowest in diabetic rats. Increased AGE/RAGE expression was associated with the contractility changes in diabetic rats.

  16. Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases.

    PubMed

    Grillo, M A; Colombatto, S

    2008-06-01

    Advanced glycation end-products (AGEs) are formed from the so-called Amadori products by rearrangement followed by other reactions giving rise to compounds bound irreversibly. The structure of some of them is shown and the mechanism of formation is described. Several AGE binding molecules (Receptors for AGE, RAGE) are known and it is thought that many of the effects caused by AGEs are mediated by RAGE. Some of these were shown to be toxic, and called TAGE. The mechanism of detoxification of glyoxal and methylglyoxal by the glyoxalase system is described and also the possibility to eliminate glycated proteins by deglycation enzymes. Compounds able to inhibit AGEs formation are also taken into consideration.

  17. Age as an independent factor for the development of neuropathy in diabetic patients.

    PubMed

    Popescu, Simona; Timar, Bogdan; Baderca, Flavia; Simu, Mihaela; Diaconu, Laura; Velea, Iulian; Timar, Romulus

    2016-01-01

    Population aging is unprecedented, without parallel in the history of humanity. As type 2 diabetes mellitus is predominantly more prevalent in aging populations, this creates a major public health burden. Older adults with diabetes have the highest rates of major lower-extremity amputation, myocardial infarction, visual impairment, and end-stage renal disease of any age group. The aims of our study were to assess whether age is an independent factor for the occurrence of diabetic neuropathy (DN), and to evaluate the relationship between the presence and the severity of DN and the diabetes duration and blood glucose level. In this study, we enrolled 198 patients, previously diagnosed with type 2 diabetes mellitus. For all patients, we measured hemoglobin A1c (HbA1c), lipid profile, and body mass index and we assessed the presence and severity of DN using the evaluation of clinical signs and symptoms. Patients had a median age of 62 years, with a median of diabetes duration of 7 years; 55.1% of the patients were men and the average HbA1c in the cohort was 8.2%. The prevalence of DN according to Michigan Neuropathy Screening Instrument was 28.8%, being significantly and positively correlated with higher age (65 vs 59 years; P=0.001) and HbA1c (8.6% vs 8.0%; P=0.027). No significant correlations were observed between the severity of DN and diabetes duration, body mass index (31.9 vs 29.9 kg/m(2)), or the number of centimeters exceeding the normal waist circumference (25.2 vs 17.3 cm; P=0.003). In conclusion, age influences the presence of DN, independent on other risk factors. This influence persists even after adjusting for other, very important risk factors, like blood glucose level or diabetes duration.

  18. Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk

    PubMed Central

    Brand, Judith S.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Sharp, Stephen J.; Ong, Ken K.; Khaw, Kay-Tee; Ardanaz, Eva; Amiano, Pilar; Boeing, Heiner; Chirlaque, Maria-Dolores; Clavel-Chapelon, Françoise; Crowe, Francesca L.; de Lauzon-Guillain, Blandine; Duell, Eric J.; Fagherazzi, Guy; Franks, Paul W.; Grioni, Sara; Groop, Leif C.; Kaaks, Rudolf; Key, Timothy J.; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez, María-José; Slimani, Nadia; Teucher, Birgit; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L.; Feskens, Edith J.M.; Langenberg, Claudia; Forouhi, Nita G.; Riboli, Elio; Wareham, Nicholas J.

    2013-01-01

    OBJECTIVE Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk. RESEARCH DESIGN AND METHODS Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied. RESULTS Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04–1.69), 1.09 (0.90–1.31), 0.97 (0.86–1.10), and 0.85 (0.70–1.03) for women with menopause at ages <40, 40–44, 45–49, and ≥55 years, respectively, relative to those with menopause at age 50–54 years. The HR per SD younger age at menopause was 1.08 (1.02–1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [1.01–1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05). CONCLUSIONS Early menopause is associated with a greater risk of type 2 diabetes. PMID:23230098

  19. Myosteatosis increases with aging and is associated with incident diabetes in African ancestry men

    PubMed Central

    Miljkovic, I; Kuipers, AL; Cvejkus, R; Bunker, CH; Patrick, AL; Gordon, CL; Zmuda, JM

    2015-01-01

    Objective Skeletal muscle fat infiltration (known as myosteatosis) is greater in African compared with European ancestry men and may play an important role in the development of type 2 diabetes (T2D). However, prospective studies examining the magnitude of changes in myosteatosis with aging and their metabolic consequences are sparse. Methods We examined longitudinal changes in peripheral quantitative computed tomography measured calf myosteatosis [inter-muscular fat (mm2) and skeletal muscle density as a measure of intra-muscular fat (mg/cm3)] in 1,515 Afro-Caribbean men aged 40+ years recruited without regard to their health status. Results During an average of 6.2 years of follow-up, we observed an age-related increase in inter-muscular fat and a decrease in skeletal muscle density (all P<0.0001), which remained significant in those who lost weight, gained weight, or remained weight-stable (all P<0.0001). In addition, muscle density loss accelerated with increasing age (P<0.0001). Increased inter-muscular fat during follow-up was associated with an increased incident risk of T2D independent of factors known to be associated with T2D (Odds ratios per 1-SD increase in inter-muscular fat=1.29; 95% CI=1.08-1.53). Conclusions Our findings suggest that both inter- and intra- muscular fat increase with advancing age and that inter-muscular fat contributes to development of T2D among African ancestry men. PMID:26694517

  20. Neuropsychological Impairment in School-Aged Children Born to Mothers With Gestational Diabetes.

    PubMed

    Bolaños, Lourdes; Matute, Esmeralda; Ramírez-Dueñas, María de Lourdes; Zarabozo, Daniel

    2015-10-01

    The aim of this study was to determine whether school-aged children born to mothers with gestational diabetes show delays in their neuropsychological development. Several key neuropsychological characteristics of 32 children aged 7 to 9 years born to mothers with gestational diabetes were examined by comparing their performance on cognitive tasks to that of 28 children aged 8 to 10 years whose mothers had glucose levels within normal limits during pregnancy. The gestational diabetes group showed low performance on graphic, spatial, and bimanual skills and a higher presence of soft neurologic signs. Lower scores for general intellectual level and the working memory index were also evident. Our results suggest that gestational diabetes is associated with mild cognitive impairment.

  1. Resveratrol prevents the impairment of advanced glycosylation end products (AGE) on macrophage lipid homeostasis by suppressing the receptor for AGE via peroxisome proliferator-activated receptor gamma activation.

    PubMed

    Zhang, Yihua; Luo, Zhidan; Ma, Liqun; Xu, Qiang; Yang, Qihong; Si, Liangyi

    2010-05-01

    Advanced glycosylation end products (AGE) and its receptor (RAGE) axis is involved in the regulation of lipid homeostasis and is critical in the pathogenesis of diabetic atherosclerosis. We investigated the protective role of resveratrol against the AGE-induced impairment on macrophage lipid homeostasis. In THP-1-derived macrophages, RAGE was dose-dependently induced by AGE and played a key role in the AGE-induced cholesterol accumulation. Resveratrol markedly reduced RAGE expression via peroxisome proliferator-activated receptor (PPAR) gamma but not PPARalpha or AMP-activated protein kinase. Importantly, pretreatment with resveratrol significantly ameliorated AGE-induced up-regulation of scavenger receptor-A (SR-A) and down-regulation of ATP-binding cassette (ABC) A1 and ABCG1 and thus effectively prevented the cholesterol accumulation in macrophages as shown by cellular cholesterol analysis and oil red O staining. Moreover, blockade of PPARgamma abolished all these effects of resveratrol. Collectively, our results indicate that resveratrol prevents the impairment of AGE on macrophage lipid homeostasis partially by suppressing RAGE via PPARgamma activation, which might provide new insight into the protective role of resveratrol against diabetic atherosclerosis.

  2. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

    PubMed Central

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-01-01

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies. PMID:26907255

  3. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells.

    PubMed

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

    2016-02-19

    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  4. Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling.

    PubMed

    Tang, Youcai; Chen, Anping

    2014-05-01

    Non-alcoholic steatohepatitis (NASH) is a major risk factor for hepatic fibrogenesis. NASH is often found in diabetic patients with hyperglycemia. Hyperglycemia induces non-enzymatic glycation of proteins, yielding advanced glycation end-products (AGEs). Effects of AGEs are mainly mediated by two categories of cytoplasmic membrane receptors. Receptor for AGEs (RAGE) is associated with increased oxidative stress and inflammation, whereas AGE receptor-1 (AGE-R1) is involved in detoxification and clearance of AGEs. Activation of hepatic stellate cells (HSC) is crucial to the development of hepatic fibrosis. We recently reported that AGEs stimulated HSC activation likely by inhibiting gene expression of AGE-R1 and inducing gene expression of RAGE in HSC, which were eliminated by the antioxidant curcumin. This study is to test our hypothesis that curcumin eliminates the effects of AGEs on the divergent regulation of the two receptors of AGEs in HSC by interrupting the AGE-caused activation of leptin signaling, leading to the inhibition of HSC activation. We observed herein that AGEs activated leptin signaling by inducing gene expression of leptin and its receptor in HSC. Like AGEs, leptin differentially regulated gene expression of RAGE and AGE-R1. Curcumin eliminated the effects of AGEs in HSC by interrupting leptin signaling and activating transcription factor NF-E2 p45-related factor 2 (Nrf2), leading to the elevation of cellular glutathione and the attenuation of oxidative stress. In conclusions, curcumin eliminated the effects of AGEs on the divergent regulation of gene expression of RAGE and AGE-R1 in HSC by interrupting the AGE-caused activation of leptin signaling, leading to the inhibition of HSC activation.

  5. Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling

    PubMed Central

    Tang, Youcai; Chen, Anping

    2014-01-01

    Nonalcoholic steatohepatitis (NASH) is a major risk factor for hepatic fibrogenesis. NASH is often found in diabetic patients with hyperglycemia. Hyperglycemia induces non-enzymatic glycation of proteins, yielding advanced glycation end-products (AGEs). Effects of AGEs are mainly mediated by two categories of cytoplasmic membrane receptors. Receptor for AGEs (RAGE) is associated with increased oxidative stress and inflammation, whereas AGE receptor-1 (AGE-R1) is involved in detoxification and clearance of AGEs. Activation of hepatic stellate cells (HSC) is crucial to the development of hepatic fibrosis. We recently reported that AGEs stimulated HSC activation likely by inhibiting gene expression of AGE-R1 and inducing gene expression of RAGE in HSC, which were eliminated by the antioxidant curcumin. This study is to test our hypothesis that curcumin eliminates the effects of AGEs on the divergent regulation of the two receptors of AGEs in HSC by interrupting the AGEs-caused activation of leptin signaling, leading to the inhibition of HSC activation. We observed herein that AGEs activated leptin signaling by inducing gene expression of leptin and its receptor in HSC. Like AGEs, leptin differentially regulated gene expression of RAGE and AGE-R1. Curcumin eliminated the effects of AGEs in HSC by interrupting leptin signaling and activating transcription factor Nrf2, leading to the elevation of cellular glutathione and the attenuation of oxidative stress. In conclusions, curcumin eliminated the effects of AGEs on the divergent regulation of gene expression of RAGE and AGE-R1 in HSC by interrupting the AGEs-caused activation of leptin signaling, leading to the inhibition of HSC activation. PMID:24614199

  6. Alendronate Can Improve Bone Alterations in Experimental Diabetes by Preventing Antiosteogenic, Antichondrogenic, and Proadipocytic Effects of AGEs on Bone Marrow Progenitor Cells

    PubMed Central

    2016-01-01

    Bisphosphonates such as alendronate are antiosteoporotic drugs that inhibit the activity of bone-resorbing osteoclasts and secondarily promote osteoblastic function. Diabetes increases bone-matrix-associated advanced glycation end products (AGEs) that impair bone marrow progenitor cell (BMPC) osteogenic potential and decrease bone quality. Here we investigated the in vitro effect of alendronate and/or AGEs on the osteoblastogenic, adipogenic, and chondrogenic potential of BMPC isolated from nondiabetic untreated rats. We also evaluated the in vivo effect of alendronate (administered orally to rats with insulin-deficient Diabetes) on long-bone microarchitecture and BMPC multilineage potential. In vitro, the osteogenesis (Runx2, alkaline phosphatase, type 1 collagen, and mineralization) and chondrogenesis (glycosaminoglycan production) of BMPC were both decreased by AGEs, while coincubation with alendronate prevented these effects. The adipogenesis of BMPC (PPARγ, intracellular triglycerides, and lipase) was increased by AGEs, and this was prevented by coincubation with alendronate. In vivo, experimental Diabetes (a) decreased femoral trabecular bone area, osteocyte density, and osteoclastic TRAP activity; (b) increased bone marrow adiposity; and (c) deregulated BMPC phenotypic potential (increasing adipogenesis and decreasing osteogenesis and chondrogenesis). Orally administered alendronate prevented all these Diabetes-induced effects on bone. Thus, alendronate could improve bone alterations in diabetic rats by preventing the antiosteogenic, antichondrogenic, and proadipocytic effects of AGEs on BMPC. PMID:27840829

  7. Utilization of Advanced Modalities in the Management of Diabetic Charcot Neuroarthropathy

    PubMed Central

    Pappalardo, Jennifer; Fitzgerald, Ryan

    2010-01-01

    Technological advances have allowed reconstructive foot and ankle surgeons greater opportunity to provide significant limb salvage options to those patients who present with significant lower extremity deformity due to diabetic Charcot neuroarthropathy. Paradigms that promote the utilization of these advanced modalities have demonstrated significant improved limb salvage outcomes in this challenging patient population and have consequently improved the quality of life for patients. The purpose of this review is to discuss current concepts in Charcot reconstruction. PMID:20920430

  8. Pathophysiology of diabetic erectile dysfunction: potential contribution of vasa nervorum and advanced glycation endproducts.

    PubMed

    Cellek, S; Cameron, N E; Cotter, M A; Muneer, A

    2013-01-01

    Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat medically despite advances in pharmacotherapeutic approaches in the field. This unmet need has resulted in a recent re-focus on the pathophysiology, in order to understand the cellular and molecular mechanisms leading to ED in diabetes. Diabetes-induced ED is often resistant to PDE5 inhibitor treatment, thus there is a need to discover targets that may lead to novel approaches for a successful treatment. The aim of this brief review is to update the reader in some of the latest development on that front, with a particular focus on the role of impaired neuronal blood flow and the formation of advanced glycation endproducts.

  9. An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon.

    PubMed

    Skovgaard, Dorthe; Svensson, Rene B; Scheijen, Jean; Eliasson, Pernilla; Mogensen, Pernille; Hag, Anne Mette F; Kjær, Michael; Schalkwijk, Casper G; Schjerling, Peter; Magnusson, Stig P; Couppé, Christian

    2017-03-01

    Advanced Glycation Endproducts (AGEs) accumulate in long-lived tissue proteins like collagen in bone and tendon causing modification of the biomechanical properties. This has been hypothesized to raise the risk of orthopedic injury such as bone fractures and tendon ruptures. We evaluated the relationship between AGE content in the diet and accumulation of AGEs in weight-bearing animal Achilles tendon. Two groups of mice (C57BL/6Ntac) were fed with either high-fat diet low in AGEs high-fat diet (HFD) (n = 14) or normal diet high in AGEs (ND) (n = 11). AGE content in ND was six to 50-fold higher than HFD The mice were sacrificed at week 40 and Achilles and tail tendons were carefully excised to compare weight and nonweight-bearing tendons. The amount of the AGEs carboxymethyllysine (CML), methylglyoxal-derived hydroimidazolone (MG-H1) and carboxyethyllysine (CEL) in Achilles and tail tendon was measured using ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and pentosidine with high-pressure liquid chromatography (HPLC) with fluorescent detection. AGEs in Achilles tendon were higher than in tail tendon for CML (P < 0.0001), CEL (P < 0.0001), MG-H1 and pentosidine (for both ND and HFD) (P < 0.0001). The AGE-rich diet (ND) resulted in an increase in CML (P < 0.0001), MG-H1 (P < 0.001) and pentosidine (P < 0.0001) but not CEL, in Achilles and tail tendon. This is the first study to provide evidence for AGE accumulation in injury-prone, weight-bearing Achilles tendon associated with intake of an AGE-rich diet. This indicates that food-derived AGEs may alter tendon properties and the development of tendon injuries.

  10. AGEs Induced Autophagy Impairs Cutaneous Wound Healing via Stimulating Macrophage Polarization to M1 in Diabetes

    PubMed Central

    Guo, Yuanyuan; Lin, Cai; Xu, Peng; Wu, Shan; Fu, Xiujun; Xia, Weidong; Yao, Min

    2016-01-01

    Autophagy is essential in physiological and pathological processes, however, the role of autophagy in cutaneous wound healing and the underlying molecular mechanism remain elusive. We hypothesized that autophagy plays an important role in regulating wound healing. Here, we show that enhanced autophagy negatively impacts on normal cutaneous healing process and is related to chronic wounds as demonstrated by the increased LC3 in diabetic mice skin or patients’ chronic wounds. In addition, inhibition of autophagy by 3-MA restores delayed healing in C57BL/6 or db/db mice, demonstrating that autophagy is involved in regulating wound healing. Furthermore, we identify that macrophage is a major cell type underwent autophagy in wounds and increased autophagy induces macrophages polarization into M1 with elevated CD11c population and gene expressions of proinflammatory cytokines. To explore the mechanism underlying autophagy-impaired wound healing, we tested the role of IRF8, a regulator of autophagy, in autophagy-modulated macrophages polarization. IRF8 activation is up-regulating autophagy and M1 polarization of macrophages after AGEs (advanced glycation endproducts) treatment, blocking the IRF8 with shIRF8 inhibits autophagic activity and M1 polarization. In summary, this study elucidates that AGEs induces autophagy and modulates macrophage polarization to M1 via IRF8 activation in impairment of cutaneous wound healing. PMID:27805071

  11. Definition of advanced age in HIV infection: looking for an age cut-off.

    PubMed

    Blanco, José R; Jarrín, Inmaculada; Vallejo, Manuel; Berenguer, Juan; Solera, Carmen; Rubio, Rafael; Pulido, Federico; Asensi, Victor; del Amo, Julia; Moreno, Santiago

    2012-09-01

    The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged <25 years at start of HAART, those aged 50-54, 55-59, 60-64, 65-59, and 70 or older were 32% (aHR: 0.68, 95% CI: 0.52-0.87), 29% (aHR: 0.71, 95% CI: 0.53-0.96), 34% (aHR: 0.66, 95% CI: 0.46-0.95), 39% (aHR: 0.61, 95% CI: 0.37-1.00), and 43% (aHR: 0.57, 95% CI: 0.31-1.04) less likely to experience an IR. The VR was similar across all age groups. Finally, patients aged 50-59 showed a 3-fold increase (aHR: 3.58; 95% CI: 1.07-11.99) in their risk of death compared to those aged <30 years. In HIV infection, patients aged ≥50 years have a poorer immunological response to HAART and a poorer survival. This age could be used to define medically advanced age in HIV-infected people.

  12. Definition of Advanced Age in HIV Infection: Looking for an Age Cut-Off

    PubMed Central

    Jarrín, Inmaculada; Vallejo, Manuel; Berenguer, Juan; Solera, Carmen; Rubio, Rafael; Pulido, Federico; Asensi, Victor; del Amo, Julia; Moreno, Santiago

    2012-01-01

    Abstract The age of 50 has been considered as a cut-off to discriminate older subjects within HIV-infected people according to the Centers for Disease Control and Prevention (CDC). However, the International AIDS Society (IAS) mentions 60 years of age and the Department of Health and Human Services (DHHS) makes no consideration. We aimed to establish an age cut-off that could differentiate response to highly active antiretroviral therapy (HAART) and, therefore, help to define advanced age in HIV-infected patients. CoRIS is an open, prospective, multicenter cohort of HIV adults naive to HAART at entry (January 2004 to October 2009). Survival, immunological response (IR) (CD4 increase of more than 100 cell/ml), and virological response (VR) (HIV RNA less than 50 copies/ml) were compared among 5-year age intervals at start of HAART using Cox proportional hazards models, stratified by hospital and adjusted for potential confounders. Among 5514 patients, 2726 began HAART. During follow-up, 2164 (79.4%) patients experienced an IR, 1686 (61.8%) a VR, and 54 (1.9%) died. Compared with patients aged <25 years at start of HAART, those aged 50–54, 55–59, 60–64, 65–59, and 70 or older were 32% (aHR: 0.68, 95% CI: 0.52–0.87), 29% (aHR: 0.71, 95% CI: 0.53–0.96), 34% (aHR: 0.66, 95% CI: 0.46–0.95), 39% (aHR: 0.61, 95% CI: 0.37–1.00), and 43% (aHR: 0.57, 95% CI: 0.31–1.04) less likely to experience an IR. The VR was similar across all age groups. Finally, patients aged 50–59 showed a 3-fold increase (aHR: 3.58; 95% CI: 1.07–11.99) in their risk of death compared to those aged <30 years. In HIV infection, patients aged ≥50 years have a poorer immunological response to HAART and a poorer survival. This age could be used to define medically advanced age in HIV-infected people. PMID:22607516

  13. Prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in southwest China

    PubMed Central

    Liu, Ya; Hu, Rong; Ouyang, Ling-yun; Liu, Jian-xiong; Li, Xiu-jun; Yi, Yan-jing; Wang, Tzung-Dau; Zhao, Shui-ping

    2017-01-01

    This study aimed to assess the prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a cross-sectional survey was conducted in 4021 hypertensive patients aged 40 to 79 years living in Chengdu and Chongqing, China. Fasting plasma glucose (FPG) and 2h plasma glucose (2-hPG) in an oral glucose-tolerance test (OGTT) were used for assessments. Whether the patients previously had diabetes (DM) was determined by their own reports. The survey was carried out by the same questionnaire for all respondents. DM prevalence was 32.0% in hypertensive patients aged 40 to 79 years in Southwest China, with the rates of 29.6% and 33.5% in men and women, respectively (P<0.001). DM prevalence increased with age age and body-mass index. DM prevalence rates were 16.9%, 24.7%, 38.2% and 41.9% in hypertensive patients aged 40–49, 50–59, 60–69 and over 70, respectively. DM prevalence were 30.6%, 27.9%, 37.1%, and 37.4%, for BMI<18.5, 18.5–24.9, 25.0–29.9, and ≥30, respectively. Prevalence of unrecognized DM were 20.8% in hypertensive patients aged 40 to 79 years in Southwest China. Using only fasting blood glucose testing without OGTT would have resulted in 65.0% of missed DM diagnosis in these newly diagnosed patients. The prevalence of DM and unrecognized DM were high in hypertensive patients aged 40 to 79 years in Southwest China.These findings indicate that hypertensive patients aged 40 to 79 years should regularly submit to community-based OGTT screening for timely DM diagnosis. PMID:28192474

  14. McCune-Albright syndrome revealed by hyperthyroidism at advanced age.

    PubMed

    Elhaï, Muriel; Meunier, Marine; Kahan, André; Cormier, Catherine

    2011-12-01

    We report a case of a 38-year-old woman admitted to our service for diagnosis of osteolytic lesions. She suffered from back, lumbar and costal pain at the time a hyperthyroidism, related to multinodular goiter, was diagnosed. The pain remained despite the cure of hyperthyroidism. Cutaneous examination revealed café au lait skin spots. Analysis of the phosphocalcic metabolism allowed the diagnosis of phosphate diabetes. X-ray showed lytic lesions involving the ribs with thinning of the cortex and vertebral fractures of the dorsal spine. The computed tomography revealed lytic lesions with a typical "ground glass" appearance involving the spine, ribs, sternum, iliac bones and sacrum. The presence of this clinical triad allowed the diagnosis of McCune-Albright syndrome (MAS). The treatment consisted in vitamin D supplementation, and high doses of both oral phosphate and calcitriol to treat the phosphate diabetes as well as cycles of intravenous pamidronate administration to relieve bone pain. We report an uncommon case of the diagnosis of MAS at an advanced age following hyperthyroidism. We believe that the disease was revealed by an increase in bone turnover due to hyperthyroidism.

  15. Searching for the Kinkeepers: Historian Gender, Age, and Type 2 Diabetes Family History

    ERIC Educational Resources Information Center

    Giordimaina, Alicia M.; Sheldon, Jane P.; Kiedrowski, Lesli A.; Jayaratne, Toby Epstein

    2015-01-01

    Kinkeepers facilitate family communication and may be key to family medical history collection and dissemination. Middle-aged women are frequently kinkeepers. Using type 2 diabetes (T2DM) as a model, we explored whether the predicted gender and age effects of kinkeeping can be extended to family medical historians. Through a U.S. telephone survey,…

  16. When aging-onset diabetes is coming across with Alzheimer disease: comparable pathogenesis and therapy.

    PubMed

    Tang, Jun; Pei, Yijin; Zhou, Guangji

    2013-08-01

    Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose because of the insulin-resistance and insulin-deficiency in Type 2, while the insulin deficiency due to destruction of islet cells in the pancreas in Type 1. The development of Type 2 diabetes is caused by a combination of lifestyle and genetic factors. Aging patients with diabetes are at increased risk of developing cognitive and memory dysfunctions, which is one of the significant symptoms of Alzheimer disease (AD). Also, over 2/3 of AD patients were clinically indentified with impairment of glucose. Cognitive dysfunction would be associated with poor self-care ability in diabetes patients. This review will briefly summarize the current knowledge of the pathogenesis of these two diseases and highlight similarities in their pathophysiologies. Furthermore, we will shortly discuss recent progress in the insulin-targeted strategy, aiming to explore the inner linkage between these two diseases in aging populations.

  17. Prevalence and Associated Factors of Diabetes and Impaired Fasting Glucose in Chinese Hypertensive Adults Aged 45 to 75 Years

    PubMed Central

    Zhang, Yan; Ma, Wei; Fan, Fangfang; Wang, Binyan; Xing, Houxun; Tang, Genfu; Wang, Xiaobin; Xu, Xin; Xu, Xiping; Huo, Yong

    2012-01-01

    Objective This study examined the prevalence of impaired fasting glucose (IFG) and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45–75 years. Methods A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG) ≥7.0mmol/l] and IFG (6.1–6.9mmol/l) were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes. Results The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥25kg/m2), abdominal obesity (waist circumference ≥90cm for men and ≥80cm for women), non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal) were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR) 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal) were important independent associated factors for IFG. Conclusion In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG

  18. An Expert Opinion on Advanced Insulin Pump Use in Youth with Type 1 Diabetes.

    PubMed

    Bode, Bruce W; Kaufman, Francine R; Vint, Nan

    2017-03-01

    Among children and adolescents with type 1 diabetes mellitus, the use of insulin pump therapy has increased since its introduction in the early 1980s. Optimal management of type 1 diabetes mellitus depends on sufficient understanding by patients, their families, and healthcare providers on how to use pump technology. The goal for the use of insulin pump therapy should be to advance proficiency over time from the basics taught at the initiation of pump therapy to utilizing advanced settings to obtain optimal glycemic control. However, this goal is often not met, and appropriate understanding of the full features of pump technology can be lacking. The objective of this review is to provide an expert perspective on the advanced features and use of insulin pump therapy, including practical guidelines for the successful use of insulin pump technology, and other considerations specific to patients and healthcare providers.

  19. Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study.

    PubMed

    Furukawa, S; Sakai, T; Niiya, T; Miyaoka, H; Miyake, T; Yamamoto, S; Maruyama, K; Ueda, T; Senba, H; Todo, Y; Torisu, M; Minami, H; Onji, M; Tanigawa, T; Matsuura, B; Hiasa, Y; Miyake, Y

    2017-01-01

    Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

  20. Modulation of advanced glycation end products by candesartan in patients with diabetic kidney disease--a dose-response relationship study.

    PubMed

    Saha, Sandeep A; LaSalle, Brian K; Clifton, G Dennis; Short, Robert A; Tuttle, Katherine R

    2010-01-01

    Advanced glycation end products (AGEs) are proinflammatory mediators implicated in the pathogenesis of diabetic kidney disease (DKD). In this study, dose-dependent effects of angiotensin receptor blockade on urinary AGEs were evaluated in patients with DKD. Patients with type 2 diabetes and proteinuria ≥500 mg/d (n = 11) were compared with diabetic controls without DKD (n = 10) and normal controls (n = 11). After a 2-week washout period, DKD participants were treated with candesartan doses progressively increasing from 8, 16, 32, to 64 mg/d every 3 weeks for a total of 12 weeks. Other antihypertensive agents were adjusted to maintain stable blood pressure. At baseline and after each dosing period, blood pressure measurements and 24-hour urine collections were obtained. Urinary carboxymethyl lysine, an AGE biomarker, was reduced over the 12-week dose escalation protocol (r = 0.38, P = 0.01) in DKD participants. Creatinine clearance increased slightly, but albuminuria was unaffected by candesartan administration. Baseline urinary transforming growth factor-β₁ excretion was lower in DKD participants than in controls and did not change during the study period. Reducing kidney exposure to AGEs may be a mechanism of protection by angiotensin receptor blockade in DKD. AGEs may also impact the diabetic kidney through mechanisms independent of transforming growth factor-β₁.

  1. Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides

    NASA Astrophysics Data System (ADS)

    Ahmed, Azaj; Shamsi, Anas; Bano, Bilqees

    2017-01-01

    Advanced glycation end products (AGEs) are at the core of variety of diseases ranging from diabetes to renal failure and hence gaining wide consideration. This study was aimed at characterizing the AGEs of phytocystatin isolated from mustard seeds (YMP) when incubated with different monosaccharides (glucose, ribose and mannose) using fluorescence, ultraviolet, circular dichroism (CD) spectroscopy and microscopy. Ribose was found to be the most potent glycating agent as evident by AGEs specific fluorescence and absorbance. YMP exists as a molten globule like structure on day 24 as depicted by high ANS fluorescence and altered intrinsic fluorescence. Glycated YMP as AGEs and ribose induced aggregates were observed at day 28 and 32 respectively. In our study we have also examined the anti-aggregative potential of polyphenol, resveratrol. Our results suggested the anti-aggregative behavior of resveratrol as it prevented the in vitro aggregation of YMP, although further studies are required to decode the mechanism by which resveratrol prevents the aggregation.

  2. Beneficial effect of Corni Fructus, a constituent of Hachimi-jio-gan, on advanced glycation end-product-mediated renal injury in Streptozotocin-treated diabetic rats.

    PubMed

    Yamabe, Noriko; Kang, Ki Sung; Goto, Eiko; Tanaka, Takashi; Yokozawa, Takako

    2007-03-01

    Previous investigations have demonstrated that Hachimi-jio-gan, a Chinese prescription consisting of eight crude drugs, has a therapeutic potential in diabetes and diabetic nephropathy, using these model rats. To add to these findings, we performed this study to assess whether one of the crude drugs, Corni Fructus (Cornus officinalis SIEB. et ZUCC.), had an effect on streptozotocin-induced diabetic rats as a major active constituent, compared with an inhibitor of advanced glycation end-product (AGE) formation, aminoguanidine. Diabetic rats were orally administrated Corni Fructus extract (50, 100, 200 mg/kg body weight/d) or aminoguanidine (100 mg/kg body weight/d). Treatment with Corni Fructus for 10 d suppressed hyperglycemia, proteinuria, renal AGE formation, and related protein expressions, i.e., receptor for AGEs, nuclear factor-kappaB, transforming growth factor-beta1, and Nepsilon-(carboxymethyl)lysine, in the same way as with aminoguanidine. However, improvement of renal function, shown via serum creatinine (Cr) and Cr clearance, was superior to aminoguanidine treatment. In conclusion, the present study supported the hypothesis that Corni Fructus plays an important role against diabetic pathogenesis, i.e., reducing glucose toxicities, up-regulating renal function, and consequently ameliorating glycation-associated renal damage; thus, this study may provide a new recognition of crude drugs to clarify the mechanisms of Chinese prescriptions.

  3. Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice.

    PubMed

    Currais, Antonio; Prior, Marguerite; Lo, David; Jolivalt, Corinne; Schubert, David; Maher, Pamela

    2012-12-01

    Mounting evidence supports a link between diabetes, cognitive dysfunction, and aging. However, the physiological mechanisms by which diabetes impacts brain function and cognition are not fully understood. To determine how diabetes contributes to cognitive dysfunction and age-associated pathology, we used streptozotocin to induce type 1 diabetes (T1D) in senescence-accelerated prone 8 (SAMP8) and senescence-resistant 1 (SAMR1) mice. Contextual fear conditioning demonstrated that T1D resulted in the development of cognitive deficits in SAMR1 mice similar to those seen in age-matched, nondiabetic SAMP8 mice. No further cognitive deficits were observed when the SAMP8 mice were made diabetic. T1D dramatically increased Aβ and glial fibrillary acidic protein immunoreactivity in the hippocampus of SAMP8 mice and to a lesser extent in age-matched SAMR1 mice. Further analysis revealed aggregated Aβ within astrocyte processes surrounding vessels. Western blot analyses from T1D SAMP8 mice showed elevated amyloid precursor protein processing and protein glycation along with increased inflammation. T1D elevated tau phosphorylation in the SAMR1 mice but did not further increase it in the SAMP8 mice where it was already significantly higher. These data suggest that aberrant glucose metabolism potentiates the aging phenotype in old mice and contributes to early stage central nervous system pathology in younger animals.

  4. Correlates of Age Onset of Type 2 Diabetes Among Relatively Young Black and White Adults in a Community

    PubMed Central

    Nguyen, Quoc Manh; Xu, Ji-Hua; Chen, Wei; Srinivasan, Sathanur R.; Berenson, Gerald S.

    2012-01-01

    OBJECTIVE The risk factors for middle-age onset of type 2 diabetes are well known. However, information is scant regarding the age onset of type 2 diabetes and its correlates in community-based black and white relatively young adults. RESEARCH DESIGN AND METHODS This prospective cohort study consisted of normoglycemic (n = 2,459) and type 2 diabetic (n = 144) adults aged 18–50 years who were followed for an average of 16 years. RESULTS The incidence rate of the onset of type 2 diabetes was 1.6, 4.3, 3.9, and 3.4 per 1,000 person-years for age-groups 18–29, 30–39, and 40–50 and total sample, respectively. Incidences of diabetes increased with age by race and sex groups (P for trend ≤0.01); higher in black females versus white females and blacks versus whites in total sample (P < 0.05). In a multivariable Cox model, baseline parental diabetes (hazard ratio [HR] 5.24) and plasma insulin were significantly associated with diabetes incidence at the youngest age (18–29 years); black race, BMI, and glucose at age 30–39 years; female sex, parental diabetes (HR 2.44), BMI, ratio of triglycerides and HDL cholesterol (TG/HDL-C ratio), and glucose at age 40–50 years; and black race, parental diabetes (HR 2.44), BMI, TG/HDL-C ratio, and glucose in whole cohort. Further, patients with diabetes, regardless of age onset, displayed a significantly higher prevalence of maternal history of diabetes at baseline (P < 0.01). CONCLUSIONS In relatively young adults, predictability of baseline cardiometabolic risk factors along with race, sex, and parental history of diabetes for the onset of type 2 diabetes varied by age-group. These findings have implications for early prevention and intervention in relatively young adults. PMID:22399694

  5. Immunological biomarkers: Catalysts for translational advances in autoimmune diabetes

    PubMed Central

    Ahmed, S T; Akirav, E; Bradshaw, E; Buckner, J; McKinney, E; Quintana, F J; Waldron-Lynch, F; Nepom, J

    2013-01-01

    In a recent workshop organized by the JDRF focused on the ‘Identification and Utilization of Robust Biomarkers in Type1 Diabetes’, leaders in the field of type 1 diabetes (T1D)/autoimmunity and assay technology came together from academia, government and industry to assess the current state of the field, evaluate available resources/technologies and identify gaps that need to be filled for moving the field of T1D research forward. The highlights of this workshop are discussed in this paper, as well as the proposal for a larger, planned consortium effort, incorporating a JDRF Biomarker Core, to foster collaboration and accelerate progress in this critically needed area of T1D research. PMID:23574315

  6. Coming of age: the artificial pancreas for type 1 diabetes.

    PubMed

    Thabit, Hood; Hovorka, Roman

    2016-09-01

    The artificial pancreas (closed-loop system) addresses the unmet clinical need for improved glucose control whilst reducing the burden of diabetes self-care in type 1 diabetes. Glucose-responsive insulin delivery above and below a preset insulin amount informed by sensor glucose readings differentiates closed-loop systems from conventional, threshold-suspend and predictive-suspend insulin pump therapy. Insulin requirements in type 1 diabetes can vary between one-third-threefold on a daily basis. Closed-loop systems accommodate these variations and mitigate the risk of hypoglycaemia associated with tight glucose control. In this review we focus on the progress being made in the development and evaluation of closed-loop systems in outpatient settings. Randomised transitional studies have shown feasibility and efficacy of closed-loop systems under supervision or remote monitoring. Closed-loop application during free-living, unsupervised conditions by children, adolescents and adults compared with sensor-augmented pumps have shown improved glucose outcomes, reduced hypoglycaemia and positive user acceptance. Innovative approaches to enhance closed-loop performance are discussed and we also present the outlook and strategies used to ease clinical adoption of closed-loop systems.

  7. Advanced maternal age and risk perception: A qualitative study

    PubMed Central

    2012-01-01

    Background Advanced maternal age (AMA) is associated with several adverse pregnancy outcomes, hence these pregnancies are considered to be “high risk.” A review of the empirical literature suggests that it is not clear how women of AMA evaluate their pregnancy risk. This study aimed to address this gap by exploring the risk perception of pregnant women of AMA. Methods A qualitative descriptive study was undertaken to obtain a rich and detailed source of explanatory data regarding perceived pregnancy risk of 15 women of AMA. The sample was recruited from a variety of settings in Winnipeg, Canada. In-depth interviews were conducted with nulliparous women aged 35 years or older, in their third trimester, and with singleton pregnancies. Interviews were recorded and transcribed verbatim, and content analysis was used to identify themes and categories. Results Four main themes emerged: definition of pregnancy risk, factors influencing risk perception, risk alleviation strategies, and risk communication with health professionals. Conclusions Several factors may influence women's perception of pregnancy risk including medical risk, psychological elements, characteristics of the risk, stage of pregnancy, and health care provider’s opinion. Understanding these influential factors may help health professionals who care for pregnant women of AMA to gain insight into their perspectives on pregnancy risk and improve the effectiveness of risk communication strategies with this group. PMID:22988825

  8. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice.

    PubMed

    Wu, Jin; Guan, Tian-jun; Zheng, Shirong; Grosjean, Fabrizio; Liu, Weicheng; Xiong, Huabao; Gordon, Ronald; Vlassara, Helen; Striker, Gary E; Zheng, Feng

    2011-10-01

    Inflammation has a key role in diabetic nephropathy (DN) progression. Pentosan polysulfate (PPS) has been shown to decreases interstitial inflammation and glomerulosclerosis in 5/6 nephrectomized rats. Since PPS has an excellent long-term safety profile in interstitial cystitis treatment, and we recently found that old diabetic C57B6 mice develop DN characterized by extensive tubulointerstitial inflammatory lesions that mimics human DN, we examined the effect of PPS on old diabetic mice. We also examined the anti-inflammatory properties of PPS in renal cells in vitro. Diabetes was induced with streptozotocin in 18 months female (early aging) C57B6 mice. Mice were then randomized to receive oral PPS (25 mg/kg/day) or water for 4 months. The effect of PPS on NF-κB activation and on TNFα, high glucose or advanced glycation end products (AGEs) stimulated proinflammatory gene expression in renal cells was examined. We found that PPS treatment preserved renal function, significantly reduced albuminuria, and markedly decreased the severity of renal lesions, including tubulointerstitial inflammation. PPS also reduced upregulation of TNFα and proinflammatory genes in aging diabetic kidneys. Furthermore, PPS suppressed NF-κB, decreased the proinflammatory actions of TNFα, and decreased high glucose and AGEs stimulated MCP-1 production in vitro. Finally, PPS decreased TNFα-induced increase in albumin permeability in podocyte monolayers. In conclusion, PPS treatment largely prevents the development/progression of nephropathy in aging diabetic mice. As this may be mediated by suppression of TNFα, high glucose, and AGE-stimulated NF-κB activation and inflammation in vitro, the in vivo blockade of DN may be due to the anti-inflammatory properties of PPS.

  9. Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats.

    PubMed

    Baynes, John; Murray, David B

    2009-01-01

    This study investigated the temporal relationship between cardiomyopathy and renal pathology in the type II diabetic Zucker diabetic fatty (ZDF) rat. We hypothesized that changes in renal function will precede the development of cardiac dysfunction in the ZDF rat. Animals (10 weeks old) were divided into four experimental groups: Lean Control (fa/?) LC(n = 7), untreated ZDF rats (n = 7) sacrificed at 16 weeks of age, and LC (n = 7) untreated ZDF rats (n = 9) sacrificed at 36 weeks of age. LV structural/functional parameters were assessed via Millar conductance catheter. Renal function was evaluated via markers of proteinuria and evidence of hydronephrosis. LV mass was significantly less in the ZDF groups at both time points compared to age-matched LC. End diastolic volume was increased by 16% at 16 weeks and by 37% at 36 weeks of age (p < 0.05 vs. LC). End diastolic pressure and end systolic volume were significantly increased (42% and 27%respectively) at 36 weeks of age in the ZDF compared to LC. Kidney weights were significantly increased at both 16 and 36 week in ZDF animals (p < 0.05 vs. LC). Increased urinary albumin and decreased urinary creatinine were paralleled by a marked progression in the severity of hydronephrosis from 16 to 36 weeks of age in the ZDF group. In summary, there is evidence of progressive structural and functional changes in both the heart and kidney, starting as early as 16 weeks,without evidence that one pathology precedes or causes the other in the ZDF model of type II diabetes.

  10. How can we utilize livers from advanced aged donors for liver transplantation for hepatitis C?

    PubMed

    Uemura, Tadahiro; Nikkel, Lucas E; Hollenbeak, Christopher S; Ramprasad, Varun; Schaefer, Eric; Kadry, Zakiyah

    2012-06-01

    Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score (P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score.

  11. Increased serum levels of the specific advanced glycation end product methylglyoxal-derived hydroimidazolone are associated with retinopathy in patients with type 2 diabetes mellitus.

    PubMed

    Fosmark, Dag Sigurd; Torjesen, Peter A; Kilhovd, Bente K; Berg, Tore J; Sandvik, Leiv; Hanssen, Kristian F; Agardh, Carl-David; Agardh, Elisabet

    2006-02-01

    Advanced glycation end products (AGEs) are thought to play a major pathogenic role in diabetic retinopathy. The most important AGE is unknown, but as increased serum methylglyoxal-derived hydroimidazolone has been demonstrated in patients with type 2 diabetes mellitus, the aim of the present study was to elucidate possible associations between serum levels of hydroimidazolone and retinopathy in patients with type 2 diabetes mellitus. We recruited 227 patients with type 2 diabetes mellitus and retinopathy ranging from none to proliferative. Level of retinopathy was determined from 7 standard field stereo photographs per eye according to the Early Treatment Diabetic Retinopathy Study. The patients were 66 +/- 11 years old, with a known diabetes duration of 14 +/- 9 years. Serum levels of hydroimidazolone were determined with a competitive immunoassay. Serum levels of hydroimidazolone were increased in nonproliferative (median, 4.50 U/mL; interquartile range, 3.69-5.77 U/mL) and proliferative retinopathy (median, 4.88 U/mL; interquartile range, 3.70-6.52 U/mL) compared with patients without retinopathy (median, 4.02 U/mL; interquartile range, 3.47-4.88 U/mL) (P = .008 and .002, respectively). There was no association between hydroimidazolone and hemoglobin A1c (r = 0.04, P = .57). In addition, patients with proliferative retinopathy and a relatively short known duration of diabetes, that is, less than the median of 14 years, had increased serum levels of hydroimidazolone (median, 6.91 U/mL; interquartile range, 4.70-8.91 U/mL) compared with those with nonproliferative retinopathy (median, 4.34; interquartile range, 3.86-5.53U/mL, P = .015). Serum levels of hydroimidazolone are increased in type 2 diabetic patients with retinopathy. This association is independent of hitherto known associated factors, such as hemoglobin A1c.

  12. The impact of salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes.

    PubMed

    Barzilay, Joshua I; Jablonski, Kathleen A; Fonseca, Vivian; Shoelson, Steven E; Goldfine, Allison B; Strauch, Christopher; Monnier, Vincent M

    2014-04-01

    OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine [measured as furosine]) and AGE levels (glyoxal and methylglyoxal hydroimidazolones [G-(1)H, MG-(1)H], carboxymethyllysine [CML], carboxyethyllysine [CEL], pentosidine) were measured in patient serum samples. RESULTS Forty-eight weeks of salsalate treatment lowered levels of HbA1c and serum furosine (P < 0.001) and CML compared with placebo. The AGEs CEL and G-(1)H and MG-(1)H levels were unchanged, whereas pentosidine levels increased more than twofold (P < 0.001). Among salsalate users, increases in adiponectin levels were associated with lower HbA1c levels during follow-up (P < 0.001). Changes in renal and inflammation factor levels were not associated with changes in levels of early or late glycation factors. Pentosidine level changes were unrelated to changes in levels of renal function, inflammation, or cytokines. CONCLUSIONS Salsalate therapy was associated with a reduction in early but not late glycation end products. There was a paradoxical increase in serum pentosidine levels suggestive of an increase in oxidative stress or decreased clearance of pentosidine precursor.

  13. Differential effects of insulin on peripheral diabetes-related changes in mitochondrial bioenergetics: involvement of advanced glycosylated end products.

    PubMed

    Remor, Aline Pertile; de Matos, Filipe José; Ghisoni, Karina; da Silva, Thiago Lenoir; Eidt, Greici; Búrigo, Marília; de Bem, Andreza Fabro; Silveira, Paulo César Lock; de León, Andrés; Sanchez, Maria Cecilia; Hohl, Alexandre; Glaser, Viviane; Gonçalves, Carlos-Alberto; Quincozes-Santos, André; Borba Rosa, Rafael; Latini, Alexandra

    2011-11-01

    Large scale clinical trials have demonstrated that an intensive antihyperglycemic treatment in diabetes mellitus (DM) in individuals reduces the incidence of micro- and macrovascular complications, e.g. nephropathy, retinopathy, DM-accelerated atherosclerosis, myocardial infarction, or limb amputations. Here, we investigated the effect of short- and long-term insulin administration on mitochondrial function in peripheral tissues of streptozotocin (STZ)-induced hyperglycemic rats. In addition, the in vitro effect of methylglyoxal (MG), advanced glycation end products (AGEs) and human diabetic plasma on mitochondrial activity was investigated in skeletal muscle and liver mitochondria and in rat skin primary fibroblasts. Hyperglycemic STZ rats showed tissue-specific patterns of energy deficiency, evidenced by reduced activities of complexes I, II and/or IV after 30 days of hyperglycemia in heart, skeletal muscle and liver; moreover, cardiac tissue was found to be the most sensitive to the diabetic condition, since energy metabolism was impaired after 10 days of the hyperglycemia. Insulin-induced tight glycemic control was effective in protecting against the hyperglycemia-induced inhibition of mitochondrial enzyme activities. Furthermore, the long-term hormone replacement (30 days) also increased these activities in kidney from STZ-treated animals, where the hyperglycemic state did not modify the electron transport activity. Results from in vitro experiments indicate that mitochondrial impairment could result from oxidative stress-induced accumulation of MG and/or AGEs. Further investigations demonstrated that human plasma AGE accumulation elicits reduced mitochondrial function in skin fibroblast. These data suggest that persistent hyperglycemia results in tissue-specific patterns of energy deficiency and that early and continuous insulin therapy is necessary to maintain proper mitochondrial metabolism.

  14. Pravastatin inhibits advanced glycation end products (AGEs)-induced proximal tubular cell apoptosis and injury by reducing receptor for AGEs (RAGE) level.

    PubMed

    Ishibashi, Yuji; Yamagishi, Sho-ichi; Matsui, Takanori; Ohta, Keisuke; Tanoue, Ryuichiro; Takeuchi, Masayoshi; Ueda, Seiji; Nakamura, Kei-ichiro; Okuda, Seiya

    2012-08-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) axis play a role in diabetic nephropathy. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease. However, the effects of statin on AGEs-induced tubular cell damage remain unknown. We examined here whether and how pravastatin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was analyzed in an enzyme-linked immunosorbent assay. Asymmetric dimethylarginine (ADMA) expression was evaluated by immunostaining. Pravastatin dose-dependently inhibited the AGEs-induced up-regulation of RAGE mRNA level, ROS generation and apoptosis in human renal proximal tubular cells. Further, AGEs decreased mRNA level of dimethylarginine dimethylaminohydrolase-2, an enzyme that mainly degrades asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase and subsequently increased ADMA generation in tubular cells, both of which were also prevented by pravastatin. Geranylgeranyl pyrophosphate (GGPP) treatment blocked all of the effects of pravastatin on tubular cells. We found that rosuvastatin also significantly blocked the AGEs-induced increase in RAGE mRNA level and ROS generation, both of which were prevented by GGPP. Our present study suggests that pravastatin could inhibit the AGEs-induced apoptosis and ADMA generation in tubular cells by suppressing RAGE expression probably via inhibition of GGPP synthesis. Pravastatin may exert beneficial effects on tubular damage in diabetic nephropathy by blocking the AGEs-RAGE axis.

  15. Suppression of antioxidant Nrf-2 and downstream pathway in H9c2 cells by advanced glycation end products (AGEs) via ERK phosphorylation.

    PubMed

    Ko, Shun-Yao; Chang, Shu-Shing; Lin, I-Hsuan; Chen, Hong-I

    2015-11-01

    Diabetic cardiomyopathy is related to oxidative stress and correlated with the presence of advanced glycation end products (AGEs). In a clinical setting, AGEs can be detected in patients presenting diabetic cardiomyopathy; however, the underlying mechanism has yet to be elucidated. In our previous study, AGEs increase cell hypertrophy via ERK phosphorylation in a process closely related to ROS production. Thus, we propose that AGEs regulate the antioxidant gene nuclear factor-erythroid 2-related factor (Nrf-2). In H9c2 cells treated with AGEs, the expression of Nrf-2 was reduced; however, ERK phosphorylation was shown to increase. Treatment with H2O2 was also shown to increase Nrf-2 and ERK phosphorylation. In cells pretreatment with ROS scavenger NAC, the effects of H2O2 were reduced; however, the effects of the AGEs remained largely unchanged. Conversely, when cells were pretreated with PD98059 (ERK inhibitor), the expression of Nrf-2 was recovered following treatment with AGEs. Our results suggest that AGEs inhibit Nrf-2 via the ERK pathway; however, this influence is partly associated with ROS. Our finding further indicated that AGEs possess both ROS-dependent and ROS-independent pathways, resulting in a reduction in Nrf-2. This report reveals an important mechanism underlying the regulation of diabetic cardiomyopathy progression by AGEs.

  16. Receptor for advanced glycation end as drug targets in diabetes-induced skin lesion.

    PubMed

    Chen, Xiang-Fang; Tang, Wei; Lin, Wei-Dong; Liu, Zi-Yu; Lu, Xiao-Xiao; Zhang, Bei; Ye, Fei; Liu, Zhi-Min; Zou, Jun-Jie; Liao, Wan-Qing

    2017-01-01

    The involvement of the receptor for advanced glycation end (RAGE) in different diseases has been reviewed in great detail, previously, but the effects of diabetic drugs on RAGE-induced skin lesion during long course diabetes remains poorly understood. In the present study, we have shown that RAGE was overexpressed in both diabetic rats and human keratinocytes (HaCaT cells). Cell cycle arrest and apoptosis as well as alternations of relative protein levels were also found in diabetic rats and HaCaT cells with overexpression of RAGE that were rectified by metformin (Met) treatment. Moreover, overexpression of RAGE was also found to induce secretions of TNF-α, IL-1β, IL-6, ICAM-1 and COX-2 in HaCaT cells, and Met treatment corrected these inflammatory factor secretions. In addition, treatment with Met markedly reduced RAGE overexpression-induced p38 and NF-κB activation. Taken together, the findings of the present study have demonstrated, for the first time that Met protects HaCaT cells against diabetes-induced injuries and inflammatory responses through inhibiting activated RAGE.

  17. Receptor for advanced glycation end as drug targets in diabetes-induced skin lesion

    PubMed Central

    Chen, Xiang-Fang; Tang, Wei; Lin, Wei-Dong; Liu, Zi-Yu; Lu, Xiao-Xiao; Zhang, Bei; Ye, Fei; Liu, Zhi-Min; Zou, Jun-Jie; Liao, Wan-Qing

    2017-01-01

    The involvement of the receptor for advanced glycation end (RAGE) in different diseases has been reviewed in great detail, previously, but the effects of diabetic drugs on RAGE-induced skin lesion during long course diabetes remains poorly understood. In the present study, we have shown that RAGE was overexpressed in both diabetic rats and human keratinocytes (HaCaT cells). Cell cycle arrest and apoptosis as well as alternations of relative protein levels were also found in diabetic rats and HaCaT cells with overexpression of RAGE that were rectified by metformin (Met) treatment. Moreover, overexpression of RAGE was also found to induce secretions of TNF-α, IL-1β, IL-6, ICAM-1 and COX-2 in HaCaT cells, and Met treatment corrected these inflammatory factor secretions. In addition, treatment with Met markedly reduced RAGE overexpression-induced p38 and NF-κB activation. Taken together, the findings of the present study have demonstrated, for the first time that Met protects HaCaT cells against diabetes-induced injuries and inflammatory responses through inhibiting activated RAGE. PMID:28337263

  18. Detection of erythrocytes influenced by aging and type 2 diabetes using atomic force microscope

    SciTech Connect

    Jin, Hua; Xing, Xiaobo; Zhao, Hongxia; Chen, Yong; Huang, Xun; Ma, Shuyuan; Ye, Hongyan; Cai, Jiye

    2010-01-22

    The pathophysiological changes of erythrocytes are detected at the molecular scale, which is important to reveal the onset of diseases. Type 2 diabetes is an age-related metabolic disorder with high prevalence in elderly (or old) people. Up to now, there are no treatments to cure diabetes. Therefore, early detection and the ability to monitor the progression of type 2 diabetes are very important for developing effective therapies. Type 2 diabetes is associated with high blood glucose in the context of insulin resistance and relative insulin deficiency. These abnormalities may disturb the architecture and functions of erythrocytes at molecular scale. In this study, the aging- and diabetes-induced changes in morphological and biomechanical properties of erythrocytes are clearly characterized at nanometer scale using atomic force microscope (AFM). The structural information and mechanical properties of the cell surface membranes of erythrocytes are very important indicators for determining the healthy, diseased or aging status. So, AFM may potentially be developed into a powerful tool in diagnosing diseases.

  19. Increased Serum Insulin Exposure Does Not Affect Age or Stage of Pancreatic Adenocarcinoma Diagnosis in Patients with Diabetes Mellitus

    PubMed Central

    Chao, David T.; Shah, Nilesh H.; Zeh, Herbert J.; Bahary, Nathan; Whitcomb, David C.; Brand, Randall E.

    2015-01-01

    Objectives In considering whether medications that increase insulin levels accelerate pancreatic adenocarcinoma (PC) development, we hypothesized that PC patients with diabetes mellitus (DM) who used exogenous insulin or insulin-stimulating medications should have an earlier age of diagnosis or present with more advanced disease. Methods Patients enrolled in our PC registry from 6/1/2003 to 5/31/2012 were stratified according to treatment solely with insulin, insulin-stimulating medications, or insulin-independent medications. Age of PC diagnosis, PC stage, and years between DM and PC diagnoses were analyzed among the cohorts. Results Of 122 DM patients (mean age: 67.4 ± 10.2 years), the mean age of PC diagnosis within the insulin-only (n=40), insulin-stimulating (n=11), insulin-independent (n=71), and non-DM (n=321) cohorts were 68.7 ± 10.5 years, 69.6 ± 10.8 years, 66.3 ± 9.7 years, and 65.5 ± 10.5 years, respectively. No significant difference among the age of PC diagnosis was observed based on duration or type of DM treatment. There was no correlation between PC stage and increased insulin exposure. Conclusions Anti-DM medications that increase exposure to insulin do not appear to accelerate PC development using outcomes of mean age of PC diagnosis, PC stage, or duration between DM and PC diagnoses. PMID:26418902

  20. A Growing Troubling Triad: Diabetes, Aging, and Falls

    PubMed Central

    Crews, Ryan T.; Yalla, Sai V.; Fleischer, Adam E.; Wu, Stephanie C.

    2013-01-01

    There is a significant and troubling link between diabetes (DM) and falls in the elderly. Individuals with DM are prone to fall for reasons such as decreased sensorimotor function, musculoskeletal/neuromuscular deficits, foot and body pain, pharmacological complications, and specialty (offloading) footwear devices. Additionally, there is some concern that DM patients are prone to have more severe problems with falls than non-DM individuals. Fractures, poorer rehabilitation, and increased number of falls are all concerns. Fortunately, efforts to mitigate falls by DM patients show promise. A number of studies have shown that balance, strength, and gait training may be utilized to successfully reduce fall risk in this population. Furthermore, new technologies such as virtual reality proprioceptive training may be able to provide this reduced risk within a safe training environment. PMID:23476773

  1. A growing troubling triad: diabetes, aging, and falls.

    PubMed

    Crews, Ryan T; Yalla, Sai V; Fleischer, Adam E; Wu, Stephanie C

    2013-01-01

    There is a significant and troubling link between diabetes (DM) and falls in the elderly. Individuals with DM are prone to fall for reasons such as decreased sensorimotor function, musculoskeletal/neuromuscular deficits, foot and body pain, pharmacological complications, and specialty (offloading) footwear devices. Additionally, there is some concern that DM patients are prone to have more severe problems with falls than non-DM individuals. Fractures, poorer rehabilitation, and increased number of falls are all concerns. Fortunately, efforts to mitigate falls by DM patients show promise. A number of studies have shown that balance, strength, and gait training may be utilized to successfully reduce fall risk in this population. Furthermore, new technologies such as virtual reality proprioceptive training may be able to provide this reduced risk within a safe training environment.

  2. Lycopene powers the inhibition of glycation-induced diabetic nephropathy: a novel approach to halt the AGE-RAGE axis menace.

    PubMed

    Tabrez, Shams; Al-Shali, Khalid Zaki; Ahmad, Saheem

    2015-01-01

    There are accumulating evidences suggesting that interaction between advanced glycation end products (AGEs) and their receptors (RAGEs) induces oxidative stress and subsequently encourages inflammatory reactions, thereby resulting in progressive alteration in renal architecture and function. Interventions that reduce the tissue burden of AGEs have yielded significant positive results in inhibiting the progression of diabetic complications such as diabetic nephropathy. Lycopene, a carotenoid, plays an important role in protection against oxidative stress and hence might prove an efficient antiglycating agent. Current study investigates the effect of lycopene in downregulating the menace caused by ribose-induced glycation both in vitro and in vivo. We observed that treatment with lycopene decelerated the ribose induced AGE formation in HK-2 cells and in rat kidneys thereby downregulating the expression RAGE. HK-2 cells with decreased levels of RAGE showed a decline in nuclear factor κB (NFκB) and matrix metalloproteinase 2 (MMP 2) expressions. Administration of ribose not only induced hyperglycemia in Wistar rats but also developed diabetic nephropathy (DN). However, lycopene was found effective in relieving the biochemical symptoms of DN. Thus lycopene provides protection against development of diabetic nephropathy and ameliorates renal function by halting AGE-RAGE axis.

  3. Cavernous antioxidant effect of green tea, epigallocatechin-3-gallate with/without sildenafil citrate intake in aged diabetic rats.

    PubMed

    Mostafa, T; Sabry, D; Abdelaal, A M; Mostafa, I; Taymour, M

    2013-08-01

    This study aimed to assess the cavernous antioxidant effect of green tea (GT), epigallocatechin-3-gallate (EGCG) with/without sildenafil citrate intake in aged diabetic rats. One hundred and four aged male white albino rat were divided into controls that received ordinary chow, streptozotocin (STZ)-induced aged diabetic rats, STZ-induced diabetic rats on infused green tea, induced diabetic rats on epigallocatechin-3-gallate and STZ-induced diabetic rats on sildenafil citrate added to EGCG. After 8 weeks, dissected cavernous tissues were assessed for gene expression of eNOS, cavernous malondialdehyde (MDA), glutathione peroxidase (GPx), cyclic guanosine monophosphate (cGMP), and serum testosterone (T). STZ-induced diabetic rats on GT demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats. Diabetic rats on EGCG demonstrated significant increase in cavernous eNOS, cGMP, GPx and significant decrease in cavernous MDA compared with diabetic rats or diabetic rats on GT. Diabetic rats on EGCG added to sildenafil showed significant increase in cavernous eNOS, cGMP and significant decrease in cavernous MDA compared with other groups. Serum T demonstrated nonsignificant difference between the investigated groups. It is concluded that GT and EGCG have significant cavernous antioxidant effects that are increased if sildenafil is added.

  4. Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia's ageing population?

    PubMed

    Scott, David; de Courten, Barbora; Ebeling, Peter R

    2016-10-03

    The incidence of type 2 diabetes is increasing in Australia's older adult population. Sarcopenia, the age-related decline in skeletal muscle mass, quality and function, may make a significant but under-appreciated contribution to increasing the risk of type 2 diabetes. As skeletal muscle is the largest insulin-sensitive tissue in the body, low muscle mass in sarcopenia likely results in reduced capacity for glucose disposal. Age-related declines in muscle quality, including increased mitochondrial dysfunction and fat infiltration, are also implicated in skeletal muscle inflammation and subsequent insulin resistance. Prospective studies have shown that low muscle mass and strength are associated with increased risk of incident type 2 diabetes. Prevalent type 2 diabetes also appears to exacerbate progression of sarcopenia in older adults. Recently developed operational definitions and the inclusion of sarcopenia in the International classification of diseases, 10th revision, clinical modification, provide impetus for clinicians to diagnose and treat sarcopenia in older patients. Simple assessments to diagnose sarcopenia can potentially play a role in primary and secondary prevention of type 2 diabetes in older patients. Lifestyle modification programs for older adults with type 2 diabetes, particularly for those with sarcopenia, should incorporate progressive resistance training, along with adequate intakes of protein and vitamin D, which may improve both functional and metabolic health and prevent undesirable decreases in muscle mass associated with weight loss interventions. As some older adults with type 2 diabetes have a poor response to exercise, clinicians must ensure that lifestyle modification programs are appropriately prescribed, regularly monitored and modified if necessary.

  5. Effects of a new advanced glycation inhibitor, LR-90, on mitigating arterial stiffening and improving arterial elasticity and compliance in a diabetic rat model: aortic impedance analysis

    PubMed Central

    Satheesan, S; Figarola, J L; Dabbs, T; Rahbar, S; Ermel, R

    2014-01-01

    BACKGROUND AND PURPOSE We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on the progression of aortic pathology. EXPERIMENTAL APPROACH STZ-induced diabetic rats were treated with or without LR-90 (50 mg L-1 in drinking water) for 8 weeks and compared with control groups. Arterial BP measurements, various metabolic parameters, aortic histopathology, collagen cross-linking, AGE accumulation, and RAGE protein expression in aortic tissue were determined. Pulsatile parameters were evaluated using a standard Fourier series expansion technique and impulse response function of the filtered aortic input impedance spectra. KEY RESULTS LR-90 reduced glycated haemoglobin and triglycerides levels, although it had no effect on the glycaemic status. LR-90 did not affect arterial BP, but prevented the diabetes-induced increase in peripheral resistance and variations in aortic distensibility, as it reduced aortic characteristic impedance by 21%. LR-90 also prevented the elevation in wave reflection factor, as indicated by a 22.5% reduction and an associated increase of 23.5% in wave transit time, suggesting it prevents the augmentation of the systolic load of the left ventricle. Moreover, LR-90 inhibited collagen cross-linking and the accumulation of AGE and RAGE in the vasculature of diabetic rats. CONCLUSIONS AND IMPLICATIONS Treatment with LR-90 may impart significant protection against diabetes-induced aortic stiffening and cardiac hypertrophy and provides an additional therapeutic option for treatment of AGE associated diabetic complications. PMID:24611770

  6. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  7. Factors associated with the age of the onset of diabetes in women aged 50 years or more: a population-based study

    PubMed Central

    Valadares, Ana L R; Machado, Vanessa S S; Costa-Paiva, Lúcia S; de Sousa, Maria H; Pinto-Neto, Aarão M

    2014-01-01

    Objective Investigate factors associated with the onset of diabetes in women aged more than 49 years. Design and methods Cross-sectional, population-based study using self-reports with 622 women. The dependent variable was the age of occurrence of diabetes using the life table method. Cox multiple regression models were adjusted to analyse the onset of diabetes according to predictor variables. Sociodemographic, clinical and behavioural factors were evaluated. Results Of the 622 women interviewed, 22.7% had diabetes. The mean age at onset was 56 years. The factors associated with the age of occurrence of diabetes were self-rated health (very good, good) (coefficient=−0.792; SE of the coefficient=0.215; p=0.0001), more than two individuals living in the household (coefficient=0.656, SE of the coefficient=0.223; p=0.003), and body mass index (BMI) (kg/m2) at 20–30 years of age (coefficient= 0.056, SE of the coefficient=0.023; p=0.014). Conclusions Self-rated health considered good or very good was associated with a higher rate of survival without diabetes. Sharing a home with two or more other people and a weight increase at 20–30 years of age was associated with the onset of type 2 diabetes. PMID:25428628

  8. Risk Factors for the Development and Progression of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus and Advanced Diabetic Retinopathy

    PubMed Central

    Yun, Kyung-Jin; Kim, Hye Ji; Kim, Mee Kyoung; Kwon, Hyuk-Sang; Baek, Ki-Hyun; Roh, Young Jung

    2016-01-01

    Background Some patients with type 2 diabetes mellitus (T2DM) do not develop diabetic kidney disease (DKD) despite the presence of advanced diabetic retinopathy (DR). We aimed to investigate the presence of DKD and its risk factors in patients with T2DM and advanced DR. Methods We conducted a cross-sectional study in 317 patients with T2DM and advanced DR. The phenotypes of DKD were divided into three groups according to the urine albumin/creatinine ratio (uACR, mg/g) and estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): no DKD (uACR <30 and eGFR ≥60), non-severe DKD (uACR ≥30 or eGFR <60), and severe DKD (uACR ≥30 and eGFR <60). Mean systolic and diastolic blood pressure, mean glycosylated hemoglobin (HbA1c) level, and HbA1c variability (standard deviation [SD] of serial HbA1c values or HbA1c-SD) were calculated for the preceding 2 years. Results The prevalence of no DKD, non-severe DKD, and severe DKD was 37.2% (n=118), 37.0% (n=117), and 25.8% (n=82), respectively. HbA1c-SD and the triglyceride/high density lipoprotein cholesterol (TG/HDL-C) ratio correlated positively with uACR and negatively with eGFR. Multiple linear regression analyses showed that the HbA1c-SD and TG/HDL-C ratio were significantly related with eGFR. Multiple logistic regression analyses after adjusting for several risk factors showed that HbA1c-SD and the TG/HDL-C ratio were significant risk factors for severe DKD. Conclusion The prevalence of DKD was about 60% in patients with T2DM and advanced DR. HbA1c variability and TG/HDL-C ratio may affect the development and progression of DKD in these patients. PMID:27766790

  9. Neurodevelopmental outcome at early school age of children born to mothers with gestational diabetes

    PubMed Central

    Ornoy, A; Wolf, A; Ratzon, N; Greenbaum, C; Dulitzky, M

    1999-01-01

    AIMS—To study the metabolic derangements in the second half of pregnancy caused by gestational diabetes, on the long term development of children.
METHODS—The neuropsychological function of 32 school age children born to 32 mothers with well controlled gestational diabetes and 57 control children matched by age, birth order, and parental socioeconomic status was studied.
RESULTS—There were no differences in head circumference and height, but the children born to diabetic mothers were heavier. The verbal IQ scores of index children below the age of 9 years were lower than those of control children. No differences were found between the groups in various sensory and motor functions and in the Touwen and Prechtl neurological test. The young index group children performed less well than controls in fine and gross motor functions, as observed on the Bruininks-Oseretzky test of motor proficiency. The scores of young children born to mothers with gestational diabetes were also lower than controls on the Pollack tapper test, and there were more index group children who scored abnormally on the parents' Conners questionnaire. No correlation was found between the performance of the index group children on various neurodevelopmental tests and the severity of perinatal complications. The differences tended to disappear with age.
CONCLUSIONS—Gestational diabetes, as a result of the metabolic abnormalities in the second half of pregnancy, induces long term minor neurological deficits which are more pronounced in younger children. There does not seem to be any direct relation between the appearance of congenital anomalies and neurodevelopmental outcome.

 PMID:10375355

  10. Inhibition of fluorescent advanced glycation end products (AGEs) of human serum albumin upon incubation with 3-β-hydroxybutyrate.

    PubMed

    Bohlooli, M; Moosavi-Movahedi, A A; Taghavi, F; Saboury, A A; Maghami, P; Seyedarabi, A; Moosavi-Movahedi, F; Ahmad, F; Shockravi, A; Habibi-Rezaei, M

    2014-06-01

    Advanced glycation end products (AGEs), which are the final products of glycation, have a major role in diabetic complication and neurodegenerative disorders. The 3-β-hydroxybutyrate (3BHB), a ketone body which is produced by the liver, can be detected in increased concentrations in individuals post fasting and prolonged exercises and in diabetic (type I) patients. In this study, the inhibitory effect of 3BHB on AGEs formation by glucose from the human serum albumin (HSA) was studied at physiological conditions after 35 days of incubation, using physical techniques such as circular dichroism and fluorescence spectroscopy, as well as differential scanning calorimetry (DSC). The fluorescence intensity measurements of glycated HSA by glucose (GHSA) in the presence of 3BHB indicate a decrease in AGEs formation. The DSC deconvolution profile results also confirm the protective role of 3BHB on incubated with glucose by preventing the enthalpy reduction of the HSA tail segment, compared with the deconvolution profile seen for incubated with glucose alone. The concentration of 3BHB used in this study is in accordance with the concentration detected in the body of individuals post fasting and prolonged exercises.

  11. Genome-wide association studies in aging-related processes such as diabetes mellitus, atherosclerosis and cancer.

    PubMed

    Kronenberg, Florian

    2008-01-01

    Recent technological developments allow to genotype several hundreds of thousands of genetic variants in a single person in one step. This enables genome-wide association studies (GWAS) by genotyping a large number of patients with diseases of interest and controls at reasonable costs. Compared to a hypothesis-driven candidate gene approach the hypothesis-free GWAS can identify new susceptibility genes without making any a priori biological assumptions. They permit to identify genes involved in pathways which until now were unknown to be involved in a certain phenotype. GWAS are therefore a new and very powerful tool to identify genetic contributors to aging-related phenotypes. This paper provides a short overview about design and methods of GWAS and reviews recent advances in the identification of susceptibility genes for type 2 diabetes mellitus, atherosclerosis and cancer using GWAS.

  12. Searching for the Kinkeepers: Historian Gender, Age, and Type 2 Diabetes Family History.

    PubMed

    Giordimaina, Alicia M; Sheldon, Jane P; Kiedrowski, Lesli A; Jayaratne, Toby Epstein

    2015-12-01

    Kinkeepers facilitate family communication and may be key to family medical history collection and dissemination. Middle-aged women are frequently kinkeepers. Using type 2 diabetes (T2DM) as a model, we explored whether the predicted gender and age effects of kinkeeping can be extended to family medical historians. Through a U.S. telephone survey, nondiabetic Mexican Americans (n = 385), Blacks (n = 387), and Whites (n = 396) reported family histories of T2DM. Negative binomial regressions used age and gender to predict the number of affected relatives reported. Models were examined for the gender gap, parabolic age effect, and gender-by-age interaction predicted by kinkeeping. Results demonstrated support for gender and parabolic age effects but only among Whites. Kinkeeping may have application to the study of White family medical historians, but not Black or Mexican American historians, perhaps because of differences in family structure, salience of T2DM, and/or gender roles.

  13. The evaluation of retinal circulation in advanced diabetic retinopathy before and after panretinal laser photocoagulation by scanning laser opthalmoscope

    NASA Astrophysics Data System (ADS)

    Okano, Tadashi

    2005-07-01

    I investigated the effects of panretinal laser photocoagulation (PRP) on the velocity of retinal circulation in diabetic retinopathy. The retinal circulation was evaluated by means of rapid serial fluorescein angiography (FAG), employing scanning laser ophthalmoscope. FAG was conducted at the rate of 30 frames per seconds in video-tape. Disc-to-macula transit time (DMTT) was defined as the parameter to evaluate the retinal circulation. Diabetic 28 eyes with advanced diabetic retinopathy were examined to measure the DMTT before and after PRP. Normal 30 eyes used as control. Mean DMTT decreased from 9.8+/-1.5 seconds before PRP to 8.2+/-1.5 seconds after PRP in 28 diabetic eyes. The value with improvement after PRP was significantly shorter than the value before PRP ( p < 0.05 ). These values before and after PRP were significantly longer than that (3.7+/-0.7 seconds ) in normal 30 eyes ( p < 0.01 ). Retinal circulation is retarded in diabetic retinopathy. The retardation of retinal circulation in diabetic retinopathy improves after PRP, but the value after PRP can not recover until the control level. This study was performed to reveal therapeutic effect to panretinal laser photocoagulation (PRP) for the retardation of retinal circulation in diabetic retinopathy. I investigated the effects of PRP on the velocity of retinal circulation in patients with advanced diabetic retinopathy.

  14. Adverse Effects of Diabetes Mellitus on the Skeleton of Aging Mice.

    PubMed

    Portal-Núñez, Sergio; Ardura, Juan Antonio; Lozano, Daniel; Bolívar, Oskarina Hernández; López-Herradón, Ana; Gutiérrez-Rojas, Irene; Proctor, Alexander; van der Eerden, Bram; Schreuders-Koedam, Marijke; van Leeuwen, Johannes; Alcaraz, María José; Mulero, Francisca; de la Fuente, Mónica; Esbrit, Pedro

    2016-03-01

    In the present study, the possibility that a diabetic (DM) status might worsen age-related bone deterioration was explored in mice. Male CD-1 mice aged 2 (young control group) or 16 months, nondiabetic or made diabetic by streptozotocin injections, were used. DM induced a decrease in bone volume, trabecular number, and eroded surface, and in mineral apposition and bone formation rates, but an increased trabecular separation, in L1-L3 vertebrae of aged mice. Three-point bending and reference point indentation tests showed slight changes pointing to increased frailty and brittleness in the mouse tibia of diabetic old mice. DM was related to a decreased expression of both vascular endothelial growth factor and its receptor 2, which paralleled that of femoral vasculature, and increased expression of the pro-adipogenic gene peroxisome proliferator-activated receptor γ and adipocyte number, without affecting β-catenin pathway in old mouse bone. Concomitant DM in old mice failed to affect total glutathione levels or activity of main anti-oxidative stress enzymes, although xanthine oxidase was slightly increased, in the bone marrow, but increased the senescence marker caveolin-1 gene. In conclusion, DM worsens bone alterations of aged mice, related to decreased bone turnover and bone vasculature and increased senescence, independently of the anti-oxidative stress machinery.

  15. Influence of Age at Diagnosis and Time-Dependent Risk Factors on the Development of Diabetic Retinopathy in Patients with Type 1 Diabetes

    PubMed Central

    Forga, Luis; Goñi, María José; Cambra, Koldo; García-Mouriz, Marta; Iriarte, Ana

    2016-01-01

    Aim. To determine the influence of age at onset of type 1 diabetes and of traditional vascular risk factors on the development of diabetic retinopathy, in a cohort of patients who have been followed up after onset. Methods. Observational, retrospective study. The cohort consists of 989 patients who were followed up after diagnosis for a mean of 10.1 (SD: 6.8) years. The influence of age at diagnosis, glycemic control, duration of diabetes, sex, blood pressure, lipids, BMI, and smoking is analyzed using Cox univariate and multivariate models with fixed and time-dependent variables. Results. 135 patients (13.7%) developed diabetic retinopathy. The cumulative incidence was 0.7, 5.9, and 21.8% at 5-, 10-, and 15-year follow-up, respectively. Compared to the group with onset at age <10 years, the risk of retinopathy increased 2.5-, 3-, 3.3-, and 3.7-fold in the groups with onset at 10–14, 15–29, 30–44, and >44 years, respectively. During follow-up we also observed an association between diabetic retinopathy and HbA1c levels, HDL-cholesterol, and diastolic blood pressure. Conclusion. The rate of diabetic retinopathy is higher in patients who were older at type 1 diabetes diagnosis. In addition, we confirmed the influence of glycemic control, HDL-cholesterol, and diastolic blood pressure on the occurrence of retinopathy. PMID:27213158

  16. Age-related differences in biomedical and folk beliefs as causes for diabetes and heart disease among Mexican origin adults.

    PubMed

    Palmquist, Aunchalee E L; Wilkinson, Anna V; Sandoval, Juan-Miguel; Koehly, Laura M

    2012-08-01

    An understanding of health beliefs is key to creating culturally appropriate health services for Hispanic populations in the US. In this study we explore age-based variations in causal beliefs for heart disease and diabetes among Mexican origin adults in Houston, TX. This cross-sectional study included 497 adults of Mexican origin. Participants were asked to indicate the importance of biomedically defined and folk illness-related risk factors as causes for heart disease and diabetes. Biomedical risk factors were ranked highest as causes of diabetes and heart disease among all participants. Folk illness-related factors were ranked below biomedical factors as causes of heart disease among all age groups. Susto was ranked above the median as a risk factor for diabetes among older participants. Age-related differences in causal beliefs may have implications for designing culturally appropriate health services, such as tailored diabetes interventions for older Mexican origin adults.

  17. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    SciTech Connect

    Matsui, Takanori; Yamagishi, Sho-ichi; Takeuchi, Masayoshi; Ueda, Seiji; Fukami, Kei; Okuda, Seiya

    2009-07-24

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}). Although nifedipine did not affect expression levels of PPAR-{gamma}, it increased the PPAR-{gamma} transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-{gamma} activation.

  18. Hearing Loss as a Function of Aging and Diabetes Mellitus: A Cross Sectional Study

    PubMed Central

    Park, Dong Choon; Kim, MyungGu; Chung, Ji Hyun; Kim, Sang Hoon; Yeo, Seung Geun

    2014-01-01

    Background Although hearing loss may be caused by various factors, it is also a natural phenomenon associated with the aging process. This study was designed to assess the contributions of diabetes mellitus (DM) and hypertension, both chronic diseases associated with aging, as well as aging itself, to hearing loss in health screening examinees. Methods This study included 37,773 individuals who underwent health screening examinations from 2009 to 2012. The relationships between hearing threshold and subject age, hearing threshold at each frequency based on age group, the degree of hearing loss and the presence or absence of hypertension and DM were evaluated. Results The prevalence of hearing loss increased with age, being 1.6%, 1.8%, 4.6%, 14.0%, 30.8%, and 49.2% in subjects in their twenties, thirties, forties, fifties, sixties, and seventies, respectively (p<0.05). Hearing value per frequency showed aging-based changes, in the order of 6000, 4000, 2000, 1000 and 500 Hz, indicating greater hearing losses at high frequencies. The degree of hearing loss ranged from mild to severe. Aging and DM were correlated with the prevalence of hearing loss (p<0.05). There was no statistically significant association between hearing loss and hypertension after adjusting for age and DM. Conclusions The prevalence of hearing loss increases with age and the presence of DM. Hearing loss was greatest at high frequencies. In all age groups, mild hearing loss was the most common form of hearing loss. PMID:25549095

  19. Cardiovascular disease and type 1 diabetes: prevalence, prediction and management in an ageing population

    PubMed Central

    Lee, Siang Ing; Patel, Mitesh; Jones, Christopher M.; Narendran, Parth

    2015-01-01

    Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1D). However, evidence of its risks and management is often extrapolated from studies in type 2 diabetic (T2D) patients or the general population. This approach is unsatisfactory given that the underlying pathology, demographics and natural history of the disease differ between T1D and T2D. Furthermore, with a rising life expectancy, a greater number of T1D patients are exposed to the cardiovascular (CV) risk factors associated with an ageing population. The aim of this review is to examine the existing literature around CVD in T1D. We pay particular attention to CVD prevalence, how well we manage risk, potential biomarkers, and whether the studies included the older aged patients (defined as aged over 65). We also discuss approaches to the management of CV risk in the older aged. The available data suggest a significant CVD burden in patients with T1D and poor management of CV risk factors. This is underpinned by a poor evidence base for therapeutic management of CV risk specifically for patients with T1D, and in the most relevant population – the older aged patients. We would suggest that important areas remain to be addressed, particularly exploring the risks and benefits of therapeutic approaches to CVD management in the older aged. PMID:26568811

  20. Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R)

    PubMed Central

    Gunnlaugsdottir, E.; Halldorsdottir, S.; Klein, R.; Eiriksdottir, G.; Klein, B. E.; Benediktsson, R.; Harris, T. B.; Launer, L. J.; Aspelund, T.; Gudnason, V.

    2012-01-01

    Aims/hypothesis We aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus. Methods The study population consisted of 4,994 persons aged ≥67 years, who participated in the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA1c ≥6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses. Results The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA1c, insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria. Conclusions/interpretation Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged. PMID:22134840

  1. Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes

    PubMed Central

    Hackett, Geoffrey; Jones, Peter W; Strange, Richard C; Ramachandran, Sudarshan

    2017-01-01

    AIM To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men. METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I/untreated and PDE5I/treated; and (3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality (logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age (OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated (OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated (OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated (OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln (mortality) was plotted against age. The probability of mortality and 95%CI (from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5I and TRT reduce mortality in diabetes. PDE5I, alone and with the other treatments significantly alter age related mortality in diabetic men. PMID:28344753

  2. Advanced glycation end products

    PubMed Central

    Gkogkolou, Paraskevi; Böhm, Markus

    2012-01-01

    Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. They have been etiologically implicated in numerous diabetes- and age-related diseases. Strategies inhibiting AGE accumulation and signaling seem to possess a therapeutic potential in these pathologies. However, still little is known on the precise role of AGEs during skin aging. In this review the existing literature on AGEs and skin aging will be reviewed. In addition, existing and potential anti-AGE strategies that may be beneficial on skin aging will be discussed. PMID:23467327

  3. Coronary heart disease in patients with diabetes: part I: recent advances in prevention and noninvasive management.

    PubMed

    Berry, Colin; Tardif, Jean-Claude; Bourassa, Martial G

    2007-02-13

    Diabetes mellitus (DM) is a worldwide epidemic. Its prevalence is rapidly increasing in both developing and developed countries. Coronary heart disease (CHD) is highly prevalent and is the major cause of morbidity and mortality in diabetic patients. The purpose of this review is to assess the clinical impact of recent advances in the epidemiology, prevention, and management of CHD in diabetic patients. A systematic review of publications in this area, referenced in MEDLINE in the past 5 years (2000 to 2005), was undertaken. Patients with CHD and prediabetic states should undergo lifestyle modifications aimed at preventing DM. Pharmacological prevention of DM is also promising but requires further study. In patients with CHD and DM, routine use of aspirin and an angiotensin-converting enzyme inhibitor (ACE-I)--unless contraindicated or not tolerated-and strict glycemic, blood pressure, and lipid control are strongly recommended. The targets for secondary prevention in these patients are relatively well defined, but the strategies to achieve them vary and must be individualized. Intense insulin therapy might be needed for glycemic control, and high-dose statin therapy might be needed for lipid control. For blood pressure control, ACE-Is and angiotensin receptor blockers are considered as first-line therapy. Noncompliance, particularly with lifestyle measures, and underprescription of evidence-based therapies remain important unsolved problems.

  4. Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones.

    PubMed

    Alemán-González-Duhart, D; Tamay-Cach, F; Álvarez-Almazán, S; Mendieta-Wejebe, J E

    2016-01-01

    The present review summarizes the current advances in the biochemical and physiological aspects in the treatment of type 2 diabetes mellitus (DM2) with thiazolidinediones (TZDs). DM2 is a metabolic disorder characterized by hyperglycemia, triggering the abnormal activation of physiological pathways such as glucose autooxidation, polyol's pathway, formation of advance glycation end (AGE) products, and glycolysis, leading to the overproduction of reactive oxygen species (ROS) and proinflammatory cytokines, which are responsible for the micro- and macrovascular complications of the disease. The treatment of DM2 has been directed toward the reduction of hyperglycemia using different drugs such as insulin sensitizers, as the case of TZDs, which are able to lower blood glucose levels and circulating triglycerides by binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ) as full agonists. When TZDs interact with PPARγ, the receptor regulates the transcription of different genes involved in glucose homeostasis, insulin resistance, and adipogenesis. However, TZDs exhibit some adverse effects such as fluid retention, weight gain, hepatotoxicity, plasma-volume expansion, hemodilution, edema, bone fractures, and congestive heart failure, which limits their use in DM2 patients.

  5. Current Advances in the Biochemical and Physiological Aspects of the Treatment of Type 2 Diabetes Mellitus with Thiazolidinediones

    PubMed Central

    Alemán-González-Duhart, D.; Tamay-Cach, F.; Álvarez-Almazán, S.

    2016-01-01

    The present review summarizes the current advances in the biochemical and physiological aspects in the treatment of type 2 diabetes mellitus (DM2) with thiazolidinediones (TZDs). DM2 is a metabolic disorder characterized by hyperglycemia, triggering the abnormal activation of physiological pathways such as glucose autooxidation, polyol's pathway, formation of advance glycation end (AGE) products, and glycolysis, leading to the overproduction of reactive oxygen species (ROS) and proinflammatory cytokines, which are responsible for the micro- and macrovascular complications of the disease. The treatment of DM2 has been directed toward the reduction of hyperglycemia using different drugs such as insulin sensitizers, as the case of TZDs, which are able to lower blood glucose levels and circulating triglycerides by binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ) as full agonists. When TZDs interact with PPARγ, the receptor regulates the transcription of different genes involved in glucose homeostasis, insulin resistance, and adipogenesis. However, TZDs exhibit some adverse effects such as fluid retention, weight gain, hepatotoxicity, plasma-volume expansion, hemodilution, edema, bone fractures, and congestive heart failure, which limits their use in DM2 patients. PMID:27313601

  6. The impact of managing school-aged children's diabetes: the role of child behavior problems and parental discipline strategies.

    PubMed

    Wilson, Anna C; DeCourcey, Wendy M; Freeman, Kurt A

    2009-09-01

    Models of diabetes management in children emphasize family relationships, particularly parent-child interactions. In adolescents, parental involvement in disease-specific management relates to better health and adherence. However, information about parental involvement in disease management for young children is limited and mixed. This study investigated behavior problems of school-aged children with Type 1 Diabetes Mellitus (T1DM) in association with parent discipline strategies and parents' perceptions of (1) time spent managing diabetes and (2) the impact their child's diabetes has on their discipline strategies. Parents of children ages 5-12 with T1DM completed standardized measures of child misbehavior, parent discipline strategies, and responded to questions regarding perceived time spent managing diabetes, and perceived impact of diabetes on ability to discipline. Results showed child mealtime misbehavior was common and associated with overreactive parental discipline. Further, overreactive discipline was also associated with reports of less time spent managing child's illness. Child misbehavior was positively associated with parents' perceived amount of time spent managing diabetes and with the impact of child diabetes on discipline. Findings suggest the importance of considering parent discipline strategies and child misbehavior when working with young children with diabetes.

  7. Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes.

    PubMed

    Krings, A; Rahman, S; Huang, S; Lu, Y; Czernik, P J; Lecka-Czernik, B

    2012-02-01

    Fat occupies a significant portion of bone cavity however its function is largely unknown. Marrow fat expands during aging and in conditions which affect energy metabolism, indicating that fat in bone is under similar regulatory mechanisms as other fat depots. On the other hand, its location may determine specific functions in the maintenance of the environment for bone remodeling and hematopoiesis. We have demonstrated that marrow fat has a distinctive phenotype, which resembles both, white and brown adipose tissue (WAT and BAT, respectively). Marrow adipocytes express gene markers of brown adipocytes at levels characteristic for the BAT, including transcription factor Prdm16, and regulators of thermogenesis such as deiodinase 2 (Dio2) and PGC1α. The levels of expression of BAT-specific gene markers are decreased in bone of 24 mo old C57BL/6 and in diabetic yellow agouti A(vy)/a mice implicating functional changes of marrow fat occurring with aging and diabetes. Administration of antidiabetic TZD rosiglitazone, which sensitizes cells to insulin and increases adipocyte metabolic functions, significantly increased both, BAT (UCP1, PGC1α, Dio2, β3AR, Prdm16, and FoxC2) and WAT (adiponectin and leptin) gene expression in marrow of normoglycemic C57BL/6 mice, but failed to increase the expression of BAT, but not WAT, gene markers in diabetic mice. In conclusion, the metabolic phenotype of marrow fat combines both BAT and WAT characteristics. Decrease in BAT-like characteristics with aging and diabetes may contribute to the negative changes in the marrow environment supporting bone remodeling and hematopoiesis.

  8. Long term bone alterations in aged rats suffering type 1 diabetes.

    PubMed

    Sánchez, Luciana Marina; De Lucca, Romina Cármen; Lewicki, Marianela; Ubios, Ángela Matilde

    2016-12-01

    Increasing duration of type 1 diabetes mellitus alters bone metabolism. Clinical studies and experimental studies in long bones of rats with experimentally induced diabetes have reported a decrease in bone density. Few studies have explored this diabetes related alteration in the maxillae. Given that this finding could indicate the possible development of osteopenia in the maxilla in the long term, the present study sought to analyze alterations in alveolar bone in aged rats, 12, 18, and 24weeks after inducing diabetes, and compare alveolar bone response to that of tibial subchondral bone at the same experimental times. Thirty-six male Wistar rats, 130g body weight, were divided into 2 groups: an experimental group (E) receiving a single i.p. 60mg/kg dose of streptozotocin, and a control group (C). Both the control and experimental groups were divided into 3 sub-sets, according to the time of euthanasia: 12, 18 and 24weeks. The alveolar bone and tibiae were examined histologically and histomorphometrically. The results were analyzed using Student's t-test; a value of p<0.05 was considered statistically significant.

  9. Physical Disability Trajectories in Older Americans with and without Diabetes: The Role of Age, Gender, Race or Ethnicity, and Education

    ERIC Educational Resources Information Center

    Chiu, Ching-Ju; Wray, Linda A.

    2011-01-01

    Purpose: This research combined cross-sectional and longitudinal data to characterize age-related trajectories in physical disability for adults with and without diabetes in the United States and to investigate if those patterns differ by age, gender, race or ethnicity, and education. Design and Methods: Data were examined on 20,433 adults aged 51…

  10. Effect of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione, isolated from Averrhoa carambola L. (Oxalidaceae) roots, on advanced glycation end-product-mediated renal injury in type 2 diabetic KKAy mice.

    PubMed

    Zheng, Ni; Lin, Xing; Wen, Qingwei; Kintoko; Zhang, Shijun; Huang, Jianchun; Xu, Xiaohui; Huang, Renbin

    2013-05-10

    The roots of Averrhoa carambola L. (Oxalidaceae) have a long history of medical use in traditional Chinese medicine for treating diabetes and diabetic nephropathy. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) was isolated from the tuberous roots of A. carambola L. The purpose of this study was to investigate the beneficial effect of DMDD on the advanced glycation end-product-mediated renal injury in type 2 diabetic KKAy mice with regard to prove its efficacy by local traditional practitioners in the treatment of kidney frailties in diabetics. KKAy mice were orally administrated DMDD (12.5, 25, 50mg/kg body weight/d) or aminoguanidine (200mg/kg body weight/d) for 8 weeks. Hyperglycemia, renal AGE formation, and the expression of related proteins, such as the AGE receptor, nuclear factor-κB, transforming growth factor-β1, and N(ε)-(carboxymethyl)lysine, were markedly decreased by DMDD. Diabetes-dependent alterations in proteinuria, serum creatinine, creatinine clearance, and serum urea-N and glomerular mesangial matrix expansion were attenuated after treatment with DMDD for 8 weeks. The activities of superoxide dismutase and glutathione peroxidase, which are reduced in the kidneys of KKAy mice, were enhanced by DMDD. These findings suggest that DMDD may inhibit the progression of diabetic nephropathy and may be a therapeutic agent for regulating several pharmacological targets to treat or prevent of diabetic nephropathy.

  11. Metformin inhibits advanced glycation end products (AGEs)-induced growth and VEGF expression in MCF-7 breast cancer cells by suppressing AGEs receptor expression via AMP-activated protein kinase.

    PubMed

    Ishibashi, Y; Matsui, T; Takeuchi, M; Yamagishi, S

    2013-05-01

    Metformin use has been reported to decrease breast cancer incidence and mortality in diabetic patients. We have previously shown that advanced glycation end products (AGEs) and their receptor (RAGE) interaction stimulate growth and/or migration of pancreatic cancer and melanoma cells. However, effects of metformin on AGEs-RAGE axis in breast cancers remain unknown. We examined here whether and how metformin could block the AGEs-induced growth and vascular endothelial growth factor (VEGF) expression in MCF-7 breast cancer cells. Cell proliferation was measured with an electron coupling reagent WST-1 based colorimetric assay. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. AGEs significantly increased cell proliferation of MCF-7 cells, which was completely prevented by the treatment with 0.01 or 0.1 mM metformin or anti-RAGE antibodies. Furthermore, metformin at 0.01 mM completely suppressed the AGEs-induced upregulation of RAGE and VEGF mRNA levels in MCF-7 cells. An inhibitor of AMP-activated protein kinase, compound C significantly blocked the growth-inhibitory and RAGE and VEGF suppressing effects of metformin in AGEs-exposed MCF-7 cells. Our present study suggests that metformin could inhibit the AGEs-induced growth and VEGF expression in MCF-7 breast cancer cells by suppressing RAGE gene expression via AMP-activated protein kinase pathway. Metformin may protect against breast cancer expansion in diabetic patients by blocking the AGEs-RAGE axis.

  12. Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats

    PubMed Central

    de Assis, Adriano M.; da Silva, Jussemara S.; Rech, Anderson; Longoni, Aline; Nonose, Yasmine; Repond, Cendrine; de Bittencourt Pasquali, Matheus A.; Moreira, José C. F.; Souza, Diogo O.; Pellerin, Luc

    2016-01-01

    Diabetes mellitus (DM) causes important modifications in the availability and use of different energy substrates in various organs and tissues. Similarly, dietary manipulations such as high fat diets also affect systemic energy metabolism. However, how the brain adapts to these situations remains unclear. To investigate these issues, control and alloxan-induced type I diabetic rats were fed either a standard or a high fat diet enriched with advanced glycation end products (AGEs) (HAGE diet). The HAGE diet increased their levels of blood ketone bodies, and this effect was exacerbated by DM induction. To determine the effects of diet and/or DM induction on key cerebral bioenergetic parameters, both ketone bodies (β-hydroxybutyric acid) and lactate oxidation were measured. In parallel, the expression of Monocarboxylate Transporter 1 (MCT1) and 2 (MCT2) isoforms in hippocampal and cortical slices from rats submitted to these diets was assessed. Ketone body oxidation increased while lactate oxidation decreased in hippocampal and cortical slices in both control and diabetic rats fed a HAGE diet. In parallel, the expression of both MCT1 and MCT2 increased only in the cerebral cortex in diabetic rats fed a HAGE diet. These results suggest a shift in the preferential cerebral energy substrate utilization in favor of ketone bodies in animals fed a HAGE diet, an effect that, in DM animals, is accompanied by the enhanced expression of the related transporters. PMID:27877108

  13. Skin advanced glycation end products glucosepane and methylglyoxal hydroimidazolone are independently associated with long-term microvascular complication progression of type 1 diabetes.

    PubMed

    Genuth, Saul; Sun, Wanjie; Cleary, Patricia; Gao, Xiaoyu; Sell, David R; Lachin, John; Monnier, Vincent M

    2015-01-01

    Six skin collagen advanced glycation end products (AGEs) originally measured near to the time of the Diabetes Control and Complications Trial (DCCT) closeout in 1993 may contribute to the "metabolic memory" phenomenon reported in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. We have now investigated whether the addition of four originally unavailable AGEs (i.e., glucosepane [GSPNE], hydroimidazolones of methylglyoxal [MG-H1] and glyoxal, and carboxyethyl-lysine) improves associations with incident retinopathy, nephropathy, and neuropathy events during 13-17 years after DCCT. The complete 10-AGE panel is associated with three-step Early Treatment of Diabetic Retinopathy Study scale worsening of retinopathy (P ≤ 0.002), independent of either mean DCCT or EDIC study A1C level. GSPNE and fructose-lysine (furosine [FUR]) correlate with retinopathy progression, independently of A1C level. The complete panel also correlates with microalbuminuria (P = 0.008) and FUR with nephropathy independently of A1C level (P ≤ 0.02). Neuropathy correlates with the complete panel despite adjustment for A1C level (P ≤ 0.005). MG-H1 and FUR are dominant, independent of A1C level (P < 0.0001), whereas A1C loses significance after adjustment for the AGEs. Overall, the added set of four AGEs enhances the association of the original panel with progression risk of retinopathy and neuropathy (P < 0.04) but not nephropathy, while GSPNE and MG-H1 emerge as the principal new risk factors. Skin AGEs are robust long-term markers of microvascular disease progression, emphasizing the importance of early and sustained implementation of intensive therapy.

  14. Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits.

    PubMed

    Mehla, Jogender; Chauhan, Balwantsinh C; Chauhan, Neelima B

    2014-01-01

    Alzheimer's disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD.

  15. Miscarriage at advanced maternal age and the search for meaning.

    PubMed

    Carolan, Marsha; Wright, Rebecca J

    2017-03-01

    Although it has been documented that miscarriage is a common pregnancy outcome and more likely to happen among women aged 35 years and older, there is very little research on the quality of such a lived experience. This study features phenomenological interviews of 10 women aged 35 years and older. Theoretical frameworks of ambiguous loss and feminism guide the design and analysis. The salient themes suggest that women experience miscarriage from a physical, emotional, temporal, and social context that includes intense loss and grief, having a sense of otherness, a continuous search for meaning, and feelings of regret and self-blame.

  16. Frontal Gray Matter Atrophy in Middle Aged Adults with Type 1 Diabetes is Independent of Cardiovascular Risk Factors and Diabetes Complications

    PubMed Central

    Hughes, Timothy M.; Ryan, Christopher M.; Aizenstein, Howard J.; Nunley, Karen; Gianaros, Peter J.; Miller, Rachel; Costacou, Tina; Strotmeyer, Elsa S.; Orchard, Trevor J.; Rosano, Caterina

    2013-01-01

    Aims To determine if regional gray matter volume (GMV) differences in middle-aged adults with and without type-1 diabetes (T1D) are localized in areas most vulnerable to aging, e.g. fronto-subcortical networks; and if these differences are explained by cardiovascular risk factors and diabetes complications. Methods Regional GMV was computed using 3 Tesla MRI of 104 adults with a childhood onset of T1D (mean age: 49+7 and duration: 41±6 years) and 151 adults without diabetes (mean age: 40+6). A Bonferroni threshold (n=45, p≤0.001) was applied to account for multiple between-group comparisons and analyses were repeated in an age- and gender-matched subset of participants with T1D and controls (n=44 in each group, mean age [SD] and range: 44.0, [4.3], 17.4 and 44.6 [4.3], 17.0, respectively). Results Compared to controls, T1D patients had smaller GMV in the frontal lobe (6 to 19% smaller) and adjacent supramarginal and postcentral gyri (8 to 13% smaller). Between-group differences were independent of age, waist circumference, systolic blood pressure, fasting total cholesterol and smoking status and were similar in sensitivity analyses restricted to age- and gender-matched participants. Associations between GMV and diabetes complications were not significant. Conclusions These findings extend the notion of accelerated brain aging in T1D to middle-aged adults. The pathophysiology of frontal gray matter atrophy and its impact on future development of disability and dementia need further study, especially as middle-aged T1D patients progress to older age. PMID:23994432

  17. Transportation and Aging: A Research Agenda for Advancing Safe Mobility

    ERIC Educational Resources Information Center

    Dickerson, Anne E.; Molnar, Lisa J.; Eby, David W.; Adler, Geri; Bedard, Michel; Berg-Weger, Marla; Classen, Sherrilene; Foley, Daniel; Horowitz, Amy; Kerschner, Helen; Page, Oliver; Silverstein, Nina M.; Staplin, Loren; Trujillo, Leonard

    2007-01-01

    Purpose: We review what we currently know about older driver safety and mobility, and we highlight important research needs in a number of key areas that hold promise for achieving the safety and mobility goals for the aging baby boomers and future generations of older drivers. Design and Methods: Through the use of a framework for transportation…

  18. Recommendations for managing cutaneous disorders associated with advancing age

    PubMed Central

    Humbert, Philippe; Dréno, Brigitte; Krutmann, Jean; Luger, Thomas Anton; Triller, Raoul; Meaume, Sylvie; Seité, Sophie

    2016-01-01

    The increasingly aged population worldwide means more people are living with chronic diseases, reduced autonomy, and taking various medications. Health professionals should take these into consideration when managing dermatological problems in elderly patients. Accordingly, current research is investigating the dermatological problems associated with the loss of cutaneous function with age. As cell renewal slows, the physical and chemical barrier function declines, cutaneous permeability increases, and the skin becomes increasingly vulnerable to external factors. In geriatric dermatology, the consequences of cutaneous aging lead to xerosis, skin folding, moisture-associated skin damage, and impaired wound healing. These problems pose significant challenges for both the elderly and their carers. Most often, nurses manage skin care in the elderly. However, until recently, little attention has been paid to developing appropriate, evidence-based, skincare protocols. The objective of this paper is to highlight common clinical problems with aging skin and provide some appropriate advice on cosmetic protocols for managing them. A review of the literature from 2004 to 2014 using PubMed was performed by a working group of six European dermatologists with clinical and research experience in dermatology. Basic topical therapy can restore and protect skin barrier function, which relieves problems associated with xerosis, prevents aggravating moisture-associated skin damage, and enhances quality of life. In conclusion, the authors provide physicians with practical recommendations to assist them in implementing basic skin care for the elderly in an integrated care approach. PMID:26929610

  19. Impact of trace element changes on dehydroepiandrosterone sulfate in healthy and diabetic states among middle-age and elderly Egyptians.

    PubMed

    El Husseiny, Noha M; Said, Elham Sobhy; El Shahat Mohamed, Naglaa; Othman, Azza Ismail

    2011-12-01

    The aim of this study was to confirm if there is a link between the alteration in blood levels of trace elements (chromium, copper, lead, cadmium, and zinc) and dehydroepiandrosterone sulfate (DHEAS) in healthy and diabetic states. This study is the first study to test these parameters in Egyptians. The study included 150 subjects divided into the following four groups: healthy middle-aged, healthy elderly, middle-aged diabetics, and elderly diabetics. Our results revealed a statistically significant decrease in the level of DHEAS in the elderly compared to middle-aged healthy and diabetic groups (p < 0.05). There was a significant difference between the middle-aged groups with respect to zinc, copper, chromium, and cadmium levels. Zinc and copper were lower in the diabetic subjects while chromium and cadmium were higher in the same group in comparison to healthy subjects. In the elderly groups, there were significant increases in chromium and cadmium levels in diabetic subjects rather than healthy ones. There was a significant increase in the thiobarbituric acid reactive substance level in the elderly healthy and diabetic groups and a significant decrease in the glutathione level in the elderly groups. There was no correlation between the levels of trace elements and DHEAS or between the levels of DHEAS, oxidants, and antioxidants in all of the tested groups. In conclusion, only the DHEAS level was correlated with age. There was no difference between the diabetic and healthy groups with respect to the levels of trace elements, with the exception of chromium and cadmium, which suggests the effect of pollution on the pathogenesis of diabetes in Egyptians. No correlation existed between the levels of DHEAS and trace elements, oxidants, and antioxidants. Finally, we believe that there is a large regional variation in the levels of trace elements due to different environmental exposure and nutritional factors which are responsible for contradictory results

  20. Interactions of hearing loss and Diabetes Mellitus in the middle age CBA/CaJ mouse model of presbycusis

    PubMed Central

    Vasilyeva, Olga N.; Frisina, Susan T.; Zhu, Xiaoxia; Walton, Joseph P.; Frisina, Robert D.

    2009-01-01

    Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects. The current study prospectively assessed hearing abilities in middle age CBA/CaJ mice with Type 1 diabetes mellitus (T1DM) (STZ injection) or Type 2 diabetes mellitus (T2DM) (high fat diet), for a period of 6 months. Blood glucose, body weight and auditory tests (Auditory Brainstem Response-ABR, Distortion Product Otoacoustic Emissions-DPOAE) were evaluated at baseline and every 2 months. Tone and broadband noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (~32g), but there was a significant (~5g) decline in the T1DM, while T2DM exhibited ~10g weight gain. Blood glucose levels significantly increased: 3 fold for T1DM, 1.3 fold for T2DM; with no significant changes in controls. ABR threshold elevations were found for both types of diabetes, but were most pronounced in the T2DM, starting as early as 2 months after induction of diabetes. A decline of mean DPOAE amplitudes was observed in both diabetic groups at high frequencies, and for the T2DM at low frequencies. In contrast to ABR thresholds, tone and noise thresholds in the inferior colliculus were lower for both diabetic groups. Induction of diabetes in middle-aged CBA/CaJ mice promotes amplification of age-related peripheral hearing loss which makes it a suitable model for studying the interaction of age-related hearing loss and diabetes. On the other hand, initial results of effects from very high blood glucose level (T1DM) on the auditory midbrain showed disruption of central inhibition, increased response synchrony or enhanced excitation in the inferior colliculus. PMID:19271313

  1. Advanced Glycation End Products (AGE) Potently Induce Autophagy through Activation of RAF Protein Kinase and Nuclear Factor κB (NF-κB).

    PubMed

    Verma, Neeharika; Manna, Sunil K

    2016-01-15

    Advanced glycation end products (AGE) accumulate in diabetic patients and aging people because of high amounts of three- or four-carbon sugars derived from glucose, thereby causing multiple consequences, including inflammation, apoptosis, obesity, and age-related disorders. It is important to understand the mechanism of AGE-mediated signaling leading to the activation of autophagy (self-eating) that might result in obesity. We detected AGE as one of the potent inducers of autophagy compared with doxorubicin and TNF. AGE-mediated autophagy is inhibited by suppression of PI3K and potentiated by the autophagosome maturation blocker bafilomycin. It increases autophagy in different cell types, and that correlates with the expression of its receptor, receptor for AGE. LC3B, the marker for autophagosomes, is shown to increase upon AGE stimulation. AGE-mediated autophagy is partially suppressed by inhibitor of NF-κB, PKC, or ERK alone and significantly in combination. AGE increases sterol regulatory element binding protein activity, which leads to an increase in lipogenesis. Although AGE-mediated lipogenesis is affected by autophagy inhibitors, AGE-mediated autophagy is not influenced by lipogenesis inhibitors, suggesting that the turnover of lipid droplets overcomes the autophagic clearance. For the first time, we provide data showing that AGE induces several cell signaling cascades, like NF-κB, PKC, ERK, and MAPK, that are involved in autophagy and simultaneously help with the accumulation of lipid droplets that are not cleared effectively by autophagy, therefore causing obesity.

  2. Association Between Age at Menarche and Gestational Diabetes Mellitus: The Australian Longitudinal Study on Women's Health.

    PubMed

    Schoenaker, Danielle A J M; Mishra, Gita D

    2017-03-05

    In this study, we aimed to examine the association between age at menarche and gestational diabetes mellitus (GDM). Data were from 4,749 women participating in the Australian Longitudinal Study on Women's Health between 2000 and 2012. Age at menarche was reported at baseline in 2000 when women were aged 22-27 years. During 12 years of follow-up, information on GDM diagnosis was obtained for each live birth. Log-binomial regression analysis was used to estimate relative risks and 95% confidence intervals. Analyses adjusted for mother's highest completed educational qualification, nulliparity, polycystic ovary syndrome, physical activity, and body mass index. Mean age at menarche was 12.9 years (standard deviation, 1.4). A first diagnosis of GDM was reported by 357 women (7.5%). Compared with women with menarche at age 13 years, women who had their first menstruation at age ≤11 years had a 51% higher risk of developing GDM (95% confidence interval: 1.10, 2.07) after adjustment for GDM risk factors. Our findings indicate that a young age at menarche may identify women at higher risk of GDM. Further prospective studies are needed to confirm our findings and to elucidate the role of early-life exposures in age at menarche and subsequent GDM risk.

  3. Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease in non diabetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiologic studies indicate that the risks for major age-related debilities including coronary heart disease, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains...

  4. Middle-Aged Independent-Living African Americans' Selections for Advance Directives: A Case Study

    ERIC Educational Resources Information Center

    McDaniel, Brenda J.

    2013-01-01

    The purpose of this collective embedded qualitative case study was to examine the perspectives of three middle-aged independent-living African Americans who had participated in the process of advance care planning (ACP) and completed at least two advance directives (ADs), a Durable Power of Attorney for Health Care (DPAHC) and a Living Will (LW).…

  5. New Advanced Technology to Improve Prediction and Prevention of Type 1 Diabetes

    DTIC Science & Technology

    2005-11-01

    who do not. The 3 major complications to be evaluated are diabetic nephropathy , diabetic neuropathy, and diabetic retinopathy. This is an...families for diabetic nephropathy , autonomic neuropathy, and retinopathy. Body The title of this study is “Genetic Screening in Diabetes .” This is an...susceptibility and/or development of diabetic nephropathy , neuropathy, and retinopathy. It is expected that WRAMC will enroll up to 100 probands and

  6. Age and family relationship accentuate the risk of insulin-dependent diabetes mellitus (IDDM) in relatives of patients with IDDM

    SciTech Connect

    Cantor, A.B.; Krischer, J.P.; Cuthbertson, D.D.

    1995-12-01

    The international community of diabetologists is rapidly becomine involved in intervention trials aimed at preventing insulin-dependent diabetes in high risk relatives. Whereas age and relationship to a proband with insulin-dependent diabetes mellitus interacting with detected islet cell autoantibodies (ICA) are risk factors, their independent contribution to that risk remains unclear. In a prospective study of 6851 nondiabetic relatives of 2742 probands conducted between 1979-1993, we found age, but not relationship, to be a dramatic risk variable in ICA-positive persons as estimated by the Cox regression model. The 5-yr risk of insulin-dependent diabetes mellitus was 66% for those found to have ICA detectable before age 10 yr, falling progressively to less than 16% for ICA-positive relatives over age 40 yr. In ICA-negative relatives, age and relationship are independent prognostic variables. 15 refs., 4 figs., 2 tabs.

  7. Advances in Protective Coatings and Their Application to Ageing Aircraft

    DTIC Science & Technology

    2000-04-01

    Materials for the Structure f Aging Aircraft [les Nouveaux Materiaux metalliques pour les structures des aeronefs d’ancienne generation] To order the...corrosion through design, the selection of military and civil aircraft during the last thirty years. Research materials that are resistant to corrosion and...fluid resistance and greater flexibility. New methods of paint stripping and novel processes for the 2.1 Design repair of pre-treatments and metal

  8. Psychometrics in aging and dementia: advances in geropsychological assessments.

    PubMed

    Oswald, W D; Fleischmann, U M

    1985-12-01

    Description, explanation and prediction of changes occurring in old age, which are based on intervention, are outlined as a basic goal in gerontological research. Appropriate psychological assessment techniques are necessary to reach this goal. The Nuremberg Gerontopsychological Inventory (NAI) is introduced as a set of psychological measurements which enable reliable, valid and sensitive evaluation of intervention-induced changes in old age. Four independent assessment levels, i.e. standardized performance tests, observer-ratings, self-ratings and a personality rating are the core components of this inventory. All assessment techniques are adapted for elderly subjects. Standard scores are available for the age range 55-90 years. Interrelations between the applied independent assessment levels are reported and taken to link different aspects of intervention-induced changes. Measuring psychological performance thus gains practical significance, e.g. in terms of activities-of-daily-living. From 14 independent studies the drug sensitivity of the applied measurements is shown. Finally, some recommendations for future psychometrical research are given.

  9. Electrophysiological Advances on Multiple Object Processing in Aging

    PubMed Central

    Mazza, Veronica; Brignani, Debora

    2016-01-01

    EEG research conducted in the past 5 years on multiple object processing has begun to define how the aging brain tracks the numerosity of the objects presented in the visual field for different goals. We review the recent EEG findings in healthy older individuals (age range: 65–75 years approximately) on perceptual, attentional and memory mechanisms-reflected in the N1, N2pc and contralateral delayed activity (CDA) components of the EEG, respectively-during the execution of a variety of cognitive tasks requiring simultaneous processing of multiple elements. The findings point to multiple loci of neural changes in multi-object analysis, and suggest the involvement of early perceptual mechanisms, attentive individuation and working memory (WM) operations in the neural and cognitive modification due to aging. However, the findings do not simply reflect early impairments with a cascade effect over subsequent stages of stimulus processing, but in fact highlight interesting dissociations between the effects occurring at the various stages of stimulus processing. Finally, the results on older adults indicate the occurrence of neural overactivation in association to good levels of performance in easy perceptual contexts, thus providing some hints on the existence of compensatory phenomena that are associated with the functioning of early perceptual mechanisms. PMID:26973520

  10. Categories of manual asymmetry and their variation with advancing age.

    PubMed

    Teixeira, Luis A

    2008-06-01

    Manual asymmetries were analyzed in 18- to 63-year-old right-handers in different motor tasks. This analysis aimed at describing the asymmetry profile for each task and assessing their stability across ages. For this purpose, performance of the right and left hands were analyzed in the following aspects: simple reaction time, rate of sequential finger movements, maximum grip force, accuracy in anticipatory timing, rate of repetitive tapping, and rate of drawing movements. In addition, stability of manual preference across ages was assessed through the Edinburgh inventory (Oldfield, 1971). The results indicated different profiles of manual asymmetry, with identification of three categories across tasks: symmetric performance (asymmetry indices close to zero), inconsistent asymmetry (asymmetry indices variable in magnitude and direction), and consistent asymmetry (asymmetry indices favoring a single hand). The different profiles observed in the young adults were stable across ages with two exceptions: decreased lateral asymmetry for maximum grip force and increased asymmetry for sequential drawing in older individuals. These results indicate that manual asymmetries are task specific. Such task specificity is interpreted to be the result of different sensorimotor requirements imposed by each motor task in association with motor experiences accumulated over the lifetime. Analysis of manual preference showed that strength of preference for the right hand was greater in older individuals.

  11. Health state utilities in patients with diabetic retinopathy, diabetic macular oedema and age-related macular degeneration: a systematic review

    PubMed Central

    2013-01-01

    Background Health state utility values (HSUVs) are important in the assessment of the cost effectiveness of new interventions. In the case of visual conditions, models generally tend have tended to be built around a set of health states defined by visual acuity (VA). The aim of this review was to assess the impact of VA on HSUVs in patients with diabetic retinopathy, diabetic macular oedema or age-related macular degeneration. Methods A systematic literature search was undertaken in major bibliographic databases to identify articles reporting on the relationship between HSUVs and vision. Data were extracted for population characteristics, visual levels and estimated utilities. Evidence from reported statistical models, where available, was considered in the evaluation of vision in the better-seeing eye and the worse-seeing eye. Due to the heterogeneity of included studies, a narrative synthesis was undertaken. Results Of the 17 relevant studies, 9 studies had data that could be used in the analysis of the impact of vision on HSUVs. Visual loss was associated with a marked impact on health utilities. However, the relationship was not comparable between conditions or by measure of HSUVs. Key results included the finding that overall, self-rated time-trade off estimates were more likely to discriminate between different VA levels than EQ-5D values. Additionally, a stronger correlation was observed between HSUVs and better-seeing eye VA compared to worse-seeing eye VA. Conclusions Visual acuity has a significant impact on HSUVs. Nevertheless, care must be taken in the interpretation and use of estimates in cost-effectiveness models due to differences in measures and population diversity. PMID:24304921

  12. Thyroid function and anti-thyroid antibodies in Iranian patients with type 1 diabetes mellitus: influences of age and sex.

    PubMed

    Sharifi, Faranak; Ghasemi, Leila; Mousavinasab, Nouraddin

    2008-03-01

    Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease (ATD).Genetic susceptibility for autoantibody formation in association with ATD and type 1 diabetes mellitus has been described with varying frequencies, but there is still debate about its prevailing situation in Iran. We have therefore investigated the prevalence of anti-thyroid peroxidase (anti-TPO) and anti thyroglubolin (Anti TG) antibodies in type 1 diabetic patients, and compared the effect of age and sex on the thyroid autoimmunity in patients with type 1 diabetes mellitus in Iran.Ninety one subjects with type 1 diabetes mellitus and one hundred and sixty three unrelated normal controls under the age of thirty years were recruited for the detection of anti-TPO and anti-TG. Radio Immuno Assay and chemiluminescence methods were used for anti-TPO and anti-TG detection respectively.Among 91 type 1 diabetic patients, 36 (39.6%) were positive for anti-TPO and 27(30%) were positive for antiTG. Anti-TPO antibodies were detected only in 6.7% of control group. Comparing with those without thyroid autoimmunity, there was a female preponderance for the type 1 diabetic patients with thyroid autoimmunity (female: male, 28:14 vs. 28:20 respectively). Among the type 1 diabetic patients those with thyroid autoimmunity, tended to be older (p: 0.04) and to have higher TSH concentration (p: 0.03). Patients with high anti-TPO levels had longer duration of diabetes (P: 0.02).The presence of anti-TPO in 39.6% of our type 1 diabetic patients comparing with 8.5% of normal subjects confirmed the strong association of ATD and type 1 diabetes mellitus.

  13. Development, relative validity, and reliability of a food frequency questionnaire for a case-control study on dietary advanced glycation end products and diabetes complications.

    PubMed

    Luevano-Contreras, Claudia; Durkin, Taylor; Pauls, Maria; Chapman-Novakofski, Karen

    2013-12-01

    Dietary advanced glycation end products (dAGEs) could be involved on diabetes complications, yet their quantification is not standardized. The objective of this study was to design a food frequency questionnaire (FFQ) for dAGEs, and to assess its reliability and validity. For the design, data from 30 subjects was used. The final instrument had 90 food items. To measure reliability and validity, 20 participants with type 2 diabetes filled out twice the FFQ (FFQ-T1, FFQ-T2) and 7-day food records (7-dFR). The Shrout-Fleiss coefficient was 0.98 showing good reliability. For validation, the results for the weighted kappa were 0.55 (moderate agreement) for FFQ-T1 and 0.64 (good agreement) for FFQ-T2, and 75% and 80% of subjects respectively were correctly classified into tertiles; Bland-Altman graphics showed no systematic bias. This FFQ is comparable to 7-dFR for measuring dAGEs. To our knowledge, this is the first questionnaire designed to measure specifically dAGEs.

  14. The use of an extract of Hypericum perforatum and Azadirachta indica in a neuropathic patient with advanced diabetic foot.

    PubMed

    Iabichella, Maria Letizia; Caruso, Claudio; Lugli, Marzia

    2014-11-06

    The successful use of an extract of Hypericum flowers (Hypericum perforatum) and nimh oil (Azadirachta indica; Hyperoil) in foot wounds with exposed bone in a patient with bilateral advanced diabetic ulcers, has been reported previously. It was hypothesised that this amelioration was linked with the improved glycaemic control and peripheral microvascular circulation. In this case report, the surprisingly successful outcome of another patient using Hyperoil for infection damaged diabetic foot, without prior use of surgical procedure, is described. The patient had no macrovascular pattern impairment. Diabetic foot healing paralleled with controlled local infection and enhanced glycaemic control. The outcome of this patient suggests that the effectiveness of this inexpensive therapy using Hyperoil for diabetic foot is not only linked with the presence of severe microvascular disorder, but also with the appropriate local treatment for ulcer being a must for its recovery.

  15. Role of N–epsilon- carboxy methyl lysine, advanced glycation end products and reactive oxygen species for the development of nonproliferative and proliferative retinopathy in type 2 diabetes mellitus

    PubMed Central

    Choudhuri, Subhadip; Dutta, Deep; Sen, Aditi; Chowdhury, Imran Hussain; Mitra, Bhaskar; Mondal, Lakshmi Kanta; Saha, Avijit; Bhadhuri, Gautam

    2013-01-01

    Purpose The aim of the present study was to evaluate the collective role of N-epsilon–carboxy methyl lysine (Nε-CML), advanced glycation end-products (AGEs), and reactive oxygen species (ROS) for the development of retinopathy among type 2 diabetic subjects. Methods Seventy type 2 diabetic subjects with nonproliferative diabetic retinopathy (NPDR), 105 subjects with proliferative diabetic retinopathy (PDR), and 102 patients with diabetes but without retinopathy (DNR) were enrolled in this study. In addition, 95 normal individuals without diabetes were enrolled as healthy controls in this study. Serum and vitreous Nε-CML and AGEs were measured by enzyme-linked immunosorbent assay. The peripheral blood mononuclear cell (PBMC) ROS level was measured by flow cytometric analysis. Serum and PBMC total thiols were measured by spectrophotometry. Results Serum AGEs and Nε-CML levels were significantly elevated in subjects with PDR (p<0.0001) and NPDR (p=0.0297 and p<0.0001, respectively) compared to DNR subjects. Further vitreous AGEs and Nε-CML levels were found to be significantly high among PDR subjects compared to the control group (p<0.0001). PBMC ROS production was found to be strikingly high among NPDR (p<0.0001) and PDR (p<0.0001) subjects as compared to the DNR group. Serum and PBMC total thiol levels were remarkably decreased in NPDR (p<0.0001 and p=0.0043, respectively) and PDR (p=0.0108 and p=0.0332 respectively) subjects than those were considered as DNR. Conclusions Our findings suggest that Nε-CML and ROS are the key modulators for the development of nonproliferative retinopathy among poorly controlled type 2 diabetic subjects. Furthermore, AGEs under persistent oxidative stress and the deprived antioxidant state might instigate the pathogenic process of retinopathy from the nonproliferative to the proliferative state. PMID:23378723

  16. Advancing the Aging and Technology Agenda in Gerontology

    PubMed Central

    Schulz, Richard; Wahl, Hans-Werner; Matthews, Judith T.; De Vito Dabbs, Annette; Beach, Scott R.; Czaja, Sara J.

    2015-01-01

    Interest in technology for older adults is driven by multiple converging trends: the rapid pace of technological development; the unprecedented growth of the aging population in the United States and worldwide; the increase in the number and survival of persons with disability; the growing and unsustainable costs of caring for the elderly people; and the increasing interest on the part of business, industry, and government agencies in addressing health care needs with technology. These trends have contributed to the strong conviction that technology can play an important role in enhancing quality of life and independence of older individuals with high levels of efficiency, potentially reducing individual and societal costs of caring for the elderly people. The purpose of this “Forum” position article is to integrate what we know about older adults and technology systems in order to provide direction to this vital enterprise. We define what we mean by technology for an aging population, provide a brief history of its development, introduce a taxonomy for characterizing current technology applications to older adults, summarize research in this area, describe existing development and evaluation processes, identify factors important for the acceptance of technology among older individuals, and recommend future directions for research in this area. PMID:25165042

  17. Advancing the Aging and Technology Agenda in Gerontology.

    PubMed

    Schulz, Richard; Wahl, Hans-Werner; Matthews, Judith T; De Vito Dabbs, Annette; Beach, Scott R; Czaja, Sara J

    2015-10-01

    Interest in technology for older adults is driven by multiple converging trends: the rapid pace of technological development; the unprecedented growth of the aging population in the United States and worldwide; the increase in the number and survival of persons with disability; the growing and unsustainable costs of caring for the elderly people; and the increasing interest on the part of business, industry, and government agencies in addressing health care needs with technology. These trends have contributed to the strong conviction that technology can play an important role in enhancing quality of life and independence of older individuals with high levels of efficiency, potentially reducing individual and societal costs of caring for the elderly people. The purpose of this "Forum" position article is to integrate what we know about older adults and technology systems in order to provide direction to this vital enterprise. We define what we mean by technology for an aging population, provide a brief history of its development, introduce a taxonomy for characterizing current technology applications to older adults, summarize research in this area, describe existing development and evaluation processes, identify factors important for the acceptance of technology among older individuals, and recommend future directions for research in this area.

  18. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson's Disease.

    PubMed

    Claassen, Daniel O; Dobolyi, David G; Isaacs, David A; Roman, Olivia C; Herb, Joshua; Wylie, Scott A; Neimat, Joseph S; Donahue, Manus J; Hedera, Peter; Zald, David H; Landman, Bennett A; Bowman, Aaron B; Dawant, Benoit M; Rane, Swati

    2016-05-01

    Advancing age and disease duration both contribute to cortical thinning in Parkinson's disease (PD), but the pathological interactions between them are poorly described. This study aims to distinguish patterns of cortical decline determined by advancing age and disease duration in PD. A convenience cohort of 177 consecutive PD patients, identified at the Vanderbilt University Movement Disorders Clinic as part of a clinical evaluation for Deep Brain Stimulation (age: M= 62.0, SD 9.3), completed a standardized clinical assessment, along with structural brain Magnetic Resonance Imaging scan. Age and gender matched controls (n=53) were obtained from the Alzheimer Disease Neuroimaging Initiative and Progressive Parkinson's Marker Initiative (age: M= 63.4, SD 12.2). Estimated changes in cortical thickness were modeled with advancing age, disease duration, and their interaction. The best-fitting model, linear or curvilinear (2(nd), or 3(rd) order natural spline), was defined using the minimum Akaike Information Criterion, and illustrated on a 3-dimensional brain. Three curvilinear patterns of cortical thinning were identified: early decline, late decline, and early-stable-late. In contrast to healthy controls, the best-fit model for age related changes in PD is curvilinear (early decline), particularly in frontal and precuneus regions. With advancing disease duration, a curvilinear model depicts accelerating decline in the occipital cortex. A significant interaction between advancing age and disease duration is evident in frontal, motor, and posterior parietal areas. Study results support the hypothesis that advancing age and disease duration differentially affect regional cortical thickness and display regional dependent linear and curvilinear patterns of thinning.

  19. [Cognitive capacity in advanced age: initial results of the Berlin Aging Study].

    PubMed

    Lindenberger, U; Baltes, P B

    1995-01-01

    This study reports data on intellectual functioning in old and very old age from the Berlin Aging Study (N = 516; age range = 70-103 years; mean age = 85 years). A psychometric battery of 14 tests was used to assess five cognitive abilities: reasoning, memory, and perceptual speed from the broad fluid-mechanical as well as knowledge and fluency from the broad crystallized-pragmatic domains. Cognitive abilities had a negative linear relationship with age, with more pronounced age-based reductions in fluid-mechanical than crystallized-pragmatic abilities. At the same time, ability intercorrelations formed a highly positive manifold, and did not follow the fluid-crystallized distinction. Interindividual variability was of about equal magnitude across the entire age range studied. There was, however, no evidence for substantial sex differences. As to origins of individual differences, indicators of sensory and sensorimotor functioning were more powerful predictors of intellectual functioning than cultural-biographical variables, and the two sets of predictors were, consistent with theoretical expectations, differentially related to measures of fluid-mechanical (perceptual speed) and crystallized pragmatic (knowledge) functioning. Results, in general indicative of sizeable and general losses with age, are consistent with the view that aging-induced biological influences are a prominent source of individual differences in intellectual functioning in old and very old age. Longitudinal follow-ups are underway to examine the role of cohort effects, selective mortality, and interindividual differences in change trajectories.

  20. Prevention of Obesity and Type 2 Diabetes with Aged Citrus Peel (Chenpi) Extract.

    PubMed

    Guo, Jingjing; Tao, Hanlin; Cao, Yong; Ho, Chi-Tang; Jin, Shengkang; Huang, Qingrong

    2016-03-16

    Chenpi is the dry peel of the plant Citrus reticulata Blanco after an aging processing. It has been used as an antidigestive and anti-inflammatory traditional medicine, as well as culinary seasoning and dietary supplement, in China. However, its efficacy and underlying scientific mechanism have not been sufficiently investigated. Chenpi is uniquely enriched with a high content of 5-demethylated polymethoxyflavones (5-OH PMFs). The effect of chenpi extract on improving metabolic features was examined using high-fat diet (HFD)-induced obesity/diabetes mouse model. Oral administration of 0.25 and 0.5% chenpi extract in food over 15 weeks markedly prevented HFD-induced obesity, hepatic steatosis, and diabetic symptoms. The beneficial effect is associated with 5'-adenosine monophosphate-activated protein kinase (AMPK) activation in adipose tissue. Our results indicate that 5-OH PMFs-enriched chenpi extract is effective in preventing obesity and type 2 diabetes, and its effect might be related to improvement in lipid metabolism associated with activation of the AMPK pathway.

  1. Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns

    PubMed Central

    Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

    2016-01-01

    We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20–90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD. PMID:27045845

  2. Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns.

    PubMed

    Habes, M; Janowitz, D; Erus, G; Toledo, J B; Resnick, S M; Doshi, J; Van der Auwera, S; Wittfeld, K; Hegenscheid, K; Hosten, N; Biffar, R; Homuth, G; Völzke, H; Grabe, H J; Hoffmann, W; Davatzikos, C

    2016-04-05

    We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.

  3. New Advanced Technology to Improve Prediction and Prevention of Type 1 Diabetes

    DTIC Science & Technology

    2006-11-01

    32 Genetic Screening in Diabetes : Candidate Gene Analysis for Diabetic Nephropathy University of Hawaii... treatment and prevention of life threatening disease. The overall goal of the research project is to provide a means to genetically test diabetic ...patients for their inherited risk for developing the 3 principal complications of diabetes , i.e., nephropathy , neuropathy, and retinopathy. The

  4. Advanced glycation end products (AGEs) and its receptors in the pathogenesis of hyperthyroidism.

    PubMed

    Caspar-Bell, Gudrun; Dhar, Indu; Prasad, Kailash

    2016-03-01

    Oxidative stress has been implicated in the pathogenesis of hyperthyroidism and its complications. Interaction of advanced glycation end products (AGEs) with receptor RAGE (receptor for AGEs) generates reactive oxygen species. Soluble receptor for AGEs (sRAGE) competes with RAGE for binding with AGEs and attenuates the generation of ROS. Low levels sRAGE and high levels AGEs would generate more ROS leading to hyperthyroidism and its complications. The objectives are to determine if levels of serum sRAGE are low and the levels of AGEs and AGEs/sRAGE are high in patients with hyperthyroidism. The study subjects comprised of 33 patients with hyperthyroidism and 20 controls. Levels of serum sRAGE were lower, while that of AGEs and AGEs/sRAGE were higher in patients compared to controls, being significant only for sRAGE and AGEs/sRAGE. When the levels of sRAGE, AGEs, and AGEs/sRAGE were assessed for hyperthyroidism associated with different diseases, the levels of sRAGE were lower in Hashimoto disease, and levels of AGEs were higher in patients with Graves' disease compared to control. The levels of AGEs/sRAGE were elevated in an all except patients with Hashimoto disease. The levels of AGEs, sRAGE, or AGEs/RAGE were not correlated with age, weight, and blood pressures except systolic pressure which was inversely correlated with sRAGE. The levels of sRAGE were negatively correlated with AGEs and AGEs/sRAGE. The levels of AGEs/sRAGE were positively correlated with AGEs. In conclusion, low levels of sRAGE, and high levels of AGEs and AGEs/sRAGE are risk biomarkers in the pathogenesis hyperthyroidism and its complications.

  5. Association of genetic variants in the receptor for advanced glycation end products gene with diabetic retinopathy

    PubMed Central

    Yu, Weihong; Yang, Jingyun; Sui, Wenda; Qu, Bin; Huang, Ping; Chen, Youxin

    2016-01-01

    Abstract Background: Diabetic retinopathy (DR) is a major sight-threatening diabetic complication. Previous studies have examined the association of DR with multiple genetic variants in the receptor for advanced glycation end products (RAGE) gene, with inconsistent results. Objective: To perform a systematic literature search and conduct meta-analyses to examine the association of genetic variants in RAGE with DR. Data sources: PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. Study eligibility criteria and participants: Studies were on human subjects; the studies were case–control ones and included subjects who had DR and those who did not have DR; and the studies provided genotype data for genetic variants in RAGE, separately for subjects who had and did not have DR, or provided odds ratios (ORs) and the 95% confidence intervals (CIs), or provided sufficient data for the calculation of OR and the 95% CI. Study appraisal and synthesis methods: We used OR as a measure of association, and used random-effects model in all the meta-analyses. Between-study heterogeneity was assessed using I2, and publication bias was evaluated using Egger test. Results: A total of 13 studies met the eligibility criteria and were included in our analyses. We found that Gly82Ser was significantly associated with DR (OR = 2.40, 95% CI: 1.46–3.97; P = 0.001) using a recessive model. -374T/A also showed significant association with DR under a dominant model (OR = 1.21, 95% CI: 1.03–1.43; P = 0.023). We did not find a significant association of DR with other genetic variants in RAGE. Limitations: The number of included studies is small for some genetic variants; duration of diabetes varied across studies; most studies were conducted in Asia; and it is not clear whether the observed association can be generalized to other ethnicities; and we could not control for other potential confounding factors. Conclusions and implications of key findings: We found that Gly82Ser in RAGE

  6. Phacoemulsification without preoperative mydriasis in patients with age-related cataract associated with type 2 diabetes

    PubMed Central

    Joshi, Rajesh Subhash

    2016-01-01

    Aim To study the effect of intracameral injection of preservative-free lignocaine to induce pupil dilatation, without using any preoperative dilating eyedrops or intraoperative mydriatics in patients with age-related cataract associated with type 2 diabetes mellitus. Design This was a prospective, observational, and interventional case series conducted at a tertiary eyecare center in rural India. Materials and methods A total of 32 patients underwent phacoemulsification under topical anesthesia for visually significant cataract. Preoperative pupillary diameter was measured 3 days prior to surgical procedure under mydriatics (tropicamide 0.8%, phenylephrine hydrochloride 5%). Intraoperative pupillary dilatation was achieved by 1% intracameral lignocaine solution alone. Effective phacoemulsification time (EPT), total surgical time, and final pupillary diameter were recorded at the conclusion of surgery. Results The average duration of diabetes was 11.2 (range 5–25) years. There was no difference in dilatation by preoperative pupil-dilating drops (5.2±0.5 mm, range 3–8.3 mm) and intracameral 1% lignocaine during the surgical procedure (P=0.63). There was a negative correlation (r=−0.92) between diabetes duration and dilatation of pupils with dilating drops and intracameral lignocaine. The duration of the surgery, EPT, and phacoemulsification chop had statistically insignificant effects on mydriasis, while the grade of the nucleus had a statistically significant effect on mydriasis. Intracameral lignocaine had no significant effect on blood pressure or pulse. There were no surgical complications that could have compromised the visual outcome. None of the patients developed macular edema in a follow-up period of 3 months; 28 patients (87.5%) had best-corrected visual acuity from 20/30 to 20/20. Conclusion Intracameral lignocaine 1% provides sufficient mydriasis for the safe phacoemulsification of cataract in patients with type 2 diabetes of variable duration

  7. Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes

    PubMed Central

    Lee, Alan C. H.; Lam, Joanne K. Y.; Shiu, Sammy W. M.; Wong, Ying; Betteridge, D. John; Tan, Kathryn C. B.

    2015-01-01

    Background The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. Methods Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). Results RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c. Conclusion Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE. PMID:26325204

  8. Effect of dietary prebiotic supplementation on advanced glycation, insulin resistance and inflammatory biomarkers in adults with pre-diabetes: a study protocol for a double-blind placebo-controlled randomised crossover clinical trial

    PubMed Central

    2014-01-01

    Background Advanced glycation endproducts (AGEs) contribute to the development of vascular complications of diabetes and have been recently implicated in the pathogenesis of diabetes. Since AGEs are generated within foodstuffs upon food processing, it is increasingly recognised that the modern diet is replete with AGEs. AGEs are thought to stimulate chronic low-grade inflammation and promote oxidative stress and have been linked to the development of insulin resistance. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of type 2 diabetes in susceptible individuals. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host, but its effect on advanced glycation is unknown. The aim of this article is to describe the methodology of a double-blind placebo-controlled randomised crossover trial designed to determine the effect of 12 week consumption of a prebiotic dietary supplement on the advanced glycation pathway, insulin sensitivity and chronic low-grade inflammation in adults with pre-diabetes. Methods/Design Thirty adults with pre-diabetes (Impaired Glucose Tolerance or Impaired Fasting Glucose) aged between 40–60 years will be randomly assigned to receive either 10 grams of prebiotic (inulin/oligofructose) daily or 10 grams placebo (maltodextrin) daily for 12 weeks. After a 2-week washout period, study subjects will crossover to receive the alternative dietary treatment for 12 weeks. The primary outcome is the difference in markers of the advanced glycation pathway carboxymethyllysine (CML) and methylglyoxal (MG) between experimental and control treatments. Secondary outcomes include HbA1c, insulin sensitivity, lipid levels, blood pressure, serum glutathione, adiponectin, IL-6, E-selectin, myeloperoxidase, C-reactive protein, Toll-like Receptor 4 (TLR4), soluble receptor

  9. Nanomedicine for treatment of diabetes in an aging population: state-of-the-art and future developments.

    PubMed

    Krol, Silke; Ellis-Behnke, Rutledge; Marchetti, Piero

    2012-09-01

    Nowadays diabetes, especially type 2 diabetes (which is strongly related to the Western diet and life-style), has developed worldwide into an epidemic disease. Nanomedicine aims to provide novel tools for diagnosis, therapy and point-of-care management of patients. Several nanotechnological approaches were developed to improve life quality for patients with insulin-dependent diabetes. They facilitate blood glucose management by non-invasive glucose measurement as well as insulin administration mainly by delivering the fragile protein as protected and targeted formulation via nasal or oral route. In the present review the oral or nasal insulin delivery by polymeric nanoparticles is discussed with focus on physiological change either related to the disease, diabetes or age-related metabolic variations influencing insulin release and bioavailability. One critical point is that new generations of targeted nanoparticle based drugs are developed and optimized for certain metabolic conditions. These conditions may change with age or disease. The influence of age-related factors such as immaturity in very young age, metabolic and physiologic changes in old age or insufficient animal models are still under-investigated not only in nanomedicine but also generally in pharmacology. Summarizing it can be noted that the bioavailability of insulin administered via routes others than subcutaneously is comparably low (max. 60%). Moreover factors like changed gut permeability as described for diabetes type 1 or other metabolic peculiarities such as insulin resistance in case of type 2 diabetes also play a role in affecting the development of novel nanoparticulated drug preparations and can be responsible for unsuccessful translation of promising animal results into human therapy. In future insulin nanoparticle development for diabetes must consider not only requirements imposed by the drug but also metabolic changes inflicted by disease or by age. Moreover new approaches are

  10. Physical Disability Trajectories in Older Americans With and Without Diabetes: The Role of Age, Gender, Race or ethnicity, and Education

    PubMed Central

    Chiu, Ching-Ju; Wray, Linda A.

    2011-01-01

    Purpose: This research combined cross-sectional and longitudinal data to characterize age-related trajectories in physical disability for adults with and without diabetes in the United States and to investigate if those patterns differ by age, gender, race or ethnicity, and education. Design and Methods: Data were examined on 20,433 adults aged 51 and older from the 1998 to 2006 Health and Retirement Study. Multilevel models and a cohort-sequential design were applied to quantitatively depict the age norm of physical disability after age 50. Results: Adults with diabetes not only experience greater levels of physical disability but also faster rates of deterioration over time. This pattern is net of attrition, time-invariant sociodemographic factors, and time-varying chronic disease conditions. Differences in physical disability between adults with and without diabetes were more pronounced in women, non-White, and those of lower education. The moderating effects of gender and education remained robust even after controlling for selected covariates in the model. Implications: This study highlighted the consistently greater development of disability over time in adults with diabetes and particularly in those who are women, non-White, or adults of lower education. Future studies are recommended to examine the mechanisms underlying the differential effects of diabetes on physical disability by gender and education. PMID:20713455

  11. Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers.

    PubMed

    Chera, Simona; Baronnier, Delphine; Ghila, Luiza; Cigliola, Valentina; Jensen, Jan N; Gu, Guoqiang; Furuyama, Kenichiro; Thorel, Fabrizio; Gribble, Fiona M; Reimann, Frank; Herrera, Pedro L

    2014-10-23

    Total or near-total loss of insulin-producing β-cells occurs in type 1 diabetes. Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which β-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity. The process involves the contribution of islet non-β-cells; specifically, glucagon-producing α-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation. Here we show the influence of age on β-cell reconstitution from heterologous islet cells after near-total β-cell loss in mice. We found that senescence does not alter α-cell plasticity: α-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after β-cell loss. In contrast, before puberty there is no detectable α-cell conversion, although β-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing δ-cells. The juveniles display 'somatostatin-to-insulin' δ-cell conversion, involving dedifferentiation, proliferation and re-expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-β-cell origins is thus enabled throughout life via δ- or α-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy.

  12. Predicting Absolute Risk of Type 2 Diabetes Using Age and Waist Circumference Values in an Aboriginal Australian Community

    PubMed Central

    2015-01-01

    Objectives To predict in an Australian Aboriginal community, the 10-year absolute risk of type 2 diabetes associated with waist circumference and age on baseline examination. Method A sample of 803 diabetes-free adults (82.3% of the age-eligible population) from baseline data of participants collected from 1992 to 1998 were followed-up for up to 20 years till 2012. The Cox-proportional hazard model was used to estimate the effects of waist circumference and other risk factors, including age, smoking and alcohol consumption status, of males and females on prediction of type 2 diabetes, identified through subsequent hospitalisation data during the follow-up period. The Weibull regression model was used to calculate the absolute risk estimates of type 2 diabetes with waist circumference and age as predictors. Results Of 803 participants, 110 were recorded as having developed type 2 diabetes, in subsequent hospitalizations over a follow-up of 12633.4 person-years. Waist circumference was strongly associated with subsequent diagnosis of type 2 diabetes with P<0.0001 for both genders and remained statistically significant after adjusting for confounding factors. Hazard ratios of type 2 diabetes associated with 1 standard deviation increase in waist circumference were 1.7 (95%CI 1.3 to 2.2) for males and 2.1 (95%CI 1.7 to 2.6) for females. At 45 years of age with baseline waist circumference of 100 cm, a male had an absolute diabetic risk of 10.9%, while a female had a 14.3% risk of the disease. Conclusions The constructed model predicts the 10-year absolute diabetes risk in an Aboriginal Australian community. It is simple and easily understood and will help identify individuals at risk of diabetes in relation to waist circumference values. Our findings on the relationship between waist circumference and diabetes on gender will be useful for clinical consultation, public health education and establishing WC cut-off points for Aboriginal Australians. PMID:25876058

  13. Incidence of Type 1 Diabetes in Sweden Among Individuals Aged 0–34 Years, 1983–2007

    PubMed Central

    Dahlquist, Gisela G.; Nyström, Lennarth; Patterson, Christopher C.

    2011-01-01

    OBJECTIVE To clarify whether the increase in childhood type 1 diabetes is mirrored by a decrease in older age-groups, resulting in younger age at diagnosis. RESEARCH DESIGN AND METHODS We used data from two prospective research registers, the Swedish Childhood Diabetes Register, which included case subjects aged 0–14.9 years at diagnosis, and the Diabetes in Sweden Study, which included case subjects aged 15–34.9 years at diagnosis, covering birth cohorts between 1948 and 2007. The total database included 20,249 individuals with diabetes diagnosed between 1983 and 2007. Incidence rates over time were analyzed using Poisson regression models. RESULTS The overall yearly incidence rose to a peak of 42.3 per 100,000 person-years in male subjects aged 10–14 years and to a peak of 37.1 per 100,000 person-years in female subjects aged 5–9 years and decreased thereafter. There was a significant increase by calendar year in both sexes in the three age-groups <15 years; however, there were significant decreases in the older age-groups (25- to 29-years and 30- to 34-years age-groups). Poisson regression analyses showed that a cohort effect seemed to dominate over a time-period effect. CONCLUSIONS Twenty-five years of prospective nationwide incidence registration demonstrates a clear shift to younger age at onset rather than a uniform increase in incidence rates across all age-groups. The dominance of cohort effects over period effects suggests that exposures affecting young children may be responsible for the increasing incidence in the younger age-groups. PMID:21680725

  14. The role of childhood social position in adult type 2 diabetes: evidence from the English Longitudinal Study of Ageing

    PubMed Central

    2014-01-01

    Background Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father’s job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father’s manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood

  15. Hyperinsulinemia/Diabetes, Hearing, and Aging in the University of Wisconsin Calorie Restriction Monkeys

    PubMed Central

    Fowler, Cynthia G.; Chiasson, Kirstin Beach; Colman, Ricki; Kemnitz, Joseph W.; Beasley, T. Mark; Weindruch, Richard

    2015-01-01

    The purpose of this study was to determine the effects of hyperinsulinemia/Type 2 diabetes mellitus (HI-T2DM) on hearing impairment using rhesus monkeys to obtain control over diet and lifestyle factors that confound human studies. The study is a retrospective evaluation of rhesus monkeys from the Wisconsin National Primate Research Center (WNPRC) study on caloric restriction and aging. The research questions were the following: 1. Is HI-T2DM related to hearing impairment? 2. If so, what is the site of lesion in the auditory system? and 3. What physiological factors affect the risk of hearing loss in HI-T2DM? Three groups of eight monkeys each were matched by sex and age; the caloric restricted (CR) monkeys had a reduced risk of diabetes, the normal control (NL) group had a normal risk, and the hyperinsulinemia/diabetes (HI-D) group had already developed HI-T2DM. Auditory testing included distortion product otoacoustic emissions (DPOAEs) with f2 frequencies from 2211–8837 Hz and auditory brainstem responses (ABRs) obtained with clicks and tone bursts (8, 16, and 32 kHz). DPOAEs had signal-to-noise ratios 8–17 dB larger in the NL group than in the HID and CR groups, signifying that cochlear function was best in the NL group. ABR thresholds were 5–8 dB better in the NL group than in the HI-D group, although no significant differences across the groups were evident for the thresholds, latencies, interwave intervals, or amplitudes. Correlations were significant for quadratic relations between body mass index (BMI) and DPOAE, with largest DPOAEs for animals in the middle of the BMI range. ABR thresholds elicited with 16 and 32 kHz signals were significantly correlated, positively with BMI and HbA1c, and negatively with KG (glucose tolerance), SI (insulin sensitivity index) and DI (disposition index). These findings suggest that the hearing loss associated with HI-T2DM is predominantly cochlear, and auditory structures underlying the higher frequencies are at risk

  16. Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus

    PubMed Central

    Russo, Giuseppina; Pintaudi, Basilio; Giorda, Carlo; Lucisano, Giuseppe; Nicolucci, Antonio; Cristofaro, Maria Rosaria; Suraci, Concetta; Mulas, Maria Franca; Napoli, Angela; Rossi, Maria Chiara; Manicardi, Valeria

    2015-01-01

    Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men. Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM. Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P < 0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups. Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk. PMID:25873960

  17. Mortality Measurement at Advanced Ages: A Study of the Social Security Administration Death Master File.

    PubMed

    Gavrilov, Leonid A; Gavrilova, Natalia S

    2011-01-01

    Accurate estimates of mortality at advanced ages are essential to improving forecasts of mortality and the population size of the oldest old age group. However, estimation of hazard rates at extremely old ages poses serious challenges to researchers: (1) The observed mortality deceleration may be at least partially an artifact of mixing different birth cohorts with different mortality (heterogeneity effect); (2) standard assumptions of hazard rate estimates may be invalid when risk of death is extremely high at old ages and (3) ages of very old people may be exaggerated. One way of obtaining estimates of mortality at extreme ages is to pool together international records of persons surviving to extreme ages with subsequent efforts of strict age validation. This approach helps researchers to resolve the third of the above-mentioned problems but does not resolve the first two problems because of inevitable data heterogeneity when data for people belonging to different birth cohorts and countries are pooled together. In this paper we propose an alternative approach, which gives an opportunity to resolve the first two problems by compiling data for more homogeneous single-year birth cohorts with hazard rates measured at narrow (monthly) age intervals. Possible ways of resolving the third problem of hazard rate estimation are elaborated. This approach is based on data from the Social Security Administration Death Master File (DMF). Some birth cohorts covered by DMF could be studied by the method of extinct generations. Availability of month of birth and month of death information provides a unique opportunity to obtain hazard rate estimates for every month of age. Study of several single-year extinct birth cohorts shows that mortality trajectory at advanced ages follows the Gompertz law up to the ages 102-105 years without a noticeable deceleration. Earlier reports of mortality deceleration (deviation of mortality from the Gompertz law) at ages below 100 appear to be

  18. Mortality Measurement at Advanced Ages: A Study of the Social Security Administration Death Master File

    PubMed Central

    Gavrilov, Leonid A.; Gavrilova, Natalia S.

    2011-01-01

    Accurate estimates of mortality at advanced ages are essential to improving forecasts of mortality and the population size of the oldest old age group. However, estimation of hazard rates at extremely old ages poses serious challenges to researchers: (1) The observed mortality deceleration may be at least partially an artifact of mixing different birth cohorts with different mortality (heterogeneity effect); (2) standard assumptions of hazard rate estimates may be invalid when risk of death is extremely high at old ages and (3) ages of very old people may be exaggerated. One way of obtaining estimates of mortality at extreme ages is to pool together international records of persons surviving to extreme ages with subsequent efforts of strict age validation. This approach helps researchers to resolve the third of the above-mentioned problems but does not resolve the first two problems because of inevitable data heterogeneity when data for people belonging to different birth cohorts and countries are pooled together. In this paper we propose an alternative approach, which gives an opportunity to resolve the first two problems by compiling data for more homogeneous single-year birth cohorts with hazard rates measured at narrow (monthly) age intervals. Possible ways of resolving the third problem of hazard rate estimation are elaborated. This approach is based on data from the Social Security Administration Death Master File (DMF). Some birth cohorts covered by DMF could be studied by the method of extinct generations. Availability of month of birth and month of death information provides a unique opportunity to obtain hazard rate estimates for every month of age. Study of several single-year extinct birth cohorts shows that mortality trajectory at advanced ages follows the Gompertz law up to the ages 102–105 years without a noticeable deceleration. Earlier reports of mortality deceleration (deviation of mortality from the Gompertz law) at ages below 100 appear to be

  19. Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end product-induced protein arginine methyltranferase-1 expression.

    PubMed

    Ojima, Ayako; Ishibashi, Yuji; Matsui, Takanori; Maeda, Sayaka; Nishino, Yuri; Takeuchi, Masayoshi; Fukami, Kei; Yamagishi, Sho-ichi

    2013-01-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, contributes to diabetic nephropathy. We have found that glucagon-like peptide-1 (GLP-1) inhibits the AGE-induced inflammatory reactions in endothelial cells. However, effects of GLP-1 on the AGE-RAGE-ADMA axis are unknown. This study examined the effects of GLP-1 on reactive oxygen species (ROS) generation, gene expression of protein arginine methyltransfetase-1 (PRMT-1), an enzyme that mainly generates ADMA, and ADMA levels in human proximal tubular cells. Streptozotocin-induced diabetic rats received continuous i.p. infusion of 0.3 μg of vehicle or 1.5 μg of the GLP-1 analog exendin-4 per kilogram of body weight for 2 weeks. We further investigated whether and how exendin-4 treatment reduced ADMA levels and renal damage in streptozotocin-induced diabetic rats. GLP-1 inhibited the AGE-induced RAGE and PRMT-1 gene expression, ROS, and ADMA generation in tubular cells, which were blocked by small-interfering RNAs raised against GLP-1 receptor. Exendin-4 treatment decreased gene expression of Rage, Prmt-1, Icam-1, and Mcp-1 and ADMA level; reduced urinary excretions of 8-hydroxy-2'-deoxyguanosine and albumin; and improved histopathologic changes of the kidney in diabetic rats. Our present study suggests that GLP-1 receptor agonist may inhibit the AGE-RAGE-mediated ADMA generation by suppressing PRMT-1 expression via inhibition of ROS generation, thereby protecting against the development and progression of diabetic nephropathy.

  20. A prospective observational study of quality of diabetes care in a shared care setting: trends and age differences (ZODIAC-19)

    PubMed Central

    van Hateren, Kornelis J J; Drion, Iefke; Kleefstra, Nanne; Groenier, Klaas H; Houweling, Sebastiaan T; van der Meer, Klaas; Bilo, Henk J G

    2012-01-01

    Objective The Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study was initiated in 1998 to investigate the effects of shared care for patients with type 2 diabetes mellitus (T2DM) in the Netherlands, and to reduce the number of diabetes-related complications. Benchmarking the performance of diabetes care was and is an important aspect of this study. We aimed to investigate trends in diabetes care, within the ZODIAC study for a wide variety of quality indicators during a long follow-up period (1998–2008), with special interest for different age groups. Design Prospective observational cohort study. Setting Primary care, Zwolle, The Netherlands. Participants Patients with T2DM. Methods A dataset of quality measures was collected annually during the patient's visit to the practice nurse or general practitioner. Linear time trends from 1998 to 2008 were estimated using linear mixed models in which we adjusted for age and gender. Age was included in the model as a categorical variable: for each follow-up year all participants were categorised into the categories <60, 60–75 and >75 years. Differences in trends between the age categories were investigated by adding an interaction term to the model. Results The number of patients who were reported to participate increased in the period 1998–2008 from 1622 to 27 438. All quality indicators improved in this study, except for body mass index. The prevalence albuminuria decreased in an 11-year-period from 42% to 21%. No relevant differences between the trends for the three age categories were observed. During all years of follow-up, mean blood pressure and body mass index were the lowest and highest, respectively, in the group of patients <60 years (data not shown). Conclusions Quality of diabetes care within the Dutch ZODIAC study, a shared care project, has considerably improved in the period 1998–2008. There were no relevant differences between trends across various age categories

  1. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    PubMed

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M; Mahmoudi, Morteza; De Rooij, Felix W M; Sijbrands, Eric; Peppelenbosch, Maikel P; Rezaee, Farhad

    2015-10-06

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

  2. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    PubMed Central

    Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs. PMID:26337083

  3. Advancing age increases sperm chromatin damage and impairs fertility in peroxiredoxin 6 null mice

    PubMed Central

    Ozkosem, Burak; Feinstein, Sheldon I.; Fisher, Aron B.; O’Flaherty, Cristian

    2015-01-01

    Due to socioeconomic factors, more couples are choosing to delay conception than ever. Increasing average maternal and paternal age in developed countries over the past 40 years has raised the question of how aging affects reproductive success of males and females. Since oxidative stress in the male reproductive tract increases with age, we investigated the impact of advanced paternal age on the integrity of sperm nucleus and reproductive success of males by using a Prdx6−/− mouse model. We compared sperm motility, cytoplasmic droplet retention sperm chromatin quality and reproductive outcomes of young (2-month-old), adult (8-month-old), and old (20-month-old) Prdx6−/− males with their age-matched wild type (WT) controls. Absence of PRDX6 caused age-dependent impairment of sperm motility and sperm maturation and increased sperm DNA fragmentation and oxidation as well as decreased sperm DNA compaction and protamination. Litter size, total number of litters and total number of pups per male were significantly lower in Prdx6−/− males compared to WT controls. These abnormal reproductive outcomes were severely affected by age in Prdx6−/− males. In conclusion, the advanced paternal age affects sperm chromatin integrity and fertility more severely in the absence of PRDX6, suggesting a protective role of PRDX6 in age-associated decline in the sperm quality and fertility in mice. PMID:25796034

  4. Advancing Age, Advantaged Youth: Parental Age and the Transmission of Resources to Children

    ERIC Educational Resources Information Center

    Powell, Brian; Steelman, Lala Carr; Carini, Robert M.

    2006-01-01

    Using data from the National Education Longitudinal Study of 1988, we identify parental age as influential in the parental provision of economic resources, social capital and cultural capital to adolescents, as well as in parental educational expectations for their children. At the bivariate level, the relationship is curvilinear, suggesting that…

  5. Age-dependent systemic DNA damage in early Type 2 Diabetes mellitus.

    PubMed

    Rogulj, Dinko; El Aklouk, Ismail; Konjevoda, Paško; Ljubić, Spomenka; Pibernik Okanović, Mirjana; Barbir, Ante; Luburić, Marijana; Radman, Maja; Budinski, Ninoslav; Vučić Lovrenčić, Marijana

    2017-03-30

    Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM. Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, gamma-glutamyl transpeptidase (GGT), uric acid, C-reactive protein (CRP), total leukocyte/neutrophil count, and urinary 8-hidroxy-deoxyguanosine (u-8-OHdG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications. BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-OHdG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Higher 8-OHdG in older subjects with T2DM suggests that both aging process and diabetes could contribute to the development of DNA damage. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

  6. Shear wave elastography imaging for assessing the chronic pathologic changes in advanced diabetic kidney disease

    PubMed Central

    Hassan, Kamal; Loberant, Norman; Abbas, Nur; Fadi, Hassan; Shadia, Hassan; Khazim, Khaled

    2016-01-01

    Objective The assessment of the grade of renal fibrosis in diabetic kidney disease (DKD) requires renal biopsy, which may be associated with certain risks. To assess the severity of chronic pathologic changes in DKD, we performed a quantitative analysis of renal parenchymal stiffness in advanced DKD, using shear wave elastography (SWE) imaging. Patients and methods Twenty-nine diabetic patients with chronic kidney disease (CKD) grades 3–4 due to DKD, and 23 healthy subjects were enrolled. Combined conventional ultrasound and SWE imaging were performed on all participants. The length, width, and cortical thickness and stiffness were recorded for each kidney. Results Cortical thickness was lower in patients with DKD than in healthy subjects (13.8±2.2 vs 14.8±1.6 mm; P=0.002) and in DKD patients with CKD grade 4 than in those with grade 3 (13.0±3.5 vs 14.7±2.1 mm; P<0.001). Cortical stiffness was greater in patients with DKD than in healthy subjects (23.72±14.33 vs 9.02±2.42 kPa; P<0.001), in DKD patients with CKD grade 4 than in those with grade 3 (30.4±16.2 vs 14.6±8.1 kPa; P<0.001), and in DKD patients with CKD grade 3b, than in those with CKD grade 3a (15.7±6.7 vs 11.0±4.2 kPa; P=0.03). Daily proteinuria was higher in DKD patients with CKD grade 4 than in those with grade 3 (5.52±0.96 vs 1.13±0.72; P=0.001), and in DKD patients with CKD grade 3b, than in those with CKD grade 3a (1.59±0.59 vs 0.77±0.48; P<0.001). Cortical stiffness was inversely correlated with the estimated glomerular filtration rate (r=−0.65, P<0.001) and with cortical thickness (r=−0.43, P<0.001) in patients with DKD. Conclusions In patients with advanced DKD, SWE imaging may be utilized as a simple and practical method for quantitative evaluation of the chronic morphological changes and for the differentiation between CKD grades. PMID:27853373

  7. Diabetes.

    PubMed

    Lomberk, Gwen

    2009-01-01

    Pancreatologists have often divided research of the pancreas based upon the origin of the function or disease, namely the endocrine or exocrine pancreas. In fact, as a result, many of our meetings and conferences have followed separate paths. Interestingly, among patients with chronic pancreatitis and pancreatic cancer, both disorders of the exocrine pancreas, diabetes is common. However, the clinical features of the diabetes associated with these two differ. Peripheral insulin resistance and hyperinsulinemia are the predominant diabetic traits in pancreatic cancer, while reduced islet cell mass and impaired insulin secretion are observed more often in chronic pancreatitis. The causal relationship between diabetes and pancreatic cancer remains an intriguing but unanswered question. Since diabetes often precedes pancreatic cancer, it is regarded as a potential risk factor for malignancy. On the other hand, there remains the possibility that pancreatic cancer secretes diabetogenic factors. Regardless of how the science ultimately illuminates this issue, there is increasing interest in utilizing screening for diabetes to aid early detection of pancreatic tumor lesions. Therefore, in this issue of Pancreatology and the Web, we explore the topic of diabetes to keep us alert to this very important association, even if we study diseases of the exocrine pancreas.

  8. Exercise interventions in polypathological aging patients that coexist with diabetes mellitus: improving functional status and quality of life.

    PubMed

    Cadore, Eduardo Lusa; Izquierdo, Mikel

    2015-06-01

    In elderly populations, diabetes is associated with reduced muscle strength, poor muscle quality, and accelerated loss of muscle mass. In addition, diabetes mellitus increases risk for accelerated aging and for the development of frailty syndrome. This disease is also associated with a polypathological condition, and its complications progressively affect quality of life and survival. Exercise interventions, including resistance training, represent the cornerstones of diabetes management, especially in patients at severe functional decline. This review manuscript aimed to describe the beneficial effects of different exercise interventions on the functional capacity of elderly diabetics, including those at polypathological condition. The SciELO, Science Citation Index, MEDLINE, Scopus, SPORTDiscus, and ScienceDirect databases were searched from 1980 to 2015 for articles published from original scientific investigations. In addition to the beneficial effects of exercise interventions on glycemic control, and on the cardiovascular risk factors associated with diabetes, physical exercise is an effective intervention to improve muscle strength, power output, and aerobic power and functional capacity in elderly diabetic patients. Thus, a combination of resistance and endurance training is the most effective exercise intervention to promote overall physical fitness in these patients. In addition, in diabetic patients with frailty and severe functional decline, a multicomponent exercise program including strength and power training, balance exercises, and gait retraining may be an effective intervention to reduce falls and improve functional capacity and quality of life in these patients.

  9. Diabetes Mellitus and Younger Age Are Risk Factors for Hyperphosphatemia in Peritoneal Dialysis Patients.

    PubMed

    Imtiaz, Rameez; Hawken, Steven; McCormick, Brendan B; Leung, Simon; Hiremath, Swapnil; Zimmerman, Deborah L

    2017-02-17

    Hyperphosphatemia has been associated with adverse outcomes in patients with end stage kidney disease (ESKD). The purpose of this study was to determine risk factors for hyperphosphatemia in ESKD patients treated with peritoneal dialysis (PD). This information will be used to develop a patient specific phosphate binder application to facilitate patient self-management of serum phosphate. Adult PD patients documented their food, beverage, and phosphate binder intake for three days using a dietitian developed food journal. Phosphate content of meals was calculated using the ESHA Food Processor SQL Software (ESHA Research, Salem, UT, USA). Clinic biochemistry tests and an adequacy assessment (Baxter Adequest program) were done. Univariate logistic regression was used to determine predictors of serum phosphate >1.78 mmol/L. A multivariable logistic regression model was then fit including those variables that achieved a significance level of p < 0.20 in univariate analyses. Sixty patients (38 men, 22 women) completed the protocol; they were 60 ± 17 years old, 50% had a history of diabetes mellitus (DM) and 33% had hyperphosphatemia (PO₄ > 1.78 mmol/L). In univariate analysis, the variables associated with an increased risk of hyperphosphatemia with a p-value < 0.2 were male gender (p = 0.13), younger age (0.07), presence of DM (0.005), higher dose of calcium carbonate (0.08), higher parathyroid serum concentration (0.08), lower phosphate intake (0.03), lower measured glomerular filtration rate (0.15), higher phosphate excretion (0.11), and a higher body mass index (0.15). After multivariable logistic regression analysis, younger age (odds ratio (OR) 0.023 per decade, 95% confidence interval (CI) 0.00065 to 0.455; p = 0.012), presence of diabetes (OR 11.40, 95 CI 2.82 to 61.55; p = 0.0003), and measured GFR (OR 0.052 per mL/min decrease; 95% CI 0.0025 to 0.66) were associated with hyperphosphatemia. Our results support that younger age and diabetes mellitus are

  10. Diabetes Mellitus and Younger Age Are Risk Factors for Hyperphosphatemia in Peritoneal Dialysis Patients

    PubMed Central

    Imtiaz, Rameez; Hawken, Steven; McCormick, Brendan B.; Leung, Simon; Hiremath, Swapnil; Zimmerman, Deborah L.

    2017-01-01

    Hyperphosphatemia has been associated with adverse outcomes in patients with end stage kidney disease (ESKD). The purpose of this study was to determine risk factors for hyperphosphatemia in ESKD patients treated with peritoneal dialysis (PD). This information will be used to develop a patient specific phosphate binder application to facilitate patient self-management of serum phosphate. Adult PD patients documented their food, beverage, and phosphate binder intake for three days using a dietitian developed food journal. Phosphate content of meals was calculated using the ESHA Food Processor SQL Software (ESHA Research, Salem, UT, USA). Clinic biochemistry tests and an adequacy assessment (Baxter Adequest program) were done. Univariate logistic regression was used to determine predictors of serum phosphate >1.78 mmol/L. A multivariable logistic regression model was then fit including those variables that achieved a significance level of p < 0.20 in univariate analyses. Sixty patients (38 men, 22 women) completed the protocol; they were 60 ± 17 years old, 50% had a history of diabetes mellitus (DM) and 33% had hyperphosphatemia (PO4 > 1.78 mmol/L). In univariate analysis, the variables associated with an increased risk of hyperphosphatemia with a p-value < 0.2 were male gender (p = 0.13), younger age (0.07), presence of DM (0.005), higher dose of calcium carbonate (0.08), higher parathyroid serum concentration (0.08), lower phosphate intake (0.03), lower measured glomerular filtration rate (0.15), higher phosphate excretion (0.11), and a higher body mass index (0.15). After multivariable logistic regression analysis, younger age (odds ratio (OR) 0.023 per decade, 95% confidence interval (CI) 0.00065 to 0.455; p = 0.012), presence of diabetes (OR 11.40, 95 CI 2.82 to 61.55; p = 0.0003), and measured GFR (OR 0.052 per mL/min decrease; 95% CI 0.0025 to 0.66) were associated with hyperphosphatemia. Our results support that younger age and diabetes mellitus are

  11. Advancing Age and 30-Day Adverse Outcomes Following Non-Emergent General Surgical Operations

    PubMed Central

    Gajdos, Csaba; Kile, Deidre; Hawn, Mary T.; Finlayson, Emily; Henderson, William G.; Robinson, Thomas N.

    2014-01-01

    Background While some single center studies have demonstrated that major surgical operations are safe to perform in older adults, most multicenter database studies find advancing age to independently predict adverse postoperative outcomes. We hypothesized that thirty-day postoperative mortality, complications, failure to rescue rates and postoperative length of stay will increase with advancing age. Design Retrospective cohort study. Setting Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participants Patients undergoing non-emergent major general surgical operations between 2005 and 2008 were studied. Measures Postoperative outcomes of interest were complications occurring within 30 days of the index operation, return to OR within 30 days, failure to rescue after a postoperative complication, post-surgical length of stay and 30 day mortality. Results A total of 165,600 patients were studied. The rates of postoperative mortality, overall morbidity, and each type of postoperative complication increased as age increased. The rates of failure to rescue after each type of postoperative complication also increased with age. Mortality rates in patients ≥80 following renal insufficiency (43.3%), stroke (36.5%), myocardial infarction (35.6%), and pulmonary complications (25-39%) were particularly high. Median postoperative length of stay increased with age following surgical site infection, UTI, pneumonia, return to OR, and overall morbidity, but not after venous thromboembolism, stroke, myocardial infarction, renal insufficiency, failure to wean from the ventilator or reintubations. Conclusion Thirty-day mortality, complications and failure to rescue rates increase with advancing age following non-emergent general surgical operations. Patients over 80 years of age have especially high mortality following renal, cardiovascular, and pulmonary complications. As patient age advances, surgeons need to be

  12. Comparison of the nerve fiber layer of type 2 diabetic patients without glaucoma with normal subjects of the same age and sex

    PubMed Central

    Takis, Alexandros; Alonistiotis, Dimitrios; Panagiotidis, Dimitrios; Ioannou, Nikolaos; Papaconstantinou, Dimitris; Theodossiadis, Panagiotis

    2014-01-01

    Background The retinal nerve fiber layer (RNFL) thickness in patients with diabetes mellitus type 2 was compared to normal subjects of similar age and sex, having first excluded any risk factors for glaucoma. The correlation between the RNFL thickness and the severity of diabetic retinopathy was investigated at its primary stages and with other ocular and diabetic parameters. Methods A prospective, case series study was carried out. Twenty-seven diabetic patients without diabetic retinopathy, 24 diabetic patients with mild retinopathy, and 25 normal, age-matched subjects underwent a complete ophthalmological examination and imaging with scanning laser polarimetry for the evaluation of the RNFL. Multivariate analysis was applied in order to investigate the correlation between RNFL and diabetic parameters, such as age, duration of diabetes, insulin therapy, levels of glycosylated hemoglobin; and ocular parameters, such as cup to disc ratio, levels of normal intraocular pressure, and central corneal thickness. Results The mean inferior average of RNFL and the temporal-superior-nasal-inferior-temporal standard deviation were statistically significantly lower in both diabetic groups, and the nerve fiber index was higher (P=0.04) compared to the normal group. There was no statistically significant difference between the diabetic groups. The factor analysis showed no significant correlation between the RNFL and the previously mentioned diabetic and ocular parameters. Conclusion The existence of diabetes should be seriously considered in evaluating the results of scanning laser polarimetry. Multivariate analysis for RNFL was used for the first time. PMID:24596452

  13. Mindful Sustainable Aging: Advancing a Comprehensive Approach to the Challenges and Opportunities of Old Age

    PubMed Central

    Nilsson, Håkan; Bülow, Pia H.; Kazemi, Ali

    2015-01-01

    The primary aim of this article is to present a new concept called mindful sustainable aging (MSA), which is informed by mindfulness practices that support the physical, the mental, and especially, the social and the existential dimensions of old life. The concept of MSA is discussed and compared with four influential psychosocial theories in the field of gerontology, i.e., activity theory, disengagement theory, successful aging theory and gerotranscendence theory. The article ends with reviewing research on how mindfulness practice can help to manage, diminish and/or improve a number of serious physical conditions that are common among older people. The potential of mindfulness when it comes to facilitating for older adults in their quest for spiritual and existential meaning is discussed extensively throughout the article. PMID:27247673

  14. Mindful Sustainable Aging: Advancing a Comprehensive Approach to the Challenges and Opportunities of Old Age.

    PubMed

    Nilsson, Håkan; Bülow, Pia H; Kazemi, Ali

    2015-08-01

    The primary aim of this article is to present a new concept called mindful sustainable aging (MSA), which is informed by mindfulness practices that support the physical, the mental, and especially, the social and the existential dimensions of old life. The concept of MSA is discussed and compared with four influential psychosocial theories in the field of gerontology, i.e., activity theory, disengagement theory, successful aging theory and gerotranscendence theory. The article ends with reviewing research on how mindfulness practice can help to manage, diminish and/or improve a number of serious physical conditions that are common among older people. The potential of mindfulness when it comes to facilitating for older adults in their quest for spiritual and existential meaning is discussed extensively throughout the article.

  15. Impact of population aging on trends in diabetes prevalence: A meta-regression analysis of 160,000 Japanese adults

    PubMed Central

    Charvat, Hadrien; Goto, Atsushi; Goto, Maki; Inoue, Machiko; Heianza, Yoriko; Arase, Yasuji; Sone, Hirohito; Nakagami, Tomoko; Song, Xin; Qiao, Qing; Tuomilehto, Jaakko; Tsugane, Shoichiro; Noda, Mitsuhiko; Inoue, Manami

    2015-01-01

    Aims/Introduction To provide age- and sex-specific trends, age-standardized trends, and projections of diabetes prevalence through the year 2030 in the Japanese adult population. Materials and Methods In the present meta-regression analysis, we included 161,087 adults from six studies and nine national health surveys carried out between 1988 and 2011 in Japan. We assessed the prevalence of diabetes using a recorded history of diabetes or, for the population of individuals without known diabetes, either a glycated hemoglobin level of ≥6.5% (48 mmol/mol) or the 1999 World Health Organization criteria (i.e., a fasting plasma glucose level of ≥126 mg/dL and/or 2-h glucose level of ≥200 mg/dL in the 75-g oral glucose tolerance test). Results For both sexes, prevalence appeared to remain unchanged over the years in all age categories except for men aged 70 years or older, in whom a significant increase in prevalence with time was observed. Age-standardized diabetes prevalence estimates based on the Japanese population of the corresponding year showed marked increasing trends: diabetes prevalence was 6.1% among women (95% confidence interval [CI] 5.5–6.7), 9.9% (95% CI 9.2–10.6) among men, and 7.9% (95% CI 7.5–8.4) among the total population in 2010, and was expected to rise by 2030 to 6.7% (95% CI 5.2–9.2), 13.1% (95% CI 10.9–16.7) and 9.8% (95% CI 8.5–12.0), respectively. In contrast, the age-standardized diabetes prevalence using a fixed population appeared to remain unchanged. Conclusions This large-scale meta-regression analysis shows that a substantial increase in diabetes prevalence is expected in Japan during the next few decades, mainly as a result of the aging of the adult population. PMID:26417410

  16. Surface exposure dating of Little Ice Age ice cap advances on Disko Island, West Greenland

    NASA Astrophysics Data System (ADS)

    Lane, Timothy; Jomelli, Vincent; Rinterknecht, Vincent; Brunstein, Daniel; Schimmelpfennig, Irene; Swingedouw, Didier; Favier, Vincent; Masson-Delmotte, Valerie

    2015-04-01

    Little Ice Age (LIA: 1200-1920 AD) glacier advances in Greenland often form the most extensive positions of Greenland Ice Sheet (GrIS) ice cap and margins since the Early Holocene. Across Greenland these advances are commonly represented by un-vegetated moraines, usually within 1-5 km of the present ice margin. However, chronological constraints on glacier advances during this period are sparse, meaning that GrIS and ice cap behavior and advance/retreat chronology remains poorly understood during this period. At present the majority of ages are based on historical accounts, ice core data, and radiocarbon ages from proglacial threshold lakes. However, developments in the accuracy and precision of surface exposure methods allow dating of LIA moraine boulders, permitting an opportunity to better understand of ice dynamics during this period. Geomorphological mapping and surface exposure dating (36Cl) were used to interpret moraine deposits from the Lyngmarksbræen on Disko Island, West Greenland. A Positive Degree Day (PDD) model was used to estimate Equilibrium Line Altitude (ELA) and mass balance changes for two distinct paleo-glacial extents. Three moraines (M1, M2, and M3) were mapped in the field, and sampled for 36Cl surface exposure dating. The outermost moraine (M1) was of clearly different morphology to the inner moraines, and present only in small fragments. M2 and M3 were distinct arcuate termino-lateral moraines within 50 m of one another, 1.5 km from the present ice margin. The weighted average of four 36Cl ages from M1 returned an early Holocene age of 8.4 ± 0.6 ka. M2 (four samples) returned an age of 0.57 ± 0.04 ka (1441 AD) and M3 (four samples) returned an age of 0.28 ± 0.02 ka (1732 AD). These surface exposure ages represent the first robustly dated Greenlandic ice cap moraine sequence from the LIA. The two periods of ice cap advance and marginal stabilisation are similar to recorded periods of LIA GrIS advance in west Greenland, constrained

  17. Cosmogenic 10Be constraints on Little Ice Age glacial advances in the eastern Tian Shan, China

    NASA Astrophysics Data System (ADS)

    Li, Yanan; Li, Yingkui; Harbor, Jon; Liu, Gengnian; Yi, Chaolu; Caffee, Marc W.

    2016-04-01

    Presumed Little Ice Age (LIA) glacial advances, represented by a set of fresh, sharp-crested, boulder covered and compact moraines a few hundred meters downstream from modern glaciers, have been widely recognized in the Central Asian highlands. However, few studies have constrained the formation ages of these moraines. We report 31 10Be exposure ages from presumed LIA moraines in six glacial valleys in the Urumqi River headwater area and the Haxilegen Pass area of the eastern Tian Shan, China. Our results reveal that the maximum LIA glacial extent occurred mainly around 430 ± 100 yr, a cold and wet period as indicated by proxy data from ice cores, tree rings, and lake sediments in Central Asia. We also dated a later glacial advance to 270 ± 55 yr. However, 10Be exposure ages on several presumed LIA moraines in front of small, thin glaciers are widely scattered and much older than the globally recognized timing of the LIA. Historical topographic maps indicate that most glaciers were more extensive in the early 1960s, and two of our 10Be sample sites were located close to the ice front at that time. Boulders transported by these small and thin glaciers may be reworked from deposits originally formed prior to the LIA glacial advances, producing apparently old and widely scattered exposure ages due to varied nuclide inheritance. Other published ages indicated an earlier LIA advance around 790 ± 300 yr in the easternmost Tian Shan, but in our study area the more extensive advance around 430 ± 100 yr likely reworked or covered deposits from this earlier event.

  18. Usefulness of Photodynamic Diagnosis and Therapy using Talaporfin Sodium for an Advanced-aged Patient with Inoperable Gastric Cancer (a secondary publication)

    PubMed Central

    Oinuma, Takeshi

    2014-01-01

    Background and aims: In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of elderly people being treated for cancer is increasing concomitantly. However, with the increase in age, the numbers of prior complications also increase. This is especially so in the advanced-aged patients, defined in Japan as those over the age of 85. Such complications may be too high risk for radical surgery and a less invasive treatment is warranted. Photodynamic therapy (PDT) is a noninvasive treatment approved by the Japanese National Health Insurance for the treatment of early stage superficial type esophageal and gastric cancers, early stage uterine cervical cancers and dysplasia, and early and advanced lung cancer. We report herein on the efficacy of palliative PDT using talaporfin sodium (Laserphyrin®) for a case of inoperable gastric cancer. Material and methods: The patient was an 87-year-old-man, a diabetic with histories of diabetic nephropathy, cerebral infarction and myocardial infarction. This patient was first diagnosed as having gastric cancer in 2007 but surgery and chemotherapy were contraindicated due to his poor physical status and poor renal function, respectively, owing to the anticipated side effects. The patient was referred to our institution after hearing of PDT in 2009. He was treated with 1 course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with photodynamic diagnosis (PDD) during the period from September, 2009 to June, 2011. Results: The massive gastric cancer located in the cardia was successfully treated with 4 PDT sessions without any serious complications; therefore the patient was able to orally ingest food until his death due to natural causes other than the cancer, in October, 2011. Conclusion: Talaporfin sodium PDT is safe and effective treatment for advanced-aged patients suffering from inoperable gastric cancer. PMID

  19. 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

  20. Comorbidity and health care visit burden in working-age commercially insured patients with diabetic macular edema

    PubMed Central

    Kiss, Szilárd; Chandwani, Hitesh S; Cole, Ashley L; Patel, Vaishali D; Lunacsek, Orsolya E; Dugel, Pravin U

    2016-01-01

    Purpose To examine the comorbidity profile and update estimates of health care resource utilization for commercially insured, working-age adults with diabetic macular edema (DME) relative to a matched comparison group of diabetic adults without DME. Additional comparisons were made in the subgroup of pseudophakic patients. Patients and methods A retrospective matched-cohort study of commercially insured diabetic adults aged 18–63 years was conducted using medical and outpatient pharmacy claims (July 1, 2008–June 30, 2013). Outcomes included diabetes-related and ocular comorbidities and health care resource utilization (any health care visit days, outpatient visit days, inpatient visit days, emergency room visits, eye care-related visit days, unique medications) in the 12-month post-index period. Results All diabetes-related and ocular comorbidities were significantly more prevalent in DME cases versus non-DME controls (P<0.05). A significantly greater proportion of DME cases utilized eye care-related visits compared with non-DME controls (P<0.001). DME cases had almost twice the mean number of total health care visit days compared to non-DME controls (28.6 vs 16.9 days, P<0.001), with a minority of visit days being eye care-related (mean 5.1 vs 1.5 days, P<0.001). Similar trends were observed in pseudophakic cohorts. Conclusion This working-age DME population experienced a mean of 29 health care visit days per year. Eye care-related visit days were a minority of the overall visit burden (mean 5 days) emphasizing the trade-offs DME patients face between managing DME and their overall diabetic disease. Insights into the complex comorbidity profile and health care needs of diabetic patients with DME will better inform treatment decisions and help optimize disease management. PMID:27994438

  1. Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans.

    PubMed Central

    Duggirala, R; Blangero, J; Almasy, L; Dyer, T D; Williams, K L; Leach, R J; O'Connell, P; Stern, M P

    1999-01-01

    Since little is known about chromosomal locations harboring type 2 diabetes-susceptibility genes, we conducted a genomewide scan for such genes in a Mexican American population. We used data from 27 low-income extended Mexican American pedigrees consisting of 440 individuals for whom genotypic data are available for 379 markers. We used a variance-components technique to conduct multipoint linkage analyses for two phenotypes: type 2 diabetes (a discrete trait) and age at onset of diabetes (a truncated quantitative trait). For the multipoint analyses, a subset of 295 markers was selected on the basis of optimal spacing and informativeness. We found significant evidence that a susceptibility locus near the marker D10S587 on chromosome 10q influences age at onset of diabetes (LOD score 3.75) and is also linked with type 2 diabetes itself (LOD score 2.88). This susceptibility locus explains 63.8%+/-9.9% (P=. 000016) of the total phenotypic variation in age at onset of diabetes and 65.7%+/-10.9% (P=.000135) of the total variation in liability to type 2 diabetes. Weaker evidence was found for linkage of diabetes and of age at onset to regions on chromosomes 3p, 4q, and 9p. In conclusion, our strongest evidence for linkage to both age at onset of diabetes and type 2 diabetes itself in the Mexican American population was for a region on chromosome 10q. PMID:10090898

  2. Recent advances in understanding the genetic architecture of type 2 diabetes

    PubMed Central

    Mohlke, Karen L.; Boehnke, Michael

    2015-01-01

    Genome-wide association (GWAS) and sequencing studies are providing new insights into the genetic basis of type 2 diabetes (T2D) and the inter-individual variation in glycemic traits, including levels of glucose, insulin, proinsulin and hemoglobin A1c (HbA1c). At the end of 2011, established loci (P < 5 × 10−8) totaled 55 for T2D and 32 for glycemic traits. Since then, most new loci have been detected by analyzing common [minor allele frequency (MAF)>0.05] variants in increasingly large sample sizes from populations around the world, and in trans-ancestry studies that successfully combine data from diverse populations. Most recently, advances in sequencing have led to the discovery of four loci for T2D or glycemic traits based on low-frequency (0.005 < MAF ≤ 0.05) variants, and additional low-frequency, potentially functional variants have been identified at GWAS loci. Established published loci now total ∼88 for T2D and 83 for one or more glycemic traits, and many additional loci likely remain to be discovered. Future studies will build on these successes by identifying additional loci and by determining the pathogenic effects of the underlying variants and genes. PMID:26160912

  3. The role of collagen crosslinks in ageing and diabetes - the good, the bad, and the ugly

    PubMed Central

    Snedeker, Jess G.; Gautieri, Alfonso

    2014-01-01

    Summary The non-enzymatic reaction of proteins with glucose (glycation) is a topic of rapidly growing importance in human health and medicine. There is increasing evidence that this reaction plays a central role in ageing and disease of connective tissues. Of particular interest are changes in type-I collagens, long-lived proteins that form the mechanical backbone of connective tissues in nearly every human organ. Despite considerable correlative evidence relating extracellular matrix (ECM) glycation to disease, little is known of how ECM modification by glucose impacts matrix mechanics and damage, cell-matrix interactions, and matrix turnover during aging. More daunting is to understand how these factors interact to cumulatively affect local repair of matrix damage, progression of tissue disease, or systemic health and longevity. This focused review will summarize what is currently known regarding collagen glycation as a potential driver of connective tissue disease. We concentrate attention on tendon as an affected connective tissue with large clinical relevance, and as a tissue that can serve as a useful model tissue for investigation into glycation as a potentially critical player in tissue fibrosis related to ageing and diabetes. PMID:25489547

  4. The Benefits, Limitations, and Cost-Effectiveness of Advanced Technologies in the Management of Patients With Diabetes Mellitus

    PubMed Central

    Vigersky, Robert A.

    2015-01-01

    Background: Hypoglycemia mitigation is critical for appropriately managing patients with diabetes. Advanced technologies are becoming more prevalent in diabetes management, but their benefits have been primarily judged on the basis of hemoglobin A1c. A critical appraisal of the effectiveness and limitations of advanced technologies in reducing both A1c and hypoglycemia rates has not been previously performed. Methods: The cost of hypoglycemia was estimated using literature rates of hypoglycemia events resulting in hospitalizations. A literature search was conducted on the effect on A1c and hypoglycemia of advanced technologies. The cost-effectiveness of continuous subcutaneous insulin infusion (CSII) and real-time continuous glucose monitors (RT-CGM) was reviewed. Results: Severe hypoglycemia in insulin-using patients with diabetes costs $4.9-$12.7 billion. CSII reduces A1c in some but not all studies. CSII improves hypoglycemia in patients with high baseline rates. Bolus calculators improve A1c and improve the fear of hypoglycemia but not hypoglycemia rates. RT-CGM alone and when combined with CSII improve A1c with a neutral effect on hypoglycemia rates. Low-glucose threshold suspend systems reduce hypoglycemia with a neutral effect on A1c, and low-glucose predictive suspend systems reduce hypoglycemia with a small increase in plasma glucose levels. In short-term studies, artificial pancreas systems reduce both hypoglycemia rates and plasma glucose levels. CSII and RT-CGM are cost-effective technologies, but their wide adoption is limited by cost, psychosocial, and educational factors. Conclusions: Most currently available technologies improve A1c with a neutral or improved rate of hypoglycemia. Advanced technologies appear to be cost-effective in diabetes management, especially when including the underlying cost of hypoglycemia. PMID:25555391

  5. Composite estimates of physiological stress, age, and diabetes in American Samoans.

    PubMed

    Crews, Douglas E

    2007-07-01

    Composite estimates of physiological stress such as allostatic load (AL) were developed to help assess cumulative impacts of psychosocial and physical stressors on the body. Physiological responses to stress generally accelerate somatic wear-and-tear and chronic degenerative conditions (CDCs). Following McEwen (Neuropsychopharmacology 22 (1999) 108-124) and others, primary physiological mediators of somatic stress responses include glucocorticoids (cortisol), catecholamines (adrenaline and noradrenaline), and serum dihydroepiandosterone-sulfate (DHEA-S). Conversely, blood pressure (BP), serum HDL and total cholesterol, glycated hemoglobin (HbA1c), and waist/hip (w/h) ratio are modulated by such hormones, thereby acting as secondary mediators of stress response. When these risk factors are aggregated into a composite score, higher stress loads are associated with increased risks for days of school/work missed, functional losses, morbidity, and mortality in US samples. To examine stress loads in American Samoans, data on all 6 secondary mediators along with estimates of body habitus (i.e. height, weight, circumferences, skinfolds) and physiology (i.e. fasting insulin, LDLc, triglycerides, fasting glucose) were measured on 273 individuals residing on Tutuila Island in 1992. Four combinations of these physiological factors were used to determine composite estimates of stress. These were then assessed by sex for associations with age and the presence of diabetes. Composite estimates of stress load were higher in Samoan women than men. Associations with age tended to be low and negative in men, but positive in women, appearing to reflect cultural circumstances and population history. Stress load scores also were higher among those with diabetes than those without among both men and women. These results suggest that composite estimates of stress may be useful for assessing future risks of CDC's and the senescent processes that may underlie them in cross-cultural research.

  6. THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM

    EPA Science Inventory

    THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM (CHC13). A McDonald, Y M Sey and J E Simmons. NHEERL, ORD, U.S. EPA, RTP, NC.
    Disinfection, by chlorination or by ozonation followed by treatment with either chlorine or chloramine, of water containi...

  7. Influence of neighbourhood socioeconomic position on the transition to type II diabetes in older Mexican Americans: the Sacramento Area Longitudinal Study on Aging

    PubMed Central

    Garcia, Lorena; Lee, Anne; Zeki Al Hazzouri, Adina; Neuhaus, John M; Aiello, Allison; Elfassy, Tali; Haan, Mary N

    2016-01-01

    Objective To examine the influence of neighbourhood socioeconomic position (NSEP) on development of diabetes over time. Design A longitudinal cohort study. Setting The data reported were from the Sacramento Area Latino Study on Aging, a longitudinal study of the health of 1789 older Latinos. Participants Community-dwelling older Mexican Americans residing in the Sacramento Metropolitan Statistical Area. Main outcome Multistate Markov regression were used to model transitions through four possible states over time: 1=normal; 2=pre-diabetic; 3=diabetic; and 4=death without diabetes. Results At baseline, nearly 50% were non-diabetic, 17.5% were pre-diabetic and nearly 33% were diabetic. At the end of follow-up, there were a total of 824 people with type 2 diabetes. In a fully adjusted MSM regression model, among non-diabetics, higher NSEP was not associated with a transition to pre-diabetes. Among non-diabetics, higher NSEP was associated with an increased risk of diabetes (HR=1.66, 95% CI 1.14 to 2.42) and decreased risk of death without diabetes (HR: 0.56, 95% CI 0.33 to 0.96). Among pre-diabetics, higher NSEP was significantly associated with a transition to non-diabetic status (HR: 1.22, 95% CI 0.99 to 1.50). Adjusting for BMI, age, education, physical activity, smoking, alcohol consumption, medical insurance and nativity did not affect this relationship. Conclusions Our findings show that high NSEP poses higher risk of progression from normal to diabetes compared with a lower risk of death without diabetes. This work presents a possibility that these associations are modified by nativity or culture. PMID:27515749

  8. Advanced Colorectal Adenomas in Patients Under 45 Years of Age Are Mostly Sporadic

    PubMed Central

    Nalbantoglu, ILKe; Watson, Rao; Goodwin, Jonathan; Safar, Elyas; Chokshi, Reena V.; Azar, Riad R.; Davidson, Nicholas O.

    2014-01-01

    Background The presence of advanced adenomas in younger individuals is a criterion for Lynch syndrome (LS). However, the utility of screening advanced adenomas for loss of mismatch repair (MMR) protein expression to identify suspected LS remains unclear. Aims Determine the prevalence of MMR defects to understand whether these patients harbor a defined genetic risk for CRC. Methods The study cohort included adult patients ≤45 years of age with advanced adenomas (villous histology, ≥1 cm in diameter, ≥3 polyps of any size) endoscopically removed between 2001 and 2011. Clinical records were reviewed along with detailed pathological review and immunohistochemical MMR analysis. Results A total of 76 (40.1 % male, age 40.6 ± 5.4 years) patients met inclusion and exclusion criteria. Indications for colonoscopy were gastrointestinal (GI) bleeding 39 (51.3 %), CRC in a first-degree relative 17 (22.4 %) and somatic GI symptoms 20 (26.3 %). Index colonoscopy revealed a median of 1 adenoma (range 1–4), mean diameter of 12.9 ±7.1 mm, 40 (52.6 %) with villous histology. The mean follow-up duration was 3.3 ± 2 years. Recurrent adenomas developed in 24 (31.6 %), of which 8 (10.5 %) were advanced adenomas; none of these patients developed CRC. One of 66 (1.5 %) adenomas available for immunohistochemical (IHC) testing revealed loss of MLH1 and PMS2. Conclusions IHC screening of advanced adenomas from patients younger than 45 years of age identified potential LS in one of 64 patients. The low yield of IHC screening in this population suggests that universal IHC screening of advanced adenomas from patients younger than 45 years of age for MMR defects is not an efficient strategy for identifying LS subjects. PMID:24925148

  9. Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification.

    PubMed

    Li, Shi-Yan; Du, Min; Dolence, E Kurt; Fang, Cindy X; Mayer, Gabriele E; Ceylan-Isik, Asli F; LaCour, Karissa H; Yang, Xiaoping; Wilbert, Christopher J; Sreejayan, Nair; Ren, Jun

    2005-04-01

    Evidence suggests that aging, per se, is a major risk factor for cardiac dysfunction. Oxidative modification of cardiac proteins by non-enzymatic glycation, i.e. advanced glycation endproducts (AGEs), has been implicated as a causal factor in the aging process. This study was designed to examine the role of aging on cardiomyocyte contractile function, cardiac protein oxidation and oxidative modification. Mechanical properties were evaluated in ventricular myocytes from young (2-month) and aged (24-26-month) mice using a MyoCam system. The mechanical indices evaluated were peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening/relengthening (+/- dL/dt). Oxidative stress and protein damage were evaluated by glutathione and glutathione disulfide (GSH/GSSG) ratio and protein carbonyl content, respectively. Activation of NAD(P)H oxidase was determined by immunoblotting. Aged myocytes displayed a larger cell cross-sectional area, prolonged TR90, and normal PS, +/- dL/dt and TPS compared with young myocytes. Aged myocytes were less tolerant of high stimulus frequency (from 0.1 to 5 Hz) compared with young myocytes. Oxidative stress and protein oxidative damage were both elevated in the aging group associated with significantly enhanced p47phox but not gp91phox expression. In addition, level of cardiac AGEs was approximately 2.5-fold higher in aged hearts than young ones determined by AGEs-ELISA. A group of proteins with a molecular range between 50 and 75 kDa with pI of 4-7 was distinctively modified in aged heart using one- or two-dimension SDS gel electrophoresis analysis. These data demonstrate cardiac diastolic dysfunction and reduced stress tolerance in aged cardiac myocytes, which may be associated with enhanced cardiac oxidative damage, level of AGEs and protein modification by AGEs.

  10. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation

    SciTech Connect

    Matsui, Takanori; Yamagishi, Sho-ichi; Takeuchi, Masayoshi; Ueda, Seiji; Fukami, Kei; Okuda, Seiya

    2010-07-23

    Research highlights: {yields} Nifedipine inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma}. {yields} GW9662 treatment alone increased RAGE mRNA levels in tubular cells. {yields} Nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-{beta} gene expression in tubular cells, all of which were blocked by GW9662. -- Abstract: There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. We examined here whether and how nifedipine blocked the AGE-induced tubular cell damage. Nifedipine, but not amlodipine, a control CCB, inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}). GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression

  11. Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

    PubMed Central

    Nunley, Karen A.; Ryan, Christopher M.; Jennings, J. Richard; Aizenstein, Howard J.; Zgibor, Janice C.; Costacou, Tina; Boudreau, Robert M.; Miller, Rachel; Orchard, Trevor J.; Saxton, Judith A.

    2015-01-01

    OBJECTIVE The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI

  12. Implications of Advancing Paternal Age: Does It Affect Offspring School Performance?

    PubMed Central

    Svensson, Anna C.; Abel, Kathryn; Dalman, Christina; Magnusson, Cecilia

    2011-01-01

    Average paternal age is increasing in many high income countries, but the implications of this demographic shift for child health and welfare are poorly understood. There is equivocal evidence that children of older fathers are at increased risk of neurodevelopmental disorders and reduced IQ. We therefore report here on the relationship between paternal age and a composite indicator of scholastic achievement during adolescence, i.e. compulsory school leaving grades, among recent birth cohorts in Stockholm County where delayed paternity is notably common. We performed a record-linkage study comprising all individuals in Stockholm County who finished 9 years of compulsory school from 2000 through 2007 (n = 155,875). Data on school leaving grades and parental characteristics were retrieved from administrative and health service registers and analyzed using multiple linear regression. Advancing paternal age at birth was not associated with a decrease in school leaving grades in adolescent offspring. After adjustment for year of graduation, maternal age and parental education, country of birth and parental mental health service use, offspring of fathers aged 50 years or older had on average 0.3 (95% CI −3.8, 4.4) points higher grades than those of fathers aged 30–34 years. In conclusion, advancing paternal age is not associated with poorer school performance in adolescence. Adverse effects of delayed paternity on offspring cognitive function, if any, may be counterbalanced by other potential advantages for children born to older fathers. PMID:21957460

  13. Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)

    EPA Science Inventory

    Susceptibility of Diabetic Rats to Pulmonary and Systemic Effects of Inhaled Photochemically-Aged Atmosphere and Ozone (O3)MC Schladweiler1, SJ Snow2, QT Krantz1, C King1, JD Krug2, N Modak2, A Henriquez3, V Bass4, DJ Miller3, JE Richards1, EH Boykin1, R Jaskot1, MI Gilmour1 and ...

  14. Effects of Two Different Dietary Patterns on Inflammatory Markers, Advanced Glycation End Products and Lipids in Subjects without Type 2 Diabetes: A Randomised Crossover Study.

    PubMed

    Kim, Yoona; Keogh, Jennifer B; Clifton, Peter M

    2017-03-29

    Epidemiological studies suggest that consumption of red and processed meat and refined grains are associated with type 2 diabetes and metabolic syndrome and increased inflammatory and fibrinolytic markers. We hypothesised that a diet high in red and processed meat and refined grains (HMD) would increase inflammatory markers and advanced glycation end products (AGEs) compared with a diet high in dairy, whole grains, nuts and legumes (HWD). We performed a randomised crossover study of two four-week interventions in 51 participants without type 2 diabetes (15 men and 36 women aged 35.1 ± 15.6 years; body mass index: 27.7 ± 6.9 kg/m²). No baseline measurements were performed. Plasma fluorescent AGEs, carboxymethyllysine, glucose, insulin, lipids, hs-CRP, interleukin 6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) were analysed after four weeks on each diet. IL-6, hs-CRP, AGEs and carboxymethyllysine were not different between diets but PAI-1 was higher after the HMD than after HWD ((median and interquartile range) 158, 81 vs. 121, 53 ng/mL p < 0.001). PAI-1 on the HWD diet was inversely correlated with whole grains intake (p = 0.007). PAI-1 was inversely correlated with insulin sensitivity index (r = -0.45; p = 0.001) and positively correlated with serum total cholesterol (r = 0.35; p = 0.012) and serum triglyceride (r = 0.32; p = 0.021) on HMD. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000519651).

  15. Pharmacologic management of types 1 and 2 diabetes mellitus and their complications in women of childbearing age.

    PubMed

    Mukherjee, Mimi S; Coppenrath, Valerie A; Dallinga, Bree A

    2015-02-01

    The numbers of women of childbearing age with pregestational diabetes mellitus (diabetes existing before pregnancy) are increasing, primarily because more patients are developing type 2 diabetes at younger ages. The teratogenicity associated with hyperglycemia in early pregnancy is well documented, and tight glucose control minimizes the risk of congenital malformation. Preconception planning is essential; thus contraception that does not worsen complications of diabetes is desirable. In addition, because contraceptives are not 100% effective, the treatment of elevated blood glucose levels, hypertension, and dyslipidemia in these women requires consideration of unplanned pregnancy. We summarized the literature to aid clinicians in choosing individualized treatment that minimizes risk in case pregnancy occurs and maximizes benefit in preventing the complications of diabetes. In women with well-controlled diabetes without vascular disease, all contraceptive methods are safe. Intrauterine devices are recommended due to their minimal effects on risk factors for diabetic complications and their lack of reliance on patient adherence for efficacy. Among insulins, the insulin analogs-insulin lispro, insulin aspart, and insulin detemir-offer patients greater convenience than regular insulin and NPH insulin, and they are safe in case of unplanned pregnancy. Of the noninsulin agents, glyburide and metformin are the safest during pregnancy, but many of the other agents pose minimal risk as long as they are withdrawn during early pregnancy. The risks and benefits of angiotensin-converting enzyme inhibitors in women with compelling indications must be weighed individually. In hypertensive patients at a high risk for unplanned pregnancy, nifedipine should be considered due to literature supporting its safety during early pregnancy. Pravastatin is recommended for women with dyslipidemia who are using effective contraception because there have been no reports of birth defects with

  16. Evaluation of the antioxidant and anti-glication effects of the hexane extract from Piper auritum leaves in vitro and beneficial activity on oxidative stress and advanced glycation end-product-mediated renal injury in streptozotocin-treated diabetic rats.

    PubMed

    Perez Gutierrez, Rosa Martha; Flores Cotera, Luis B; Gonzalez, Adriana Maria Neira

    2012-10-09

    The aim of this study was to investigate the antioxidant activity of hexane extracts from leaves of Piper auritum (HS). Eight complementary in vitro test methods were used, including inhibition of DPPH· radicals, nitric oxide, superoxide anion, ion-chelating, ABTS, oxygen radical absorbance capacity, β-carotene bleaching and peroxy radical scavenging. The results indicated that HS possesses high antioxidant activity. To add to these finding we tested the effect against oxidative stress in liver, pancreas and kidney in diabetic rats. Low levels of SOD, CAT, GPx and GSH in diabetic rats were reverted to near normal values after treatment with HS. These results suggest that P. auritum prevents oxidative stress, acting as a suppressor of liver cell damage. Given the link between glycation and oxidation, we proposed that HS might possess significant in vitro antiglycation activity. Our data confirmed the inhibitory effect of HS on bovine serum albumin, serum glycosylated protein, glycation of LDL, and glycation hemoglobin. The effect of HS on diabetic renal damage was investigated using streptozotocin-induced diabetic rats. The oral administration of HS at a dose of 200 and 400 mg/kg body weight/day for 28 days significantly reduced advanced glycation endproduct (AGE) formation, elevated renal glucose and thiobarbituric acid-reactive substance levels in the kidneys of diabetic rats. This implies that HS would alleviate the oxidative stress under diabetes through the inhibition of lipid peroxidation. These findings indicate that oxidative stress is increased in the diabetic rat kidney and that HS can prevent renal damage associated with diabetes by attenuating the oxidative stress.

  17. Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention

    PubMed Central

    Wu, Yanling; Ding, Yanping; Tanaka, Yoshimasa; Zhang, Wen

    2014-01-01

    Type 2 diabetes is a serious and common chronic disease resulting from a complex inheritance-environment interaction along with other risk factors such as obesity and sedentary lifestyle. Type 2 diabetes and its complications constitute a major worldwide public health problem, affecting almost all populations in both developed and developing countries with high rates of diabetes-related morbidity and mortality. The prevalence of type 2 diabetes has been increasing exponentially, and a high prevalence rate has been observed in developing countries and in populations undergoing “westernization” or modernization. Multiple risk factors of diabetes, delayed diagnosis until micro- and macro-vascular complications arise, life-threatening complications, failure of the current therapies, and financial costs for the treatment of this disease, make it necessary to develop new efficient therapy strategies and appropriate prevention measures for the control of type 2 diabetes. Herein, we summarize our current understanding about the epidemiology of type 2 diabetes, the roles of genes, lifestyle and other factors contributing to rapid increase in the incidence of type 2 diabetes. The core aims are to bring forward the new therapy strategies and cost-effective intervention trials of type 2 diabetes. PMID:25249787

  18. Immunogenicity of DNA-advanced glycation end product fashioned through glyoxal and arginine in the presence of Fe³⁺: its potential role in prompt recognition of diabetes mellitus auto-antibodies.

    PubMed

    Shahab, Uzma; Tabrez, Shams; Khan, M Salman; Akhter, Firoz; Khan, Mohd Sajid; Saeed, Mohd; Ahmad, Khurshid; Srivastava, A K; Ahmad, Saheem

    2014-08-05

    Glyoxal, methylglyoxal and 3-deoxyglucosones are reactive dicarbonyl compounds, which transform free amino groups of proteins and lipoproteins macromolecule into advanced glycation end-products (AGEs). AGEs play a significant role in the pathophysiology of aging and diabetic complications because of their genotoxic effect. Glyoxal also reacts with free amino group of nucleic acids resulting in the formation of DNA-AGEs. The present study reports the genotoxicity and immunogenicity of AGEs formed by Glyoxal-Arginine-Fe(3+) (G-Arg-Fe(3+)) system as a glycating agent. Immunogenicity of native and G-Arg-Fe(3+)-DNA was probed in female rabbits. Immunofluorescence suggests the presence of immune complex deposition in the kidney section of immunized rabbits. Spectroscopic analysis and melting temperature indicates the structural modification in the human DNA. The modified human DNA is found to be highly immunogenic, whereas unmodified form was simply non-immunogenic. This study shows the presence of auto-antibodies against G-Arg-Fe(3+) modified human DNA in the sera of diabetes type 1 and in few cases type 2 patients due to secondary complications of nephropathy. The glyco-oxidative lesions have also been detected in the lymphocyte DNA isolated from patients having type 1 and type 2 diabetes. The results show structural perturbations generating new epitopes in G-Arg-Fe(3+)-DNA rendering it pretty immunogenic.

  19. Advanced glycation end products (AGEs) increase human mesangial foam cell formation by increasing Golgi SCAP glycosylation in vitro.

    PubMed

    Yuan, Yang; Zhao, Lei; Chen, Yaxi; Moorhead, John F; Varghese, Zac; Powis, Stephen H; Minogue, Shane; Sun, Zilin; Ruan, Xiong Z

    2011-07-01

    Advanced glycation end products (AGEs) is one of the causative factors of diabetic nephropathy, which is associated with lipid accumulation in glomeruli. This study was designed to investigate whether N(ε)-(carboxymethyl) lysine (CML; a member of the AGEs family) increases lipid accumulation by impairing the function of sterol-regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) in human mesangial cells (HMCs). Intracellular cholesterol content was assessed by Oil Red O staining and quantitative assay. The expression of molecules controlling cholesterol homeostasis was examined using real-time quantitative RT-PCR and Western blotting. The activity of Golgi-processing enzymes was determined using enzyme-based methods, and the translocation of SCAP from the endoplasmic reticulum (ER) to the Golgi was detected by confocal microscopy. CML increased cholesterol accumulation in HMCs. Exposure to CML increased expression and abnormal translocation of SCAP from the ER to the Golgi even in the presence of a high concentration of LDL. The increased SCAP translocation carried more SREBP-2 to the Golgi for activation by proteolytic cleavages, enhancing transcription of 3-hydroxy-3-methylclutaryl-CoA reductase and the LDL receptor. CML increased Golgi mannosidase activity, which may enhance glycosylation of SCAP. This prolonged the half-life and enhanced recycling of SCAP between the ER and the Golgi. The effects of CML were blocked by inhibitors of Golgi mannosidases. AGEs (CML) increased lipid synthesis and uptake, thereby causing foam cell formation via increasing transcription and protein glycosylation of SCAP in HMCs. These data imply that inhibitors of Golgi-processing enzymes might have a potential renoprotective role in prevention of mesangial foam cell formation.

  20. Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects.

    PubMed

    Forbes, Josephine M; Sourris, Karly C; de Courten, Maximilian P J; Dougherty, Sonia L; Chand, Vibhasha; Lyons, Jasmine G; Bertovic, David; Coughlan, Melinda T; Schlaich, Markus P; Soldatos, Georgia; Cooper, Mark E; Straznicky, Nora E; Kingwell, Bronwyn A; de Courten, Barbora

    2014-02-01

    It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = -0.31; p < 0.05). In addition, fasting (r = -0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

  1. Relationship of decrease in fecundity with advancing age to structural changes in mouse endometrium

    PubMed Central

    SHIMIZU, KIYOSHI; YAMADA, JINZO

    2000-01-01

    The aim of this study was to determine whether a relationship exists between decrease in fecundity and structural changes in the antimesometrial endometrium of the mouse. Fecundity was calculated as the number of animals showing a placental sign/number of copulated animals ×100 (%). Structural changes in the endometrium were examined by electron microscopy. A negative correlation between age and fecundity was found. Fecundity was 50% at 7 mo of age. At this age, amorphous material appeared in the region between the basement membrane deep to the luminal epithelium and the subepithelial cells. This material was sometimes attached to the basement membrane. It increased in amount with advancing age, as fecundity decreased. The structure of the uterine luminal epithelial cells did not alter with age. The results indicated that decrease in fecundity with advancing age is correlated with the appearance of amorphous material beneath the basal lamina of the endometrial epithelium. It is suggested that this could impair communication between the luminal epithelium and the endometrial stroma, which plays an important role in implantation. PMID:10697293

  2. Effects of fresh, aged and cooked garlic extracts on short- and long-term memory in diabetic rats

    PubMed Central

    Sarkaki, Alireza; Valipour Chehardacheric, Saeed; Farbood, Yaghoub; Mansouri, Seyed Mohammad Taghi; Naghizadeh, Bahareh; Basirian, Effat

    2013-01-01

    Objective: The present study was hypothesized to investigate the beneficial effects of fresh, aged, and cooked garlic extracts on blood glucose and memory of diabetic rats induced by streptozocine (STZ). Material and Methods: Diabetes was induced by an intraperitoneal injection of STZ (60 mg/kg body weight). An oral dose of 1000 mg/kg of each garlic extract was given daily for 4 weeks after diabetes induction. Five days after STZ injection, five groups were formed: Control (intact) rats (Cont) + Vehicle of garlic extract (normal saline) (Veh), STZ + Veh, STZ + Fresh (row) garlic (FG), STZ + Aged garlic (AG), and STZ + cooked (boiled) garlic (CG). In order to assess the passive avoidance memory, rats were gently placed on the wooden platform, and latency to step-down (SDL) was recorded as initial phase, after then a light electrical shock [0.3 mA, 3 sec, Alternative current (AC)] was delivered to their foot paw. The retrieval tests were done for short- and long-term memories, respectively. Blood glucose was assayed by glucometer before and after treatment with STZ and garlic extracts. Results: Hyperglycemia induced by STZ decreased short-term memory in both diabetic males and females rats significantly compared with the controls (p<0.001 and p<0.01). Fresh and cooked but not aged garlic extracts decreased blood glucose in diabetic males and increased memory in both diabetic male and female rats significantly (p<0.05 and p<0.01). Conclusions: STZ causes elevation of the blood glucose and resulted in memory deficits, possibly viafree radicals production in brain tissue. Garlic has some bioactive chemicals including allicin and sulfur compound (OSC) which could lower the blood glucose during chronic hyperglycemia, inhibit free radicals production in brain, and improve short-term (but not long-term) memory. PMID:25050258

  3. Younger Dryas Age advance of Franz Josef Glacier in the Southern Alps of New Zealand

    SciTech Connect

    Denton, G.H. ); Hendy, C.H. )

    1994-06-03

    A corrected radiocarbon age of 11,050 [+-] 14 years before present for an advance of the Franz Josef Glacier to the Waiho Loop terminal moraine on the western flank of New Zealand's Southern Alps shows that glacier advance on a South Pacific island was synchronous with initiation of the Younger Dryas in the North Atlantic region. Hence, cooling at the beginning of the Younger Dryas probably reflects global rather than regional forcing. The source for Younger Dryas climatic cooling may thus lie in the atmosphere rather than in a North Atlantic thermohaline switch. 36 refs., 2 figs., 1 tab.

  4. Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age.

    PubMed

    Brubaker, Aleah L; Rendon, Juan L; Ramirez, Luis; Choudhry, Mashkoor A; Kovacs, Elizabeth J

    2013-02-15

    Advanced age is associated with alterations in innate and adaptive immune responses, which contribute to an increased risk of infection in elderly patients. Coupled with this immune dysfunction, elderly patients demonstrate impaired wound healing with elevated rates of wound dehiscence and chronic wounds. To evaluate how advanced age alters the host immune response to cutaneous wound infection, we developed a murine model of cutaneous Staphylococcus aureus wound infection in young (3-4 mo) and aged (18-20 mo) BALB/c mice. Aged mice exhibit increased bacterial colonization and delayed wound closure over time compared with young mice. These differences were not attributed to alterations in wound neutrophil or macrophage TLR2 or FcγRIII expression, or age-related changes in phagocytic potential and bactericidal activity. To evaluate the role of chemotaxis in our model, we first examined in vivo chemotaxis in the absence of wound injury to KC, a neutrophil chemokine. In response to a s.c. injection of KC, aged mice recruited fewer neutrophils at increasing doses of KC compared with young mice. This paralleled our model of wound infection, where diminished neutrophil and macrophage recruitment was observed in aged mice relative to young mice despite equivalent levels of KC, MIP-2, and MCP-1 chemokine levels at the wound site. This reduced leukocyte accumulation was also associated with lower levels of ICAM-1 in wounds from aged mice at early time points. These age-mediated defects in early neutrophil recruitment may alter the dynamics of the inflammatory phase of wound healing, impacting macrophage recruitment, bacterial clearance, and wound closure.

  5. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

    PubMed

    Iyengar, Sudha K; Sedor, John R; Freedman, Barry I; Kao, W H Linda; Kretzler, Matthias; Keller, Benjamin J; Abboud, Hanna E; Adler, Sharon G; Best, Lyle G; Bowden, Donald W; Burlock, Allison; Chen, Yii-Der Ida; Cole, Shelley A; Comeau, Mary E; Curtis, Jeffrey M; Divers, Jasmin; Drechsler, Christiane; Duggirala, Ravi; Elston, Robert C; Guo, Xiuqing; Huang, Huateng; Hoffmann, Michael Marcus; Howard, Barbara V; Ipp, Eli; Kimmel, Paul L; Klag, Michael J; Knowler, William C; Kohn, Orly F; Leak, Tennille S; Leehey, David J; Li, Man; Malhotra, Alka; März, Winfried; Nair, Viji; Nelson, Robert G; Nicholas, Susanne B; O'Brien, Stephen J; Pahl, Madeleine V; Parekh, Rulan S; Pezzolesi, Marcus G; Rasooly, Rebekah S; Rotimi, Charles N; Rotter, Jerome I; Schelling, Jeffrey R; Seldin, Michael F; Shah, Vallabh O; Smiles, Adam M; Smith, Michael W; Taylor, Kent D; Thameem, Farook; Thornley-Brown, Denyse P; Truitt, Barbara J; Wanner, Christoph; Weil, E Jennifer; Winkler, Cheryl A; Zager, Philip G; Igo, Robert P; Hanson, Robert L; Langefeld, Carl D

    2015-08-01

    Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

  6. Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)

    PubMed Central

    Kretzler, Matthias; Keller, Benjamin J.; Adler, Sharon G.; Best, Lyle G.; Bowden, Donald W.; Burlock, Allison; Chen, Yii-Der Ida; Cole, Shelley A.; Comeau, Mary E.; Curtis, Jeffrey M.; Divers, Jasmin; Drechsler, Christiane; Duggirala, Ravi; Elston, Robert C.; Guo, Xiuqing; Huang, Huateng; Hoffmann, Michael Marcus; Howard, Barbara V.; Ipp, Eli; Kimmel, Paul L.; Klag, Michael J.; Knowler, William C.; Kohn, Orly F.; Leak, Tennille S.; Leehey, David J.; Li, Man; Malhotra, Alka; März, Winfried; Nair, Viji; Nelson, Robert G.; Nicholas, Susanne B.; O’Brien, Stephen J.; Pahl, Madeleine V.; Parekh, Rulan S.; Pezzolesi, Marcus G.; Rasooly, Rebekah S.; Rotimi, Charles N.; Rotter, Jerome I.; Schelling, Jeffrey R.; Seldin, Michael F.; Shah, Vallabh O.; Smiles, Adam M.; Smith, Michael W.; Taylor, Kent D.; Thameem, Farook; Thornley-Brown, Denyse P.; Truitt, Barbara J.; Wanner, Christoph; Weil, E. Jennifer; Winkler, Cheryl A.; Zager, Philip G.; Igo, Robert P.; Hanson, Robert L.; Langefeld, Carl D.

    2015-01-01

    Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD. PMID:26305897

  7. DIABETES

    PubMed Central

    Natarajan, Loki

    2015-01-01

    A new study shows that statin therapy before diagnosis of diabetes mellitus is not associated with an increased risk of microvascular disease and might even be beneficial for retinopathy and neuropathy. These data suggest a potential protective effect of statins in specific complications, which should be further investigated in randomized controlled trials. PMID:25366041

  8. Diabetes

    MedlinePlus

    ... retinopathy gets worse, it may lead to blindness.Laser surgery can often be used to treat or slow down retinopathy, especially if the problem is found early. People who have diabetes should have an eye exam once a year.Warning signs of eye problemsCall your doctor if you ...

  9. Effects of combined lipoic acid and pyridoxine on albuminuria, advanced glycation end-products, and blood pressure in diabetic nephropathy.

    PubMed

    Noori, Nazanin; Tabibi, Hadi; Hosseinpanah, Farhad; Hedayati, Mehdi; Nafar, Mohsen

    2013-01-01

    This study was designed to investigate the effects of combined administration of lipoic acid and pyridoxine on albuminuria, oxidative stress, blood pressure, serum advanced glycation end-products, nitric oxide (NO), and endothelin-1 in patients with diabetic nephropathy. Thirty-four patients were randomly assigned to either a supplement group or a placebo group. The patients in the supplement group received 800 mg lipoic acid and 80 mg pyridoxine daily for 12 weeks, whereas the placebo group received corresponding placebos. Urinary albumin, serum malondialdehyde (MDA), and systolic blood pressure decreased significantly in the supplement group compared to the placebo group (p < 0.05). Serum NO increased in the supplement group compared to the placebo group (p < 0.05). Serum pentosidine and carboxymethyl lysine decreased significantly in the supplement group at the end of week 12 compared to baseline (p < 0.05). No statistically significant differences were observed between the two groups in mean changes of serum endothelin-1, glucose, and diastolic blood pressure. The present study indicates that combined administration of lipoic acid and pyridoxine improves albuminuria in patients with diabetic nephropathy by reducing oxidative stress, advanced glycation end-products, and systolic blood pressure. The reduction in microalbuminuria may be of benefit in retarding the progression of diabetic nephropathy.

  10. Red meat, dietary heme iron, and risk of type 2 diabetes: the involvement of advanced lipoxidation endproducts.

    PubMed

    White, Desley L; Collinson, Avril

    2013-07-01

    There is growing evidence of disordered iron homeostasis in the diabetic condition, with links proposed between dietary iron intakes and both the risk of disease and the risk of complications of advanced disease. In the United States, Britain, and Canada, the largest dietary contributors of iron are cereals and cereal products and meat and meat products. This review discusses the findings of cohort studies and meta-analyses of heme iron and red meat intakes and the risk of type 2 diabetes. These suggest that processed red meat is associated with increased risk, with high intakes of red meat possibly also associated with a small increased risk. Historically, humans have relied on large quantities of heme iron and red meat in their diets, and therefore it is paradoxical that iron from meat sources should be associated with the risk of type 2 diabetes. A reason for this association may be drawn from studies of dietary advanced glycation and lipoxidation endproducts present in processed food and the mechanisms by which insulin output by pancreatic islet cells might be influenced by the protein modifications present in processed red meat.

  11. Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

    PubMed

    Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy

    2013-01-01

    PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.

  12. Age-Dependent Loss of Tolerance to an Immunodominant Epitope of Glutamic Acid Decarboxylase in Diabetic prone RIP-B7/DR4 Mice

    PubMed Central

    Gebe, John A.; Unrath, Kellee A; Falk, Ben A.; Ito, Kouichi; Wen, Li; Daniels, Terri L.; Lernmark, Åke; Nepom, Gerald T.

    2007-01-01

    We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice, and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4+/FoxP3+ cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23% with a mean onset age of 40 weeks and is similar to that reported for RIP-B7/DR0401 mice. A gender preference is observed in that 38% of female mice become diabetic compared to 8% of male mice. PMID:16979383

  13. Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.

    PubMed

    Gebe, John A; Unrath, Kellee A; Falk, Ben A; Ito, Kouichi; Wen, Li; Daniels, Terri L; Lernmark, Ake; Nepom, Gerald T

    2006-12-01

    We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice is 23% with a mean onset age of 40 weeks and is similar to that reported for RIP-B7/DR0401 mice. A gender preference is observed in that 38% of female mice become diabetic compared to 8% of male mice.

  14. Linolenic acid prevents early and advanced glycation end-products (AGEs) modification of albumin.

    PubMed

    Prasanna, Govindarajan; Saraswathi, N T

    2017-02-01

    In this study, we report the protective effects of linolenic acid towards the formation of early (HbA1c) and advanced glycation end-products (AGEs) based on fluorescence, circular dichroism, confocal microscopy and molecular interaction studies. Linolenic acid was found to be a potent inhibitor of AGEs formed by both glucose and fructose. The HbA1c (early glycation product) level was found to be reduced to 7.4% when compared to glycated control (8.4%). Similarly, linolenic acid also inhibited the methylglyoxal mediated AGEs formation. Circular dichroism spectroscopy studies suggested that the protective effect of linolenic acid for the helical structure of albumin. The molecular interaction studies showed that linolenic acid interacts with arginine residues of albumin with high affinity. Results suggested linolenic acid to be a potent antiglycation compound and also it could be a better lead compound for AGE inhibition.

  15. Chemical modification of proteins by lipids in diabetes.

    PubMed

    Baynes, John W

    2003-09-01

    Advanced glycation and lipoxidation end-products (AGE/ALE) increase in tissue proteins with age and at an accelerated rate in diabetes. This Review focuses on the nature and source of AGEs/ALEs and the factors affecting their formation in tissue and plasma proteins. Lipids are identified as an important source of chemical modification of proteins in diabetes, and the role of diabetes, dyslipidemia and renal disease in formation of AGEs/ALEs is reviewed. The article concludes with a discussion of ELISA assays for AGEs/ALEs and the merits of measuring AGEs/ALEs in the clinical laboratory.

  16. Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

    NASA Technical Reports Server (NTRS)

    Rianon, N.; McCormick, J.; Ambrose, C.; Smith, S. M.; Fisher-Hoch, S.

    2016-01-01

    The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (=50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level =8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations

  17. Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial

    PubMed Central

    Sohrab, Golbon; Angoorani, Pooneh; Tohidi, Maryam; Tabibi, Hadi; Kimiagar, Masoud; Nasrollahzadeh, Javad

    2015-01-01

    Introduction Diabetes mellitus characterized by hyperglycemia could increase oxidative stress and formation of advanced glycated end-products (AGEs), which contribute to diabetic complications. The purpose of this study was to assess the effect of pomegranate juice (PJ) containing natural antioxidant on lipid peroxidation and plasma AGEs in patients with type 2 diabetes (T2D). Materials and methods In a randomized, double-blind, placebo-controlled trial, 44 patients (age range 56±6.8 years), T2D were randomly assigned to one of two groups: group A (PJ, n=22) and group B (Placebo, n=22). At the baseline and the end of 12-week intervention, biochemical markers including fasting plasma glucose, insulin, oxidative stress, and AGE markers including carboxy methyl lysine (CML) and pentosidine were assayed. Results At baseline, there were no significant differences in plasma total antioxidant capacity (TAC) levels between the two groups, but malondialdehyde (MDA) decreased levels were significantly different (P<0.001). After 12 weeks of intervention, TAC increased (P<0.05) and MDA decreased (P<0.01) in the PJ group when compared with the placebo group. However, no significant differences were observed in plasma concentration of CML and pentosidine between the two groups. Conclusions The study showed that PJ decreases lipid peroxidation. Therefore, PJ consumption may delay onset of T2D complications related to oxidative stress. PMID:26355954

  18. Angiogenic inhibitors for older patients with advanced colorectal cancer: Does the age hold the stage?

    PubMed Central

    Aprile, Giuseppe; Fontanella, Caterina; Lutrino, Eufemia Stefania; Ferrari, Laura; Casagrande, Mariaelena; Cardellino, Giovanni Gerardo; Rosati, Gerardo; Fasola, Gianpiero

    2013-01-01

    Although major progress has been achieved in the treatment of advanced colorectal cancer (CRC) with the employment of antiangiogenic agents, several questions remain on the use of these drugs in older patients. Since cardiovascular, renal and other comorbidities are common in the elderly, an accurate assessment of the patients’ conditions should be performed before a treatment decision is made. Since most CRC patients enrolled in clinical trials testing antiangiogenic drugs were aged < 65 years, the efficacy and tolerability of these agents in elderly patients has not been adequately explored. Data suggest that patients with advanced CRC derive similar benefit from bevacizumab treatment regardless of age, but the advantage of other antiangiogenic drugs in the same class of patients appears more blurred. Literature data suggest that specific antiangiogenic-related toxicities such as hypertension or arterial thromboembolic events may be higher in the elderly than in the younger patients. In addition, it should be emphasized that the patients included in the clinical studies discussed herein were selected and therefore may not be representative of the usual elderly population. Advanced age alone should not discourage the use of bevacizumab. However, a careful patients’ selection and watchful monitoring of toxicities are required to optimize the use of antiangiogenics in this population. PMID:23847406

  19. Direct Social Support and Long-term Health Among Middle-Aged and Older Adults With Type 2 Diabetes Mellitus

    PubMed Central

    2013-01-01

    Objectives. This study examined whether or not direct social support is associated with long-term health among middle-aged and older adults with diabetes mellitus. Method. Direct social support was assessed at baseline (2003) for 1,099 adults with type 2 diabetes mellitus from the Health and Retirement Study. Self-reported health status was examined at baseline and in 4 biennial survey waves (2003–2010). A series of ordinal logistic regression models examined whether or not the 7-item Diabetes Care Profile scale was associated with a subsequent change in health status over time. Additional analyses examined whether or not individual components of direct social support were associated with health status change. Results. After adjusting for baseline covariates, greater direct social support as measured by the Diabetes Care Profile was associated with improved health outcomes over time; however, this trend was not significant (p = .06). The direct social support measures that were associated with improved health over follow-up were support for taking medicines (odds ratio [OR] = 1.22), physical activity (OR = 1.26), and going to health care providers (OR = 1.22; all p < .05). Discussion. Interventions that specifically target improving specific aspects of diabetes social support may be more effective in improving long-term health than less targeted efforts. PMID:24150176

  20. The changes in the hypothalamo-pituitary-gonadal axis of streptozotocin-treated male rats depend from age at diabetes onset.

    PubMed

    Pitton, I; Bestetti, G E; Rossi, G L

    1987-01-01

    The influence of age at diabetes onset and of capillary microangiopathy on the severity and evolution of hypothalamo-pituitary-gonadal changes was studied morphologically and morphometrically in male rats 4 and 8 months after streptozotocin injection. At each time period we studied 2 groups of rats, one made diabetic before (age 1 month), the other after puberty (age 3 months), and compared them with corresponding controls. The size of hypothalamic axons, numerical density and size of pituitary gonadotrophs, size of testicular tubules, and basement membrane thickness of retinal capillaries were measured. Major differences were found at 8 months. Changes of pituitary glands (i.e. small and numerous gonadotrophs) and testes (i.e. small tubular size) were more important in pre- than in postpubertal diabetic rats. This was a consequence of the aggravating prepubertal diabetes between 4 and 8 months. On the contrary, these changes partially regressed in postpubertal diabetic animals. Pituitary and testicular changes were correlated. Other lesions, such as swollen axonal processes in the hypothalamus, increased thickness of seminiferous epithelium and of capillary basement membranes, though very evident in diabetics, were independent from age at induction. Neither microangiopathy nor glycemia were correlated with any other change which confirmed their secondary role in diabetic neuroendocrine disorders. Thus, two types of diabetic disorders of the hypothalamo-pituitary-gonadal axis could be distinguished: 1) those with irreversible effects on immature yet partially reversible effects on mature structures; and 2) those independent from age at induction.

  1. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

    PubMed

    Chang, Anne Lynn S; Lewis, Karl D; Arron, Sarah T; Migden, Michael R; Solomon, James A; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F; Sekulic, Aleksandar

    2016-11-15

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age.

  2. Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma

    PubMed Central

    Chang, Anne Lynn S.; Lewis, Karl D.; Arron, Sarah T.; Migden, Michael R.; Solomon, James A.; Yoo, Simon; Day, Bann-Mo; McKenna, Edward F.; Sekulic, Aleksandar

    2016-01-01

    Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age. PMID:27764798

  3. Berberine exerts renoprotective effects by regulating the AGEs-RAGE signaling pathway in mesangial cells during diabetic nephropathy.

    PubMed

    Qiu, Yuan-Ye; Tang, Li-Qin; Wei, Wei

    2017-03-05

    In this study, we explored the effect of berberine treatment on the AGEs-RAGE pathway in a rat model of diabetic nephropathy, and we investigated the mechanism by which key factors caused kidney injury and the effects of berberine. In vivo, berberine improved fasting blood glucose, body weight, the majority of biochemical and renal function parameters and histopathological changes in the diabetic kidney. Western blotting and immunohistochemistry revealed significant increases in the levels of AGEs, RAGE, P-PKC-β and TGF-β1 in injured kidneys, and these levels were markedly decreased by treatment with berberine. In vitro, berberine inhibited mesangial cell proliferation. Cells treated with berberine showed reduced levels of AGEs, accompanied by decreased RAGE, p-PKC and TGF-β1 levels soon afterwards. Berberine exhibited renoprotective effects in diabetic nephropathy rats, and the molecular mechanism was associated with changes in the levels and regulation of the AGEs-RAGE-PKC-β-TGF-β1 signaling pathway.

  4. Altered basal and stimulated accumbens dopamine release in obese OLETF rats as a function of age and diabetic status

    PubMed Central

    Anderzhanova, Elmira; Covasa, Mihai; Hajnal, Andras

    2011-01-01

    The Otsuka Long Evans Tokushima Fatty (OLETF) rat lacking the CCK-1 receptor is hyperphagic, prefers palatable and high caloric meals, and gradually develops obesity and type-2 diabetes. To determine dopamine levels in this strain, we used in-vivo quantitative (no-net flux) microdialyis at three different ages representing non-diabetic (8 weeks), pre-diabetic (18 weeks), and diabetic (56 weeks) stages in OLETF and age-matched lean LETO controls. Results showed significantly elevated basal dopamine levels in the caudomedial nucleus accumbens of OLETF rats compared to LETO at younger ages (8 weeks: 20.10 ± 5.61 nM vs. 15.85 ± 5.63 nM; 18 weeks: 7.37 ± 3.71 nM vs. 4.75 ± 1.25 nM, Mean ± SD). In contrast, at 56 weeks of age, a profound decline in extracellular dopamine concentrations was seen in both strains with a tendency for a greater effect in OLETF rats (1.78 ± 0.40 nM vs. 2.39 ± 0.42 nM). Further, extracellular fraction, an index for reuptake, was higher in 56-week old OLETF compared to LETO (0.648 ± 0.049 vs. 0.526 ± 0.057). Potassium-stimulated dopamine efflux revealed an increased capacity of vesicular pool in OLETF rats compared to LETO across all age groups with an accentuated strain difference at 56 weeks. These findings demonstrate altered striatal dopamine functions (i.e. increased stimulated release and uptake) in obese OLETF rat. This could be due to the lack of functional CCK-1 receptors, or metabolic and hormonal factors associated with the development of obesity and insulin resistance, or both. PMID:17553848

  5. Mobile Applications for Diabetics: A Systematic Review and Expert-Based Usability Evaluation Considering the Special Requirements of Diabetes Patients Age 50 Years or Older

    PubMed Central

    Quade, Mandy; Kirch, Wilhelm

    2014-01-01

    Background A multitude of mhealth (mobile health) apps have been developed in recent years to support effective self-management of patients with diabetes mellitus type 1 or 2. Objective We carried out a systematic review of all currently available diabetes apps for the operating systems iOS and Android. We considered the number of newly released diabetes apps, range of functions, target user groups, languages, acquisition costs, user ratings, available interfaces, and the connection between acquisition costs and user ratings. Additionally, we examined whether the available applications serve the special needs of diabetes patients aged 50 or older by performing an expert-based usability evaluation. Methods We identified relevant keywords, comparative categories, and their specifications. Subsequently, we performed the app review based on the information given in the Google Play Store, the Apple App Store, and the apps themselves. In addition, we carried out an expert-based usability evaluation based on a representative 10% sample of diabetes apps. Results In total, we analyzed 656 apps finding that 355 (54.1%) offered just one function and 348 (53.0%) provided a documentation function. The dominating app language was English (85.4%, 560/656), patients represented the main user group (96.0%, 630/656), and the analysis of the costs revealed a trend toward free apps (53.7%, 352/656). The median price of paid apps was €1.90. The average user rating was 3.6 stars (maximum 5). Our analyses indicated no clear differences in the user rating between free and paid apps. Only 30 (4.6%) of the 656 available diabetes apps offered an interface to a measurement device. We evaluated 66 apps within the usability evaluation. On average, apps were rated best regarding the criterion “comprehensibility” (4.0 out of 5.0), while showing a lack of “fault tolerance” (2.8 out of 5.0). Of the 66 apps, 48 (72.7%) offered the ability to read the screen content aloud. The number of

  6. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema.

    PubMed

    Fong, Angie H C; Lai, Timothy Y Y

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed.

  7. Vasoconstricting effect of angiotensin II in human hand veins: influence of aging, diabetes mellitus and hypertension.

    PubMed

    Harada, Kazuhiro; Ohmori, Masami; Fujimura, Akio

    2002-09-01

    We examined human hand veins to determine whether venoconstricting response to angiotensin II (Ang II) and noradrenaline (NA) was influenced by aging or such diseases as diabetes mellitus (DM) and hypertension (HT). Twenty healthy male subjects (20-73 years), and 8 male patients with non-insulin-dependent DM and 8 male patients with essential HT were included in this study. A constant dose (50 ng/min) of Ang II or increasing dose (2-256 ng/min) of NA was infused into the dorsal hand vein and its diameter was measured using a linear variable differential transformer. The constant infusion of Ang II caused rapid desensitization or tachyphylaxis. The venoconstriction by Ang II in the 8 elderly subjects (58 to 73 years) was significantly (p<0.05) larger than that in the 8 young subjects (20 to 36 years) from 6 to 18 min after the start of the infusion (after 6 min: 63.6+/-11.6 (mean+/-SD)% vs. 39.9+/-20.8%, 12 min: 34.0+/-11.9% vs. 12.0+/-12.0%). However, the venoconstriction by Ang II in the patients with DM or HT was not significantly different from that in the 9 age-matched control subjects. No significant difference in venoconstrictor response to NA was observed between the young and elderly subjects, nor between the control subjects and the patients with DM or HT. These findings indicated that venoconstrictor response to Ang II might be greater in the elderly but might not be influenced by DM nor HT.

  8. Beyond Diabetes: Does Obesity-Induced Oxidative Stress Drive the Aging Process?

    PubMed Central

    Salmon, Adam B.

    2016-01-01

    Despite numerous correlative data, a causative role for oxidative stress in mammalian longevity has remained elusive. However, there is strong evidence that increased oxidative stress is associated with exacerbation of many diseases and pathologies that are also strongly related to advanced age. Obesity, or increased fat accumulation, is one of the most common chronic conditions worldwide and is associated with not only metabolic dysfunction but also increased levels of oxidative stress in vivo. Moreover, obesity is also associated with significantly increased risks of cardiovascular disease, neurological decline and cancer among many other diseases as well as a significantly increased risk of mortality. In this review, we investigate the possible interpretation that the increased incidence of these diseases in obesity may be due to chronic oxidative stress mediating segmental acceleration of the aging process. Understanding how obesity can alter cellular physiology beyond that directly related to metabolic function could open new therapeutic areas of approach to extend the period of healthy aging among people of all body composition. PMID:27438860

  9. Advancing paternal age and offspring violent offending: A sibling-comparison study

    PubMed Central

    Kuja-Halkola, Ralf; Pawitan, Yudi; D’Onofrio, Brian M; Långström, Niklas; Lichtenstein, Paul

    2013-01-01

    Children born to older fathers are at higher risk to develop severe psychopathology (e.g., schizophrenia and bipolar disorder), possibly due to increased de novo mutations during spermatogenesis with older paternal age. Since severe psychopathology is correlated with antisocial behavior, we examined possible associations between advancing paternal age and offspring violent offending. Interlinked Swedish national registers provided information on fathers’ age at childbirth and violent criminal convictions in all offspring born 1958–1979 (n=2,359,921). We used ever committing a violent crime and number of violent crimes as indices of violent offending. The data included information on multiple levels; we compared differentially exposed siblings in within-family analyses to rigorously test causal influences. In the entire population, advancing paternal age predicted offspring violent crime according to both indices. Congruent with a causal effect, this association remained for rates of violent crime in within-family analyses. However, in within-analyses, we found no association with ever committing a violent crime, suggesting that factors shared by siblings (genes and environment) confounded this association. Life-course-persistent criminality has been proposed to have a partly biological etiology; our results agree with a stronger biological effect (i.e., de novo mutations) on persistent violent offending. PMID:22781852

  10. Self and identity in advanced old age: validation of theory through longitudinal case analysis.

    PubMed

    Coleman, P G; Ivani-Chalian, C; Robinson, M

    1999-10-01

    Case studies drawn from a 20-year longitudinal study of aging were examined for the support they provide to two theoretical viewpoints on the self in later life: one focusing on management of self-esteem, the other on development of identity as story. The five cases selected for scrutiny represented diverse trajectories of self-esteem. They furnished ample illustrations of certain key aspects of both theories, including assimilative processes of coping, depression related to absence of accommodation, maintenance of life story themes, and life review processes. They did not, however, give strong support to the dichotomy, drawn within both theoretical models, between younger and older old age. Examples of accommodation, disengagement, and self-transcendence, hypothesized to typify advanced old age, were relatively few in number and emerged only toward the very end of life. It is argued that examination of prototypical cases provides a useful approach to validating and developing theory. A conclusion drawn from this study is that more analysis should be carried out on the lives of persons who exemplify the theoretically ideal characteristics of advanced old age.

  11. Advancing paternal age and offspring violent offending: a sibling-comparison study.

    PubMed

    Kuja-Halkola, Ralf; Pawitan, Yudi; D'Onofrio, Brian M; Långström, Niklas; Lichtenstein, Paul

    2012-08-01

    Children born to older fathers are at higher risk to develop severe psychopathology (e.g., schizophrenia and bipolar disorder), possibly because of increased de novo mutations during spermatogenesis with older paternal age. Because severe psychopathology is correlated with antisocial behavior, we examined possible associations between advancing paternal age and offspring violent offending. Interlinked Swedish national registers provided information on fathers' age at childbirth and violent criminal convictions in all offspring born from 1958 to 1979 (N = 2,359,921). We used ever committing a violent crime and number of violent crimes as indices of violent offending. The data included information on multiple levels; we compared differentially exposed siblings in within-family analyses to rigorously test causal influences. In the entire population, advancing paternal age predicted offspring violent crime according to both indices. Congruent with a causal effect, this association remained for rates of violent crime in within-family analyses. However, in within-family analyses, we found no association with ever committing a violent crime, suggesting that factors shared by siblings (genes and environment) confounded this association. Life-course persistent criminality has been proposed to have a partly biological etiology; our results agree with a stronger biological effect (i.e., de novo mutations) on persistent violent offending.

  12. [Age and sex variations of HbA(1C) in a French population without known diabetes aged 6 to 79 years].

    PubMed

    Gusto, Gaëlle; Vol, Sylviane; Born, Catherine; Balkau, Beverley; Lamy, Jocelyne; Bourderioux, Christiane; Lantieri, Olivier; Tichet, Jean

    2011-01-01

    HbA(1C) is being used for screening and diagnosing diabetes. We determined mean values of HbA(1C) according to age and sex in a large population without known diabetes, in a wide age range 6-79  years. 5,138 men and women without known diabetes aged 6-79  years participated in a routine health examination provided by their medical insurance. HbA(1C) was assessed on an HPLC analyzer aligned with a DCCT method. HbA(1C) was approximately normally distributed in both men and women. Mean (SD) HbA(1C) were, for men vs women, in percentages 5.3 (0.4) vs 5.2 (0.3), in mmol/mol 34 (5) vs 34 (4) and in estimated blood glucose in mmol/L 5.83 (0.67) vs 5.75 (0.53). HbA(1C) increased with age by 0.08% every 10  years and this was attenuated to a 0.04% increase after adjustment on fasting plasma glucose. Between 15 and 49  years, women had lower values than men (p < 0.0001), but no sex differences were observed before and after this age range. In our population, 0.6% had HbA(1C) greater or equal to 6.5% and 88% (96% of men and 73% of women) of them had fasting plasma glucose greater or equal to 6,1 mmol/L. Threshold of 6.0% selected 2.8% of our population.

  13. [What advances have been made in the treatment of diabetic foot problems?].

    PubMed

    Clavel, Sylvaine

    2012-04-01

    Diabetic foot problems remain, even today, a major world public health issue. The identification of patients at risk, diagnosis, prevention, assessment and treatments are all aspects of the approach to this pathology.

  14. A structured approach to evaluating aging of the advanced test reactor

    SciTech Connect

    Dwight, J.E.

    1990-01-01

    An aging evaluation program has been developed for the United States Department of Energy's Advanced Test Reactor to support the current goal of operation through the year 2014 and beyond. The Aging Evaluation and Life Extension Program (AELEX) employs a three-phased approach. In Phases 1 and 2, now complete, components were identified, categorized and prioritized. Critical components were selected and aging mechanisms for the critical components identified. An initial evaluation of the critical components was performed and extended life operation for the plant appears to be both technically and economically feasible. Detailed evaluations of the critical components are now in progress in the early stages of Phase 3. Some results are available. Evaluations of many non-critical components and refinements to the program based on probabilistic risk assessment results will follow in later stages of Phase 3. 6 refs., 2 figs., 5 tabs.

  15. Advanced paternal age effects in neurodevelopmental disorders—review of potential underlying mechanisms

    PubMed Central

    Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

    2017-01-01

    Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders. PMID:28140401

  16. Translating Advances from the Basic Biology of Aging into Clinical Application

    PubMed Central

    Kirkland, James L.

    2013-01-01

    Recently, lifespan and healthspan have been extended in experimental animals using interventions that are potentially translatable into humans. A great deal of thought and work are needed beyond the usual steps in drug development to advance these findings into clinical application. Realistic pre-clinical and clinical trials paradigms need to be devised. Focusing on subjects with symptoms of age-related diseases or frailty or who are at imminent risk of developing these problems, measuring effects on short-term, clinically relevant outcomes, as opposed to long-term outcomes such as healthspan or lifespan, and developing biomarkers and outcome measures acceptable to regulatory agencies will be important. Research funding is a major roadblock, as is lack of investigators with combined expertise in the basic biology of aging, clinical geriatrics, and conducting investigational new drug clinical trials. Options are reviewed for developing a path from the bench to the bedside for interventions that target fundamental aging processes. PMID:23237984

  17. Diabetes mellitus and risk of age-related macular degeneration: a systematic review and meta-analysis.

    PubMed

    Chen, Xue; Rong, Shi Song; Xu, Qihua; Tang, Fang Yao; Liu, Yuan; Gu, Hong; Tam, Pancy O S; Chen, Li Jia; Brelén, Mårten E; Pang, Chi Pui; Zhao, Chen

    2014-01-01

    Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00-1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00-1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44-1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13-1.49) and late AMD (OR, 1.16; 95% CI, 1.11-1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96-1.26), 1.48 (95% CI, 1.44-1.51), and 1.15 (95% CI, 1.11-1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association.

  18. Diabetes Mellitus and Risk of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

    PubMed Central

    Chen, Xue; Rong, Shi Song; Xu, Qihua; Tang, Fang Yao; Liu, Yuan; Gu, Hong; Tam, Pancy O. S.; Chen, Li Jia; Brelén, Mårten E.; Pang, Chi Pui; Zhao, Chen

    2014-01-01

    Age-related macular degeneration (AMD) is a major cause of severe vision loss in elderly people. Diabetes mellitus is a common endocrine disorder with serious consequences, and diabetic retinopathy (DR) is the main ophthalmic complication. DR and AMD are different diseases and we seek to explore the relationship between diabetes and AMD. MEDLINE, EMBASE, and the Cochrane Library were searched for potentially eligible studies. Studies based on longitudinal cohort, cross-sectional, and case-control associations, reporting evaluation data of diabetes as an independent factor for AMD were included. Reports of relative risks (RRs), hazard ratios (HRs), odds ratio (ORs), or evaluation data of diabetes as an independent factor for AMD were included. Review Manager and STATA were used for the meta-analysis. Twenty four articles involving 27 study populations were included for meta-analysis. In 7 cohort studies, diabetes was shown to be a risk factor for AMD (OR, 1.05; 95% CI, 1.00–1.14). Results of 9 cross-sectional studies revealed consistent association of diabetes with AMD (OR, 1.21; 95% CI, 1.00–1.45), especially for late AMD (OR, 1.48; 95% CI, 1.44–1.51). Similar association was also detected for AMD (OR, 1.29; 95% CI, 1.13–1.49) and late AMD (OR, 1.16; 95% CI, 1.11–1.21) in 11 case-control studies. The pooled ORs for risk of neovascular AMD (nAMD) were 1.10 (95% CI, 0.96–1.26), 1.48 (95% CI, 1.44–1.51), and 1.15 (95% CI, 1.11–1.21) from cohort, cross-sectional and case-control studies, respectively. No obvious divergence existed among different ethnic groups. Therefore, we find diabetes a risk factor for AMD, stronger for late AMD than earlier stages. However, most of the included studies only adjusted for age and sex; we thus cannot rule out confounding as a potential explanation for the association. More well-designed prospective cohort studies are still warranted to further examine the association. PMID:25238063

  19. Effects of advanced aging on the neural correlates of successful recognition memory

    PubMed Central

    Wang, Tracy H.; Kruggel, Frithjof; Rugg, Michael D.

    2009-01-01

    Functional neuroimaging studies have reported that the neural correlates of retrieval success (old>new effects) are larger and more widespread in older than in young adults. In the present study we investigated whether this pattern of age-related ‘over-recruitment’ continues into advanced age. Using functional magnetic resonance imaging (fMRI), retrieval-related activity from two groups (N = 18 per group) of older adults aged 84–96 yrs (‘old-old’) and 64–77 yrs (‘young-old’) was contrasted. Subjects studied a series of pictures, half of which were presented once, and half twice. At test, subjects indicated whether each presented picture was old or new. Recognition performance of the old-old subjects for twice-studied items was equivalent to that of the young-old subjects for once-studied items. Old>new effects common to the two groups were identified in several cortical regions, including medial and lateral parietal and prefrontal cortex. There were no regions where these effects were of greater magnitude in the old-old group, and thus no evidence of over-recruitment in this group relative to the young-old individuals. In one region of medial parietal cortex, effects were greater (and only significant) in the young-old group. The failure to find evidence of over-recruitment in the old-old subjects relative to the young-old group, despite their markedly poorer cognitive performance, suggests that age-related over-recruitment effects plateau in advanced age. The findings for the medial parietal cortex underscore the sensitivity of this cortical region to increasing age. PMID:19428399

  20. Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring

    PubMed Central

    Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

    2014-01-01

    While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

  1. Probit Models to Investigate Prevalence of Total Diagnosed and Undiagnosed Diabetes among Aged 45 Years or Older Adults in China

    PubMed Central

    Yin, Minghui; Augustin, Balekouzou; Shu, Chang; Qin, Tingting; Yin, Ping

    2016-01-01

    The aims of this study are to identify the most important predictors of total diagnosed and undiagnosed diabetes and estimate the mean change in the predicted probability among aged 45+ adults in China. We used baseline data collected from 2011 wave of the China Health and Retirement Longitudinal Study (CHARLS) (n = 9,513). First, we estimated the prevalence of diagnosed, measured, total diagnosed, and undiagnosed diabetes. Second, we used probit models to determine whether individual attributes, socioeconomic characteristics and behavioral health factors, including smoking, alcohol consumption, obesity, central obesity, are associated with total diagnosed and undiagnosed diabetes. We also consider other factors, including contact with medical system, hypertension and urban/rural settings. Third, we estimated average marginal effects of variables in probit models. Among Chinese people aged 45+, the prevalence of diagnosed, measured, total diagnosed and undiagnosed diabetes were 5.8% (95%CI, 5.3%-6.3%), 14.7% (95%CI, 14.0%-15.4%), 17.0% (95%CI, 16.3%-17.7%), 11.3% (95%CI, 10.6%-12.0%), respectively. The probability of total diagnosed diabetes is 3.3% (95% CI, 1.2%-5.3%) and 10.2% (95% CI, 7.0%-13.5%) higher for overweight and obesity than normal BMI, 5.0% (95% CI, 3.0%-7.1%) higher for central obesity than normal waist circumference, 5.4% (95% CI, 3.7%-7.0%) higher for hypertensive than normotensive and 1.8% (95% CI, 0.8%- 2.7%) higher in urban areas than in rural areas, respectively. The probability of undiagnosed diabetes is 2.7% (95% CI, 1.2%-4.2%) and 7.2% (95% CI, 4.7%-9.6%) higher for overweight and obesity than normal BMI, 2.6% (95% CI, 0.9%-4.4%) higher for central obesity than normal waist circumference and 2.6% (95% CI, 1.2%-4.0%) higher for hypertensive than normotensive, respectively, and -1.5% (95% CI, -2.5% to -0.5%) lower for individuals who were in contact with the medical system. Greater focus on prevention of diabetes is necessary for obesity

  2. [Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention].

    PubMed

    Cantú-Brito, Carlos; Mimenza-Alvarado, Alberto; Sánchez-Hernández, Juan José

    2010-01-01

    Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension.

  3. Oral squamous cell carcinoma among Yemenis: Onset in young age and presentation at advanced stage

    PubMed Central

    Al-Mohaya, Maha; Abdulhuq, Mahmoud; Al-Mandili, Ahmad; Al-Anazi, Yousef

    2012-01-01

    Objectives: Oral cancer represents a health burden worldwide. Up to 90% of oral cancer cases are squamous cell carcinomas (SCC). The data on oral SCC in Yemen are lacking. The objective of this study therefore was to describe and analyze the demographic, clinical and histological characteristics of Yemeni patients with oral SCC. Study Design: In this cross-sectional study, two sets of retrospective data for Yemeni cancer patients were obtained officially by two different registries. Patients with oral SCC were included. Their ages were dichotomized using 40 and 45 years alternately as individual cut-points for young and old patients. The patients` demographic, clinical and histological characteristics were statistically analyzed. Results: There were 457 Yemenis with oral SCC; 253 patients (55.4%) were men. The overall mean age was 58.15±14.11 years. The tongue was the most affected oral sub-site accounting for 53% of the reported cases. The well and moderately differentiated oral SCC accounted for 55.5% and 25.6% of the total cases respectively. Noteworthy, 62 patients (14%) were affected by the age of ?40; this increased to 105 patients (23%) aged ?45 years. Additionally, a high proportion of oral SCC patients (62%, 283) were diagnosed at advanced tumor stages (regional extension or metastasized). The distributions of histological grades and tumor stages in young and old patients were significantly different (P=0.006 and 0.026 respectively). Conclusion: The relative frequency of oral SCC among Yemeni young people is high. Unfortunately, most of oral SCC patients in Yemen were diagnosed at advanced stage. Key words:Oral squamous cell carcinoma, Yemen, young patients, advanced stage. PMID:24558559

  4. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

    PubMed Central

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-01-01

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26–74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D. PMID:27029739

  5. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.

    PubMed

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-03-31

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.

  6. Heberprot-P: a novel product for treating advanced diabetic foot ulcer.

    PubMed

    Berlanga, Jorge; Fernández, José I; López, Ernesto; López, Pedro A; del Río, Amaurys; Valenzuela, Carmen; Baldomero, Julio; Muzio, Verena; Raíces, Manuel; Silva, Ricardo; Acevedo, Boris E; Herrera, Luis

    2013-01-01

    Diabetic foot ulcer is a principal diabetic complication. It has been shown that diabetic patients have decreased growth factor concentrations in their tissues, particularly epidermal growth factor. Growth factor shortage impairs wound healing, which leads to chronic nonhealing wounds and sometimes eventual amputation. Ischemic diabetic foot ulcer is the most difficult to treat and confers the highest amputation risk. Injecting epidermal growth factor deep into the wound bottom and contours encourages a more effective pharmacodynamic response in terms of granulation tissue growth and wound closure. Epidermal growth factor injected into the ulcer matrix may also result in association with extracellular matrix proteins, thus enhancing cell proliferation and migration. Heberprot-P is an innovative Cuban product containing recombinant human epidermal growth factor for peri- and intra-lesional infiltration; evidence reveals it accelerates healing of deep and complex ulcers, both ischemic and neuropathic, and reduces diabetes-related amputations. Clinical trials of Heberprot-P in patients with diabetic foot ulcers have shown that repeated local infiltration of this product can enhance healing of chronic wounds safely and efficaciously. As a result, Heberprot-P was registered in Cuba in 2006, and in 2007 was included in the National Basic Medications List and approved for marketing. It has been registered in 15 other countries, enabling treatment of more than 100,000 patients. Heberprot-P is a unique therapy for the most complicated and recalcitrant chronic wounds usually associated with high amputation risk. Local injection in complex diabetic wounds has demonstrated a favorable risk-benefit ratio by speeding healing, reducing recurrences and attenuating amputation risk. Further testing and deployment worldwide of Heberprot-P would provide an opportunity to assess the product's potential to address an important unmet medical need.

  7. The effects of n-3 long-chain polyunsaturated fatty acid supplementation on AGEs and sRAGE in type 2 diabetes mellitus.

    PubMed

    Kurt, Asuman; Andican, Gülnur; Siva, Zeynep Oşar; Andican, Ahat; Burcak, Gülden

    2016-12-01

    In diabetes mellitus, chronic hyperglycemia leads to formation of advanced glycation end products (AGEs). Binding of AGEs to receptors of AGE (RAGE) causes deleterious effects. In populations with a high consumption of n-3 long-chain polyunsaturated fatty acids, a lower prevalence of diabetes mellitus has been reported. We aimed to investigate the effects of n-3 fatty acid (EPA and DHA) supplementation on the levels of AGEs (carboxymethyl lysine (CML) and pentosidine), sRAGE, and nuclear factor kappa B (NF-kB) in type 2 diabetes mellitus (T2DM). T2DM patients (n = 38) treated with oral hypoglycemic agents, without insulin were supplemented with n-3 fatty acids (1.2 g/day) for 2 months. Plasma CML, pentosidine, sRAGE, and NF-kB levels were measured by ELISA both before and after the supplementation. n-3 fatty acid supplementation significantly reduced fasting glucose (p < 0.01), glycated hemoglobin (HbA1c) (p < 0.05), and pentosidine (p < 0.05) levels. The supplementation induced percentage changes in pentosidine and HbA1c and in pentosidine and creatinine were observed to be correlated (r = 0.349, p < 0.05) and (r = 0.377, p < 0.05), respectively. Waist circumference and systolic and diastolic pressures were significantly decreased due to n-3 supplementation (p < 0.001, p < 0.01, p < 0.01), respectively. Our results show that supplementation with n-3 fatty acid has beneficial effects on waist circumference; systolic and diastolic blood pressures; and the levels of glucose, HbA1c, and pentosidine in T2DM patients. However, the supplementation failed to decrease these parameters to the reference ranges for healthy subjects. In addition, the supplementation did not appear to induce any significant differences in CML, sRAGE, or NF-kB.

  8. Advanced paternal age and childhood cancer in offspring: A nationwide register-based cohort study.

    PubMed

    Urhoj, Stine Kjaer; Raaschou-Nielsen, Ole; Hansen, Anne Vinkel; Mortensen, Laust Hvas; Andersen, Per Kragh; Nybo Andersen, Anne-Marie

    2017-03-03

    Cancer initiation is presumed to occur in utero for many childhood cancers and it has been hypothesized that advanced paternal age may have an impact due to the increasing number of mutations in the sperm DNA with increasing paternal age. We examined the association between paternal age and specific types of childhood cancer in offspring in a large nationwide cohort of 1,904,363 children born in Denmark from 1978 through 2010. The children were identified in the Danish Medical Birth Registry and were linked to information from other national registers, including the Danish Cancer Registry. In total, 3,492 children were diagnosed with cancer before the age of 15 years. The adjusted hazard ratio of childhood cancer according to paternal age was estimated using Cox proportional hazards regressions. We found a 13% (95% confidence interval: 4-23%) higher hazard rate for every 5 years advantage in paternal age for acute lymphoblastic leukemia, while no clear association was found for acute myeloid leukemia (hazard ratio pr. 5 years = 1.02, 95% confidence interval: 0.80-1.30). The estimates for neoplasms in the central nervous system suggested a lower hazard rate with higher paternal age (hazard ratio pr. 5 years = 0.92, 95% confidence interval: 0.84-1.01). No clear associations were found for the remaining childhood cancer types. The findings suggest that paternal age is moderately associated with a higher rate of childhood acute lymphoblastic leukemia, but not acute myeloid leukemia, in offspring, while no firm conclusions could be made for other specific cancer types.

  9. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  10. Dimerumic acid attenuates receptor for advanced glycation endproducts signal to inhibit inflammation and diabetes mediated by Nrf2 activation and promotes methylglyoxal metabolism into d-lactic acid.

    PubMed

    Lee, Bao-Hong; Hsu, Wei-Hsuan; Hsu, Ya-Wen; Pan, Tzu-Ming

    2013-07-01

    This study was designed to evaluate the effects of dimerumic acid (DMA) on receptor for advanced glycation endproducts (RAGE) signal activation and THP-1 monocyte inflammation treated with S100b, a specific ligand of RAGE. We found that DMA inhibited inflammatory cytokine production via upregulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and alleviated oxidative stress through attenuation of p47phox translocation to the membrane of S100b-treated THP-1 monocytes. We found that DMA activated Nrf2 mediated by the p38 kinase pathway in THP-1 monocytes. However, anti-inflammatory activity of DMA was attenuated by Nrf2 siRNA treatment. In an animal model, methylglyoxal (MG; 200mg/kg bw) was chosen to induce diabetes in Balb/C mice (6 weeks) in this work. The in vivo verification of anti-inflammation in peripheral blood mononuclear cells by DMA treatment was confirmed by tumor necrosis factor-α and interleukin-1β measurements. Oral glucose tolerance test, insulin tolerance test, hyperinsulinemia, and hyperglycemia were improved in MG-treated mice by DMA treatment and these effects were greater than those of silymarin and N-acetylcysteine. Furthermore, DMA increased hepatic glyoxalase mRNA and glutathione mediated by Nrf2 activation to metabolize MG into d-lactic acid, thereby reducing serum and hepatic AGE levels and suppressing inflammatory factor generation in MG-treated mice. However, DMA did not exert the antiglycation activity in MG-bovine serum albumin incubation. Taken together, the results indicate that DMA is a novel antioxidant and Nrf2 activator that lowers AGE levels and may prove to be an effective treatment for diabetes.

  11. Reduction of diabetic foot ulcer healing times through use of advanced treatment modalities.

    PubMed

    Mulder, Gerit; Tenenhaus, Mayer; D'Souza, Gehaan F

    2014-12-01

    Diabetic wounds are a major health care problem associated with delayed healing and high amputation rates. This review systematically evaluated newer wound care therapies for the treatment of diabetic wounds. More recent means of approaching diabetic foot ulcers include various dressings, off-loading shoes, and bioengineered skin constructs and growth factors. Electrical stimulation, phototherapy, electromagnetic fields, and shockwave therapy have been further proposed as potential treatments. A brief overview of these treatments is presented using peer-reviewed evidenced-based literature. A review of the literature demonstrated that treatment of diabetic wounds has focused on either prevention of the wounds in the form of off-loading shoes or adequate protective dressings or on direct treatment of wounds with bioengineered skin constructs, growth factors, or medical devices that accelerate wound healing. The authors' conclusion, following extensive literature review, is that although excellent national and international guidelines exist regarding suggested approaches to the treatment of the diabetic foot ulcer, there is no definitive or universal consensus on the choice of specific treatment modalities. The importance of optimizing comorbidities and the disease state, hemodynamics, local and peripheral skin and wound care, and metabolic challenges while reducing biological and bacterial burden and minimizing trauma remain the primary approach, followed by choice of the most appropriate treatment material or product.

  12. Successful aging: Advancing the science of physical independence in older adults.

    PubMed

    Anton, Stephen D; Woods, Adam J; Ashizawa, Tetso; Barb, Diana; Buford, Thomas W; Carter, Christy S; Clark, David J; Cohen, Ronald A; Corbett, Duane B; Cruz-Almeida, Yenisel; Dotson, Vonetta; Ebner, Natalie; Efron, Philip A; Fillingim, Roger B; Foster, Thomas C; Gundermann, David M; Joseph, Anna-Maria; Karabetian, Christy; Leeuwenburgh, Christiaan; Manini, Todd M; Marsiske, Michael; Mankowski, Robert T; Mutchie, Heather L; Perri, Michael G; Ranka, Sanjay; Rashidi, Parisa; Sandesara, Bhanuprasad; Scarpace, Philip J; Sibille, Kimberly T; Solberg, Laurence M; Someya, Shinichi; Uphold, Connie; Wohlgemuth, Stephanie; Wu, Samuel Shangwu; Pahor, Marco

    2015-11-01

    The concept of 'successful aging' has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. A consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults.

  13. Ameliorating Effect of Akebia quinata Fruit Extracts on Skin Aging Induced by Advanced Glycation End Products.

    PubMed

    Shin, Seoungwoo; Son, Dahee; Kim, Minkyung; Lee, Seungjun; Roh, Kyung-Baeg; Ryu, Dehun; Lee, Jongsung; Jung, Eunsun; Park, Deokhoon

    2015-11-12

    The accumulation of free radicals and advanced glycation end products (AGEs) in the skin plays a very important role in skin aging. Both are known to interact with each other. Therefore, natural compounds or extracts that possess both antioxidant and antiglycation activities might have great antiageing potential. Akebia quinata fruit extract (AQFE) has been used to treat urinary tract inflammatory disease in traditional Korean and Chinese medicines. In the present study, AQFE was demonstrated to possess antioxidant and antiglycation activity. AQFE protects human dermal fibroblasts (HDFs) from oxidative stress and inhibits cellular senescence induced by oxidative stress. We also found that AQFE inhibits glycation reaction between BSA and glucose. The antiglycation activity of AQFE was dose-dependent. In addition, the antiglycation activity of AQFE was confirmed in a human skin explant model. AQFE reduced CML expression and stimulated fibrillin-1 expression in comparison to the methyglyoxal treatment. In addition, the possibility of the extract as an anti-skin aging agent has also been clinically validated. Our analysis of the crow's feet wrinkle showed that there was a decrease in the depth of deep furrows in RI treated with AQFE cream over an eight-week period. The overall results suggest that AQFE may work as an anti-skin aging agent by preventing oxidative stress and other complications associated with AGEs formation.

  14. Extracellular superoxide dismutase deficiency impairs wound healing in advanced age by reducing neovascularization and fibroblast function

    PubMed Central

    Fujiwara, Toshihiro; Duscher, Dominik; Rustad, Kristine C.; Kosaraju, Revanth; Rodrigues, Melanie; Whittam, Alexander J.; Januszyk, Michael; Maan, Zeshaan N.; Gurtner, Geoffrey C.

    2016-01-01

    Advanced age is characterized by impairments in wound healing, and evidence is accumulating that this may be due in part to a concomitant increase in oxidative stress. Extended exposure to reactive oxygen species (ROS) is thought to lead to cellular dysfunction and organismal death via the destructive oxidation of intra-cellular proteins, lipids and nucleic acids. Extracellular superoxide dismutase (ecSOD/SOD3) is a prime antioxidant enzyme in the extracellular space that eliminates ROS. Here, we demonstrate that reduced SOD3 levels contribute to healing impairments in aged mice. These impairments include delayed wound closure, reduced neovascularization, impaired fibroblast proliferation and increased neutrophil recruitment. We further establish that SOD3 KO and aged fibroblasts both display reduced production of TGF-β1, leading to decreased differentiation of fibroblasts into myofibroblasts. Taken together, these results suggest that wound healing impairments in ageing are associated with increased levels of ROS, decreased SOD3 expression and impaired extracellular oxidative stress regulation. Our results identify SOD3 as a possible target to correct age-related cellular dysfunction in wound healing. PMID:26663425

  15. Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks

    PubMed Central

    Gómez-Serrano, María; Camafeita, Emilio; García-Santos, Eva; López, Juan A.; Rubio, Miguel A.; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2016-01-01

    Obesity is a main global health issue and an outstanding cause of morbidity and mortality predisposing to type 2 diabetes (T2DM) and cardiovascular diseases. Huge research efforts focused on gene expression, cellular signalling and metabolism in obesity have improved our understanding of these disorders; nevertheless, to bridge the gap between the regulation of gene expression and changes in signalling/metabolism, protein levels must be assessed. We have extensively analysed visceral adipose tissue from age-, T2DM- and gender-matched obese patients using high-throughput proteomics and systems biology methods to identify new biomarkers for the onset of T2DM in obesity, as well as to gain insight into the influence of aging and gender in these disorders. About 250 proteins showed significant abundance differences in the age, T2DM and gender comparisons. In diabetic patients, remarkable gender-specific hallmarks were discovered regarding redox status, immune response and adipose tissue accumulation. Both aging and T2DM processes were associated with mitochondrial remodelling, albeit through well-differentiated proteome changes. Systems biology analysis highlighted mitochondrial proteins that could play a key role in the age-dependent pathophysiology of T2DM. Our findings could serve as a framework for future research in Translational Medicine directed at improving the quality of life of obese patients. PMID:27160966

  16. Characteristics of basal insulin requirements by age and gender in Type-1 diabetes patients using insulin pump therapy.

    PubMed

    Scheiner, Gary; Boyer, Bret A

    2005-07-01

    Establishment of appropriate basal insulin levels is an essential component of intensive insulin therapy. While the existence of a "dawn phenomenon" is widely recognized, the present study sought to establish whether diurnal basal insulin patterns exist in Type-1 diabetes, and whether these patterns vary by age and gender. Participant data was drawn from 322 Type-1 insulin pump users treated at a private diabetes education practice in suburban Philadelphia. All participants completed a battery of fasting tests designed to match basal insulin levels to endogenous glucose production and insulin sensitivity. Analysis of resultant basal patterns revealed significant differences between juvenile (age < or =20) and adult (age >20) basal insulin patterns. The younger group exhibited a more pronounced and sustained night-time peak; the older group exhibiting a briefer and less pronounced early-morning peak. Lower overall basal insulin requirements were found in the youngest (age < or =10) and oldest (age >60) groups. No noteworthy gender differences were found. Results can serve as a guide for clinicians when initiating and fine-tuning patients who utilize basal/bolus insulin therapy.

  17. Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin dependent diabetes mellitus.

    PubMed

    Chakraborty, Goutam; Thumpayil, Sherin; Lafontant, David-Erick; Woubneh, Wolde; Toney, Jeffrey H

    2009-11-01

    Yellow KK mice carrying the 'yellow obese' gene Ay are a well established polygenic model for human non-insulin dependent diabetes mellitus. These animals develop marked adiposity and decreased glucose tolerance relative to their control littermates, KK mice. The authors monitored glucose tolerance in KK-Ay mice over time and observed a significant (Page-dependent improvement (13.3% by 175 d of age and 36.4% by 212 d of age, relative to 85 d of age). During the same time period, body weight and food and water consumption were relatively constant. The authors also measured plasma levels of endocrine hormones that are important in diabetes. Levels of insulin were approximately 8 times higher and levels of amylin 3 times higher in 220-d-old KK-Ay mice than in 180-d-old mice, whereas levels of glucagon-like peptide 1, glucagon and leptin remained relatively constant. These findings suggest that KK-Ay mice undergo an age-dependent improvement of glucose tolerance when maintained on a normal diet for 25 weeks or longer, due in part to increases in plasma levels of insulin and amylin.

  18. Screening of Undiagnosed Hypothyroidism in Elderly Persons with Diabetes according to Age-Specific Reference Intervals for Serum Thyroid Stimulating Hormone and the Impact of Antidiabetes Drugs

    PubMed Central

    Teixeira, Patricia de Fatima dos Santos; Vaisman, Mario

    2016-01-01

    Background. Studies have suggested that hypothyroidism is more frequent in the elderly with diabetes mellitus. However, an adaptation of TSH levels to age should be considered in this assessment. Some antidiabetes drugs reportedly interfere with TSH levels. The objectives of this study were to evaluate the prevalence of undiagnosed hypothyroidism in patients with diabetes and the influence of antidiabetes drugs. Material and Methods. 1160 subjects, 60 years and older (751 with diabetes), were studied; results were compared according to diabetes treatment and with persons without diabetes. TSH, FT4, antithyroperoxidase, fasting glucose, and HbA1c were measured. Results and Discussion. 6.4% of patients with diabetes had hypothyroidism, a higher prevalence compared with persons without diabetes (5.1%), but lower than observed in many studies. The use of age-specific TSH reference interval (RI) could explain this difference. Patients taking metformin (MTF) had TSH (showed in medians) slightly lower (2.8 mU/L) than those not on MTF (3.3 mU/L), p < 0.05. MTF doses influenced TSH levels. Conclusions. The use of specific TSH RI could avoid the misdiagnosis of hypothyroidism in elderly with diabetes. Patients in use of MTF as single drug had lower TSH than those using other medications and persons without diabetes. PMID:27403442

  19. Regional differences in incidence and clinical presentation of type 1 diabetes in children aged under 15 years in Croatia

    PubMed Central

    Stipančić, Gordana; La Grasta Sabolić, Lavinia; Požgaj Šepec, Marija; Radica, Ana; Skrabić, Veselin; Severinski, Srećko; Kujundžić Tiljak, Mirjana

    2012-01-01

    Aim To determine regional differences in the incidence, incidence trends, and clinical presentation of type 1 diabetes in children under the age of 15 years in Croatia in a 9-year period (1995-2003). Methods We included the patients who had been diagnosed with the disease and had started the insulin treatment before they were 15 years old. Regional differences between eastern, central, and southern Croatia were observed. The gross incidence was expressed by the number of newly diagnosed type 1 diabetes patients in 100 000 children of the same age and sex per year, ie, for the 0-14 age group, and for the 0-4, 5-9, and 10-14 subgroups. Results The highest incidence was observed in southern Croatia (10.91 per 100 000/y) and the lowest in central Croatia (8.64 per 100 000/y), and in eastern Croatia the incidence was 8.93 per 100 000/y. All three regions showed a growing incidence trend, which was significant only in eastern and southern Croatia. There was 35.9% of patients with diabetic ketoacidosis in eastern Croatia, 41.7% in central Croatia, and 31.3% in southern Croatia. Conclusion Croatian regions show differences in the incidence, incidence trends, and disease presentation of type 1 diabetes. A further follow-up is needed to establish whether the regional differences are a consequence of the population dynamics in the observed period or they will continue to exist, pointing to differences in environmental risk factors. PMID:22522992

  20. Relationship Between Skin Intrinsic Fluorescence—an Indicator of Advanced Glycation End Products—and Upper Extremity Impairments in Individuals With Diabetes Mellitus

    PubMed Central

    Shah, Kshamata M.; Clark, B. Ruth; McGill, Janet B.; Lang, Catherine E.; Maynard, John

    2015-01-01

    Background Accumulation of advanced glycation end products (AGEs) is thought to contribute to limited joint mobility in people with diabetes mellitus (DM), but the relationships among AGEs, shoulder structural changes, movement, and disability are not understood. Objective The purpose of this study was to determine the differences and relationships among skin intrinsic fluorescence (SIF), a proxy measure of AGEs, biceps and supraspinatus tendon thickness, upper extremity movement, and disability in groups with and without DM. Design This was a cross-sectional, case-control study. Methods Fifty-two individuals participated: 26 with type 2 DM and 26 controls matched for sex, age, and body mass index. The main outcome measures were: SIF; biceps and supraspinatus tendon thickness; 3-dimensional peak shoulder motion; and Disability of the Arm, Shoulder and Hand (DASH) questionnaire scores. Results Mean SIF measurements were 19% higher in the DM group compared with the control group (P<.05). Biceps tendons (mean and 95% confidence interval [CI]) (4.7 mm [4.4, 5.0] versus 3.2 mm [2.9, 3.5]) and supraspinatus tendons (6.4 mm [5.9, 6.8] versus 4.9 mm [4.4, 5.3]) were thicker and peak humerothoracic elevation (139° [135°, 146°] versus 150° [146°, 155°]) and glenohumeral external rotation (35° [26°, 46°] versus 51° [41°, 58°]) were reduced in the DM group compared with the control group (P<.05). In the DM group, SIF was correlated to biceps tendon thickness, DASH score, and shoulder motion (r=.44–.51, P<.05). The SIF score and shoulder strength explained 64% of the DASH scores (P<.01). Limitations Because this was a cross-sectional study design, a cause-effect relationship could not be established. Conclusions Accumulation of AGEs in the connective tissues of individuals with DM appears to be associated with increased tendon thickness and decreased shoulder joint mobility and upper extremity function. Physical therapists should be aware of these possible

  1. Advanced glycation end products, oxidative stress and metalloproteinases are altered in the cerebral microvasculature during aging.

    PubMed

    Safciuc, Florentina; Constantin, Alina; Manea, Adrian; Nicolae, Manuela; Popov, Doina; Raicu, Monica; Alexandru, Dorin; Constantinescu, Elena

    2007-11-01

    Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.

  2. Barriers to eye care among people aged 40 years and older with diagnosed diabetes, 2006-2010.

    PubMed

    Chou, Chiu-Fang; Sherrod, Cheryl E; Zhang, Xinzhi; Barker, Lawrence E; Bullard, Kai McKeever; Crews, John E; Saaddine, Jinan B

    2014-01-01

    OBJECTIVE We examine barriers to receiving recommended eye care among people aged ≥40 years with diagnosed diabetes. RESEARCH DESIGN AND METHODS We analyzed 2006-2010 Behavioral Risk Factor Surveillance System data from 22 states (n = 27,699). Respondents who had not sought eye care in the preceding 12 months were asked the main reason why. We categorized the reasons as cost/lack of insurance, no need, no eye doctor/travel/appointment, and other (meaning everything else). We used multinomial logistic regression to control for race/ethnicity, education, income, and other selected covariates. RESULTS Among adults with diagnosed diabetes, nonadherence to the recommended annual eye examinations was 23.5%. The most commonly reported reasons for not receiving eye care in the preceding 12 months were "no need" and "cost or lack of insurance" (39.7 and 32.3%, respectively). Other reasons were "no eye doctor," "no transportation" or "could not get appointment" (6.4%), and "other" (21.5%). After controlling for covariates, adults aged 40-64 years were more likely than those aged ≥65 years (relative risk ratio [RRR] = 2.79; 95% CI 2.01-3.89) and women were more likely than men (RRR = 2.33; 95% CI 1.75-3.14) to report "cost or lack of insurance" as their main reason. However, people aged 40-64 years were less likely than those aged ≥65 years to report "no need" (RRR = 0.51; 95% CI 0.39-0.67) as their main reason. CONCLUSIONS Addressing concerns about "cost or lack of insurance" for adults under 65 years and "no perceived need" among those 65 years and older could help improve eye care service utilization among people with diabetes.

  3. Barriers to Eye Care Among People Aged 40 Years and Older With Diagnosed Diabetes, 2006–2010

    PubMed Central

    Chou, Chiu-Fang; Sherrod, Cheryl E.; Zhang, Xinzhi; Barker, Lawrence E.; Bullard, Kai McKeever; Crews, John E.; Saaddine, Jinan B.

    2016-01-01

    OBJECTIVE We examine barriers to receiving recommended eye care among people aged ≥40 years with diagnosed diabetes. RESEARCH DESIGN AND METHODS We analyzed 2006–2010 Behavioral Risk Factor Surveillance System data from 22 states (n = 27,699). Respondents who had not sought eye care in the preceding 12 months were asked the main reason why. We categorized the reasons as cost/lack of insurance, no need, no eye doctor/travel/appointment, and other (meaning everything else). We used multinomial logistic regression to control for race/ethnicity, education, income, and other selected covariates. RESULTS Among adults with diagnosed diabetes, nonadherence to the recommended annual eye examinations was 23.5%. The most commonly reported reasons for not receiving eye care in the preceding 12 months were “no need” and “cost or lack of insurance” (39.7 and 32.3%, respectively). Other reasons were “no eye doctor,” “no transportation” or “could not get appointment” (6.4%), and “other” (21.5%). After controlling for covariates, adults aged 40–64 years were more likely than those aged ≥65 years (relative risk ratio [RRR] = 2.79; 95% CI 2.01–3.89) and women were more likely than men (RRR = 2.33; 95% CI 1.75–3.14) to report “cost or lack of insurance” as their main reason. However, people aged 40–64 years were less likely than those aged ≥65 years to report “no need” (RRR = 0.51; 95% CI 0.39–0.67) as their main reason. CONCLUSIONS Addressing concerns about “cost or lack of insurance” for adults under 65 years and “no perceived need” among those 65 years and older could help improve eye care service utilization among people with diabetes. PMID:24009300

  4. Presence of dopa and amino acid hydroperoxides in proteins modified with advanced glycation end products (AGEs): amino acid oxidation products as a possible source of oxidative stress induced by AGE proteins.

    PubMed Central

    Fu, S; Fu, M X; Baynes, J W; Thorpe, S R; Dean, R T

    1998-01-01

    Glycation and subsequent Maillard or browning reactions of glycated proteins, leading to the formation of advanced glycation end products (AGEs), are involved in the chemical modification of proteins during normal aging and have been implicated in the pathogenesis of diabetic complications. Oxidative conditions accelerate the browning of proteins by glucose, and AGE proteins also induce oxidative stress responses in cells bearing AGE receptors. These observations have led to the hypothesis that glycation-induced pathology results from a cycle of oxidative stress, increased chemical modification of proteins via the Maillard reaction, and further AGE-dependent oxidative stress. Here we show that the preparation of AGE-collagen by incubation with glucose under oxidative conditions in vitro leads not only to glycation and formation of the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML), but also to the formation of amino acid oxidation products on protein, including m-tyrosine, dityrosine, dopa, and valine and leucine hydroperoxides. The formation of both CML and amino acid oxidation products was prevented by anaerobic, anti-oxidative conditions. Amino acid oxidation products were also formed when glycated collagen, prepared under anti-oxidative conditions, was allowed to incubate under aerobic conditions that led to the formation of CML. These experiments demonstrate that amino acid oxidation products are formed in proteins during glycoxidation reactions and suggest that reactive oxygen species formed by redox cycling of dopa or by the metal-catalysed decomposition of amino acid hydroperoxides, rather than by redox activity or reactive oxygen production by AGEs on protein, might contribute to the induction of oxidative stress by AGE proteins. PMID:9461515

  5. Effects of age, system experience, and navigation technique on driving with an advanced traveler information system.

    PubMed

    Dingus, T A; Hulse, M C; Mollenhauer, M A; Fleischman, R N; McGehee, D V; Manakkal, N

    1997-06-01

    This paper explores the effects of age, system experience, and navigation technique on driving, navigation performance, and safety for drivers who used TravTek, an Advanced Traveler Information System. The first two studies investigated various route guidance configurations on the road in a specially equipped instrumented vehicle with an experimenter present. The third was a naturalistic quasi-experimental field study that collected data unobtrusively from more than 1200 TravTek rental car drivers with no in-vehicle experimenter. The results suggest that with increased experience, drivers become familiar with the system and develop strategies for substantially more efficient and safer use. The results also showed that drivers over age 65 had difficulty driving and navigating concurrently. They compensated by driving slowly and more cautiously. Despite this increased caution, older drivers made more safety-related errors than did younger drivers. The results also showed that older drivers benefited substantially from a well-designed ATIS driver interface.

  6. A Quiet Standing Index for Testing the Postural Sway of Healthy and Diabetic Adults Across a Range of Ages

    PubMed Central

    Bollt, Erik M.; Fulk, George D.; Skufca, Joseph D.; Al-Ajlouni, Ahmad F.; Robinson, Charles J.

    2010-01-01

    A quietstanding index is developed for tracking the postural sway of healthy and diabetic adults over a range of ages. Several postural sway features are combined into a single composite feature C that increases with age a. Sway features are ranked based on the r2 -values of their linear regression models, and the composite feature is a weighted sum of selected sway features with optimal weighting coefficients determined using principal component analysis. A performance index based on both reliability and sensitivity is used to determine the optimal number of features. The features used to form C include power and distance metrics. The quiet standing index is a scalar that compares the composite feature C to a linear regression model f (a) using C′ (a) = C/f (a). For a motionless subject, C′ = 0, and when the composite feature exactly matches the healthy control (HC) model, C′ = 1. Values of C′ ≫ 1 represent excessive postural sway and may indicate impaired postural control. Diabetic neurologically intact subjects, nondiabetic peripheral neuropathy subjects (PN), and diabetic PN subjects (DPN) were evaluated. The quiet standing indexes of the PN and DPN groups showed statistically significant increases over the HC group. Changes in the quiet standing index over time may be useful in identifying people with impaired balance who may be at an increased risk of falling. PMID:19342327

  7. Recent advances in understanding the anti-diabetic actions of dietary flavonoids.

    PubMed

    Babu, Pon Velayutham Anandh; Liu, Dongmin; Gilbert, Elizabeth R

    2013-11-01

    Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables, and increasing evidence demonstrates a positive relationship between consumption of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and animal studies support the beneficial effects of dietary flavonoids on glucose and lipid homeostasis. It is encouraging that the beneficial effects of some flavonoids are at physiological concentrations and comparable to clinically-used anti-diabetic drugs; however, clinical research in this field and studies on the anti-diabetic effects of flavonoid metabolites are limited. Flavonoids act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, hepatocytes, adipocytes and skeletal myofibers. Flavonoids may exert beneficial effects in diabetes by (i) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (ii) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (iii) reducing insulin resistance, inflammation and oxidative stress in muscle and fat and (iv) increasing glucose uptake in skeletal muscle and white adipose tissue. This review highlights recent findings on the anti-diabetic effects of dietary flavonoids, including flavan-3-ols, flavanones, flavonols, anthocyanidins, flavones and isoflavones, with particular emphasis on the studies that investigated the cellular and molecular mechanisms involved in the beneficial effects of the compounds.

  8. Recent advances in understanding the anti-diabetic actions of dietary flavonoids

    PubMed Central

    Babu, Pon Velayutham Anandh; Liu, Dongmin; Gilbert, Elizabeth R.

    2013-01-01

    Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables and increasing evidence demonstrates a positive relationship between consumption of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and animal studies support the beneficial effects of dietary flavonoids on glucose and lipid homeostasis. It is encouraging that the beneficial effects of some flavonoids are at physiological concentrations and comparable to clinically-used anti-diabetic drugs; however, clinical research in this field and studies on the anti-diabetic effects of flavonoid metabolites are limited. Flavonoids act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, hepatocytes, adipocytes, and skeletal myofibers. Flavonoids may exert beneficial effects in diabetes by (i) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells, (ii) improving hyperglycemia through regulation of glucose metabolism in hepatocytes, (iii) reducing insulin resistance, inflammation and oxidative stress in muscle and fat, and (iv) increasing glucose uptake in skeletal muscle and white adipose tissue. This review highlights recent findings on the anti-diabetic effects of dietary flavonoids, including flavan-3-ols, flavanones, flavonols, anthocyanidins, flavones, and isoflavones, with particular emphasis on the studies that investigated the cellular and molecular mechanisms involved in the beneficial effects of the compounds. PMID:24029069

  9. Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy

    PubMed Central

    2014-01-01

    Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of diabetes mellitus. The pathogenesis of DSPN is not fully elucidated, but it is certainly multifactorial in nature and attributable to metabolic and microvessel disorders related to chronic hyperglycemia, diabetes duration, and several cardiovascular risk factors. Early diagnosis and appropriate management are extremely important, since up to 50% of DSPN cases may be asymptomatic, and patients are unaware of foot injury leading to foot ulcers and amputation. Simple, validated tests such as the Neuropathy Disability Score and/or Vibration Perception Threshold may be used to diagnose DSPN. Similarly, neurological dysfunction screening questionnaires should be used to assess the quality and severity of DSPN symptoms. Using both methods enables prediction of the prognosis of diabetic patients with DSPN. No causative treatment of DSPN is known, but the results of clinical trials indicate that several treatment options are highly effective in symptomatic treatment of painful DSPN. The appropriate treatment of DSPN may improve the outcome, preventing or delaying the development of numerous diabetic complications. PMID:24904671

  10. Decreased resting-state connections within the visuospatial attention-related network in advanced aging.

    PubMed

    Li, Yujie; Li, Chunlin; Wu, Qiong; Xu, Zhihan; Kurata, Tomoko; Ohno, Seiichiro; Kanazawa, Susumu; Abe, Koji; Wu, Jinglong

    2015-06-15

    Advanced aging is accompanied by a decline in visuospatial attention. Previous neuroimaging and electrophysiological studies have demonstrated dysfunction in specific brain areas related to visuospatial attention. However, it is still unclear how the functional connectivity between brain regions causes the decline of visuospatial attention. Here, we combined task and rest functional magnetic resonance imaging (fMRI) to investigate the age-dependent alterations of resting-state functional connectivity within the task-related network. Twenty-three young subjects and nineteen elderly subjects participated in this study, and a modified Posner paradigm was used to define the region of interest (ROI). Our results showed that a marked reduction in the number of connections occurred with age, but this effect was not uniform throughout the brain: while there was a significant loss of communication in the anterior portion of the brain and between the anterior and posterior cerebral cortices, communication in the posterior portion of the brain was preserved. Moreover, the older adults exhibited weakened resting-state functional connectivity between the supplementary motor area and left anterior insular cortex. These findings suggest that, the disrupted functional connectivity of the brain network for visuospatial attention that occurs during normal aging may underlie the decline in cognitive performance.

  11. Successful Aging: Advancing the Science of Physical Independence in Older Adults

    PubMed Central

    Anton, Stephen D.; Woods, Adam J.; Ashizawa, Tetso; Barb, Diana; Buford, Thomas W.; Carter, Christy S.; Clark, David J.; Cohen, Ronald A.; Corbett, Duane B.; Cruz-Almeida, Yenisel; Dotson, Vonetta; Ebner, Natalie; Efron, Philip A.; Fillingim, Roger B.; Foster, Thomas C.; Gundermann, David M.; Joseph, Anna-Maria; Karabetian, Christy; Leeuwenburgh, Christiaan; Manini, Todd M.; Marsiske, Michael; Mankowski, Robert T.; Mutchie, Heather L.; Perri, Michael G.; Ranka, Sanjay; Rashidi, Parisa; Sandesara, Bhanuprasad; Scarpace, Philip J.; Sibille, Kimberly T.; Solberg, Laurence M.; Someya, Shinichi; Uphold, Connie; Wohlgemuth, Stephanie; Wu, Samuel Shangwu; Pahor, Marco

    2015-01-01

    The concept of ‘Successful Aging’ has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults. PMID:26462882

  12. DNA methylation errors in cloned mice disappear with advancement of aging.

    PubMed

    Senda, Sho; Wakayama, Teruhiko; Arai, Yoshikazu; Yamazaki, Yukiko; Ohgane, Jun; Tanaka, Satoshi; Hattori, Naka; Yanagimachi, Ryuzo; Shiota, Kunio

    2007-01-01

    Cloned animals have various health problems. Aberrant DNA methylation is a possible cause of the problems. Restriction landmark genomic scanning (RLGS) that enabled us to analyze more than 1,000 CpG islands simultaneously demonstrated that all cloned newborns had aberrant DNA methylation. To study whether this aberration persists throughout the life of cloned individuals, we examined genome-wide DNA methylation status of newborn (19.5 dpc, n=2), adult (8-11 months old, n=3), and aged (23-27 months old, n=4) cloned mice using kidney cells as representatives. In the adult and aged groups, cloning was repeated using cumulus cells of the adult founder clone of each group as nucleus donor. Two newborn clones had three with aberrantly methylated loci, which is consistent with previous reports that all cloned newborns had DNA methylation aberrations. Interestingly, we could detect only one aberrantly methylated locus in two of the three adult clones in mid-age and none of four senescent clones, indicating that errors in DNA methylation disappear with advancement of animals' aging.

  13. The Age-Specific Quantitative Effects of Metabolic Risk Factors on Cardiovascular Diseases and Diabetes: A Pooled Analysis

    PubMed Central

    Farzadfar, Farshad; Stevens, Gretchen A.; Woodward, Mark; Wormser, David; Kaptoge, Stephen; Whitlock, Gary; Qiao, Qing; Lewington, Sarah; Di Angelantonio, Emanuele; vander Hoorn, Stephen; Lawes, Carlene M. M.; Ali, Mohammed K.; Mozaffarian, Dariush; Ezzati, Majid

    2013-01-01

    Background The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available. Methods We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models. Results Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55–64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09–2.24), followed by effects on both stroke subtypes (1.66; 1.39–1.98 for hemorrhagic stroke and 1.63; 1.57–1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29–1.61) for IHD and 1.20 (1.15–1.25) for ischemic stroke. The RRs for 5 kg/m2 higher BMI for ages 55–64 ranged from 2.32 (2.04–2.63) for diabetes, to 1.44 (1.40–1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08–1.29) for IHD and 1.14 (1.01–1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs. Conclusion Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group. PMID:23935815

  14. Cholecystokinin expression in the β-cell leads to increased β-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis.

    PubMed

    Lavine, Jeremy A; Kibbe, Carly R; Baan, Mieke; Sirinvaravong, Sirinart; Umhoefer, Heidi M; Engler, Kimberly A; Meske, Louise M; Sacotte, Kaitlyn A; Erhardt, Daniel P; Davis, Dawn Belt

    2015-11-15

    Cholecystokinin (CCK) is a peptide hormone produced in the gut and brain with beneficial effects on digestion, satiety, and insulin secretion. CCK is also expressed in pancreatic β-cells, but only in models of obesity and insulin resistance. Whole body deletion of CCK in obese mice leads to reduced β-cell mass expansion and increased apoptosis. We hypothesized that islet-derived CCK is important in protection from β-cell apoptosis. To determine the specific role of β-cell-derived CCK in β-cell mass dynamics, we generated a transgenic mouse that expresses CCK in the β-cell in the lean state (MIP-CCK). Although this transgene contains the human growth hormone minigene, we saw no expression of human growth hormone protein in transgenic islets. We examined the ability of MIP-CCK mice to maintain β-cell mass when subjected to apoptotic stress, with advanced age, and after streptozotocin treatment. Aged MIP-CCK mice have increased β-cell area. MIP-CCK mice are resistant to streptozotocin-induced diabetes and exhibit reduced β-cell apoptosis. Directed CCK overexpression in cultured β-cells also protects from cytokine-induced apoptosis. We have identified an important new paracrine/autocrine effect of CCK in protection of β-cells from apoptotic stress. Understanding the role of β-cell CCK adds to the emerging knowledge of classic gut peptides in intraislet signaling. CCK receptor agonists are being investigated as therapeutics for obesity and diabetes. While these agonists clearly have beneficial effects on body weight and insulin sensitivity in peripheral tissues, they may also directly protect β-cells from apoptosis.

  15. Failure to Modulate Attentional Control in Advanced Aging Linked to White Matter Pathology

    PubMed Central

    Van Dijk, Koene R. A.; Shire, Emily H.; Sperling, Reisa A.; Johnson, Keith A.; Buckner, Randy L.

    2012-01-01

    Advanced aging is associated with reduced attentional control and less flexible information processing. Here, the origins of these cognitive effects were explored using a functional magnetic resonance imaging task that systematically varied demands to shift attention and inhibit irrelevant information across task blocks. Prefrontal and parietal regions previously implicated in attentional control were recruited by the task and most so for the most demanding task configurations. A subset of older individuals did not modulate activity in frontal and parietal regions in response to changing task requirements. Older adults who did not dynamically modulate activity underperformed their peers and scored more poorly on neuropsychological measures of executive function and speed of processing. Examining 2 markers of preclinical pathology in older adults revealed that white matter hyperintensities (WMHs), but not high amyloid burden, were associated with failure to modulate activity in response to changing task demands. In contrast, high amyloid burden was associated with alterations in default network activity. These results suggest failure to modulate frontal and parietal activity reflects a disruptive process in advanced aging associated with specific neuropathologic processes. PMID:21765181

  16. Protective role of sulphoraphane against vascular complications in diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Matsui, Takanori

    2016-10-01

    Context Diabetes is a global health challenge. Although large prospective clinical trials have shown that intensive control of blood glucose or blood pressure reduces the risk for development and progression of vascular complications in diabetes, a substantial number of diabetic patients still experience renal failure and cardiovascular events, which could account for disabilities and high mortality rate in these subjects. Objective Sulphoraphane is a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, such as broccoli, cabbage and Brussels sprouts, and an inducer of phase II antioxidant and detoxification enzymes with anticancer properties. We reviewed here the protective role of sulphoraphane against diabetic vascular complications. Methods In this review, literature searches were undertaken in Medline and in CrossRef. Non-English language articles were excluded. Keywords [sulphoraphane and (diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic complications, vascular, cardiomyocytes, heart or glycation)] have been used to select the articles. Results There is accumulating evidence that sulphoraphane exerts beneficial effects on vascular damage in both cell culture and diabetic animal models via antioxidative properties. Furthermore, we have recently found that sulphoraphane inhibits in vitro formation of advanced glycation end products (AGEs), suppresses the AGE-induced inflammatory reactions in rat aorta by reducing receptor for AGEs (RAGE) expression and decreases serum levels of AGEs in humans. Conclusion These findings suggest that blockade of oxidative stress and/or the AGE-RAGE axis by sulphoraphane may be a novel therapeutic strategy for preventing vascular complications in diabetes.

  17. Advanced glycation end product 3 (AGE3) suppresses the mineralization of mouse stromal ST2 cells and human mesenchymal stem cells by increasing TGF-β expression and secretion.

    PubMed

    Notsu, Masakazu; Yamaguchi, Toru; Okazaki, Kyoko; Tanaka, Ken-ichiro; Ogawa, Noriko; Kanazawa, Ippei; Sugimoto, Toshitsugu

    2014-07-01

    In diabetic patients, advanced glycation end products (AGEs) cause bone fragility because of deterioration of bone quality. We previously showed that AGEs suppressed the mineralization of mouse stromal ST2 cells. TGF-β is abundant in bone, and enhancement of its signal causes bone quality deterioration. However, whether TGF-β signaling is involved in the AGE-induced suppression of mineralization during the osteoblast lineage remains unknown. We therefore examined the roles of TGF-β in the AGE-induced suppression of mineralization of ST2 cells and human mesenchymal stem cells. AGE3 significantly (P < .001) inhibited mineralization in both cell types, whereas transfection with small interfering RNA for the receptor for AGEs (RAGEs) significantly (P < .05) recovered this process in ST2 cells. AGE3 increased (P < .001) the expression of TGF-β mRNA and protein, which was partially antagonized by transfection with RAGE small interfering RNA. Treatment with a TGF-β type I receptor kinase inhibitor, SD208, recovered AGE3-induced decreases in osterix (P < .001) and osteocalcin (P < .05) and antagonized the AGE3-induced increase in Runx2 mRNA expression in ST2 cells (P < .001). Moreover, SD208 completely and dose dependently rescued AGE3-induced suppression of mineralization in both cell types. In contrast, SD208 intensified AGE3-induced suppression of cell proliferation as well as AGE3-induced apoptosis in proliferating ST2 cells. These findings indicate that, after cells become confluent, AGE3 partially inhibits the differentiation and mineralization of osteoblastic cells by binding to RAGE and increasing TGF-β expression and secretion. They also suggest that TGF-β adversely affects bone quality not only in primary osteoporosis but also in diabetes-related bone disorder.

  18. Prevalence and risk factors of diabetes mellitus in a central district in Islamic Republic of Iran: a population-based study on adults aged 40-80 years.

    PubMed

    Katibeh, M; Hosseini, S; Soleimanizad, R; Manaviat, M R; Kheiri, B; Khabazkhoob, M; Daftarian, N; Dehghan, M H

    2015-09-08

    Previous studies on type 2 diabetes mellitus in the Islamic Republic of Iran were mainly performed in provinces with large populations. This study determined the prevalence and risk factors of diabetes mellitus in an adult population (40-80 years old) from Yazd district. Multistage, systematic cluster random sampling was used in a crosssectional, population-based survey. Demographic, clinical and anthropometric data were collected, with diabetes defined as fasting blood sugar ≥ 7 mmol/L or a positive medical history of diabetes. The age- and sex-standardized prevalence of diabetes in 2090 individuals participants was 24.5% (95% CI: 22.2-26.8%), including 10.5% new cases. For each year of ageing, the prevalence of diabetes increased significantly by 4% and this trend was more pronounced in females than males. Low education and hypertension were significantly associated with diabetes prevalence. The prevalence of diabetes mellitus in Yazd is greater than the average levels nationwide and those of nearby countries.

  19. Age-Period-Cohort Analysis of 1990–2003 Incidence Time Trends of Childhood Diabetes in Italy

    PubMed Central

    Bruno, Graziella; Maule, Milena; Merletti, Franco; Novelli, Giulia; Falorni, Alberto; Iannilli, Antonio; Iughetti, Lorenzo; Altobelli, Emma; d'Annunzio, Giuseppe; Piffer, Silvano; Pozzilli, Paolo; Iafusco, Dario; Songini, Marco; Roncarolo, Federico; Toni, Sonia; Carle, Flavia; Cherubini, Valentino

    2010-01-01

    OBJECTIVE To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0–14 years in Italian registries. RESEARCH DESIGN AND METHODS This report is based on 5,180 incident cases in the period 1990–2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component. RESULTS The incidence rate was 12.26 per 100,000 person-years and significantly higher in boys (13.13 [95% CI 12.66–13.62]) than in girls (11.35 [10.90–11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22–3.67]). With respect to the calendar period 1990–1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987–1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54–0.73) in the 1975–1981 cohort to 1.38 (1.06–1.80) in the 1999–2003 cohort. The best model, however, included sex, age, and a linear time trend (drift). CONCLUSIONS Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort. PMID:20566665

  20. Race/ethnicity-, gender- and age-specific differences in micronutrient intakes of US adults with and without diabetes.

    PubMed

    Vaccaro, Joan A; Huffman, Fatma G

    2013-03-01

    Race/ethnicity-, gender- and age-specific differences in dietary micronutrient intakes of US adults ≥  21 years were assessed from National Health and Nutrition Examination Survey, 2007-2008. The participants included Black non-Hispanics, Mexican-American and White non-Hispanics who signed an informed consent form for the interview and who completed the in-person 24-h recall. Micronutrient intakes were based on the Institute of Medicines' classifications of recommended dietary allowances specific for age and gender. Likelihood of many micronutrient insufficiencies was associated with being female, over 65 years, having diabetes and minority status. Younger and female adults had a greater likelihood of iron insufficiency than male and older adults. These findings demonstrate the importance of considering the intersection of age, gender and race in setting policies for micronutrient deficiency screening, particularly in young female adults and minorities.

  1. Recent Advances in Nanotechnology-Based Diagnosis and Treatments of Diabetes.

    PubMed

    Rao, Pasupuleti Visweswara; Gan, Siew Hua

    2015-01-01

    Nanotechnology is a field encompassing nanostructures, nanomaterials and nanoparticles, which are of increasing importance to researchers and industrial players alike. Nanotechnology addresses the construction and consumption of substances and devices on the nanometer scale. Nanomedicine is a new field that combines nanotechnology with medicine to boost human health care. Nanomedicine is an interdisciplinary field that includes various areas of biology, chemistry, physics and engineering. The most important problems related to diabetes management, such as self-monitoring of blood glucose levels and insulin injections, can now be conquered due to progress in nanomedicine, which offers glucose nanosensors, the layer-by-layer technique, carbon nanotubes, quantum dots, oral insulins, microspheres, artificial pancreases and nanopumps. In this review, the key methodological and scientific characteristics of nanomedicine related to diabetes treatment, glucose monitoring and insulin administration are discussed.

  2. Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates diabetes-induced renal damage through the advanced glycation end product-related pathway in db/db mice.

    PubMed

    Park, Chan Hum; Yokozawa, Takako; Noh, Jeong Sook

    2014-08-01

    This study was conducted to examine whether oligonol, a low-molecular-weight polyphenol derived from lychee fruit, has an ameliorative effect on diabetes-induced alterations, such as advanced glycation end product (AGE) formation or apoptosis in the kidneys of db/db mice with type 2 diabetes. Oligonol [10 or 20 mg/(kg body weight · d), orally] was administered every day for 8 wk to prediabetic db/db mice, and its effect was compared with vehicle-treated db/db and normal control mice (m/m). The administration of oligonol decreased the elevated renal glucose concentrations and reactive oxygen species in db/db mice (P < 0.05). The increased serum urea nitrogen and creatinine concentrations, which reflect renal dysfunction in db/db mice, were substantially lowered by oligonol. Oligonol reduced renal protein expression of NAD(P)H oxidase subunits (p22 phagocytic oxidase and NAD(P)H oxidase-4), AGEs (except for pentosidine), and c-Jun N-terminal kinase B-targeting proinflammatory tumor necrosis factor-α (P < 0.05). Oligonol improved the expressions of antiapoptotic [B-cell lymphoma protein 2 (Bcl-2) and survivin] and proapoptotic [Bcl-2-associated X protein, cytochrome c, and caspase-3] proteins in the kidneys of db/db mice (P < 0.05). In conclusion, these results provide important evidence that oligonol exhibits a pleiotropic effect on AGE formation and apoptosis-related variables, representing renoprotective effects against the development of diabetic complications in db/db mice with type 2 diabetes.

  3. A competing-risk-based score for predicting twenty-year risk of incident diabetes: the Beijing Longitudinal Study of Ageing study

    PubMed Central

    Liu, Xiangtong; Chen, Zhenghong; Fine, Jason Peter; Liu, Long; Wang, Anxin; Guo, Jin; Tao, Lixin; Mahara, Gehendra; Yang, Kun; Zhang, Jie; Tian, Sijia; Li, Haibin; Liu, Kuo; Luo, Yanxia; Zhang, Feng; Tang, Zhe; Guo, Xiuhua

    2016-01-01

    Few risk tools have been proposed to quantify the long-term risk of diabetes among middle-aged and elderly individuals in China. The present study aimed to develop a risk tool to estimate the 20-year risk of developing diabetes while incorporating competing risks. A three-stage stratification random-clustering sampling procedure was conducted to ensure the representativeness of the Beijing elderly. We prospectively followed 1857 community residents aged 55 years and above who were free of diabetes at baseline examination. Sub-distribution hazards models were used to adjust for the competing risks of non-diabetes death. The cumulative incidence function of twenty-year diabetes event rates was 11.60% after adjusting for the competing risks of non-diabetes death. Age, body mass index, fasting plasma glucose, health status, and physical activity were selected to form the score. The area under the ROC curve (AUC) was 0.76 (95% Confidence Interval: 0.72–0.80), and the optimism-corrected AUC was 0.78 (95% Confidence Interval: 0.69–0.87) after internal validation by bootstrapping. The calibration plot showed that the actual diabetes risk was similar to the predicted risk. The cut-off value of the risk score was 19 points, marking mark the difference between low-risk and high-risk patients, which exhibited a sensitivity of 0.74 and specificity of 0.65. PMID:27849048

  4. Incidence of Prediabetes and Type 2 Diabetes among People Aged over 20 Years in Ahvaz: A 5-Year Perspective Study (2009–2014)

    PubMed Central

    Shahbazian, Hajieh; Hardani Pasand, Leila

    2016-01-01

    Background. The present study is the fourth cohort study conducted in the Middle East on the evaluation of prediabetes and type 2 diabetes, implemented in Ahvaz, Iran. Methodology. The individuals aged over twenty years who had participated in a study on the prevalence of metabolic syndrome in 2009 (Phase 1) in Ahvaz were invited again in 2014. The questionnaires were completed via interview, and anthropometric parameters were measured by standard method. The logistic regression and chi-square test were used for data analysis. Results. In the median of five-year follow-up, a number of 593 people participated in reexamination from which 396 individuals were nondiabetic in Phase 1. The incidence of diabetes and prediabetes was 21.9 and 40.6 per 1000 person-years, respectively. Among Phase 1 prediabetics, 16.8% were diagnosed with diabetes in a five-year period. The factors affecting the incidence of prediabetes among the people younger than 65 years include age, family history of diabetes, and gender. The age factor plays an important role in the transformation of prediabetes to diabetes. Conclusion. The city of Ahvaz with type 2 diabetes incidence of 13.64 per 1000 person-years is one of the areas with high incidence of diabetes in Iran. PMID:28004008

  5. A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

  6. Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes.

    PubMed

    Gómez-Serrano, María; Camafeita, Emilio; López, Juan A; Rubio, Miguel A; Bretón, Irene; García-Consuegra, Inés; García-Santos, Eva; Lago, Jesús; Sánchez-Pernaute, Andrés; Torres, Antonio; Vázquez, Jesús; Peral, Belén

    2017-04-01

    Human age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese patients by quantitating not only the corresponding abundance changes of proteins, but also the redox alterations undergone by Cys residues thereof. For that, we have resorted to a high-throughput proteomic approach based on isobaric labeling, liquid chromatography and mass spectrometry. The alterations undergone by the mitochondrial proteome revealed aging- and T2DM-specific hallmarks. Thus, while a global decrease of oxidative phosphorylation (OXPHOS) subunits was found in aging, the diabetic patients exhibited a reduction of specific OXPHOS complexes as well as an up-regulation of the anti-oxidant response. Under both conditions, evidence is shown for the first time of a link between increased thiol protein oxidation and decreased protein abundance in adipose tissue mitochondria. This association was stronger in T2DM, where OXPHOS mitochondrial- vs. nuclear-encoded protein modules were found altered, suggesting impaired mitochondrial protein translocation and complex assembly. The marked down-regulation of OXPHOS oxidized proteins and the alteration of oxidized Cys residues related to protein import through the redox-active MIA (Mitochondrial Intermembrane space Assembly) pathway support that defects in protein translocation to the mitochondria may be an important underlying mechanism for mitochondrial dysfunction in T2DM and physiological aging. The present draft of redox targets together with the quantification of protein and oxidative changes may help to better understand the role of oxidative stress in both a physiological process like aging and a pathological condition like T2DM.

  7. Could metformin be used in patients with diabetes and advanced chronic kidney disease?

    PubMed

    Chowdhury, Tahseen A; Srirathan, Danushan; Abraham, Georgi; Oei, Elizabeth L; Fan, Stanley L; McCafferty, Kieran; Yaqoob, M Magdi

    2017-02-01

    Diabetes is an important cause of end stage renal failure worldwide. As renal impairment progresses, managing hyperglycaemia can prove increasingly challenging, as many medications are contra-indicated in moderate to severe renal impairment. Whilst evidence for tight glycaemic control reducing progression to renal failure in patients with established renal disease is limited, poor glycaemic control is not desirable, and is likely to lead to progressive complications. Metformin is a first-line therapy in patients with Type 2 diabetes, as it appears to be effective in reducing diabetes related end points and mortality in overweight patients. Cessation of metformin in patients with progressive renal disease may not only lead to deterioration in glucose control, but also to loss of protection from cardiovascular disease in a cohort of patients at particularly high risk. We advocate the need for further study to determine the role of metformin in patients with severe renal disease (chronic kidney disease stage 4-5), as well as patients on dialysis, or pre-/peri-renal transplantation. We explore possible roles of metformin in these circumstances, and suggest potential key areas for further study.

  8. Advancements and challenges in generating accurate animal models of gestational diabetes mellitus.

    PubMed

    Pasek, Raymond C; Gannon, Maureen

    2013-12-01

    The maintenance of glucose homeostasis during pregnancy is critical to the health and well-being of both the mother and the developing fetus. Strikingly, approximately 7% of human pregnancies are characterized by insufficient insulin production or signaling, resulting in gestational diabetes mellitus (GDM). In addition to the acute health concerns of hyperglycemia, women diagnosed with GDM during pregnancy have an increased incidence of complications during pregnancy as well as an increased risk of developing type 2 diabetes (T2D) later in life. Furthermore, children born to mothers diagnosed with GDM have increased incidence of perinatal complications, including hypoglycemia, respiratory distress syndrome, and macrosomia, as well as an increased risk of being obese or developing T2D as adults. No single environmental or genetic factor is solely responsible for the disease; instead, a variety of risk factors, including weight, ethnicity, genetics, and family history, contribute to the likelihood of developing GDM, making the generation of animal models that fully recapitulate the disease difficult. Here, we discuss and critique the various animal models that have been generated to better understand the etiology of diabetes during pregnancy and its physiological impacts on both the mother and the fetus. Strategies utilized are diverse in nature and include the use of surgical manipulation, pharmacological treatment, nutritional manipulation, and genetic approaches in a variety of animal models. Continued development of animal models of GDM is essential for understanding the consequences of this disease as well as providing insights into potential treatments and preventative measures.

  9. Recent Demographic Developments in France: Relatively Low Mortality at Advanced Ages

    PubMed Central

    Prioux, France; Barbieri, Magali

    2013-01-01

    France had 65.3 million inhabitants as of 1 January 2012, including 1.9 million in the overseas départements. The population is slightly younger than that of the European Union as a whole. Population growth continues at the same rate, mainly through natural increase. There are now more African than European immigrants living in France. Fertility was practically stable in 2011 (2.01 children per woman), but the lifetime fertility of the 1971–1972 cohorts reached a historic low in metropolitan France (1.99 children per woman), nevertheless remaining among the highest in Europe. Abortion levels remained stable and rates among young people are no longer increasing. The marriage rate is falling and the divorce rate has stabilized (46.2 divorces per 100 marriages in 2011). The risk of divorce decreases with age, but has greatly increased among the under-70s over the last decade. Life expectancy at birth (78.4 years for men, 85.0 for women) has continued to increase at the same rate, mainly thanks to progress at advanced ages. Among European countries, France has the lowest mortality in the over-65 age group, but it ranks less well for premature mortality. PMID:24285939

  10. Immunoparesis and monoclonal gammopathy of undetermined significance are disassociated in advanced age.

    PubMed

    Cherry, Benjamin M; Costello, Rene; Zingone, Adriana; Burris, Jason; Korde, Neha; Manasanch, Elisabet; Kwok, Mary; Annunziata, Christina; Roschewski, Mark J; Engels, Eric A; Landgren, Ola

    2013-02-01

    Immunoparesis and a skewed serum free light chain (FLC) ratio are indicators of immune dysfunction predictive of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). Previous studies have reported increased prevalence of MGUS by age, but no study has examined the relationship between immunoparesis and abnormal FLC ratios in the elderly. We screened 453 older adults (median age, 80 years; range, 65-96) to characterize the patterns of immunoparesis and abnormal FLC ratio in relation to MGUS. We defined MGUS in 4.4% of the subjects; the prevalence was 12.5% among individuals of >90 years. In MGUS (vs. non-MGUS) cases, immunoparesis and abnormal FLC ratios were detected in 70.0% (vs. 49.0%; P = 0.07) and 50.0% (vs. 12.9%; P = 0.0001), respectively. Based on small numbers, MGUS patients with abnormal FLC ratio were borderline (P = 0.07) more likely to have immunoparesis. Overall, the prevalence of immunoparesis varied in a nonlinear fashion, with lowest frequencies in the youngest and oldest groups. Our observed disassociation between MGUS prevalence and impaired immunoglobulin production suggests that separate mechanisms are involved in the development of MGUS and immunoparesis in advanced age. These findings emphasize the need for molecularly defined methods to characterize myeloma precursor states and better predict progression to MM.

  11. Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes.

    PubMed

    Leete, Pia; Willcox, Abby; Krogvold, Lars; Dahl-Jørgensen, Knut; Foulis, Alan K; Richardson, Sarah J; Morgan, Noel G

    2016-05-01

    Type 1 diabetes (T1D) results from a T cell-mediated destruction of pancreatic β-cells following the infiltration of leukocytes (including CD8(+), CD4(+), and CD20(+) cells) into and around pancreatic islets (insulitis). Recently, we reported that two distinct patterns of insulitis occur in patients with recent-onset T1D from the U.K. and that these differ principally in the proportion of infiltrating CD20(+) B cells (designated CD20Hi and CD20Lo, respectively). We have now extended this analysis to include patients from the Network for Pancreatic Organ Donors with Diabetes (U.S.) and Diabetes Virus Detection (DiViD) study (Norway) cohorts and confirm that the two profiles of insulitis occur more widely. Moreover, we show that patients can be directly stratified according to their insulitic profile and that those receiving a diagnosis before the age of 7 years always display the CD20Hi profile. By contrast, individuals who received a diagnosis beyond the age of 13 years are uniformly defined as CD20Lo. This implies that the two forms of insulitis are differentially aggressive and that patients with a CD20Hi profile lose their β-cells at a more rapid rate. In support of this, we also find that the proportion of residual insulin-containing islets (ICIs) increases in parallel with age at the onset of T1D. Importantly, those receiving a diagnosis in, or beyond, their teenage years retain ∼40% ICIs at diagnosis, implying that a functional deficit rather than an absolute β-cell loss may be causal for disease onset in these patients. We conclude that appropriate patient stratification will be critical for correct interpretation of the outcomes of intervention therapies targeted to islet-infiltrating immune cells in T1D.

  12. Possible participation of receptor for advanced glycation end products (RAGE) in the origin of cancer stem cells in diabetic patients with colon cancer.

    PubMed

    Hu, Xiang; Cheng, Yong

    2013-05-01

    The association between diabetes and the associated increased risk of several solid malignancies has been the subject of investigation for many years, while potential biologic links between the two diseases are incompletely understood. The receptor for advanced glycation end-products (RAGE) signal transduction may represent a focal point in their respective contributions to malignant transformation associated diabetes. While the physiopathology of RAGE axis in promoting malignancies cannot be explained completely by the available mechanism as perpetuating inflammation at tumor microenvironment. In addition, experimental researches revealed a crucial role for upstreams of RAGE signaling pathway in maintaining the stemness properties and tumorigenicity of cancer stem cells. Hence, we hypothesized that RAGE inducing cancer stem cells may be a key determinant in the origin and progression of colon malignant tumors concomitant diabetes. Such an opinion not only bands together the seemingly disparate various complications in diabetes and colon cancers, but also has future implications for risk assessment and biopharmaceutical treatment.

  13. Pathophysiology of diabetic sexual dysfunction.

    PubMed

    Morano, S

    2003-01-01

    Sexual dysfunction is common in patients with diabetes mellitus. Vascular, neurological and hormonal alterations are involved in this complication. Many studies showed altered endothelium-dependent and neurogenic relaxations in corpus cavernosum from diabetic patients with erectile dysfunction (ED). This finding has been associated with a lack of nitric oxyde (NO) production and a significant increase in NO synthase (NOS) binding sites in penile tissues, induced by diabetes. Advanced glycation endproducts (AGEs) concur to diabetic vascular complications by quenching NO activity and by increasing the expression of mediators of vascular damage such as vascular endothelial growth factor (VEGF), possessing permeabilizing and neoangiogenic effects, and endothelin-1 (ET-1), with vaso-constricting and mitogenic action. Moreover, the differential gene expression for various growth factors in penile tissues may be involved in the pathophysiology of ED associated with diabetes. Neuropathy is also likely to be an important cause of diabetic ED: morphological alterations of autonomic nerve fibers in cavernosal tissue of patients with diabetic ED have been demonstrated. Finally, androgens enhance nNOS gene expression in the penile corpus cavernosum of rats, suggesting that they play a role in maintaining NOS activity. However, sexual dysfunctions in women with diabetes has received less attention in clinical research. Several studies suggest an increased prevalence of deficient vaginal lubrication, making sexual intercourse unpleasant. Sexual dysfunction is associated with lower overall quality of marital relation and more depressive symptoms in diabetic women.

  14. Mitigating effects of antioxidant properties of Artemisia campestris leaf extract on hyperlipidemia, advanced glycation end products and oxidative stress in alloxan-induced diabetic rats.

    PubMed

    Sefi, Mediha; Fetoui, Hamadi; Makni, Mohamed; Zeghal, Najiba

    2010-07-01

    Artemisia campestris is used as antivenom and anti-inflammatory Tunisian folk medicine. Recently, increased oxidative stress was shown to play an important role in the etiology and pathogenesis of diabetes mellitus and its complications. This study was designed to examine the effects of A. campestris leaf aqueous extract (Ac) on alloxan-induced diabetic rats by measuring glycemia, lipid profile, lipid peroxidation (MDA), protein carbonyl content (PCO), advanced oxidation protein products (AOPP), activities of both non-enzymatic and enzymatic antioxidants. Results of our study showed an increase in blood glucose levels, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), a decrease in high-density lipoprotein cholesterol (HDL-c) level and disturbed antioxidant enzyme activities (CAT, SOD, GPx) in the pancreatic tissue of diabetic rats. Furthermore, MDA, PCO and AOPP were elevated in the pancreas of the diabetic rats. The administration of Ac to diabetic rats at a dose of 200mgkg(-1)bw resulted in a significant reduction in glycemia, TC, TG, LDL-c, pancreas LPO, PCO and AOPP levels, CAT and GPx activities associated with an elevation of GSH content and SOD activity in comparison with diabetic group. We conclude that A. campestris aqueous extract may be effective for correcting hyperglycemia and preventing diabetic complications.

  15. Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus.

    PubMed

    Heida, Karst Y; Franx, Arie; van Rijn, Bas B; Eijkemans, Marinus J C; Boer, Jolanda M A; Verschuren, Monique W M; Oudijk, Martijn A; Bots, Michiel L; van der Schouw, Yvonne T

    2015-12-01

    A prospective cohort study was conducted to assess the impact of a history of hypertensive disorder of pregnancy (HDP) or gestational diabetes mellitus (GDM) on the risk and age of onset of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease (CVD) later in life, independent of hypertension and T2D. Between 1993 and 1997, 22 265 ever-pregnant women were included from the European Prospective Investigation into Cancer and Nutrition-NL study, aged 20 to 70 years at baseli