Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study).

PubMed

Dedov, Ivan; Shestakova, Marina; Benedetti, Massimo Massi; Simon, Dominique; Pakhomov, Iakov; Galstyan, Gagik

2016-05-01

To estimate type 2 diabetes mellitus (T2DM) prevalence in Russian adults. NATION is a national, epidemiological, cross-sectional study, conducted in Russia. In adults (aged 20-79 years), recruitment was stratified by age, sex, geographic region and settlement type to obtain a representative sample. Recruitment was in public areas with high numbers of people. T2DM was diagnosed by glycated haemoglobin A1c (HbA1c) levels (diabetes: HbA1c ≥6.5% [≥48mmol/mol]; pre-diabetes: HbA1c ≥5.7 to <6.5% [≥39 to <48mmol/mol]). Socio-demographic and anthropometric data were collected. Blood samples from 26,620 subjects were available. Overall, 5.4% were diagnosed with T2DM (previously diagnosed: 2.5%; previously undiagnosed: 2.9%); 19.3% were pre-diabetic. T2DM prevalence increased with age (up to 70 years) and was higher among females than males (6.1% vs. 4.7%, p<0.001). The estimated proportion of subjects with pre-diabetes and T2DM tended to increase with increasing body mass index. T2DM prevalence was higher in rural versus urban populations (6.7% vs. 5.0%, p<0.001). In the Russian adult population, 19.3% had pre-diabetes, T2DM prevalence was 5.4%, and 54% of subjects with diabetes were previously undiagnosed. These results may help to develop a new T2DM predictive, preventative and management programme in Russia. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Environmental Risk Factors for Type 1 Diabetes Mellitus Development.

PubMed

Antonela, Boljat; Ivana, Gunjača; Ivan, Konstantinović; Nikolina, Vidan; Vesna, Boraska Perica; Marina, Pehlić; Veselin, Škrabić; Tatijana, Zemunik

2017-09-01

Background Although environmental factors induce development of type 1 diabetes mellitus (T1DM) in genetically susceptible individuals, many of those factors have been uncovered. Therefore, the aim of the present study was to analyze associations of T1DM with a wide range of environmental factors. Material and Methods A case-control study was conducted on 249 diabetic and 255 healthy individuals from the Dalmatian region of South Croatia. Data regarding risk factors during pregnancy and early life period of the child were evaluated. Results History of antihypertensive intake ( p =0.04) and frequency of stressful life events during pregnancy ( p =0.01) were associated with higher risk of T1DM, while hypertension was associated with lower risk of T1DM ( p =0.01). Maternal age<25 years at delivery was associated with a higher risk of T1DM ( p =0.01).Diabetic patients had a positive family history of T1DM or T2DM ( p =0.002) more frequently than controls, while history of infectious diseases was inversely associated with the risk of T1DM ( p =0.03). A higher risk of T1DM was significantly associated with earlier introduction of cow's milk ( p =0.001), higher number of meals consumed per day ( p =0.02), higher frequency of carbohydrate ( p =0.001) and meat ( p =0.01) consumption and stressful life events during childhood ( p =0.02) while earlier introduction of fruit was associated with a lower risk of T1DM ( p =0.03) Conclusion This case-control study confirmed associations of a large number of environmental factors with development of T1DM with emphasis on the association of mother's antihypertensive intake during pregnancy, which extends our knowledge about environmental factors related with development of T1DM. © Georg Thieme Verlag KG Stuttgart · New York.

Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors: National Health and Nutrition Examination Survey (NHANES) 1999-2010.

PubMed

Zhang, Nana; Yang, Xin; Zhu, Xiaolin; Zhao, Bin; Huang, Tianyi; Ji, Qiuhe

2017-04-01

Objectives To determine whether the associations with key risk factors in patients with diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) are different using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Methods The study analysed the prevalence and association with risk factors of undiagnosed and diagnosed T2DM using a regression model and a multinomial logistic regression model. Data from the NHANES 1999-2010 were used for the analyses. Results The study analysed data from 10 570 individuals. The overall prevalence of diagnosed and undiagnosed T2DM increased significantly from 1999 to 2010. The prevalence of undiagnosed T2DM was significantly higher in non-Hispanic whites, in individuals <30 years old and in those with near optimal (130-159 mg/dl) or very high (≥220 mg/dl) non-high-density lipoprotein cholesterol levels compared with diagnosed T2DM. Body mass index, low economic status or low educational level had no effect on T2DM diagnosis rates. Though diagnosed T2DM was associated with favourable diet/carbohydrate intake behavioural changes, it had no effect on physical activity levels. Conclusion The overall T2DM prevalence increased between 1999 and 2010, particularly for undiagnosed T2DM in patients that were formerly classified as low risk.

Glutathione S-Transferase Pi-Ile 105 Val Polymorphism and Susceptibility to T2DM in Population from Turabah Region of Saudi Arabia.

PubMed

Mergani, Adil; Mansour, Ahmed Abdelkhalik; Askar, Tamer; Zahran, Rasha Nabeel; Mustafa, Adil Musa; Mohammed, Mukhtar Ahmed; Saleh, Osama Mosailhy

2016-08-01

Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative stress resulting from accumulation of free radicals in body's tissues, which especially affects beta cells in pancreas and is an important factor in the development of diabetes and its complications. Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that play important roles in decreasing ROS species and act as a kind of antioxidant defense. In a case-control study, we investigated the role of GSTP1 Ile105Val polymorphism in predisposition to T2DM in patients from Tarabah province, Saudi Arabia. The polymorphism was screened by PCR-RFLP in 90 T2DM patients and 87 healthy controls. The genotypes and alleles frequencies in cases and controls were assessed using Cochran-Armitage trend test and odds ratios (ORs), and 95 % confidence intervals (CIs) in different genetic models of inheritance were calculated. Our data indicate that G allele (Val) is associated with an increased risk for T2DM in this population in any combination (OR 4.101, 95 % CI 1.986-8.469, P = 0.00008). This indicates that individuals who are carriers for the mutant allele, either in homozygous (GG) or heterozygous (AG) state, are at fourfold higher risk for development of T2DM than other subjects in this population.

A retrospective analysis of a societal experiment among the Danish population suggests that exposure to extra doses of vitamin A during fetal development may lower type 2 diabetes mellitus (T2DM) risk later in life.

PubMed

Keller, Amélie; Ängquist, Lars; Jacobsen, Ramune; Vaag, Allan; Heitmann, Berit L

2017-03-01

Vitamin A deficiency has been associated with impaired fetal pancreatic development and increased risk of developing type 2 diabetes mellitus (T2DM). In 1962, mandatory margarine fortification with vitamin A was increased by 25 % in Denmark. We aimed to determine whether offspring of mothers who had been exposed to the extra vitamin A from fortification during pregnancy had a lower risk of developing T2DM in adult life, compared with offspring of mothers exposed to less vitamin A. Individuals from birth cohorts with the higher prenatal vitamin A exposure (born 1 December 1962-31 March 1964) and those with lower prenatal exposure (born 1 September 1959-31 December 1960) were followed up with regard to development of T2DM before 31 December 2012 in the Danish National Diabetes Registry and National Patient Register. Logistic and Cox regression analyses were performed to determine the risk of T2DM by vitamin A exposure level. A total of 193 803 individuals were followed up until midlife. Our results showed that individuals exposed prenatally to extra vitamin A from fortified margarine had a lower risk of developing T2DM than those exposed to lower levels: OR 0·88; 95 % CI 0·81, 0·95, P=0·001, after adjustment for sex. Fetal exposure to small, extra amounts of vitamin A from food fortification may reduce the risk of T2DM. These results may have public health relevance, as they demonstrate that one of the most costly chronic diseases may be prevented by food fortification - a simple and affordable public health nutrition intervention.

Socio-economic position and type 2 diabetes risk factors: patterns in UK children of South Asian, black African-Caribbean and white European origin.

PubMed

Thomas, Claudia; Nightingale, Claire M; Donin, Angela S; Rudnicka, Alicja R; Owen, Christopher G; Sattar, Naveed; Cook, Derek G; Whincup, Peter H

2012-01-01

Socio-economic position (SEP) and ethnicity influence type 2 diabetes mellitus (T2DM) risk in adults. However, the influence of SEP on emerging T2DM risks in different ethnic groups and the contribution of SEP to ethnic differences in T2DM risk in young people have been little studied. We examined the relationships between SEP and T2DM risk factors in UK children of South Asian, black African-Caribbean and white European origin, using the official UK National Statistics Socio-economic Classification (NS-SEC) and assessed the extent to which NS-SEC explained ethnic differences in T2DM risk factors. Cross-sectional school-based study of 4,804 UK children aged 9-10 years, including anthropometry and fasting blood analytes (response rates 70%, 68% and 58% for schools, individuals and blood measurements). Assessment of SEP was based on parental occupation defined using NS-SEC and ethnicity on parental self-report. Associations between NS-SEC and adiposity, insulin resistance (IR) and triglyceride differed between ethnic groups. In white Europeans, lower NS-SEC status was related to higher ponderal index (PI), fat mass index, IR and triglyceride (increases per NS-SEC decrement [95%CI] were 1.71% [0.75, 2.68], 4.32% [1.24, 7.48], 5.69% [2.01, 9.51] and 3.17% [0.96, 5.42], respectively). In black African-Caribbeans, lower NS-SEC was associated with lower PI (-1.12%; [-2.01, -0.21]), IR and triglyceride, while in South Asians there were no consistent associations between NS-SEC and T2DM risk factors. Adjustment for NS-SEC did not appear to explain ethnic differences in T2DM risk factors, which were particularly marked in high NS-SEC groups. SEP is associated with T2DM risk factors in children but patterns of association differ by ethnic groups. Consequently, ethnic differences (which tend to be largest in affluent socio-economic groups) are not explained by NS-SEC. This suggests that strategies aimed at reducing social inequalities in T2DM risk are unlikely to reduce

Type 2 diabetes mellitus unawareness, prevalence, trends and risk factors: National Health and Nutrition Examination Survey (NHANES) 1999–2010

PubMed Central

Zhang, Nana; Yang, Xin; Zhu, Xiaolin; Zhao, Bin; Huang, Tianyi

2017-01-01

Objectives To determine whether the associations with key risk factors in patients with diagnosed and undiagnosed type 2 diabetes mellitus (T2DM) are different using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Methods The study analysed the prevalence and association with risk factors of undiagnosed and diagnosed T2DM using a regression model and a multinomial logistic regression model. Data from the NHANES 1999–2010 were used for the analyses. Results The study analysed data from 10 570 individuals. The overall prevalence of diagnosed and undiagnosed T2DM increased significantly from 1999 to 2010. The prevalence of undiagnosed T2DM was significantly higher in non-Hispanic whites, in individuals <30 years old and in those with near optimal (130–159 mg/dl) or very high (≥220 mg/dl) non-high-density lipoprotein cholesterol levels compared with diagnosed T2DM. Body mass index, low economic status or low educational level had no effect on T2DM diagnosis rates. Though diagnosed T2DM was associated with favourable diet/carbohydrate intake behavioural changes, it had no effect on physical activity levels. Conclusion The overall T2DM prevalence increased between 1999 and 2010, particularly for undiagnosed T2DM in patients that were formerly classified as low risk. PMID:28415936

Cost-effectiveness analysis of trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2): positive advanced breast cancer.

PubMed

Le, Quang A; Bae, Yuna H; Kang, Jenny H

2016-10-01

The EMILIA trial demonstrated that trastuzumab emtansine (T-DM1) significantly increased the median profession-free and overall survival relative to combination therapy with lapatinib plus capecitabine (LC) in patients with HER2-positive advanced breast cancer (ABC) previously treated with trastuzumab and a taxane. We performed an economic analysis of T-DM1 as a second-line therapy compared to LC and monotherapy with capecitabine (C) from both perspectives of the US payer and society. We developed four possible Markov models for ABC to compare the projected life-time costs and outcomes of T-DM1, LC, and C. Model transition probabilities were estimated from the EMILIA and EGF100151 clinical trials. Direct costs of the therapies, major adverse events, laboratory tests, and disease progression, indirect costs (productivity losses due to morbidity and mortality), and health utilities were obtained from published sources. The models used 3 % discount rate and reported in 2015 US dollars. Probabilistic sensitivity analysis and model averaging were used to account for model parametric and structural uncertainty. When incorporating both model parametric and structural uncertainty, the resulting incremental cost-effectiveness ratios (ICER) comparing T-DM1 to LC and T-DM1 to C were $183,828 per quality-adjusted life year (QALY) and $126,001/QALY from the societal perspective, respectively. From the payer's perspective, the ICERs were $220,385/QALY (T-DM1 vs. LC) and $168,355/QALY (T-DM1 vs. C). From both perspectives of the US payer and society, T-DM1 is not cost-effective when comparing to the LC combination therapy at a willingness-to-pay threshold of $150,000/QALY. T-DM1 might have a better chance to be cost-effective compared to capecitabine monotherapy from the US societal perspective.

Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM): a meta-analysis of randomized controlled trials.

PubMed

Wang, Juan; Zhang, Xiuming; Lan, Haili; Wang, Weijia

2017-01-01

The present study was designed to systematically evaluate the clinical efficacy and safety of garlic supplement in the management of type 2 diabetes mellitus (T2DM). PubMed, EMBASE, the Cochrane Library, and China National Knowledge Internet (CNKI) were searched for relevant randomized controlled trials (RCTs) by using the terms garlic and T2DM up to April 2017. The quality of included RCTs was assessed by the Cochrane tool of risk of bias, and data of outcomes were pooled by REVMAN 5.3. Clinical factors were handled by meta-regression and subgroup analysis, and risk of publication bias was explored by inverted funnel plots. Nine RCTs involving 768 T2DM patients were included in the meta-analysis, and the dose of daily garlic (allicin) supplement ranged from 0.05g to 1.5g. A significant reduction in the level of fasting blood glucose in 1-2 weeks [SMD = -1.61, 95%CI (-2.89, -0.32)], 3-4 weeks [SMD = -2.87, 95%CI (-4.74, -1.00)], 12 weeks [SMD = -9.57, 95%CI (-12.39, -6.75)], and 24 weeks [SMD = -21.02, 95%CI (-32.47, -9.57)] was achieved in favour of the garlic group rather than the control group. Significantly decreased fructosamine and glycated hemoglobin (both in 12 and 24 weeks) were also found in garlic group. Meanwhile, significantly improved blood liquids of total cholesterol [SMD = -1.93, 95%CI (-2.98, -0.87), 3-4 weeks], high density lipoprotein [SMD = -0.41, 95%CI (-0.83, -0.00), 3-4 weeks] and low density lipoprotein [SMD = -3.47, 95%CI (-5.76, -1.18), 12 weeks] were confirmed after garlic administration. There was no significant difference in complications. Current data confirms that garlic supplement plays positive and sustained roles in blood glucose, total cholesterol, and high/low density lipoprotein regulation in the management of T2DM. Abbreviations : T2DM = type 2 diabetes mellitus; RCT = randomized controlled trial; SMD = standard mean difference; CI = confidence interval; FBG = fasting blood glucose; HbA1c = glycated

Deterioration of plasticity and metabolic homeostasis in the brain of the UCD-T2DM rat model of naturally occurring type-2 diabetes.

PubMed

Agrawal, Rahul; Zhuang, Yumei; Cummings, Bethany P; Stanhope, Kimber L; Graham, James L; Havel, Peter J; Gomez-Pinilla, Fernando

2014-09-01

The rising prevalence of type-2 diabetes is becoming a pressing issue based on emerging reports that T2DM can also adversely impact mental health. We have utilized the UCD-T2DM rat model in which the onset of T2DM develops spontaneously across time and can serve to understand the pathophysiology of diabetes in humans. An increased insulin resistance index and plasma glucose levels manifested the onset of T2DM. There was a decrease in hippocampal insulin receptor signaling in the hippocampus, which correlated with peripheral insulin resistance index along the course of diabetes onset (r=-0.56, p<0.01). T2DM increased the hippocampal levels of 4-hydroxynonenal (4-HNE; a marker of lipid peroxidation) in inverse proportion to the changes in the mitochondrial regulator PGC-1α. Disrupted energy homeostasis was further manifested by a concurrent reduction in energy metabolic markers, including TFAM, SIRT1, and AMPK phosphorylation. In addition, T2DM influenced brain plasticity as evidenced by a significant reduction of BDNF-TrkB signaling. These results suggest that the pathology of T2DM in the brain involves a progressive and coordinated disruption of insulin signaling, and energy homeostasis, with profound consequences for brain function and plasticity. All the described consequences of T2DM were attenuated by treatment with the glucagon-like peptide-1 receptor agonist, liraglutide. Similar results to those of liraglutide were obtained by exposing T2DM rats to a food energy restricted diet, which suggest that normalization of brain energy metabolism is a crucial factor to counteract central insulin sensitivity and synaptic plasticity associated with T2DM. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum metabonomics of NAFLD plus T2DM based on liquid chromatography-mass spectrometry.

PubMed

Chen, Yang; Li, Chunlong; Liu, Liyan; Guo, Fuchuan; Li, Songtao; Huang, Lina; Sun, Changhao; Feng, Rennan

2016-09-01

Nonalcoholic fatty liver disease (NAFLD), a main liver disease around the world, is closely associated with insulin resistance, type 2 diabetes mellitus (T2DM) and other metabolic diseases. The objective of this study is to identify distinct metabolites of NAFLD patients with or without T2DM. We used a biomarker-discovery population to find distinct metabolites of NAFLD patients with or without T2DM. Then, a validation population was applied to test the model of the biomarker-discovery population. All the individuals received anthropometric and common biochemical measurements. The metabolic data were analyzed by multivariable statistical analyses using ultra-high-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry. There were 7, 7, 2 metabolites in the positive electrospray ionization (ESI(+)) mode, which were identified between groups from both the biomarker-discovery and validation population. The NAFLD group showed higher concentrations of oleamide, l-phenylalanine, l-proline, bilirubin, l-palmitoylcarnitine, and PC (20:5) and a lower concentration of Lyso-PAF C-18 than those of control. Compared with the control group, the NAFLD+T2DM group displayed higher oleamide, l-leucine, LysoPC (14:0), bilirubin, tetradecenoylcarnitine, linoleyl carnitine, and tetradecadiencarnitine in serum. Tetradecenoylcarnitine and tetradecadiencarnitine were more elevated in patients with NAFLD+T2DM than in the NAFLD group. Serum metabonomic analyses displayed great metabolic changes in patients with NAFLD and NAFLD plus T2DM. Our study is beneficial in providing a further view into the pathogenesis and pathophysiology of NAFLD and NAFLD plus T2DM, which might be useful for the prevention and therapy of NAFLD and NAFLD plus T2DM. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Application of an artificial neural network model for diagnosing type 2 diabetes mellitus and determining the relative importance of risk factors.

PubMed

Borzouei, Shiva; Soltanian, Ali Reza

2018-01-01

To identify the most important demographic risk factors for a diagnosis of type 2 diabetes mellitus (T2DM) using a neural network model. This study was conducted on a sample of 234 individuals, in whom T2DM was diagnosed using hemoglobin A1c levels. A multilayer perceptron artificial neural network was used to identify demographic risk factors for T2DM and their importance. The DeLong method was used to compare the models by fitting in sequential steps. Variables found to be significant at a level of p<0.2 in a univariate logistic regression analysis (age, hypertension, waist circumference, body mass index [BMI], sedentary lifestyle, smoking, vegetable consumption, family history of T2DM, stress, walking, fruit consumption, and sex) were entered into the model. After 7 stages of neural network modeling, only waist circumference (100.0%), age (78.5%), BMI (78.2%), hypertension (69.4%), stress (54.2%), smoking (49.3%), and a family history of T2DM (37.2%) were identified as predictors of the diagnosis of T2DM. In this study, waist circumference and age were the most important predictors of T2DM. Due to the sensitivity, specificity, and accuracy of the final model, it is suggested that these variables should be used for T2DM risk assessment in screening tests.

Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database.

PubMed

Schober, E; Rami, B; Grabert, M; Thon, A; Kapellen, Th; Reinehr, Th; Holl, R W

2009-05-01

To analyse and compare clinical characteristics in young patients with maturity-onset diabetes of the young (MODY) and Type 2 diabetes mellitus (T2DM). We conducted an observational investigation using the DPV-Wiss database containing clinical data on 40 757 diabetic patients < 20 years of age from Germany and Austria. Three hundred and thirty-nine cases were clinically categorized as MODY (0.83%); 562 patients were diagnosed as T2DM (1.4%). In 20% of cases, the diagnosis of MODY was based on clinical findings only. Of the 272 subjects where genetic testing was available, 3% did not carry mutations in the three examined MODY genes. Glucokinase-MODY was commoner than HNF1A-MODY and HNF4A-MODY. Age at diagnosis was younger in MODY patients. The body mass index of T2DM was significantly higher compared with all MODY subgroups. Macrovascular risk factors such as dyslipidaemia and hypertension were commoner in T2DM, but 23% of MODY patients had dyslipidaemia and 10% hypertension. Glycaemic control was within the therapeutic target (HbA(1c) < 7.5%) in 86% of MODY and 70% of T2DM patients. The prevalence of MODY in children and adolescents in Germany and Austria is lower than that of T2DM in this age group. Dyslipidaemia and hypertension are less frequent in MODY compared with T2DM patients, but do occur.

Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM): a meta-analysis of randomized controlled trials

PubMed Central

Wang, Juan; Zhang, Xiuming; Lan, Haili; Wang, Weijia

2017-01-01

ABSTRACT The present study was designed to systematically evaluate the clinical efficacy and safety of garlic supplement in the management of type 2 diabetes mellitus (T2DM). PubMed, EMBASE, the Cochrane Library, and China National Knowledge Internet (CNKI) were searched for relevant randomized controlled trials (RCTs) by using the terms garlic and T2DM up to April 2017. The quality of included RCTs was assessed by the Cochrane tool of risk of bias, and data of outcomes were pooled by REVMAN 5.3. Clinical factors were handled by meta-regression and subgroup analysis, and risk of publication bias was explored by inverted funnel plots. Nine RCTs involving 768 T2DM patients were included in the meta-analysis, and the dose of daily garlic (allicin) supplement ranged from 0.05g to 1.5g. A significant reduction in the level of fasting blood glucose in 1–2 weeks [SMD = −1.61, 95%CI (−2.89, −0.32)], 3–4 weeks [SMD = −2.87, 95%CI (−4.74, −1.00)], 12 weeks [SMD = −9.57, 95%CI (−12.39, −6.75)], and 24 weeks [SMD = −21.02, 95%CI (−32.47, −9.57)] was achieved in favour of the garlic group rather than the control group. Significantly decreased fructosamine and glycated hemoglobin (both in 12 and 24 weeks) were also found in garlic group. Meanwhile, significantly improved blood liquids of total cholesterol [SMD = −1.93, 95%CI (−2.98, −0.87), 3–4 weeks], high density lipoprotein [SMD = −0.41, 95%CI (−0.83, −0.00), 3–4 weeks] and low density lipoprotein [SMD = −3.47, 95%CI (−5.76, −1.18), 12 weeks] were confirmed after garlic administration. There was no significant difference in complications. Current data confirms that garlic supplement plays positive and sustained roles in blood glucose, total cholesterol, and high/low density lipoprotein regulation in the management of T2DM. Abbreviations: T2DM = type 2 diabetes mellitus; RCT = randomized controlled trial; SMD = standard mean difference; CI = confidence

Prevalence and risk factors for type 2 diabetes mellitus with Prader-Willi syndrome: a single center experience.

PubMed

Yang, Aram; Kim, Jinsup; Cho, Sung Yoon; Jin, Dong-Kyu

2017-08-30

Prader-Willi syndrome (PWS) is often related to severe obesity and type-2 diabetes mellitus (T2DM). However, few studies, and none in Korea, have examined prevalence of T2DM and other variables in PWS. The aim of this study was to identify the prevalence and associated risk factors for T2DM in Korean patients with PWS. We performed a retrospective cohort study of the 84 PWS patients aged 10 or over (10.3-35.8 years of age) diagnosed with PWS at Samsung Medical Center from 1994 to 2016. We estimated occurrence of T2DM according to age (10-18 years versus >18 years), body mass index (BMI), genotype, history of growth hormone therapy, homeostasis model of assessment-insulin resistance (HOMA-IR), and the presence of dyslipidemia, hypogonadism, or central precocious puberty. Additionally, we investigated cutoff values of risk factors for development of T2DM. Twenty-nine of a total 211 patients, diagnosed with PWS over the study period, were diagnosed as having T2DM (13.7%, mean age 15.9 ± 3.6 years). In the >18 years group, obesity, HOMA-IR, and presence of dyslipidemia, hypogonadism, or central precocious puberty were associated with the occurrence of T2DM in univariate analysis. In multivariate logistic regression analysis, only obesity (p = 0.001) and HOMA-IR (p < 0.001) were significant predictive factors for T2DM. Based on the receiver operating a characteristic curve analysis, the cutoff values of HOMA-IR and BMI for predicting T2DM were >2.7 and >28.49 kg/m 2 , respectively. Of the 29 patients, seven had ≥1 microvascular complication, with non-proliferative diabetic retinopathy in 6 of 7 cases. Advanced age and HOMA-IR were positively correlated with diabetic microvascular complications (p < 0.05, Spearman correlation coefficient 0.393 and 0.434, respectively). The prevalence of diabetes in Korean PWS was similar to that in previous results. BMI and HOMA-IR were strong predictive factors for the development of T2DM in PWS. We specifically suggest

Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

PubMed

Stagi, Stefano; Lapi, Elisabetta; Seminara, Salvatore; Pelosi, Paola; Del Greco, Paolo; Capirchio, Laura; Strano, Massimo; Giglio, Sabrina; Chiarelli, Francesco; de Martino, Maurizio

2015-02-15

Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p < 0.0001) in Arm A and from 2.23 to 1.99 (p < 0.05) in Arm B. Acanthosis nigricans was significantly reduced in Arm A (13.2% to 5.6%; p < 0.05), and glycosylated-haemoglobin levels were significantly reduced in Arms A (p < 0.005). The percentage of glucose-metabolism abnormalities was reduced, although not significantly. However, the HOMA-IR index was significantly reduced in Arms A (p < 0.0001) and B (p < 0.05), with Arm A showing a significant reduction in the insulinogenic index (p < 0.05). Finally, the disposition index was significantly improved in Arms A (p < 0.0001) and B (p < 0.05). A LGI diet, particularly associated with the use of Policaptil Gel Retard, may reduce weight gain and ameliorate the metabolic syndrome and insulin-resistance parameters in obese children and adolescents with family history of obesity and T2DM.

Complications and comorbidities of T2DM in adolescents: findings from the TODAY clinical trial

PubMed Central

Tryggestad, Jeanie B.; Willi, Steven M.

2014-01-01

Summary With the rise in childhood obesity, type 2 diabetes mellitus (T2DM) has been recognized to occur in adolescents with increasing frequency. Although much is known about T2DM in adults, few studies have examined the treatment and complications of T2DM in youth. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study was designed to evaluate the efficacy of various treatments and provided a unique opportunity to study the disease progression and appearance of complications in a pediatric cohort with recent onset of the disease. In the TODAY study, hypertension was present in 11.6% of the population at baseline and increased to 33.8% by the end of the study. Prevalence of high-risk LDL-cholesterol rose from 4.5% at baseline to 10.7% at the end of the study. Microalbuminuria was found in 6.3% of the cohort at baseline and increased to 16.6%. Retinopathy was not assessed upon entry into TODAY, but was present in 13.9% of the TODAY cohort at the end of the study. Experience to date indicates that these complications and comorbidities are similar to that seen in adults, but occur on an accelerated timeline. The early manifestation of diabetes complications in youth-onset T2DM suggests that this group will be burdened with the tangible consequences of cardiovascular disease, nephropathy, and retinopathy in the third and fourth decades of life. It is hoped that through an early, aggressive approach to treatment and prevention, we may be able to curb the onset and progression of these potentially devastating outcomes. PMID:25468310

UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China.

PubMed

Su, Meifang; Chen, Xiaoying; Chen, Yue; Wang, Congyun; Li, Songtao; Ying, Xuhua; Xiao, Tian; Wang, Na; Jiang, Qingwu; Fu, Chaowei

2018-03-12

There are disparities for the association between uncoupling proteins (UCP) and type 2 diabetes (T2DM). The study was to examine the associations of genetic variants of UCP2 and UCP3 with prediabetes and T2DM in a rural Chinese population. A population-based case-control study of 397 adults with T2DM, 394 with prediabetes and 409 with normal glucose tolerance (NGT) was carried out in 2014 in a rural community in eastern China. Three groups were identified through a community survey and the prediabetes and NGT groups were frequently matched by age and gender with the T2DM group and they were not relatives of T2DM subjects. With r 2  ≥ 0.8 and minor allele frequency (MAF) ≥0.05 for tag single nucleotide polymorphisms (SNPs) with potential function, three (rs660339, rs45560234 and rs643064) and six (rs7930460, rs15763, rs647126, rs1800849, rs3781907 and rs1685356) SNPs were selected respectively for UCP2 and UCP3 and genotyped in real time using the MassARRAY system (Sequenom; USA). The haplotypes, gene-environmental interaction and association between genetic variants of UCP2 and UCP3 and prediabetes or T2DM were explored. There were no significant differences in age and sex among three study groups. After the adjustment for possible covariates, the A allele of rs1800849 in UCP3 was significantly associated with prediabetes (aOR AA vs GG  = 1.68, 95% CI: 1.02-2.78), and the association was also significant under the recessive model (aOR AA vs GA + GG  = 1.64, 95% CI: 1.02-2.66). Also, rs15763 was found to be marginally significantly associated with T2DM under dominant model (OR GA + AA vs GG  = 0.73, 95% CI: 0.52-1.03, P = 0.072). No haplotype was significantly associated with prediabetes or T2DM. Multiplicative interactions for rs660339-overweight on T2DM were observed. In addition, the AA genotype of rs660339 was associated with an increased risk of T2DM in overweight subjects (OR = 1.48, 95%CI: 0.87-2.52) but with a decreased

Negative emotions and risk for type 2 diabetes among Korean immigrants.

PubMed

Choi, Sarah E; Rush, Elizabeth B; Henry, Shayna L

2013-01-01

The purpose of this study is to examine the relationship between negative emotions and bio-behavioral risk factors among Korean immigrants at risk for type 2 diabetes (T2DM). Data were collected from 148 Korean immigrant adults who are "at risk" for T2DM as defined by having family history of T2DM in first-degree relatives, body mass index greater than 23, or history of gestational diabetes in women. Participants completed questionnaires and underwent biological measures. Negative emotions included feeling nervous, hopeless, restless, anxious, and stressed as well as depressive symptoms. High percentages of participants had T2DM risk factors including overweight, greater than normal waist to hip ratio, and blood glucose readings that are indicative of T2DM. Feeling stressed was the most commonly reported negative emotion (66%), followed by feeling anxious (51%), restless (38%), nervous (30%), and hopeless (13%). Experience of negative emotions was significantly related to behavioral risk factors; higher levels of experiencing negative emotions were related to increased soda intake and a decreased likelihood of doing at least 10 minutes of moderate exercise. Stress and anxiety were each negatively related to moderate exercise, and depressive symptoms were negatively related to both moderate and vigorous exercise. No significant relationship was found between negative emotions and biological risk factors. Findings suggest that negative emotions, individually and taken together, may be related to T2DM risk behaviors in high-risk Korean immigrants. Behavioral interventions to prevent T2DM in this population should consider assessing and addressing negative emotions.

Incidence and Risk Factors for Developing Diabetic Retinopathy Among Youth with Type 1 and Type 2 Diabetes Throughout the United States

PubMed Central

Wang, Sophia Y.; Andrews, Chris A.; Herman, William H.; Gardner, Thomas W.; Stein, Joshua D.

2017-01-01

Objectives Despite the increasing prevalence of Type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youth with DM, to compare DR rates for youth with Type 1 diabetes mellitus (T1DM) and T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youth with DR. Design Retrospective observational longitudinal cohort study. Participants Youth aged ≤ 21 years with newly diagnosed T1DM or T2DM enrolled in a large U.S. managed care network. Main Outcome Measure Hazard ratios (HR) with 95% confidence intervals (CIs) for developing DR. Methods In this study of youth aged ≤ 21 years with newly diagnosed T1DM or T2DM enrolled in a large U.S. managed care network who were under ophthalmic surveillance, we identified the incidence and timing of DR onset for youth with T1DM and T2DM. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for youth with each type of diabetes. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycosylated hemoglobin (HbA1c). Results Among the 2240 youth with T1DM and 1768 youth with T2DM, 20.1% and 7.2% developed DR, over a median follow-up of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youth with T1DM developed DR faster than youth with T2DM (P<0.0001). For every one-point increase in HbA1c, the hazard for DR increased by 20% (HR=1.20, CI 1.06–1.35) and 30% (HR=1.30, CI 1.08–1.56) among youth with T1DM and T2DM, respectively. Current guidelines suggest ophthalmic screening begin 3–5 years after initial DM diagnosis, at which point in our

Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses

PubMed Central

Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna

2018-01-01

Background Type 2 diabetes mellitus (T2DM) is a global epidemic associated with increased health expenditure, and low quality of life. Many non-genetic risk factors have been suggested, but their overall epidemiological credibility has not been assessed. Methods We searched PubMed to capture all meta-analyses and Mendelian randomization studies for risk factors of T2DM. For each association, we estimated the summary effect size, its 95% confidence and prediction interval, and the I2 metric. We examined the presence of small-study effects and excess significance bias. We assessed the epidemiological credibility through a set of predefined criteria. Results We captured 86 eligible papers (142 associations) covering a wide range of biomarkers, medical conditions, and dietary, lifestyle, environmental and psychosocial factors. Adiposity, low hip circumference, serum biomarkers (increased level of alanine aminotransferase, gamma-glutamyl transferase, uric acid and C-reactive protein, and decreased level of adiponectin and vitamin D), an unhealthy dietary pattern (increased consumption of processed meat and sugar-sweetened beverages, decreased intake of whole grains, coffee and heme iron, and low adherence to a healthy dietary pattern), low level of education and conscientiousness, decreased physical activity, high sedentary time and duration of television watching, low alcohol drinking, smoking, air pollution, and some medical conditions (high systolic blood pressure, late menarche age, gestational diabetes, metabolic syndrome, preterm birth) presented robust evidence for increased risk of T2DM. Conclusions A healthy lifestyle pattern could lead to decreased risk for T2DM. Future randomized clinical trials should focus on identifying efficient strategies to modify harmful daily habits and predisposing dietary patterns. PMID:29558518

RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

PubMed

Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

2015-12-01

The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

Negative Emotions and Risk for Type 2 Diabetes among Korean Immigrants

PubMed Central

Choi, Sarah E.; Rush, Elizabeth B.; Henry, Shayna L.

2013-01-01

Purpose The purpose of this study is to examine the relationship between negative emotions and bio-behavioral risk factors among Korean immigrants at risk for type 2 diabetes (T2DM). Methods Data were collected from 148 Korean immigrant adults who are “at risk” for T2DM as defined by having family history of T2DM in first degree relatives, body mass index greater than 23, or history of gestational diabetes in women. Participants completed questionnaires and underwent biological measures. Negative emotions included feeling nervous, hopeless, restless, anxious, and stressed as well as depressive symptoms. Results High percentages of participants had T2DM risk factors including overweight, greater than normal waist to hip ratio, and blood glucose readings that are indicative of T2DM. Feeling stressed was the most commonly reported negative emotion (66%), followed by feeling anxious (51%), restless (38%), nervous (30%), and hopeless (13%). Experience of negative emotions was significantly related to behavioral risk factors; higher levels of experiencing negative emotions were related to increased soda intake and a decreased likelihood of doing at least 10 minutes of moderate exercise. Stress and anxiety were each negatively related to moderate exercise and depressive symptoms were negatively related to both moderate and vigorous exercise. No significant relationship was found between negative emotions and biological risk factors. Conclusions Findings suggest that negative emotions, individually and taken together, may be related to T2DM risk behaviors in high-risk Korean immigrants. Behavioral interventions to prevent T2DM in this population should consider assessing and addressing negative emotions. PMID:23793726

Incidence and Risk Factors for Developing Diabetic Retinopathy among Youths with Type 1 or Type 2 Diabetes throughout the United States.

PubMed

Wang, Sophia Y; Andrews, Chris A; Herman, William H; Gardner, Thomas W; Stein, Joshua D

2017-04-01

Despite the increasing prevalence of type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youths with diabetes mellitus, to compare DR rates for youths with type 1 diabetes mellitus (T1DM) and those with T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youths with DR. Retrospective observational longitudinal cohort study. Youths aged ≤21 years with newly diagnosed T1DM or T2DM who were enrolled in a large US managed-care network. In this study of youths aged ≤21 years with newly diagnosed T1DM or T2DM who were under ophthalmic surveillance, we identified the incidence and timing of DR onset. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for participants. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycated hemoglobin A 1c fraction (HbA 1c ). Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing DR. Among the 2240 youths with T1DM and 1768 youths with T2DM, 20.1% and 7.2% developed DR over a median follow-up time of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youths with T1DM developed DR faster than youths with T2DM (P < 0.0001). For every 1-point increase in HbA 1c , the hazard for DR increased by 20% (HR = 1.20; 95% CI 1.06-1.35) and 30% (HR = 1.30; 95% CI 1.08-1.56) among youths with T1DM and T2DM, respectively. Current guidelines suggest that ophthalmic screening begin 3 to 5 years after initial diabetes mellitus diagnosis, at which point in our study, >18% of youths with T1DM had already received ≥1 DR diagnosis

[Effect of CPAP therapy on dynamic glucose level in OSAHS patients with newly diagnosed T2DM].

PubMed

Zhao, Lijun; Hui, Peilin; Xie, Yuping; Hou, Yiping; Wei, Xiaoquan; Ma, Wei; Wang, Jinfeng; Zhou, Liya; Zhang, Wenjuan

2015-11-24

To investigate the characteristic of dynamic glucose level in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with newly diagnosed type 2 diabetes mellitus (T2DM) and to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the glucose level. A total of 65 cases of patients with T2DM who were newly diagnosed by oral glucose tolerance test (OGTT) were enrolled from April 2014 to April 2015 in Gansu Provincial Hospital, and divided into simple T2DM group (n=30) and OSAHS with T2DM group (n=35) according to aponea-hypopnea index (AHI) which was monitored by polysomnography (PSG). Their general clinical data were collected, and glucose level of different periods was monitored by continuous glucose moitoring system (CGMS). Changes of glucose level were compared between two groups before and after CPAP treatment. Age, gender proportion, BMI, smoking and drinking history, glycosylated hemoglobin (HbA1c) and blood lipid profile had no significantly difference between two groups. Longer neck circumstance and higher waist-hip ration (WHR), higher systolic blood pressure and diastolic blood pressure, higher fasting plasma glucose (FPG) [(9.4 ± 3.2) vs (7.3 ± 2.1) mmol/L, P=0.028] and fasting insulin (FINS) [(19.2 ± 8.7) vs (11.1 ± 4.7) mU/L, P=0.044] level, more serious homeostasis model assessment insulin resistance (HOMA-IR) were found in OSAHS patients with T2DM when compared to patients in simple T2DM group. The average dynamic glucose level of 24 hours, daytime, nocturnal and sleep time in OSAHS with T2DM group were higher than that in the simple T2DM group (all P<0.05). The alarming times when the average dynamic glucose level of nocturnal time was more than 0.1 mmol·L⁻¹·min⁻¹ in T2DM with OSAHS was more than that in control group (P=0.001). After treatment of CPAP, the level of AHI [(5.9 ± 3.6) vs (56.7 ± 11.4) times/h, P<0.001], average dynamic glucose level of 24 hours, day, nocturnal and sleep time were obviously

Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer.

PubMed

Li, Chunze; Wang, Bei; Lu, Dan; Jin, Jin Y; Gao, Yuying; Matsunaga, Kiyoshi; Igawa, Yuriko; Nijem, Ihsan; Lu, Michael; Strasak, Alexander; Chernyukhin, Nataliya; Girish, Sandhya

2016-09-01

Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities. Four approaches were used: (1) non-compartmental analysis (NCA) comparing pharmacokinetic parameters of T-DM1 and relevant analytes across ethnic groups, (2) population pharmacokinetic (popPK) analysis assessing the impact of ethnicity on pharmacokinetics, (3) comparison of T-DM1 pharmacokinetics in Japanese patients versus the global population, and (4) exposure-response analyses assessing the impact of ethnicity on safety and efficacy. NCA pharmacokinetic parameters (T-DM1, total trastuzumab, DM1) were comparable across ethnic groups; mean cycle 1 T-DM1 AUCinf was 475, 442, and 518 day µg/mL for white (n = 461), Asian (n = 68), and others (n = 57), respectively. PopPK analysis showed that ethnicity (white, Asian, and others) was not a significant covariate for T-DM1 pharmacokinetics (n = 671). Additionally, visual predictive check plots indicated that observed pharmacokinetic profiles in Japanese patients (n = 42) were within the prediction interval generated from the final PopPK model. Exposure-response analyses showed that ethnicity was not a significant covariate impacting efficacy or hepatotoxicity risk, but there was a trend of greater thrombocytopenia risk among Asians versus non-Asians, which could not be explained by similar exposure between the ethnic groups. Most Asians with thrombocytopenia were able to continue T-DM1 using dose-adjustment rules recommended for the global population. These results suggest that T-DM1 pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities.

Diabetic retinopathy and its risk factors in patients with type 2 diabetes attending rural primary healthcare facilities in Tamil Nadu.

PubMed

Fredrick, Tony; Kaur, Prabhdeep; Murhekar, Manoj V; Jayaraman, Yuvaraj; Kolandaswamy, K; Rao, Sudha Ramachandra; David, Joseph K

2016-01-01

India has a high burden of diabetic retinopathy ranging from 12.2% to 20.4% among patients with type 2 diabetes mellitus (T2DM). A T2DM management programme was initiated in the public sector in Tamil Nadu. We estimated the prevalence of diabetic retinopathy and its associated risk factors. We did a cross-sectional survey among patients with T2DM attending two primary health centres for treatment and follow-up in Kancheepuram, Tamil Nadu in January- March 2013. We did a questionnaire-based survey, and measured blood pressure and biochemical parameters (serum creatinine, plasma glucose, etc.) of the patients. We examined their eyes by direct and indirect ophthalmoscopy and defined diabetic retinopathy using a modified classification by Klein et al. We calculated the proportion and 95% CI for the prevalence and adjusted odds ratio (AOR) for risk factors associated with diabetic retinopathy. Among the 270 patients, the mean (SD) age was 54.5 (10) years. The median duration of T2DM was 48 months. The prevalence of diabetic retinopathy was 29.6%. Overall, 65.9% of patients had hypertension, 14.4% had nephropathy (eGFR <60 mg/dl) and 67.4% had neuropathy. Among patients with comorbid conditions, 60%, 48%, 32%, and 3% were already diagnosed to have hypertension, neuropathy, retinopathy, and nephropathy, respectively. The risk factors for diabetic retinopathy were hypertension (AOR 3.2, 95% CI 1.7-6.3), duration of T2DM >5 years (AOR 6.5, 95% CI 3.6-11.7), poor glycaemic control (AOR 2.4, 95% CI 1.4-4.4), and nephropathy (AOR 2.3, 95% CI 1.1-4.6). There was a high burden of undetected retinopathy and other comorbid conditions among patients with T2DM. Early detection of comorbid conditions and glycaemic control can be improved by training care-providers and educating patients.

Insulin Resistance-Associated Interhemispheric Functional Connectivity Alterations in T2DM: A Resting-State fMRI Study

PubMed Central

Xia, Wenqing; Wang, Shaohua; Spaeth, Andrea M.; Rao, Hengyi; Wang, Pin; Yang, Yue; Huang, Rong; Cai, Rongrong; Sun, Haixia

2015-01-01

We aim to investigate whether decreased interhemispheric functional connectivity exists in patients with type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (rs-fMRI). In addition, we sought to determine whether interhemispheric functional connectivity deficits associated with cognition and insulin resistance (IR) among T2DM patients. We compared the interhemispheric resting state functional connectivity of 32 T2DM patients and 30 healthy controls using rs-fMRI. Partial correlation coefficients were used to detect the relationship between rs-fMRI information and cognitive or clinical data. Compared with healthy controls, T2DM patients showed bidirectional alteration of functional connectivity in several brain regions. Functional connectivity values in the middle temporal gyrus (MTG) and in the superior frontal gyrus were inversely correlated with Trail Making Test-B score of patients. Notably, insulin resistance (log homeostasis model assessment-IR) negatively correlated with functional connectivity in the MTG of patients. In conclusion, T2DM patients exhibit abnormal interhemispheric functional connectivity in several default mode network regions, particularly in the MTG, and such alteration is associated with IR. Alterations in interhemispheric functional connectivity might contribute to cognitive dysfunction in T2DM patients. PMID:26064945

DNA Damage Observed in Unaffected Individuals with Family History of T2DM

NASA Astrophysics Data System (ADS)

Ramesh, Nikhila; Abilash, V. G.

2017-11-01

Diabetes has been documented to cause high levels of DNA fragmentation in some cases. As diabetes is inheritable and influenced by both genetic and environmental factors, an investigation into the genomic stability of individuals who are strongly at risk of inheriting diabetes was conducted by inducing oxidative stress, as DNA damage in unaffected individuals could be a sign of onset of the disease or the presence of genetic alterations that reduce cellular defences against reactive oxygen species. In this study, alkaline comet assay was performed on isolated human leukocytes to determine whether individuals with a family history of Type 2 Diabetes Mellitus (T2DM) are more prone to DNA damage under oxidative stress. Visual scoring of comets showed that these individuals have higher degree of DNA damage compared to a control individual with no family history of Type 2 Diabetes Mellitus. Further studies with large sample could determine the presence of disabled cellular defences against oxidative stress in unaffected individuals and intervention with antioxidants could prevent or manage Type 2 Diabetes Mellitus and its complications.

T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

PubMed Central

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-01-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. PMID:24890382

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

PubMed Central

Piccolo, Brian D.; Graham, James L.; Stanhope, Kimber L.; Fiehn, Oliver; Havel, Peter J.

2016-01-01

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset. PMID:27094034

Obstructive sleep apnea as a risk factor for type 2 diabetes mellitus

PubMed Central

Rajan, Preethi; Greenberg, Harly

2015-01-01

Obstructive sleep apnea (OSA) is independently associated with cardiovascular and cardiometabolic risk in several large epidemiologic studies. OSA leads to several physiologic disturbances such as intermittent hypoxia, sleep fragmentation, and increase in autonomic tone. These disturbances have been associated with insulin resistance and type 2 diabetes mellitus (T2DM) in animal and human studies. Studies also suggest a bidirectional relationship between OSA and T2DM whereby T2DM itself might contribute to the features of OSA. Moreover, successful treatment of OSA may reduce these risks, although this is controversial. The purpose of this article is to review 1) the links and bidirectional associations between OSA and T2DM; 2) the pathogenic mechanisms that might link these two disease states; 3) the role of continuous positive airway pressure therapy in improving glucose tolerance, sensitivity, and resistance; and 4) the implications for clinical practice. PMID:26491377

Talking About Type 2 Diabetes: Family Communication From the Perspective of At-Risk Relatives.

PubMed

Myers, Melanie F; Fernandes, Sara L; Arduser, Lora; Hopper, Jennifer L; Koehly, Laura M

2015-12-01

The purpose of this study was to describe type 2 diabetes (T2DM) communication and risk reduction recommendations from the perspective of family members at risk for T2DM based on family history. Semistructured qualitative interviews were conducted with 33 individuals with a first-degree relative with T2DM. Participants were recruited from the community and a previous pharmacogenetics study. Deductive and inductive codes were applied to the transcripts. Conversations with family members with and without T2DM focused on symptoms and disease management of the family member with T2DM. With at-risk relatives, conversations also focused on prevention. Lack of perceived relevance to family members without T2DM was a barrier to communication. Recommendations to facilitate communication included education of an at-risk family member to increase awareness of risk, followed by sharing of learned information with others. Efforts are needed to increase awareness and improve communication about T2DM risk factors, familial risk, and risk reduction behaviors within families with a family history of T2DM. Family members with and without T2DM should be encouraged to communicate with their relatives about T2DM and the risk to family members. Identification of family members who can facilitate communication, education, and modeling of healthy behaviors may increase awareness and motivate at-risk individuals to engage in risk-reducing behaviors. © 2015 The Author(s).

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus.

PubMed

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-04-01

Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis.

Correlation between reactive oxygen metabolites & atherosclerotic risk factors in patients with type 2 diabetes mellitus

PubMed Central

Kotani, Kazuhiko; Tsuzaki, Kokoro; Taniguchi, Nobuyuki; Sakane, Naoki

2013-01-01

Background & objectives: Oxidative stress plays important roles in the pathophysiology of type 2 diabetes mellitus (T2DM). The diacron reactive oxygen metabolites (d-ROMs) test has been used in the clinics. The present study was aimed to investigate the correlation of the oxidative stress status, as evaluated by the d-ROMs, with atherosclerotic risk factors in T2DM patients, in comparison to controls. Methods: The study included 200 subjects (100 patients with T2DM and 100 controls; 86 males/114 females; mean age 59.0 yr). Clinical variables including the body mass index, blood pressure (BP), glucose and lipid panels, in addition to the d-ROMs, were measured. Results: Patients with T2DM showed significantly higher d-ROMs levels than controls (322 ± 60 vs. 345 ± 64 U. Carr., P<0.05). A multiple linear regression analysis revealed that systolic BP (β=0.26, P<0.05) and high-density lipoprotein cholesterol (HDL-C: β= -0.30, P<0.05) were independently and significantly correlated with the d-ROMs levels in patients with T2DM, although these correlations were not significant in the controls. The gender-based analysis showed that systolic BP (β = 0.44, P<0.05) and HDL-C (β = -0.36, P<0.05) were independently and significantly correlated with the d-ROMs levels in females with T2DM, while there was a marginally significant correlation between HDL-C and the d-ROMs levels (β = -0.36, P=0.06) in males with T2DM. Interpretation & conclusions: The present findings may reinforce the importance of BP control in female patients with T2DM, as well as the management of HDL-C in male and female patients with T2DM, under the linkage between oxidative stress and atherosclerosis. PMID:23703342

A Comparison between Decision Tree and Random Forest in Determining the Risk Factors Associated with Type 2 Diabetes.

PubMed

Esmaily, Habibollah; Tayefi, Maryam; Doosti, Hassan; Ghayour-Mobarhan, Majid; Nezami, Hossein; Amirabadizadeh, Alireza

2018-04-24

We aimed to identify the associated risk factors of type 2 diabetes mellitus (T2DM) using data mining approach, decision tree and random forest techniques using the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) Study program. A cross-sectional study. The MASHAD study started in 2010 and will continue until 2020. Two data mining tools, namely decision trees, and random forests, are used for predicting T2DM when some other characteristics are observed on 9528 subjects recruited from MASHAD database. This paper makes a comparison between these two models in terms of accuracy, sensitivity, specificity and the area under ROC curve. The prevalence rate of T2DM was 14% among these subjects. The decision tree model has 64.9% accuracy, 64.5% sensitivity, 66.8% specificity, and area under the ROC curve measuring 68.6%, while the random forest model has 71.1% accuracy, 71.3% sensitivity, 69.9% specificity, and area under the ROC curve measuring 77.3% respectively. The random forest model, when used with demographic, clinical, and anthropometric and biochemical measurements, can provide a simple tool to identify associated risk factors for type 2 diabetes. Such identification can substantially use for managing the health policy to reduce the number of subjects with T2DM .

Environmental Risk Factors for Developing Type 2 Diabetes Mellitus: A Systematic Review

PubMed Central

Dendup, Tashi; Feng, Xiaoqi; Clingan, Stephanie; Astell-Burt, Thomas

2018-01-01

Different elements of the environment have been posited to influence type 2 diabetes mellitus (T2DM). This systematic review summarizes evidence on the environmental determinants of T2DM identified in four databases. It proposes a theoretical framework illustrating the link between environment and T2DM, and briefly discusses some methodological challenges and potential solutions, and opportunities for future research. Walkability, air pollution, food and physical activity environment and roadways proximity were the most common environmental characteristics studied. Of the more than 200 reported and extracted relationships assessed in 60 studies, 82 showed significant association in the expected direction. In general, higher levels of walkability and green space were associated with lower T2DM risk, while increased levels of noise and air pollution were associated with greater risk. Current evidence is limited in terms of volume and study quality prohibiting causal inferences. However, the evidence suggests that environmental characteristics may influence T2DM prevention, and also provides a reasonable basis for further investigation with better quality data and longitudinal studies with policy-relevant environmental measures. This pursuit of better evidence is critical to support health-orientated urban design and city planning. PMID:29304014

Noninvasive Screening for Risk Factors of Type 2 Diabetes in Young, Rural, Caucasian Children

ERIC Educational Resources Information Center

Peterson, Sharon; Sheffer, Sarah; Long Roth, Sara; Bennett, Paul A.; Lloyd, Les

2010-01-01

School nurses play an important role in identifying students who are at risk for Type 2 diabetes mellitus (T2DM). Few studies have screened Caucasian students, and none have targeted rural, low-income, elementary children. The five noninvasive risk factors used for this study were family history, high body mass index (BMI) for age/sex,…

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model.

PubMed

Piccolo, Brian D; Graham, James L; Stanhope, Kimber L; Fiehn, Oliver; Havel, Peter J; Adams, Sean H

2016-06-01

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasma BCAA and other metabolites were assessed in lean control Sprague-Dawley rats (LC) and temporally during diabetes development in the UCD-T2DM rat model, i.e., prediabetic (PD) and 2 wk (D2W), 3 mo (D3M), and 6 mo (D6M) post-onset of diabetes. Plasma leucine, isoleucine, and valine concentrations were elevated only in D6M rats compared with D2W rats (by 28, 29, and 30%, respectively). This was in contrast to decreased plasma concentrations of several other amino acids in D3M and/or D6M relative to LC rats (Ala, Arg, Glu, Gln, Met, Ser, Thr, and Trp). BCAAs were positively correlated with fasting glucose and negatively correlated with plasma insulin, total body weight, total adipose tissue weight, and gastrocnemius muscle weight in the D3M and D6M groups. Multivariate analysis revealed that D3M and D6M UCD-T2DM rats had lower concentrations of amino acids, amino acid derivatives, 1,5-anhydroglucitol, and conduritol-β-opoxide and higher concentrations of uronic acids, pantothenic acids, aconitate, benzoic acid, lactate, and monopalmitin-2-glyceride relative to PD and D2W UCD-T2DM rats. The UCD-T2DM rat does not display elevated plasma BCAA concentrations until 6 mo post-onset of diabetes. With the acknowledgement that this is a rodent model of T2DM, the results indicate that elevated plasma BCAA concentrations are not necessary or sufficient to elicit an insulin resistance or T2DM onset. Copyright © 2016 the American Physiological Society.

T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

PubMed

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-10-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Exposures to road traffic, noise, and air pollution as risk factors for type 2 diabetes: A feasibility study in Bulgaria

PubMed Central

Dzhambov, Angel M; Dimitrova, Donka D

2016-01-01

Type 2 diabetes mellitus (T2DM) is a growing public health problem in Bulgaria. While individual and lifestyle determinants have been researched; till date there has been no study on environmental risks such as road traffic, noise, and air pollution. As a first step toward designing a large-scale population-based survey, we aimed at exploring the overall associations of prevalent T2DM with exposures to road traffic, noise, and air pollution. A total of 513 residents of Plovdiv city, Bulgaria were recruited. Individual data on self-reported doctor-diagnosed T2DM and confounding factors were linked to objective and self-rated exposure indicators. Logistic and log-link Poisson regressions were conducted. In the fully adjusted logistic models, T2DM was positively associated with exposures to Lden 71-80 dB (odds ratio (OR) = 4.49, 95% confidence interval (CI): 1.38, 14.68), fine particulate matter (PM)2.5 25.0-66.8 μg/m3 (OR = 1.32, 95% CI: 0.28, 6.24), benzo alpha pyrene 6.0-14.02 ng/m3 (OR = 1.76, 95% CI: 0.52, 5.98) and high road traffic (OR = 1.40, 95% CI: 0.48, 4.07). Lden remained a significant risk factor in the: Poisson regression model. Other covariates with consistently high multivariate effects were age, gender, body mass index, family history of T2DM, subjective sleep disturbance, and especially bedroom location. We concluded that residential noise exposure might be associated with elevated risk of prevalent T2DM. The inferences made by this research and the lessons learned from its limitations could guide the designing of a longitudinal epidemiological survey in Bulgaria. PMID:27157686

Postpartum Reclassification of Glycemic Status in Women with Gestational Diabetes Mellitus and Associated Risk Factors.

PubMed

Alves, Jacy Maria; Stollmeier, Aline; Leite, Isabelle Gasparetto; Pilger, Camilla Gallo; Detsch, Josiane Cristine Melchioretto; Radominski, Rosana Bento; Réa, Rosângela Roginski

2016-08-01

Objective The aims of the study were to evaluate, after pregnancy, the glycemic status of women with history of gestational diabetes mellitus (GDM) and to identify clinical variables associated with the development of type 2 diabetes mellitus (T2DM), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Methods Retrospective cohort of 279 women with GDM who were reevaluated with an oral glucose tolerance test (OGTT) after pregnancy. Characteristics of the index pregnancy were analyzed as risk factors for the future development of prediabetes (IFG or IGT), and T2DM. T2DM was diagnosed in 34 (12.2%) patients, IFG in 58 (20.8%), and IGT in 35 (12.5%). Women with postpartum T2DM showed more frequently a family history of T2DM, higher pre-pregnancy body mass index (BMI), lower gestational age, higher fasting and 2-hour plasma glucose levels on the OGTT at the diagnosis of GDM, higher levels of hemoglobin A1c, and a more frequent insulin requirement during pregnancy. Paternal history of T2DM (odds ratio [OR] = 5.67; 95% confidence interval [95%CI] = 1.64-19.59; p = 0.006), first trimester fasting glucose value (OR = 1.07; 95%CI = 1.03-1.11; p = 0.001), and insulin treatment during pregnancy (OR = 15.92; 95%CI = 5.54-45.71; p < 0.001) were significant independent risk factors for the development of T2DM. Conclusion A high rate of abnormal glucose tolerance was found in women with previous GDM. Family history of T2DM, higher pre-pregnancy BMI, early onset of GDM, higher glucose levels, and insulin requirement during pregnancy were important risk factors for the early identification of women at high risk of developing T2DM. These findings may be useful for developing preventive strategies. Thieme Publicações Ltda Rio de Janeiro, Brazil.

Type 2 diabetes mellitus in Malaysia: current trends and risk factors.

PubMed

Tee, E-S; Yap, R W K

2017-07-01

This review discussed the prevalence of diabetes mellitus (DM) in Malaysia and the associated major risk factors, namely overweight/obesity, dietary practices and physical activity in both adults and school children. Detailed analyses of such information will provide crucial information for the formulation and implementation of programmes for the control and prevention of T2DM in the country. National studies from 1996-2015, and other recent nation-wide studies were referred to. The current prevalence of DM in 2015 is 17.5%, over double since 1996. Females, older age group, Indians, and urban residents had the highest risk of DM. The combined prevalence of overweight/obesity in 2015 is 47.7% for adults. Adults did not achieve the recommended intakes for majority of the foods groups in the Malaysian Food Pyramid especially fruits and vegetables. Adults also had moderate physical activity level. Three nation-wide studies showed a prevalence ranging from 27 to 31% for combined overweight/obesity in school children. The prevalence was higher among boys, primary school age, Indian ethnicity, and even rural children are not spared. Physical activity level was also low among school children. There must be serious systematic implementation of action plans to combat the high prevalence of diabetes and associated risk factors.

Racial/ethnic Differences in Clinical and Biochemical Type 2 Diabetes Mellitus Risk Factors in Children

PubMed Central

Rosenbaum, Michael; Fennoy, Ilene; Accacha, Siham; Altshuler, Lisa; Carey, Dennis E.; Holleran, Steven; Rapaport, Robert; Shelov, Steven P.; Speiser, Phyllis W.; Ten, S.; Bhangoo, Amrit; Boucher-Berry, Claudia; Espinal, Yomery; Gupta, Rishi; Hassoun, Abeer A.; Iazetti, Loretta.; Jacques, Fabien J.; Jean, Amy M.; Klein, Michelle. L.; Levine, Robert; Lowell, Barbara; Michel, Lesley; Rosenfeld, Warren

2013-01-01

Objective To examine whether peri-adolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults. Design and Methods We examined family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other). Results Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance. Conclusion Children show some of the same racial/ethnic differences in risk factors for adiposity-related co-morbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related co-morbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history. PMID:23596082

Incidence and risk factors for type 2 diabetes mellitus in transitional Thailand: results from the Thai cohort study.

PubMed

Papier, Keren; Jordan, Susan; D'Este, Catherine; Bain, Chris; Peungson, Janya; Banwell, Cathy; Yiengprugsawan, Vasoontara; Seubsman, Sam-Ang; Sleigh, Adrian

2016-12-13

Type 2 diabetes mellitus (T2DM) is increasingly prevalent in countries undergoing rapid development, including Thailand. We assessed T2DM incidence over an 8-year period in a nationwide cohort of Thai adults. Thai Cohort Study participants were surveyed in 2005, 2009 and 2013. The analysed cohort members were aged (15-88), did not have diabetes in 2005 and were followed up by questionnaire in 2013 (n=39 507). T2DM was ascertained using self-report, which has been validated using physician interviews. We calculated the 8-year cumulative incidence of T2DM. Multivariable logistic regression assessed associations between potential risk factors and T2DM incidence. 8-year cumulative incidence of T2DM (2005 to 2013) was 177 per 10 000 (95% CI 164 to 190). Crude and age-standardised cumulative incidences of T2DM by sex were 249 per 10 000 (95% CI 226 to 272) and 222 per 10 000 (95% CI 219 to 225) for men; and 119 per 10 000 (95% CI 105 to 133) and 96 per 10 000 (95% CI 94 to 98) for women, respectively. T2DM increased significantly for both sexes with increasing age and body mass index (BMI) (p trend <0.001 for both). Residence in an urban area as a child associated with T2DM among men and women (OR=1.4, 95% CI 1.1 to 1.7 and OR=1.4, 95% CI 1.01 to 1.79); this was no longer statistically significant after adjusting for BMI. Among men, smoking (OR=1.7, 95% CI 1.3 to 2.2) and alcohol intake (OR=1.8, 95% CI 1.1 to 3.0) were associated with T2DM. This study found that the sociodemographic and lifestyle changes that have accompanied Thailand's economic development are associated with T2DM risk in a large cohort of Thai adults. Our findings highlight the need to address these transitions to prevent a further increase in the national incidence of T2DM, particularly among Thai men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women

PubMed Central

Dragsbæk, Katrine; Neergaard, Jesper S.; Laursen, Janne M.; Hansen, Henrik B.; Christiansen, Claus; Beck-Nielsen, Henning; Karsdal, Morten A.; Brix, Susanne; Henriksen, Kim

2016-01-01

Abstract The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD) in elderly Caucasian women. We further investigated if stratification of individuals not defined with MetS would add predictive power in defining future disease prevalence of individuals with MetS. The Prospective Epidemiological Risk Factor Study, a community-based cohort study, followed 3905 Danish women since 2000 (age: 70.1 ± 6.5) with no previous diagnosis of T2DM or CVD, holding all measurements used for MetS definition; central obesity, hypertension, hyperlipidemia, and hyperglycemia combined with register-based follow-up information. Elderly women with defined MetS presented a 6.3-fold increased risk of T2DM (95% confidence interval: [3.74–10.50]) and 1.7-fold increased risk of CVD (1.44–2.05) compared to women with no MetS risk factors. Subdividing the control group without defined MetS revealed that both centrally obese controls and controls holding other MetS risk factors also had increased risk of T2DM (hazard ratio (HR) = 2.21 [1.25–3.93] and HR = 1.75 [1.04–2.96]) and CVD (HR = 1.51 [1.25–1.83] and HR = 1.36 [1.15–1.60]) when compared to controls with no MetS risk factors. MetS in elderly Caucasian women increased risk of future T2DM and CVD. While not defined with MetS, women holding only some risk factors for MetS were also at increased risk of T2DM or CVD compared to women with no MetS risk factors. PMID:27603394

LC-MS/MS method for the simultaneous determination of Lys-MCC-DM1, MCC-DM1 and DM1 as potential intracellular catabolites of the antibody-drug conjugate trastuzumab emtansine (T-DM1).

PubMed

Liu, Yazhong; Zhou, Fang; Sang, Hua; Ye, Hui; Chen, Qianying; Yao, Lan; Ni, Ping; Wang, Guangji; Zhang, Jingwei

2017-04-15

Lysine-MCC-DM1, MCC-DM1 and DM1 are potential catabolites of trastuzumab emtansine (T-DM1). A convenient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to detect these catabolites simultaneously in in vitro investigations for the first time. Protein precipitation was utilized to prepare the samples. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with mobile-phase gradient elution. The calibration curves of each analyte ranging from 1 to 100nM showed good linearity (r 2 >0.995). The method was validated successfully and applied to the intracellular catabolism and regulation of T-DM1. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of gender-related differences in vitamin D levels and cardiovascular risk factors in Saudi patients with type 2 diabetes mellitus.

PubMed

Abudawood, Manal; Tabassum, Hajera; Ansar, Sabah; Almosa, Khalid; Sobki, Samia; Ali, Mir Naiman; Aljohi, Ali

2018-01-01

Diabetes is a major risk factor for cardiovascular disease (CVD) including stroke, coronary heart disease, and peripheral artery disease. It remains a leading cause of mortality throughout the world, affecting both women and men. This investigation was aimed to study gender based differences in cardiovascular risk factors of adult population with type-2 diabetes mellitus (T2DM) and to check the correlation between serum HbA1C, lipid profile and serum vitamin D levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross-sectional study involving subjects was divided into two gender based groups; normal male (800), diabetic male (800) and normal female (800) and T2DM females (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)-vitamin D in all groups. All the glycemic control parameters and lipid profile parameters were found to be significantly different in diabetic vs non-diabetic group (p < 0.001) in both genders. The results also show that vitamin D concentration decreased significantly (p < 0.001) in diabetic patients than the healthy individuals in both the genders. Vitamin-D and HbA1C were negatively correlated in both males and females in T2DM patients and significant at P < 0.05. Our study reveals that dyslipidemia remains one of the major risk factors of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.

Influence of CSN1S2 protein from Caprine milk Etawah Breed (EB) on histology of microglial cells in rat (Rattus norvegicus) Type-2 diabetes mellitus (T2DM)

NASA Astrophysics Data System (ADS)

Rika, Margareth; Fatchiyah

2017-11-01

Type-2 diabetes mellitus (T2DM) is a degenerative disease that causes an imbalance in the metabolism. The aim of this research is to determine the influences of CSN1S2 on the structure of microglial cells in T2DM. Rats (Rattus norvegicus) were divided into eight groups of treatment with looping three times each between treatment groups (CM) Control. The control is given a milk treatment with doses of 375 mg/kg (CM375), 750 mg/kg (CM750), and 1500 mg/kg (CM1500), T2DM (DMK), and T2DM with CSN1S2 375 mg/kg dose (DM375), 750mg/kg (DM750), and 1500 mg/kg (DM1500). The animal model T2DM was induced by a high-fat diet in the form of feed followed by injection of STZ (dose of 25 mg/kg of animal treatment) and treatment of CSN1S2 for 28 days. Brain organs were taken and analysed in histopathology stained by Hematoxylin-eosin (HE) and observed using Olympus BX53. Based on the results, it was concluded that CSN1S2 protein is influential for induction of microglial cell proliferation in animal models of T2DM, as immunity responds to the inflammatory condition in T2DM.

Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.

PubMed

Anand, Sonia S; Meyre, David; Pare, Guillaume; Bailey, Swneke D; Xie, Changchun; Zhang, Xiaohe; Montpetit, Alexandre; Desai, Dipika; Bosch, Jackie; Mohan, Viswanathan; Diaz, Rafael; McQueen, Matthew J; Cordell, Heather J; Keavney, Bernard; Yusuf, Salim; Gaudet, Daniel; Gerstein, Hertzel; Engert, James C

2013-09-01

To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population. In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up. Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052). T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.

The Nile Rat (Arvicanthis niloticus) as a Superior Carbohydrate-Sensitive Model for Type 2 Diabetes Mellitus (T2DM)

PubMed Central

Landstrom, Michelle; Luu, Alice; Hayes, K. C.

2018-01-01

Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complications of diabetes in humans. Since this disease represents a chronic nutritional insult based on a diet bearing a high glycemic load, the ideal model should recapitulate the underlying dietary issues. Most rodent models have three shortcomings: (1) they are genetically or chemically modified to produce diabetes; (2) unlike humans, most require high-fat feeding; (3) and they take too long to develop diabetes. By contrast, Nile rats develop diabetes rapidly (8–10 weeks) with high-carbohydrate (hiCHO) diets, similar to humans, and are protected by high fat (with low glycemic load) intake. This review describes diabetes progression in the Nile rat, including various aspects of breeding, feeding, and handling for best experimental outcomes. The diabetes is characterized by a striking genetic permissiveness influencing hyperphagia and hyperinsulinemia; random blood glucose is the best index of disease progression; and kidney failure with chronic morbidity and death are outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty liver disease (NAFLD), also described in diabetic humans, results from hepatic triglyceride and cholesterol accumulation associated with rising blood glucose. Protection is afforded by low glycemic load diets rich in certain fibers or polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify the nutritional factors and underlying genetic and molecular mechanisms that characterize human T2DM. PMID:29463026

Review of cardiometabolic risk factors in a cohort of paediatric type 1 diabetes mellitus patients.

PubMed

Donovan, A; Finner, N; O'Connor, C; Quinn, A; O'Gorman, C S

2017-05-01

Type 1 diabetes mellitus (T1DM) is a recognised risk factor for cardiometabolic disease. Other risk factors include age, gender, family history, glycaemic control, dyslipidaemia, weight, and activity levels. To estimate the point prevalence of cardiometabolic risk factors in a paediatric population with T1DM. Eighty-one patients with T1DM aged between 10 and 16 years attended during the study and 56 (69.1 %) patients agreed to participate. Mixed methods data collection included a questionnaire developed for this study, supplemented by retrospective and prospective data collected from the patient records. Of 56 subjects with T1DM, aged 12.7 ± 1.7 years (10-16 years) 26 were male and 30 were female. Mean HbA1c was 72 ± 14 mmol/mol. 53 subjects (94.6 %) had at least one additional cardiometabolic risk factor. Cardiometabolic risk factors are present in this population with T1DM. Identifying cardiometabolic risk factors in adolescent T1DM patients is the first step in prevention of future morbidity and mortality.

Pioglitazone improves the ability of learning and memory via activating ERK1/2 signaling pathway in the hippocampus of T2DM rats.

PubMed

Gao, F; Zang, L; Wu, D Y; Li, Y J; Zhang, Q; Wang, H B; Tian, G L; Mu, Y M

2017-06-09

To explore the correlation between effect of PIO (pioglitazone, PIO) on learning as well as memory and ERK1/2 (extracellular signal regulated kinase 1/2, ERK1/2) pathway in T2DM (type 2 diabetes mellitus, T2DM) rats, further to elucidate the potential mechanism of PIO in improvement of learning and memory. 12-week-old male SD rats (number of 10 per group) were randomly divided into control group (CON), T2DM group (DM) and T2DM +PIO group (DM+PG). Rats in DM and DM+PG groups were given high fat diet for 20 weeks, then treated with Streptozotocin (27mg/kg) by intraperitoneal injection at 21week. After 72h, the FBG (fasting blood glucose, FBG) was greater than 7.0mmol/L can considered T2DM rats. DM+PG group was treated with PIO (10 mg·kg -1 ·d -1 ) by gavage daily. After Hyperinsulinemic-Euglycemic Clamp Study and Morris water maze test at 30-week, all of animals were sacrificed. The expressions of RKIP (Raf-1 kinase inhibitor protein, RKIP) and ERK1/2 in hippocampus were detected using Western Blot and real-time PCR. The FBG level: DM group (7.68±0.54mmol/L) was higher than CON group (5.35±0.63mmol/L) and DM+PG group (6.07±0.84mmol/L), the differences were considered statistically significant (P <0.05). Hyperinsulinemic-Euglycemic Clamp Studies: GIR (glucose infusion rate, GIR) of DM group (21.02±5.10 mg·kg -1 ·d -1 ) was less than CON group (27.64±3.87 mg·kg -1 ·d -1 ) and DM+PG group (26.04 ±5.41 mg·kg -1 ·d -1 ), the differences were considered statistically significant (P <0.05). Morris water maze training: The escape latencies and searching platform performance of DM group (24.54±5.02s) decreased significantly compared with CON group (16.73±4.02s) and DM+PG group (18.05±4.12s) (P <0.05). Changes of RKIP, ERK, p-ERK protein relative content in rat hippocampus: Compared with CON groupand DM+PG group, the relative content of RKIP in DM group remarkably increased (P<0.01); ERK protein levels were not considered statistically significant among the

Risk factors for diabetic retinopathy in northern Chinese patients with type 2 diabetes mellitus.

PubMed

Yan, Zhi-Peng; Ma, Jing-Xue

2016-01-01

To investigate the prevalence and risk factors of diabetic retinopathy (DR) in northern Chinese patients with type 2 diabetes mellitus (T2DM). This retrospective cross-sectional study was performed between May 2011 and April 2012. A total of 1100 patients (male/female, 483/617) were included in this study. DR was defined following the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. All included patients accepted a comprehensive ophthalmic examination including retinal photographs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for age and gender. Retinopathy was present in 307 patients with a prevalence of 27.9%. In univariate logistic analysis, presence of DR was associated with longer duration of diabetes (OR, 5.70; 95%CI, 2.91-12.56), higher concentration of fasting blood glucose (OR, 12.94; 95%CI, 2.40-67.71), higher level of glycosylated hemoglobin HbA1c (OR, 5.50; 95%CI, 3.78-11.97) and insulin treatment (OR, 6.99; 95%CI, 1.39-35.12). The lifestyle of patients with T2DM including smoking, alcohol consumption and regular exercise seemed not associated with the development of DR. Our study suggests that fasting serum glucose concentration, HbA1c level, duration of diabetes and insulin treatment are potential risk factors for DR in northern Chinese patients with T2DM, while the lifestyle of included patients seems not associated with DR.

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

PubMed

Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

2015-09-01

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Preventable coronary heart disease events from control of cardiovascular risk factors in US adults with diabetes (projections from utilizing the UKPDS risk engine).

PubMed

Wong, Nathan D; Patao, Christopher; Malik, Shaista; Iloeje, Uchenna

2014-04-15

Type 2 diabetes mellitus (T2DM) carries significant risks for coronary heart disease (CHD). We examined the potential US population impact of single and composite risk factor control. Among US adults with diagnosed T2DM aged≥30 years in the National Health and Nutrition Examination Survey 2007 to 2012, we assessed CHD events preventable using the United Kingdom Prospective Diabetes Study CHD risk engine. We examined in all those not at goal the impact of statistical control of smoking, glycated hemoglobin, systolic blood pressure, and total and high-density lipoprotein cholesterol, according to the predefined criteria setting risk factors at different levels of control representing (1) "All to Goal," (2) at "Nominal Control," or (3) at "Aggressive Control." Preventable CHD events represented the difference between the number of events estimated from the control of these risk factors versus current levels of the risk factors. Of 606 men (representing 6.2 million) and 603 women (6.3 million) with DM and no previous CHD, 1.3 million men and 0.7 million women would develop a CHD event within 10 years if left uncontrolled. Controlling all risk factors to goal was projected to prevent 35% and 45% of CHD events in men and women, respectively. Nominal risk factor control was projected to prevent 36% and 38% and aggressive control 51% and 61% of CHD events, respectively. In conclusion, a significant proportion of CHD events in adults with T2DM could be prevented from composite control of risk factors often not at goal. Copyright © 2014 Elsevier Inc. All rights reserved.

Job strain as a risk factor for the onset of type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

PubMed

Huth, Cornelia; Thorand, Barbara; Baumert, Jens; Kruse, Johannes; Emeny, Rebecca Thwing; Schneider, Andrea; Meisinger, Christa; Ladwig, Karl-Heinz

2014-09-01

To examine whether job strain is associated with an increased risk of subsequent Type 2 diabetes mellitus (T2DM) development in a population-based study of men and women. Data were derived from the prospective MONICA/KORA Augsburg study. We investigated 5337 working participants aged 29 to 66 years without diabetes at one of the three baseline surveys. Job strain was measured by the Karasek job content questionnaire. High job strain was defined by the quadrant approach, where high job demands combined with low job control were classified as high job strain. Continuous job strain (quotient of job demands divided by job control) was additionally analyzed as sensitivity analysis. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards models with adjustment for age, sex, survey, socioeconomic and life-style variables, parental history of diabetes, and body mass index. During a median follow-up of 12.7 years, 291 incident cases of T2DM were observed. The participants with high job strain at baseline had a 45% higher fully adjusted risk to develop T2DM than did those with low job strain (HR = 1.45 [95% confidence interval = 1.00-2.10], p = .048). On the continuous scale, more severe job strain in the magnitude of 1 standard deviation corresponded to a 12% increased fully adjusted T2DM risk (HR = 1.12 [95% confidence interval = 1.00-1.25], p = .045). Men and women who experience high job strain are at higher risk for developing T2DM independently of traditional risk factors. Preventive strategies to combat the globally increasing T2DM epidemic should take into consideration the adverse effects of high strain in the work environment.

Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2,011 Patients.

PubMed

Pan, Jun; Xin, Lei; Wang, Dan; Liao, Zhuan; Lin, Jin-Huan; Li, Bai-Rong; Du, Ting-Ting; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Ji, Jun-Tao; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2016-04-01

Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP) and increases the mortality. The identification of risk factors for DM development may contribute to the early detection and potential risk reduction of DM in patients with CP.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of DM after the onset of CP were calculated by Kaplan-Meier method. Risk factors for DM development after the diagnosis of CP were identified by Cox proportional hazards regression model.A total of 2011 patients with CP were enrolled. During follow-up (median duration, 22.0 years), 564 patients developed DM. Cumulative rates of DM 20 and 50 years after the onset of CP were 45.8% (95% confidence interval [CI], 41.8%-50.0%) and 90.0% (95% CI, 75.4%-97.7%), respectively. Five risk factors for DM development after the diagnosis of CP were identified: male sex (hazard ratio [HR], 1.51; 95% CI, 1.08-2.11), alcohol abuse (HR, 2.00; 95% CI, 1.43-2.79), steatorrhea (HR, 1.46; 95% CI, 1.01-2.11), biliary stricture (HR, 2.25; 95% CI, 1.43-3.52), and distal pancreatectomy (HR, 3.41; 95% CI, 1.80-6.44).In conclusion, the risk of developing DM in patients with CP is not only influenced by the development of biliary stricture and steatorrhea indicating disease progression, and inherent nature of study subjects such as male sex, but also by modifiable factors including alcohol abuse and distal pancreatectomy.

Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

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

Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com; Flagella, Kelly; Beyer, Joseph

2013-12-01

Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeysmore » and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and

DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance.

PubMed

Takegawa, Naoki; Nonagase, Yoshikane; Yonesaka, Kimio; Sakai, Kazuko; Maenishi, Osamu; Ogitani, Yusuke; Tamura, Takao; Nishio, Kazuto; Nakagawa, Kazuhiko; Tsurutani, Junji

2017-10-15

Anti-HER2 therapies are beneficial for patients with HER2-positive breast or gastric cancer. T-DM1 is a HER2-targeting antibody-drug conjugate (ADC) comprising the antibody trastuzumab, a linker, and the tubulin inhibitor DM1. Although effective in treating advanced breast cancer, all patients eventually develop T-DM1 resistance. DS-8201a is a new ADC incorporating an anti-HER2 antibody, a newly developed, enzymatically cleavable peptide linker, and a novel, potent, exatecan-derivative topoisomerase I inhibitor (DXd). DS-8201a has a drug-to-antibody-ratio (DAR) of 8, which is higher than that of T-DM1 (3.5). Owing to these unique characteristics and unlike T-DM1, DS-8201a is effective against cancers with low-HER2 expression. In the present work, T-DM1-resistant cells (N87-TDMR), established using the HER2-positive gastric cancer line NCI-N87 and continuous T-DM1 exposure, were shown to be susceptible to DS-8201a. The ATP-binding cassette (ABC) transporters ABCC2 and ABCG2 were upregulated in N87-TDMR cells, but HER2 overexpression was retained. Furthermore, inhibition of ABCC2 and ABCG2 by MK571 restored T-DM1 sensitivity. Therefore, resistance to T-DM1 is caused by efflux of its payload DM1, due to aberrant expression of ABC transporters. In contrast to DM1, DXd payload of DS-8201a inhibited the growth of N87-TDMR cells in vitro. This suggests that either DXd may be a poor substrate of ABCC2 and ABCG2 in comparison to DM1, or the high DAR of DS-8201a relative to T-DM1 compensates for increased efflux. Notably, N87-TDMR xenograft tumor growth was prevented by DS-8201a. In conclusion, the efficacy of DS-8201a as a treatment for patients with T-DM1-resistant breast or gastric cancer merits investigation. © 2017 UICC.

Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk.

PubMed

Müller-Wieland, Dirk; Leiter, Lawrence A; Cariou, Bertrand; Letierce, Alexia; Colhoun, Helen M; Del Prato, Stefano; Henry, Robert R; Tinahones, Francisco J; Aurand, Lisa; Maroni, Jaman; Ray, Kausik K; Bujas-Bobanovic, Maja

2017-05-25

Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator. DM-DYSLIPIDEMIA is a Phase 3b/4, randomised, open-label, parallel group, multinational study that planned to enrol 420 individuals. Main inclusion criteria were T2DM and mixed dyslipidaemia (non-HDL-C ≥100 mg/dl [≥2.59 mmol/l], and triglycerides ≥150 and <500 mg/dl [≥1.70 and <5.65 mmol/l]) with documented atherosclerotic cardiovascular disease or ≥1 additional cardiovascular risk factor. Participants were randomised (2:1) to alirocumab 75 mg every 2 weeks (Q2W) or lipid-lowering usual care on top of maximally tolerated statin (or no statin if intolerant). If randomised to usual care, investigators were able to add their pre-specified choice of one of the following to the patient's current statin regimen: ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid, in accordance with local standard-of-care. Alirocumab-treated individuals with non-HDL-C ≥100 mg/dl at week 8 will undergo a blinded dose increase to 150 mg Q2W at week 12. The primary efficacy endpoint is non-HDL-C change from baseline to week 24 with alirocumab versus usual care; other lipid levels (including LDL-C), glycaemia-related measures, safety and tolerability will also be assessed

Relationship between perception with the quality of life of T2DM patients in Dok II Jayapura Hospital

NASA Astrophysics Data System (ADS)

Perwitasari, D. A.; Faridah, I. N.; Kulle, Y.; Yulistika, M.

2017-11-01

Diabetes mellitus disease is one of the chronic diseases which can cause a fatal risk if its management is not appropriate. The purpose of this study was to determine the relationship between perception and quality of life in Dok II Jayapura hospital. This study used an observational research design with cross sectional approach with prospective sampling in diabetic patients in internal disease policemen who were underwent outpatient treatment at Dok II Jayapura hospital. Research instruments used EQ-5D (European Quality-5 Dimension) and B-IPQ (Brief Illness Perception Quetionare). Data analysis used was univariate analysis by using percentage or mean value, bivariate using T-test or Mann-Whitney test, and multivariate using multiple linear regression. There were 80 T2DM patients who met the inclusion criteria. Based on patient demographic data, there were 29 people (36.6%) male patients and 51 people (63.8%) female patients, with mean age of patient (55.79±10.52) year. Perception has correlation with quality of life influenced by index value on treatment control (6.73±1.475) and emotional response (3.11±2.199) and by visual analog scale on understanding (5.99±1.587), duration (6.50±2.968), and personal controls (6.20±1.641). Based on the results obtained to improve the quality of life of T2DM patients that is on the index value on the control of treatment and emotional response and on visual analog scale on the understanding, duration and personal control should be changed so that the quality of life of patients increases. The family history, social status and type of treatment factors also affect the quality of life.

Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women: Challenging the current definition.

PubMed

Dragsbæk, Katrine; Neergaard, Jesper S; Laursen, Janne M; Hansen, Henrik B; Christiansen, Claus; Beck-Nielsen, Henning; Karsdal, Morten A; Brix, Susanne; Henriksen, Kim

2016-09-01

The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD) in elderly Caucasian women. We further investigated if stratification of individuals not defined with MetS would add predictive power in defining future disease prevalence of individuals with MetS.The Prospective Epidemiological Risk Factor Study, a community-based cohort study, followed 3905 Danish women since 2000 (age: 70.1 ± 6.5) with no previous diagnosis of T2DM or CVD, holding all measurements used for MetS definition; central obesity, hypertension, hyperlipidemia, and hyperglycemia combined with register-based follow-up information.Elderly women with defined MetS presented a 6.3-fold increased risk of T2DM (95% confidence interval: [3.74-10.50]) and 1.7-fold increased risk of CVD (1.44-2.05) compared to women with no MetS risk factors. Subdividing the control group without defined MetS revealed that both centrally obese controls and controls holding other MetS risk factors also had increased risk of T2DM (hazard ratio (HR) = 2.21 [1.25-3.93] and HR = 1.75 [1.04-2.96]) and CVD (HR = 1.51 [1.25-1.83] and HR = 1.36 [1.15-1.60]) when compared to controls with no MetS risk factors.MetS in elderly Caucasian women increased risk of future T2DM and CVD. While not defined with MetS, women holding only some risk factors for MetS were also at increased risk of T2DM or CVD compared to women with no MetS risk factors.

Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset type 1 and type 2 diabetes.

PubMed

Rajalakshmi, Ramachandran; Amutha, Anandakumar; Ranjani, Harish; Ali, Mohammed K; Unnikrishnan, Ranjit; Anjana, Ranjit Mohan; Narayan, K M Venkat; Mohan, Viswanathan

2014-01-01

To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). T1DM-Y(n=150) and T2DM-Y(n=150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. The prevalence of any DR was 53.3% [95% CI 45.3-61.3] in T1DM-Y (duration of diabetes: 12.4±7.4 years) and 52.7% [44.7-60.7] in T2DM-Y (11.8±8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42-2.79], waist circumference [1.28 per 5 cm;1.05-1.56] and microalbuminuria [2.39 per 50 μg;1.07-5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61-3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18-2.02], Glycated hemoglobin [1.37 per %;1.07-1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15-2.05;] were associated with DR in T2DM-Y. Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10-12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR. Copyright © 2014 Elsevier Inc. All rights reserved.

[Foot ulceration risk factors in type 2 diabetes mellitus].

PubMed

Bustos-Saldaña, Rafael; Prieto-Miranda, Sergio

2009-01-01

To identify risk factor prevalence for development of foot ulcers in patients with type 2 diabetes (DM2). A cross sectional study, of 2067 patients with DM2 from seven primary care units was conducted. A questionnaire exploring age, sex, occupation, time from diabetes mellitus diagnosis (DMD), and data concerning neuropathy, vascular changes, and presence of infections, anthropometry, and gait was applied. We found mean age, 59.96 +/- 11.47 years and time from DMD, 10.2 +/- 8.09 years. From 1360 women, 65.8 % presented the following risk factors: age, 34.7 %; schooling, 49.5 %; time from DMD, 38.8 %; occupation, 20 %; smoking, 24.3 %; alcoholism, 4.6 %; fasting glucose disturbance, 78 %; ulcer history, 10 %. In relation to associated diseases, 67.5 % of patients had one or more antecedent. The presence of risk factors in the sample was 9.716 +/- 2.52, of which 6.259 +/- 1.59 were modifiable. Patients studied presented high risk factor prevalence for development of foot ulcer. The majority of RF is potentially modifiable by adjusting patients' customs and habits.

Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

PubMed

Rawshani, Aidin; Rawshani, Araz; Franzén, Stefan; Eliasson, Björn; Svensson, Ann-Marie; Miftaraj, Mervete; McGuire, Darren K; Sattar, Naveed; Rosengren, Annika; Gudbjörnsdottir, Soffia

2017-04-18

Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population. We included all patients ≥18 years of age with T1DM who were registered in the Swedish National Diabetes Register from January 1, 1998, through December 31, 2014, a total of 33 333 patients, each matched for age and sex with 5 controls without diabetes mellitus randomly selected from the population. Patients with T1DM were categorized according to number of risk factors not at target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial infarction, heart failure hospitalization, and stroke was examined in relation to the number of risk factors at target. The mean follow-up was 10.4 years in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for each additional risk factor not at target. Adjusted hazard ratios for patients achieving all risk factor targets compared with controls were 1.31 (95% confidence interval [CI], 0.93-1.85) for all-cause mortality, 1.82 (95% CI, 1.15-2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04-3.73) for heart failure hospitalization, and 1.17 (95% CI, 0.51-2.68) for stroke. The hazard ratio for patients versus controls with none of the risk factors meeting target was 7.33 (95% CI, 5.08-10.57) for all-cause mortality, 12.34 (95% CI, 7.91-19.48) for acute myocardial infarction, 15.09 (95% CI, 9.87-23.09) for heart failure hospitalization, and 12.02 (95% CI, 7.66-18.85) for stroke. A steep-graded association exists between decreasing number of cardiovascular risk factors at target and major adverse cardiovascular outcomes among

Correlation of Lipid Profile and Risk of Developing Type 2 Diabetes Mellitus in 10-14 Year Old Children.

PubMed

Habiba, Nusrath M; Fulda, Kimberly G; Basha, Riyaz; Shah, Deep; Fernando, Shane; Nguyen, Bao; Xiong, Yi; Franks, Susan F; Matches, Sarah J; Magie, Richard D; Bowman, W Paul

2016-01-01

The role of lipid profile in predicting the risk of Type 2 diabetes mellitus (T2DM) in children is not clearly established. Our aim is to screen non-diabetic children aged 10-14 years for risk of developing T2DM and evaluate the association of abnormal lipids and socioeconomic status (SES). Data on race/ethnicity, family history, body mass index percentile, blood pressure and presence of neck pigmentation (acanthosis nigricans) were collected from 149 non-diabetic children. Using these factors, children were classified into low risk (<3 risk factors) and high risk (>3 risk factors) groups. Logistic regression model and chi-square tests were used to evaluate the association of blood lipid profile and demographic variables. Independent t-test was used to compare the ratio of Total Cholesterol (TC) and High Density Lipids (HDL) with T2DM risk. 60% of children were at high risk for developing T2DM. HDL (p<0.001), triglycerides (p=0.02) and TC/HDL ratio (p<.001) were significantly abnormal in high risk group. Low SES showed a marginal association with high risk group. There were no gender or age differences between high and low risk groups. The significant determinants associated with high risk group were modifiable factors providing an opportunity for early intervention and prevention. © 2016 The Author(s) Published by S. Karger AG, Basel.

Low levels of ApoA1 improve risk prediction of type 2 diabetes mellitus.

PubMed

Wu, Xing; Yu, Zhexin; Su, Wen; Isquith, Daniel A; Neradilek, Moni B; Lu, Ning; Gu, Fusheng; Li, Hongwei; Zhao, Xue-Qiao

Type 2 diabetes mellitus (T2DM) has reported to be a major public health crisis in China. We examined the incidence of new T2DM over 4 years for association of clinical factors and lipids with development of T2DM in a community-based population. We included 923 Chinese subjects who participated in community-organized health checkout in both 2009 and 2013. Health history was collected; physical examination was performed; biochemistry, lipids, and glucose were measured. Of 923, 819 were confirmed without T2DM in 2009 and included in the analysis. Unadjusted and adjusted logistic regression models were used to estimate the effects of clinical factors and biomarkers on the risk of new T2DM. Of 819 subjects without T2DM in 2009, 65 were identified as T2DM in 2013, 8% over 4 years. These 65 subjects, compared with those 754 without new T2DM, were older, more likely to be male and smokers. They had higher body mass index (BMI), fasting glucose, blood pressure and triglycerides, and lower levels of high-density lipoprotein-cholesterol and apolipoprotein A1 (ApoA1). Multivariate logistic regression identified larger BMI (odds ratio [OR] = 1.7; 95% confidence interval [CI], 1.22-2.39, P = .002), higher fasting glucose levels (OR = 4.2, 95% CI, 2.90-6.19, P < .001), and low levels of ApoA1 (OR = 0.51, 95% CI 0.33-0.76, P = .002) were independently associated with new T2DM. Furthermore, receiver operating characteristics curves for multivariate models for new T2DM showed that area under the curve improved from 0.87 to 0.89 when adding ApoA1 to the Framingham Diabetes Risk Scoring Model and from 0.85 to 0.89 when adding ApoA1 to a 4-variable (age, BMI, glucose, and triglycerides) Chinese model. There is a high incidence of new T2DM at 8% over 4 years among Chinese. Larger BMI, higher glucose levels, and lower levels of ApoA1 are significantly and independently associated with new T2DM. Lower ApoA1 improves the risk prediction of new type 2 diabetes when it was

Efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancer (MBC): a meta-analysis of randomized controlled trial

PubMed Central

Yan, Hongjing; Yu, Kewei; Zhang, Kaile; Liu, Linxia; Li, Yue

2017-01-01

Aims Trastuzumab emtansine (T-DM1), an antibody-drug conjugate against human epidermal growth factor receptor 2 (HER2), has been used in the treatment of patients with HER2-positive metastatic breast cancer (MBC). We conducted a meta-analysis to evaluate the efficacy and toxicity of T-DM1 for the treatment of patients with HER2-positive MBC. Materials and Methods Randomized controlled trials (RCTs), published in Pubmed, Embase, and Web of Science were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with MBC who were treated with T-DM1. Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities. Results were expressed as the hazard ratio (HR) with 95% confidence intervals (CIs). Results A total of 5 RCTs involving 3,720 patients met the inclusion criteria and were included in this meta-analysis. T-DM1 significantly prolonged PFS (HR = 0.73, 95% CI: 0.61, 0.86; P < 0.05), OS (HR = 0.68, 95% CI: 0.62, 0.74; P < 0.05), but it did not increase ORR (RR = 1.25, 95% CI: 0.94, 1.66; P = 0.148). Subgroup analysis indicated that T-DM1 significantly improved PFS when it was used as first-line (HR = 0.86, 95% CI: 0.74, 1.00; P < 0.05) or non-first-line treatment (HR = 0.65, 95% CI: 0.53, 0.81; P < 0.05). T-DM1 was associated with more frequent adverse events, including fatigue, elevated ALT, elevated AST, and thrombocytopenia, than other anti-HER2 therapies. Conclusions Based on the current evidence, T-DM1 significantly prolonged PFS and OS with a tolerated toxicity than other anti-HER2 therapies in patients with HER2-positive MBC. These findings confirm the use of T-DM1 for the treatment of patients with HER2-positive MBC. Further well-designed, multi-center RCTs needed to identify these findings. PMID:29254261

Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls.

PubMed

Shen, Yi; Zhang, Jian; Cai, Hui; Shao, Jian-Guo; Zhang, You-Yi; Liu, Yan-Mei; Qin, Gang; Qin, Yan

2015-03-19

The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.

Cytokine gene polymorphisms as risk and severity factors for juvenile dermatomyositis.

PubMed

Mamyrova, Gulnara; O'Hanlon, Terrance P; Sillers, Laura; Malley, Karen; James-Newton, Laura; Parks, Christina G; Cooper, Glinda S; Pandey, Janardan P; Miller, Frederick W; Rider, Lisa G

2008-12-01

To study tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1) cytokine polymorphisms as possible risk and protective factors, define their relative importance, and examine these as severity factors in patients with juvenile dermatomyositis (DM). TNFalpha and IL-1 cytokine polymorphism and HLA typing were performed in 221 Caucasian patients with juvenile DM, and the results were compared with those in 203 ethnically matched healthy volunteers. The genotypes TNFalpha -308AG (odds ratio [OR] 3.6), TNFalpha -238GG (OR 3.5), and IL-1alpha +4845TT (OR 2.2) were risk factors, and TNFalpha -308GG (OR 0.26) as well as TNFalpha -238AG (OR 0.22) were protective, for the development of juvenile DM. Carriage of a single copy of the TNFalpha -308A (OR 3.8) or IL-1beta +3953T (OR 1.7) allele was a risk factor, and the TNFalpha -238A (OR 0.29) and IL-1alpha +4845G (OR 0.46) alleles were protective, for juvenile DM. Random Forests classification analysis showed HLA-DRB1*03 and TNFalpha -308A to have the highest relative importance as risk factors for juvenile DM compared with the other alleles (Gini scores 100% and 90.7%, respectively). TNFalpha -308AA (OR 7.3) was a risk factor, and carriage of the TNFalpha -308G (OR 0.14) and IL-1alpha -889T (OR 0.41) alleles was protective, for the development of calcinosis. TNFalpha -308AA (OR 7.0) was a possible risk factor, and carriage of the TNFalpha -308G allele (OR 0.14) was protective, for the development of ulcerations. None of the studied TNFalpha, IL-1alpha, and IL-1beta polymorphisms were associated with the disease course, disease severity at the time of diagnosis, or the patient's sex. TNFalpha and IL-1 genetic polymorphisms contribute to the development of juvenile DM and may also be indicators of disease severity.

Uncontrolled Hypertension and Its Determinants in Patients with Concomitant Type 2 Diabetes Mellitus (T2DM) in Rural South Africa.

PubMed

Adeniyi, Oladele Vincent; Yogeswaran, Parimalaranie; Longo-Mbenza, Benjamin; Ter Goon, Daniel

2016-01-01

Paucity of data on the prevalence, treatment and control of hypertension in individuals living with type 2 diabetes mellitus (T2DM) in the rural communities of South Africa may undermine efforts to reduce the morbidity and mortality associated with cardiovascular diseases. This study examines the socio-demographic and clinical determinants of uncontrolled hypertension among individuals living with T2DM in the rural communities of Mthatha, South Africa. This cross-sectional study involved a serially selected sample of 265 individuals living with T2DM and hypertension at Mthatha General Hospital, Mthatha. Uncontrolled hypertension was defined as systolic blood pressure greater than or equal to 140 mmHg and diastolic blood pressure greater than or equal to 90mmHg in accordance with the Eight Joint National Committee Report (JNC 8) (2014). We performed univariate and multivariate logistic regression analyses to identify the significant determinants of uncontrolled hypertension. Of the total participants (n = 265), the prevalence of uncontrolled hypertension was 75.5% (n = 200). In univariate analysis of all participants, male gender (p = 0.029), age≥65 years (p = 0.016), unemployed status (p<0.0001), excessive alcohol intake (p = 0.005) and consumption of western-type diet (p<0.0001) were positively associated with uncontrolled hypertension. In multivariate logistic regression (LR method) analysis, unemployed status (p<0.0001), excessive alcohol intake (p = 0.007) and consumption of western-type diet (p<0.0001) were independently and significantly associated with uncontrolled hypertension. There is significant association between increasing number and classes of anti-hypertensive drugs and uncontrolled hypertension (p = 0.05 and 0.02, respectively). Prevalence of uncontrolled hypertension was high in individuals with concomitant hypertension and T2DM in the study population. Male sex, aging, clinic inertia, unemployed status and nutritional transitions are the most

Adherence to a healthy lifestyle and the risk of type 2 diabetes in Chinese adults.

PubMed

Lv, Jun; Yu, Canqing; Guo, Yu; Bian, Zheng; Yang, Ling; Chen, Yiping; Hu, Ximin; Hou, Wei; Chen, Junshi; Chen, Zhengming; Qi, Lu; Li, Liming

2017-10-01

Simultaneously adhering to multiple healthy lifestyle factors has been related to up to 90% reduction in type 2 diabetes (T2DM) incidence in White populations; however, little is known about whether such protective effects persist in other non-White populations. We examined the associations of six lifestyle factors with T2DM in the China Kadoorie Biobank of 461 211 participants aged 30-79 years without diabetes, cardiovascular diseases or cancer at baseline. We defined low-risk lifestyle factors as non-smoking or having stopped for reasons other than illness; alcohol consumption of <30 g/day; upper quarter of the physical activity level; diet rich in vegetables and fruits, low in red meat and with some degree of replacement of rice with wheat; body mass index (BMI) of 18.5-23.9 kg/m2; and waist-to-hip ratio (WHR) <0.90 (men)/<0.85 (women). During a median of 7.2 years of follow-up, we identified 8784 incident T2DM. In multivariable-adjusted analyses, two important risk factors for developing T2DM were higher BMI and WHR. Compared with participants without any low-risk factors, the hazard ratio [95% confidence interval (CI)] for those with at least three low-risk factors was 0.20 (0.19, 0.22). Approximately 72.6% (64.2%, 79.3%) of the incident diabetes were attributable to the combination of BMI, WHR, diet and physical activity. The population attributable risk percentage (PAR%) of diabetes appeared to be similar for men and women, and higher among urban, older and obese participants. Our findings indicate that adherence to a healthy lifestyle may substantially lower the burden of T2DM in the Chinese population. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association

Initial combination therapy with vildagliptin plus metformin in drug-naïve patients with T2DM: a 24-week real-life study from Asia.

PubMed

Chawla, Manoj; Kim, Tae Ho; Mirasol, Roberto C; Faruque, Pathan; Cooke, Kathryn; Hours-Zesiger, Peggy; Shete, Abhijit

2018-06-12

To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM). INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c) ≥ 7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7.0%, change in body weight at 12 and 24 weeks, change in HbA1c by sub-groups (baseline HbA1c, age, body mass index [BMI], dosage strength, co-morbidities) from baseline to week 24, and safety. A total of 532 patients were enrolled. The mean age, HbA1c, and BMI were 49.6 ± 11.27 years, 9.3 ± 1.57%, and 26.7 ± 4.50 kg/m 2 , respectively. Cardiovascular risk factors present at baseline were dyslipidemia (30.1%), hypertension (29.7%), and obesity (20.9%). The mean reductions in HbA1c from baseline to week 12 (-1.6 ± 1.59%) and 24 (-1.9 ± 1.70%) were statistically significant (p < .001). At 24 weeks, 39.6% of patients achieved HbA1c ≤ 7.0%, and the mean body weight reduction was -1.1 ± 2.62 kg. HbA1c reductions were consistently seen from baseline to weeks 12 and 24 in the various sub-groups. Overall, 48 (9.0%) patients reported adverse events, including one hypoglycemic episode. There were no serious adverse events or deaths. Overall, in a relatively young drug-naïve T2DM Asian study population with high baseline HbA1c and often associated with cardiovascular risk factors, vildagliptin/metformin combination therapy was associated with significant and clinically relevant HbA1c reduction from baseline. This effect was seen at week 12, was maintained over 24 weeks, and was accompanied by good tolerability.

An integrated multiple-analyte pharmacokinetic model to characterize trastuzumab emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic sampling in patients with HER2-positive metastatic breast cancer.

PubMed

Lu, Dan; Joshi, Amita; Wang, Bei; Olsen, Steve; Yi, Joo-Hee; Krop, Ian E; Burris, Howard A; Girish, Sandhya

2013-08-01

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer previously treated with trastuzumab and taxane chemotherapy. It comprises the microtubule inhibitory cytotoxic agent DM1 conjugated to the HER2-targeted humanized monoclonal antibody trastuzumab via a stable linker. To characterize the pharmacokinetics of T-DM1 in patients with metastatic breast cancer, concentrations of multiple analytes were quantified, including serum concentrations of T-DM1 conjugate and total trastuzumab (the sum of conjugated and unconjugated trastuzumab), as well as plasma concentrations of DM1. The clearance of T-DM1 conjugate is approximately 2 to 3 times faster than its parent antibody, trastuzumab. However, the clearance pathways accounting for this faster clearance rate are unclear. An integrated population pharmacokinetic model that simultaneously fits the pharmacokinetics of T-DM1 conjugate and total trastuzumab can help to elucidate the clearance pathways of T-DM1. The model can also be used to predict total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic data, thereby reducing the frequency of pharmacokinetic sampling. T-DM1 conjugate and total trastuzumab serum concentration data, including baseline trastuzumab concentrations prior to T-DM1 treatment, from phase I and II studies were used to develop this integrated population pharmacokinetic model. Based on a hypothetical T-DM1 catabolism scheme, two-compartment models for T-DM1 conjugate and trastuzumab were integrated by assuming a one-step deconjugation clearance from T-DM1 conjugate to trastuzumab. The ability of the model to predict the total trastuzumab pharmacokinetic profile based on T-DM1 conjugate pharmacokinetics and various sampling schemes of total trastuzumab

Association of parental history of diabetes with cardiovascular disease risk factors in children with type 2 diabetes.

PubMed

Law, Jennifer R; Stafford, Jeanette M; D'Agostino, Ralph B; Badaru, Angela; Crume, Tessa L; Dabelea, Dana; Dolan, Lawrence M; Lawrence, Jean M; Pettitt, David J; Mayer-Davis, Elizabeth J

2015-01-01

Determine if parental diabetes (DM) is associated with unhealthier cardiovascular disease (CVD) risk profiles in youth with type 2 diabetes (T2D), and whether associations differed by race/ethnicity. Family history was available for 382 youth with T2D from 2001 prevalent and 2002-2005 incident SEARCH for Diabetes in Youth cohorts. Parental DM was evaluated in two ways: two-category-any parent vs. no parent DM (evaluated overall and stratified by race/ethnicity); and four-category-both parents, mother only, father only, or no parent DM (evaluated overall only). Associations with hemoglobin A1c (HbA1c), fasting lipids, blood pressure (BP), and urine albumin:creatinine ratio (ACR) were examined using regression models. Overall, sample characteristics included: 35.9% male, 19.1% non-Hispanic white (NHW), mean T2D duration 26.6±22.2months, mean HbA1c 7.9%±2.5% (62.6±27.8mmol/mol). Unadjusted two-category comparisons showed that youth with parental DM had higher HbA1c, higher DBP, and higher frequency of elevated ACR. Adjusted two-category comparisons showed associations remaining in non-stratified analysis for ACR [OR (95% CI)=2.3 (1.1, 5.0)] and in NHW youth for HbA1c [6.8%±0.4 vs. 8.0±0.4 (51.1±4.8 vs. 63.9±4.2mmol/mol), p=.015], DBP (67.7%±4.5 vs. 76.9±4.4mm Hg, p=.014) and lnTG (4.7±0.3 vs. 5.3±0.3, p=.008). There were no significant findings in the adjusted four-category evaluation. Parental history of diabetes may be associated with unhealthier CVD risk factors in youth with T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

The relationship of family history and risk of type 2 diabetes differs by ancestry.

PubMed

Kral, B G; Becker, D M; Yanek, L R; Vaidya, D; Mathias, R A; Becker, L C; Kalyani, R R

2018-05-21

Type 2 diabetes (T2DM) in a first-degree relative is a risk factor for incident diabetes. Americans of African ancestry (AA) have higher rates of T2DM than Americans of European ancestry (EA). Thus, we aimed to determine whether the presence, number and kinship of affected relatives are associated with race-specific T2DM incidence in a prospective study of participants from the Genetic Study of Atherosclerosis Risk (GeneSTAR), who underwent baseline screening including a detailed family history. Nondiabetic healthy siblings (n=1405) of patients with early-onset coronary artery disease (18-59 years) were enrolled (861 EA and 544 AA) and followed for incident T2DM (mean 14±6 years). Baseline age was 46.2±7.3 years and 56% were female. T2DM occurred in 12.3% of EA and 19.1% of AA. Among EA, 32.6% had ≥1 affected first-degree relatives versus 53.1% in AA, P<0.0001. In fully adjusted Cox proportional hazard analyses, any family history was related to incident T2DM in EA (HR=2.53, 95% CI: 1.58-4.06) but not in AA (HR=1.01, 0.67-1.53). The number of affected relatives conferred incremental risk of T2DM in EA with HR=1.82 (1.08-3.06), 4.83 (2.15-10.85) and 8.46 (3.09-23.91) for 1, 2, and ≥3 affected, respectively. In AA only ≥3 affected increased risk (HR=2.45, 1.44-4.19). Specific kinship patterns were associated with incident T2DM in EA but not in AA. The presence of any first-degree relative with T2DM does not discriminate risk in AA given the high race-specific prevalence of diabetes. Accounting for the number of affected relatives may more appropriately estimate risk for incident diabetes in both races. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Association between Osteocalcin, Metabolic Syndrome, and Cardiovascular Risk Factors: Role of Total and Undercarboxylated Osteocalcin in Patients with Type 2 Diabetes

PubMed Central

Alfadda, Assim A.; Masood, Afshan; Shaik, Shaffi Ahamed; Dekhil, Hafedh

2013-01-01

Studies have demonstrated that total osteocalcin (TOC) is associated with metabolic syndrome (MetS) and therefore might influence the risk of cardiovascular disease in humans. Undercarboxylated osteocalcin (uOC) regulates insulin secretion and sensitivity in mice, but its relation to MetS in humans is unclear. We aimed to determine whether uOC is related to MetS and/or its individual components and other cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM), and whether TOC and uOC have utility in predicting the cardiovascular risk. We studied 203 T2DM patients with and without MetS. MetS was defined based on the NCEP-ATP III criteria. A correlation analysis was performed between the three outcome variables: (i) TOC, (ii) uOC, and (iii) carboxylated osteocalcin (cOC) and MetS components and other cardiovascular risk factors. Both TOC and uOC were significantly lower in patients with MetS compared to those without MetS, independent of body mass index. In patients with MetS, uOC was significantly and positively correlated with HDL cholesterol, while TOC was significantly and negatively correlated with serum triglycerides. We report for the first time that uOC is related to lipid indices in patients with T2DM. Further studies are necessary to determine whether uOC can be utilized for cardiovascular risk assessments in these patients. PMID:23653641

[Diabetic Foot Neuropathy and Related Factors in Patients With Type 2 Diabetes Mellitus].

PubMed

Chen, Tzu-Yu; Lin, Chia-Huei; Chang, Yue-Cune; Wang, Chih-Hsin; Hung, Yi-Jen; Tzeng, Wen-Chii

2018-06-01

Patients with type 2 diabetes mellitus (T2DM) face a higher risk of diabetic foot neuropathy, which increases the risk of death. The early detection of factors that influence diabetic neuropathy reduces the risk of foot lesions, including foot ulcerations, lower extremity amputation, and mortality. To explore the demographic, disease-characteristic, health-literacy, and foot-self-care-behavior factors that affect diabetic foot neuropathy in patients with T2DM. A case-control study design was employed in which cases (Michigan Neuropathy Screening Instrument, MNSI) ≥ 2 were matched to controls based on age and gender in a medical center. A total of 114 patients diagnosed with T2DM in a medical center were recruited as participants. Data were collected using a structured questionnaire. The collected data were analyzed using Fisher's exact test, Mann-Whitney U test, and logistic regression. The results of multiple logistic regression showed that glycated hemoglobin (B = 1.696, p = .041) and communication and critical health literacy (B = -0.082, p = .034) were significant factors of diabetic foot neuropathy. The findings of this study suggest that nurses should assess the health literacy of patients with T2DM before providing health education and should develop a specific foot-care intervention for individuals with poor glycemic control.

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Northern Han Chinese

PubMed Central

Rao, Ping; Zhou, Yong; Ge, Si-Qi; Wang, An-Xin; Yu, Xin-Wei; Alzain, Mohamed Ali; Veronica, Andrea Katherine; Qiu, Jing; Song, Man-Shu; Zhang, Jie; Wang, Hao; Fang, Hong-Hong; Gao, Qing; Wang, You-Xin; Wang, Wei

2016-01-01

Background: More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population. Method: In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January 2009 to October 2013. A cumulative genetic risk score (cGRS) was calculated by summation of the number of risk alleles, and a weight GRS (wGRS) was calculated as the sum of risk alleles at each locus multiplied by their effect sizes for T2DM, using the independent variants selected. Result: The allelic frequency of the “A” allele at rs17106184 (Fas-associated factor 1, FAF1) was significantly higher in the T2DM patients than that of the healthy controls (11.7% vs. 6.4%, p < 0.001). Individuals in the highestquartile of wGRS had an over three-fold increased risk for developing T2DM compared with those in the lowest quartile (odds ratio = 3.06, 95% CI = 1.92–4.88, p < 0.001) adjusted for age, sex, BMI, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The results were similar when analyzed with the cGRS. Conclusions: We confirmed the association between rs17106184 (FAF1) and T2DM in a northern Han Chinese population. The GRS calculated based on T2DM susceptibility variants may be a useful tool for predicting the T2DM susceptibility. PMID:27589775

Risk Factors for Incident Peripheral Arterial Disease in Type 2 Diabetes: Results From the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) Trial

PubMed Central

Althouse, Andrew D.; Abbott, J. Dawn; Forker, Alan D.; Bertolet, Marnie; Barinas-Mitchell, Emma; Thurston, Rebecca C.; Mulukutla, Suresh; Aboyans, Victor; Brooks, Maria Mori

2014-01-01

OBJECTIVE The aim of this article was to define risk factors for incidence of peripheral arterial disease (PAD) in a large cohort of patients with type 2 diabetes mellitus (T2DM), overall and within the context of differing glycemic control strategies. RESEARCH DESIGN AND METHODS The Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) randomized controlled trial assigned participants to insulin-sensitizing (IS) therapy versus insulin-providing (IP) therapy. A total of 1,479 participants with normal ankle-brachial index (ABI) at study entry were eligible for analysis. PAD outcomes included new ABI ≤0.9 with decrease at least 0.1 from baseline, lower extremity revascularization, or lower extremity amputation. Baseline risk factors within the overall cohort and time-varying risk factors within each assigned glycemic control arm were assessed using Cox proportional hazards models. RESULTS During an average 4.6 years of follow-up, 303 participants (20.5%) experienced an incident case of PAD. Age, sex, race, and baseline smoking status were all significantly associated with incident PAD in the BARI 2D cohort. Additional baseline risk factors included pulse pressure, HbA1c, and albumin-to-creatinine ratio (P < 0.05 for each). In stratified analyses of time-varying covariates, changes in BMI, LDL, HDL, systolic blood pressure, and pulse pressure were most predictive among IS patients, while change in HbA1c was most predictive among IP patients. CONCLUSIONS Among patients with T2DM, traditional cardiovascular risk factors were the main predictors of incident PAD cases. Stratified analyses showed different risk factors were predictive for patients treated with IS medications versus those treated with IP medications. PMID:24595631

Risk factors for incident peripheral arterial disease in type 2 diabetes: results from the Bypass Angioplasty Revascularization Investigation in type 2 Diabetes (BARI 2D) Trial.

PubMed

Althouse, Andrew D; Abbott, J Dawn; Forker, Alan D; Bertolet, Marnie; Barinas-Mitchell, Emma; Thurston, Rebecca C; Mulukutla, Suresh; Aboyans, Victor; Brooks, Maria Mori

2014-01-01

The aim of this article was to define risk factors for incidence of peripheral arterial disease (PAD) in a large cohort of patients with type 2 diabetes mellitus (T2DM), overall and within the context of differing glycemic control strategies. The Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) randomized controlled trial assigned participants to insulin-sensitizing (IS) therapy versus insulin-providing (IP) therapy. A total of 1,479 participants with normal ankle-brachial index (ABI) at study entry were eligible for analysis. PAD outcomes included new ABI ≤0.9 with decrease at least 0.1 from baseline, lower extremity revascularization, or lower extremity amputation. Baseline risk factors within the overall cohort and time-varying risk factors within each assigned glycemic control arm were assessed using Cox proportional hazards models. During an average 4.6 years of follow-up, 303 participants (20.5%) experienced an incident case of PAD. Age, sex, race, and baseline smoking status were all significantly associated with incident PAD in the BARI 2D cohort. Additional baseline risk factors included pulse pressure, HbA1c, and albumin-to-creatinine ratio (P < 0.05 for each). In stratified analyses of time-varying covariates, changes in BMI, LDL, HDL, systolic blood pressure, and pulse pressure were most predictive among IS patients, while change in HbA1c was most predictive among IP patients. Among patients with T2DM, traditional cardiovascular risk factors were the main predictors of incident PAD cases. Stratified analyses showed different risk factors were predictive for patients treated with IS medications versus those treated with IP medications.

Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors-γ2 with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status in Emirati Population

PubMed Central

Al-Safar, Habiba; Hassoun, Ahmed; Almazrouei, Shaikha; Kamal, Wala; Afandi, Bachar; Rais, Naushad

2015-01-01

Background. Transcription factor 7-like 2 gene (TCF7L2) and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2) have a profound effect on the incidence of type 2 diabetes mellitus (T2DM) and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282) of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. Methods. DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2) and rs1801282 (PPAR-γ2 P12A) variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. Results. In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127–3.461], P = 0.017), but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96) was similar in the groups tested and more than 90% population was homozygous for this allele. Conclusions. Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population. PMID:26273662

Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors- γ 2 with Type 2 Diabetes Mellitus and is Interaction with Obesity Status in Emirati Population.

PubMed

Al-Safar, Habiba; Hassoun, Ahmed; Almazrouei, Shaikha; Kamal, Wala; Afandi, Bachar; Rais, Naushad

2015-01-01

Transcription factor 7-like 2 gene (TCF7L2) and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2) have a profound effect on the incidence of type 2 diabetes mellitus (T2DM) and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282) of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status. DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2) and rs1801282 (PPAR-γ2 P12A) variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status. In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127-3.461], P = 0.017), but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96) was similar in the groups tested and more than 90% population was homozygous for this allele. Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population.

Control of risk factors for cardiovascular disease among adults with previously diagnosed type 2 diabetes mellitus: a descriptive study from a middle eastern arab population.

PubMed

Al-Lawati, Jawad A; N Barakat, Mohammed; Al-Zakwani, Ibrahim; Elsayed, Medhat K; Al-Maskari, Masoud; M Al-Lawati, Nawar; Mohammed, Ali Jaffer

2012-01-01

Despite the high burden of type 2 diabetes mellitus (T2DM) in Oman, there are scarce data from a nationally representative sample on the level of glycaemia and other cardiovascular (CVD) risk factor control. To estimate the proportion of patients with T2DM at goal for glycaemia and CVD risk factors using the National Diabetes Guidelines (NDG) and the American Diabetes Association (ADA) clinical care guidelines; and to assess the quality of selected services provided to patients with T2DM. A sample of 2,551 patients (47% men) aged ≥20 years with T2DM treated at primary health care centers was selected. Patient characteristics, medical history and treatment were collected from case notes, Diabetes Registers and computer frameworks including the use of the last 3 laboratory investigations results and blood pressure (BP) readings recorded in 2007. The overall mean age of the cohort was 54±13 years with an average median duration of diabetes of 4 (range 2 to 6) years. Over 80% of patients were overweight or obese (body mass index (BMI) of ≥25 Kg/m(2)). Sixty-nine percent were on oral anti-diabetic medication, 52% on anti-hypertensives and 40% on lipid lowering drugs. Thirty percent of patients were at goal for glycosylated haemoglobin level (<7%), 26% for BP (systolic/diastolic <130/80 mmHg), 55% for total cholesterol (<5.2 mmol/l), 4.5% for low-density lipoprotein cholesterol (<1.8 mmol/l), 52% for high-density lipoprotein cholesterol (>1 mmol/l for men, >1.3 mmol/l for women), and 61% for triglycerides (<1.7 mmol/l). Over 37% had micro-albuminuria and 5% had diabetic nephropathy. Control of hyperglycaemia and other CVD risk factor appears to be suboptimal in Omani patients with T2DM and need to be addressed in the triad of patient, physician and health system.

Diabetes Medication Assistance Service: the pharmacist's role in supporting patient self-management of type 2 diabetes (T2DM) in Australia.

PubMed

Mitchell, Bernadette; Armour, Carol; Lee, Mary; Song, Yun Ju; Stewart, Kay; Peterson, Greg; Hughes, Jeff; Smith, Lorraine; Krass, Ines

2011-06-01

To evaluate the capacity and effectiveness of trained community pharmacists in delivering the Diabetes Medication Assistance Service (DMAS) via (1) number and types of self-management support interventions (SMSIs); (2) number of goals set and attained by patients and (3) patient outcomes (glycaemic control, medication adherence and satisfaction). Pharmacists (n=109) from 90 community pharmacies in Australia were trained and credentialed to deliver the DMAS. The training focused on developing pharmacists' knowledge and skills in supporting patients' diabetes self-management. A total of 387 patients completed the trial. The mean number of SMSIs per patient was 35 (SD ±31) and the majority (87%) had at least one documented goal that was fully or partially attained. There were significant health benefits for patients including improved glycaemic control and a reduced risk of non-adherence to medications. Over 90% of DMAS patients reported improvements in their knowledge about diabetes self-management. The DMAS provides self management support in the community pharmacy for people with T2DM which may result in improved clinical outcomes. Given appropriate training in diabetes care and behavior change strategies, community pharmacists can offer programs which provide self-management support to their patients with T2DM and improve their health outcomes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes-associated osteoarthritis.

PubMed

Vaamonde-Garcia, Carlos; Courties, Alice; Pigenet, Audrey; Laiguillon, Marie-Charlotte; Sautet, Alain; Houard, Xavier; Kerdine-Römer, Saadia; Meijide, Rosa; Berenbaum, Francis; Sellam, Jérémie

2017-09-01

Epidemiological findings support the hypothesis that type 2 diabetes mellitus (T2DM) is a risk factor for osteoarthritis (OA). Moreover, OA cartilage from patients with T2DM exhibits a greater response to inflammatory stress, but the molecular mechanism is unclear. To investigate whether the antioxidant defense system participates in this response, we examined here the expression of nuclear factor-erythroid 2-related factor (Nrf-2), a master antioxidant transcription factor, and of heme oxygenase-1 (HO-1), one of its main target genes, in OA cartilage from T2DM and non-T2DM patients as well as in murine chondrocytes exposed to high glucose (HG). Ex vivo experiments indicated that Nrf-2 and HO-1 expression is reduced in T2DM versus non-T2DM OA cartilage (0.57-fold Nrf-2 and 0.34-fold HO-1), and prostaglandin E 2 (PGE 2 ) release was increased in samples with low HO-1 expression. HG-exposed, IL-1β-stimulated chondrocytes had lower Nrf-2 levels in vitro , particularly in the nuclear fraction, than chondrocytes exposed to normal glucose (NG). Accordingly, HO-1 levels were also decreased (0.49-fold) in these cells. The HO-1 inducer cobalt protoporphyrin IX more efficiently attenuated PGE 2 and IL-6 release in HG+IL-1β-treated cells than in NG+IL-1β-treated cells. Greater reductions in HO-1 expression and increase in PGE 2 /IL-6 production were observed in HG+IL-1β-stimulated chondrocytes from Nrf-2 -/- mice than in chondrocytes from wild-type mice. We conclude that the Nrf-2/HO-1 axis is a critical pathway in the hyperglucidic-mediated dysregulation of chondrocytes. Impairments in this antioxidant system may explain the greater inflammatory responsiveness of OA cartilage from T2DM patients and may inform treatments of such patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Prevalence of type 2 diabetes mellitus complications among palestinians with T2DM.

PubMed

Abu Al-Halaweh, Ahmad; Davidovitch, Nadav; Almdal, Thomas Peter; Cowan, Anna; Khatib, Samah; Nasser-Eddin, Lana; Baradia, Ziad

2017-12-01

To assess the prevalence of microvascular and macrovascular complications of type 2 diabetes (T2DM) among Palestinians. 1308 diagnosed T2DM attending four main Primary Health Care Clinics on the Southern West Bank of Palestine examined by a Mobile Diabetes Clinic team. All diabetes patients visiting the clinics during a one-month period for each clinic were included. Interviews, anthropometric measurements, physical examination, and laboratory tests: HbA1c, lipid profile, and kidney function tests analyzed in a central laboratory were obtained RESULTS: 1308 diabetes patients, including 839 females (64%), with a mean age of 57 years (SD=8.7), and mean diabetes duration 7.1 years(SD=6.25), participated. 95.3% presented as overweight (BMI >25kg/m 2 ) or obese (BMI>30kg/m 2 ) with mean BMI of 33.46 (SD=5.95). The mean HbA1c (tested in 1221 patients) was 9.21(SD=2). Only 16.1% had HbA1c <7.0%. Hypertension (blood pressure>140/90mmHg) were found in 23%, and dyslipidemia (total cholesterol>200mg/dl) was present in 37.3% of patients. 213(16.3%) had a history of the macrovascular disease (previous myocardial infarction or stroke), and 290 (25.9%) had microvascular complications. Moreover, 40 (4.9%) had advanced kidney disease with serum creatinine>1.4mg/dl. The present cross-sectional study shows poor glycemic control in Palestine, while blood pressure and lipids are less poorly controlled. The study emphasizes the need to optimize the glucose-lowering treatment and to implement diabetes care program that could face the challenge of high uncontrolled diabetes as well as complications of diabetes. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Type 2 diabetes mellitus and risk of colorectal adenoma: a meta-analysis of observational studies.

PubMed

Yu, Feifei; Guo, Yibin; Wang, Hao; Feng, Jian; Jin, Zhichao; Chen, Qi; Liu, Yu; He, Jia

2016-08-17

To summarize the relationship between type 2 diabetes mellitus (T2DM) and risk of colorectal adenomas (CRA), we performed a meta-analysis of observational studies. To find studies, we searched PubMed, Embase, the Cochrane Library, Web of Science and conference abstracts and related publications for American Society of Clinical Oncology and the European Society of Medical Oncology. Studies that reported relative risks (RRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) for the association between T2DM and risk of CRA were included. The meta-analysis assessed the relationships between T2DM and risk of CRA. Sensitivity analyses were performed in two ways: (1) by omitting each study iteratively and (2) by keeping high-quality studies only. Publication bias was detected by Egger's and Begg's tests and corrected using the trim and fill method. This meta-analysis included 17 studies with 28,999 participants and 6798 CRA cases. We found that T2DM was a risk factor for CRA (RR: 1.52; 95 % CI: 1.29-1.80), and also for the advanced adenoma (RR: 1.41; 95 % CI: 1.06-1.87). Patients with existing T2DM (RR: 1.56; 95 % CI: 1.16-2.08) or newly diagnosed T2DM (RR: 1.51; 95 % CI: 1.16-1.97) have a risk of CRA. Similar significant results were found in retrospective studies (RR: 1.57; 95 % CI: 1.30-1.89) and population based cross-sectional studies (RR: 1.46; 95 % CI: 1.21-1.89), but not in prospective studies (RR: 1.27; 95 % CI: 0.77-2.10). Our results suggested that T2DM plays a risk role in the risk of developing CRA. Consequently, medical workers should increase the rate of CRA screening for T2DM patients so that they can benefit from behavioural interventions that can help prevent the development of colorectal cancer. Additional, large prospective cohort studies are needed to make a more convincing case for these associations.

The Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus Pandemic: Part I. Increased Cardiovascular Disease Risk and the Importance of Atherogenic Dyslipidemia in Persons With the Metabolic Syndrome and Type 2 Diabetes Mellitus

PubMed Central

Ginsberg, Henry N.; MacCallum, Paul R.

2010-01-01

Both the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) confer an increased risk of coronary heart disease and cardiovascular disease (CVD). As MS and T2DM become more prevalent, there will be an associated rise in the number of individuals with or at risk for CVD and its related disorders. One major underlying cause of CVD in patients with MS or T2DM is a characteristic form of atherogenic dyslipidemia. This article reviews the evidence that demonstrates that individuals with MS or T2DM are at increased risk for CVD and highlights atherogenic dyslipidemia as an important risk factor for the development of CVD in these individuals. In an accompanying article, current pharmacotherapies available for the management of atherogenic dyslipidemia in individuals with MS or T2DM are discussed. PMID:19614799

Impact of diabetes duration and chronic pancreatitis on the association between type 2 diabetes and pancreatic cancer risk.

PubMed

Brodovicz, K G; Kou, T D; Alexander, C M; O'Neill, E A; Engel, S S; Girman, C J; Goldstein, B J

2012-12-01

To examine the impact of diabetes duration, chronic pancreatitis and other factors on pancreatic cancer risk. This retrospective cohort study using the UK General Practice Research Database compared pancreatic cancer incidence and risk in patients with type 2 diabetes mellitus (T2DM) versus patients without diabetes. Multivariate Cox regression adjusting for age, sex, history of chronic pancreatitis, gallbladder disease, obesity, smoking and alcohol use and Charlson comorbidity index was used to estimate hazard ratio (HR) [95% confidence interval, CI]. Analyses were repeated using various time windows for diabetes duration. A total of 1903 incident pancreatic cancers were identified, 436 in patients with T2DM (78.76 per 100 000 person-years [95% CI: 71.54, 86.51]) and 1467 in patients without diabetes (11.46 per 100 000 person-years [10.88, 12.06]). Pancreatic cancer risk was significant for T2DM (adjusted HR 1.80 [1.52, 2.14]), increasing age, history of chronic pancreatitis and tobacco use. For patients with chronic pancreatitis and T2DM, the adjusted HR was 12.12 [6.02, 24.40]. Incidence was highest in patients with ≥5 year duration of T2DM. In patient populations with duration of T2DM ranging from ≥1 to ≥5 years, adjusted HRs remained significant but point estimates attenuated slightly with longer duration of T2DM. Patients with T2DM had an 80% increased risk of pancreatic cancer versus patients without diabetes. Patients with T2DM and chronic pancreatitis were 12 times more likely to develop pancreatic cancer. © 2012 Blackwell Publishing Ltd.

Prevalence and risk factors for diabetic retinopathy in 17 152 patients from the island of Funen, Denmark.

PubMed

Larsen, Morten B; Henriksen, Jan Erik; Grauslund, Jakob; Peto, Tunde

2017-12-01

This study aims to estimate the prevalence and risk factors of diabetic retinopathy (DR) in patients enrolled in a large Danish quality-assuring database for diabetes: the Funen Diabetes Database (FDDB). All patients with type 1 (T1DM) and type 2 DM (T2DM) diabetes mellitus (DM) were included in a cross-sectional study. The level of DR per patient was determined based on the eye with highest level of DR. All ocular and non-ocular data were extracted at the latest examination that corresponded to the most recent DR-grading data. Data from 17 152 patients were analysed; 83.1% had T2DM. Prevalence of DR was 23.8% (T1DM: 54.3%, T2DM: 21.2%). T1/T2DM patients were statistically significantly different regarding age, duration of diabetes, BMI, systolic blood pressure (BP), cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, s-creatinine and u-albumin (p < 0.001 for all). Increasing level of DR showed statistically significant association with age, duration of diabetes, systolic BP, HbA1c, s-creatinine and u-albumine with increasing level of DR (all are p < 0.001) both T1DM/T2DM patients. The patients in FDDB had good systemic control with median values of BP, serum lipids, cholesterol and HbA1c all close to or below national guidelines at the time of data extraction, but still a high level of DR was found in this cohort. DR was more common in patients with T1DM than T2DM, but as T2DM patients are more numerous, their level of DR despite acceptable control is still concerning. Most important associated factors for higher levels of DR were age, duration of diabetes, HbA1c, s-creatinine and u-albumine. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

PPARγ gene C161T substitution alters lipid profile in Chinese patients with coronary artery disease and type 2 diabetes mellitus

PubMed Central

2010-01-01

Background Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor, which regulates gene expression of the key proteins involved in lipid metabolism, vascular inflammation, and proliferation. PPARγ may contribute to attenuating atherogenesis and postangioplasty restenosis. PPARγ C161→T substitution is associated with a reduced risk of coronary artery disease (CAD). Whether or not the gene substitution alters the risk of CAD in type 2 diabetes mellitus (T2DM) patients remains unclear. Methods A total of 556 unrelated subjects from a Chinese Han population, including 89 healthy subjects, 78 CAD patients, 86 T2DM patients, and 303 CAD combined with T2DM patients, were recruited to enroll in this study. PPARγC161→T gene polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphisms. Plasma levels of lipoproteins, apolipoproteins, glucose, and insulin were measured by ELISA or radioimmunoassay (RIA). The coronary artery lesions were evaluated by coronary angiography. Results The frequency of the 161T allele in CAD, T2DM, and CAD combined with T2DM patients was similar to that observed in the healthy control group. However, in CAD combined with T2DM patients, the group with angiographically documented moderate stenoses had a higher frequency of the 161T allele in comparison to the group with severe stenoses (P < 0.05). Moreover, in CAD with T2DM patients, the triglyceride levels and apoB in CC homozygote carriers were significantly higher than those in "T" allele carriers. Conclusions PPARγC161→T genotypes weren't significantly associated with the risk of CAD, but were markedly correlated with severity of disease vessels in patients with CAD and T2DM. Furthermore, PPARγC161→T substitution was associated with an altered adipose, but not glucose metabolism. These results indicate that the PPARγ C161→T polymorphism may reduce the risk of severe atherogenesis by modulation of

A cross-sectional study on the associations of insulin resistance with sex hormone, abnormal lipid metabolism in T2DM and IGT patients

PubMed Central

Wang, Xiaoxia; Xian, Tongzhang; Jia, Xiaofan; Zhang, Lina; Liu, Li; Man, Fuli; Zhang, Xianbo; Zhang, Jie; Pan, Qi; Guo, Lixin

2017-01-01

Abstract Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder. It is characterized by hyperglycemia, insulin resistance (IR), and relative impairment in insulin secretion. IR plays a major role in the pathogenesis of T2DM. Many previous studies have investigated the relationship between estrogen, androgen, and obesity, but few focused on the relationship between sex hormones, abnormal lipid metabolism, and IR. The goal for the present study was to identify the association of IR with sex hormone, abnormal lipid metabolism in type 2 diabetes, and impaired glucose tolerance (IGT) patients. In total 13,400 participants were analyzed based on the results of the glucose tolerance test. Using a cross-sectional study, we showed the relationship between IR and the level of sex hormones among 3 different glucose tolerance states: normal control people, IGT, and T2DM patients. We also analyzed the relationship between IR and abnormal lipid metabolism. Significantly, luteinizing, progesterone, estradiol, prolactin, and follicle-stimulating hormone levels decreased in T2DM and IGT patients compared with those in normal control people. The association between IR and lipid metabolism disorders in T2DM and IGT patients was also observed. Our clinical findings may offer new insights into understanding the mechanism of metabolic disorders and in new therapeutic methods for the treatment of the prevalence of type 2 diabetes. PMID:28658166

Interactions between genetic polymorphisms of glucose metabolizing genes and smoking and alcohol consumption in the risk of type 2 diabetes mellitus.

PubMed

Gao, Kaiping; Ren, Yongcheng; Wang, Jinjin; Liu, Zichen; Li, Jianna; Li, Linlin; Wang, Bingyuan; Li, Hong; Wang, Yaxi; Cao, Yunkai; Ohno, Kinji; Zhai, Rihong; Liang, Zhen

2017-12-01

The impact of gene-environment interaction on diabetes remains largely unknown. We aimed to investigate if interaction between glucose metabolizing genes and lifestyle factors is associated with type 2 diabetes mellitus (T2DM). Interactions between genotypes of 4 glucose metabolizing genes (MTNR1B, KCNQ1, KLF14, and GCKR) and lifestyle factors were estimated in 722 T2DM patients and 759 controls, using multiple logistic regression. No significant associations with T2DM were detected for the single nucleotide polymorphisms of MTNR1B, KLF14 and GCKR. However, rs151290 (KCNQ1) polymorphisms were found to be associated with risk of T2DM. Compared with AA, the odds ratios (ORs) of AC or CC genotypes for developing T2DM were 1.545 (P = 0.0489) and 1.603 (P = 0.0383), respectively. In stratified analyses, the associations were stronger in smokers with CC than smokers with AA (OR = 3.668, P = 0.013); drinkers with AC (OR = 5.518, P = 0.036), CC (OR = 8.691, P = 0.0095), and AC+CC (OR = 6.764, P = 0.016) than drinkers with AA. Compared with nondrinkers with AA, drinkers who carry AC and CC had 12.072-fold (P = 0.0007) and 8.147-fold (P = 0.0052) higher risk of developing T2DM. In conclusions, rs151290 (KCNQ1) polymorphisms are associated with increased risk of T2DM, alone and especially in interaction with smoking and alcohol.

Urinary incontinence in Emirati women with diabetes mellitus type 2: prevalence, risk factors and impact on life.

PubMed

Bani-issa, Wegdan; Fakhry, Randa; Al Momani, Fida

2013-11-01

To evaluate prevalence, risk factors for urinary incontinence and its impact on lives of Emirati women with diabetes mellitus type 2 (DM2). Risk factors examined were age, parity, history of urinary tract infections, body mass index (BMI) and DM2 duration. Incontinence is a known complication of DM2 with impact on women's lives. Less is known about incontinence problem among Emirati women with DM2. A cross-sectional survey design using probability sampling approach was employed to assess urinary incontinence in Emirati women with DM2. A total of 300 women with DM2, aged 20-65 years, were recruited from six healthcare centres. Data were collected over an 18-month period. A standardised incontinence questionnaire was used to assess type and frequency of incontinence within the past 12 months. Presence of weekly incontinence was the main outcome. Of the 300 women, 188 (63%) reported any incontinence, of which 48% had at least weekly episode. Both stress (n = 154, 51·3%) and urge (n = 181, 60·3%) were reported by participants, with 48 (31·1%) reporting at least weekly stress and 85 (46·9%) expressing at least weekly urge incontinence. Diabetes duration was a significant risk factor for any, stress and urge incontinence followed by age for only any and stress incontinence. BMI was a risk factor for urge incontinence. Women perceived incontinence as bothersome, disturbing their social activities and daily prayers. The prevalence of incontinence in Emirati women with DM2 is higher than that reported by women in other cultures. Risk factors identified were DM2 duration, age and obesity. Emirati women found incontinence to be a bothersome problem influencing their daily lives and prayers. Nurses in general practice should be alert to the incontinence problem by considering it as part of the routine diabetes evaluation of women, especially of those with longer duration of diabetes, obese and older. Cultural knowledge, sensitivity and individualised treatment plans need

Polymorphisms in DNA repair genes increase the risk for type 2 diabetes mellitus and hypertension.

PubMed

Das, Sambuddha; Purkayastha, Sukanya; Roy, Hirakjyoti; Sinha, Anima; Choudhury, Yashmin

2018-06-09

We investigated the effect of polymorphisms in four DNA repair genes, viz. RAD18 Arg302Gln (G>A) (rs373572), XPD Asp312Asn (G>A) (rs1799793), APE1 Asp148Glu (T>G) (rs3136820), and OGG1 Ser326Cys (C>G) (rs1052133) on the risk for type 2 diabetes mellitus (T2DM) and hypertension (HT) in association with smoking, tobacco chewing, and alcohol consumption in a population from Northeast India. The study subjects were comprised of 70 patients suffering from both T2DM and HT and 83 healthy controls. Genotyping was performed using ARMS-PCR for XPD Asp312Asn (G>A) and PCR-CTPP for RAD18 Arg302Gln (G>A), APE1 Asp148Glu (T>G) and OGG1 Ser326Cys (C>G). The RAD18 Gln/Gln genotype was found to significantly increase the risk for T2DM and HT by 30 fold. Significant high risk was observed for individuals with XPD Asn/Asn-RAD18 Arg/Gln genotypes. Smoking was found to be the single most important independent risk factor for T2DM and HT. This study concludes that RAD18 Arg302Gln and XPD Asp312Asn polymorphisms might increase the risk for T2DM and HT in association with smoking, tobacco chewing, and/or alcohol consumption, while APE1 Asp148Glu (T>G) and OGG1 Ser326Cys (C>G) polymorphisms do not contribute to such risk.

Prevalence, Awareness, and Risk Factors of Diabetic Retinopathy among Adults with Known Type 2 Diabetes Mellitus in an Urban Community in China.

PubMed

Pan, Chen-Wei; Wang, Shan; Qian, Deng-Juan; Xu, Cailian; Song, E

2017-06-01

To understand the prevalence, awareness, and risk factors for diabetic retinopathy (DR) among Chinese with known type-2 diabetes mellitus (T2DM) in eastern China communities. A community-based survey including 913 patients with known T2DM was conducted in Suzhou, China. Diabetes was defined as hemoglobin A1c (hbA1c) ≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal photographs were graded for the presence of DR using the Airlie House classification system. Binary logistic regression models were established to examine the associations of risk factors with DR and vision-threatening diabetic retinopathy (VTDR). The overall prevalence of any DR was 18.0% (95% confidence interval [CI]: 15.5-20.6%) in this population. VTDR affected 4.4% (95% CI: 3.1-5.8%) of the study participants. In multivariate analysis, the presence of DR among T2DM patients was associated with decreased age (odds ratio [OR] = 0.97; p = 0.01; per year increase), longer durations of diabetes (OR = 1.02; per year increase; p = 0.03), higher blood levels of hbA1c (OR = 1.15; per unit increase; p = 0.03). Of the 158 participants with DR, only 12 (8%) had been aware of their condition or had been diagnosed previously as having DR. The prevalence of DR among diabetes patients in eastern China was lower than those in northern China. The awareness of DR was poor, which emphasizes the pressing need for increasing the public awareness of this vision-threatening eye disorder and routine eye screening should be performed among T2DM patients in the communities.

Affecting behavior change in individuals with diabetes: findings from the Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes (SHIELD).

PubMed

Bazata, Debbra D; Robinson, Jennifer G; Fox, Kathleen M; Grandy, Susan

2008-01-01

This study evaluated whether health knowledge, attitudes, and behaviors of individuals with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus and those at high or low risk of T2DM were reflected in healthy behaviors and whether these attributes differed for T2DM respondents who did or did not see a health educator. SHIELD, a U.S. population-based study, included respondents (> or =18 years of age) with T1DM (n = 366), T2DM (n = 3897), high risk (HR, n = 5449) defined as > or =3 of the following: abdominal obesity, high body mass index, dyslipidemia, hypertension, cardiovascular disease, and low risk (LR, n = 5725) defined as < or =2 factors. T2DM respondents were more likely to receive health care professional recommendations to change their lifestyle habits (56%-62%) during their average 11 visits annually than the other groups (P < .0001). More T2DM and HR respondents tried losing weight, but fewer exercised regularly than T1DM and LR (P < .0001). T2DM respondents who saw a dietitian or health educator reported better current health and expectations for better future health, tried to make healthy food choices, and followed a prescribed eating plan than those who did not see these providers (P < .01). However, < or =30% of these T2DM respondents exercised regularly, or maintained desired weight. SHIELD findings show that respondents know and understand that improving their diet or exercise will affect their health, but the majority of respondents have not translated it into a behavior. Interaction with health educators and patient-empowering support may improve the transition to behavior change.

Relationship between healthy lifestyle behaviors and cardiovascular risk factors in Chinese patients with type 2 diabetes mellitus: a subanalysis of the CCMR-3B STUDY.

PubMed

Huang, Yuxin; Li, Jihu; Zhu, Xiaolin; Sun, Jiao; Ji, Linong; Hu, Dayi; Pan, Changyu; Tan, Wen; Jiang, Suyuan; Tao, Xiaoming

2017-06-01

This subanalysis of a cross-sectional, nationwide study was undertaken to assess the relationship between healthy lifestyle behaviors and multiple cardiovascular risk factors among people with type 2 diabetes mellitus (T2DM). Data collected from 25,454 participants, including demographics, lifestyle behaviors and cardiovascular risk profiles, were analyzed. Blood pressure control as well as blood glucose and blood lipid (3Bs) levels were measured as multi-risk factors for cardiovascular disease. Healthy lifestyle behaviors included regular exercise, nonsmoking status and no alcohol consumption. The relationship between the healthy lifestyle behavior(s) and control of 3B(s) was calculated. Of the 25,454 eligible participants, 4171 (16.4%) were current smokers, 2011 (7.9%) currently consumed alcohol, and 11,174 (43.9%) did not exercise. In total, 654 (2.6%) reported all three unhealthy lifestyle behaviors. Most participants (71.1%) had received at least a high school education and were more likely to smoke and drink as compared to those with lower education. Unhealthy lifestyle behaviors were commonly found in participants with low atherosclerosis risk, such as non-elderly people and those with an above-college education level. Unhealthy lifestyle is associated with poor 3B control and worse medication adherence. Unhealthy lifestyles are common in Chinese people with T2DM, especially in people who are non-elderly and above-college educated. Interventions aimed at changing risky lifestyle behaviors are required for improved outcomes for Chinese patients with T2DM.

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

PubMed Central

Romeo, Elisabetta L.; Nunziata, Morabito; Ruffo, Maria Concetta; Catalano, Antonino; Cucinotta, Domenico

2016-01-01

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fractures, resulting in disabilities and increased mortality. The pathophysiological mechanisms linking diabetes to osteoporosis have not been fully explained, but alterations in bone structure and quality are well described in diabetic subjects, likely due to a combination of different factors. Insulin deficiency and dysfunction, obesity and hyperinsulinemia, altered level of oestrogen, leptin, and adiponectin as well as diabetes-related complications, especially peripheral neuropathy, orthostatic hypotension, or reduced vision due to retinopathy may all be associated with an impairment in bone metabolism and with the increased risk of fractures. Finally, medications commonly used in the treatment of T2DM may have an impact on bone metabolism and on fracture risk, particularly in postmenopausal women. When considering the impact of hypoglycaemic drugs on bone, it is important to balance their potential direct effects on bone quality with the risk of falling-related fractures due to the associated hypoglycaemic risk. In this review, experimental and clinical evidence connecting bone metabolism and fracture risk to T2DM is discussed, with particular emphasis on hypoglycaemic treatments and gender-specific implications. PMID:28044077

JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice.

PubMed

Tomimoto, Daisuke; Okuma, Chihiro; Ishii, Yukihito; Kobayashi, Akio; Ohta, Takeshi; Kakutani, Makoto; Imanaka, Tsuneo; Ogawa, Nobuya

2015-09-01

Type 2 diabetes mellitus (T2DM) arises primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important in the development of T2DM, including obesity. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase 1 inhibitor, reduced body weight depending on dietary fat in diet-induced obesity (DIO) rats in our previous study. Here, the effect of JTT-553 on glucose metabolism was evaluated using body weight reduction in T2DM mice. JTT-553 was repeatedly administered to DIO and KK-A(y) mice. JTT-553 reduced body weight gain and fat weight in both mouse models. In DIO mice, JTT-553 decreased insulin, non-esterified fatty acid (NEFA), total cholesterol (TC), and liver triglyceride (TG) plasma concentrations in non-fasting conditions. JTT-553 also improved insulin-dependent glucose uptake in adipose tissues and glucose intolerance in DIO mice. In KK-A(y) mice, JTT-553 decreased glucose, NEFA, TC and liver TG plasma concentrations in non-fasting conditions. JTT-553 also decreased glucose, insulin, and TC plasma concentrations in fasting conditions. In addition, JTT-553 decreased TNF-α mRNA levels and increased GLUT4 mRNA levels in adipose tissues in KK-A(y) mice. These results suggest that JTT-553 improves insulin resistance in adipose tissues and systemic glucose metabolism through reductions in body weight. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

N-acetyltransferase 1 and 2 polymorphisms and risk of diabetes mellitus type 2 in a Saudi population.

PubMed

Al-Shaqha, Waleed M; Alkharfy, Khalid M; Al-Daghri, Nasser M; Mohammed, Abdul Khader

2015-01-01

There have been inconsistent reports on N-acetyltransferase (NAT) gene polymorphism in type 2 diabetes mellitus (T2DM), and data is particularly limited in the Arab population. Therefore, the main objective of this study was to identify whether the genetic polymorphisms of NAT1 and NAT2 play a role in susceptibility to T2DM in the Saudi population. A population-based, prospective genetic association case-control study on a Saudi population. Whole blood, anthropometric measurements and biochemistry data were collected from 369 Saudi individuals (186 T2DM patients and 183 healthy controls). DNA was isolated from the blood. Polymorphism of NAT1 and NAT2 SNPs [NAT2*7B, rs1041983(C > T); NAT2*7, rs1799931(G > A); NAT2*6A, rs1799930(G > A); NAT2*5A, rs1799929(C > T); and NAT1*11A, rs4986988(C > T)] were evaluated by allelic discrimination using real-time PCR. Subjects with T2DM had a significantly increased body mass index (BMI), waist circumference, sys.tolic and diastolic blood pressure, glucose, triglycerides, and LDL-cholesterol compared with healthy controls (P < .05). The rs1799931(G > A) genotype was detected in the control population but not in the T2DM population (P < .001). The wild type (G) allele frequency was higher in T2DM than controls (P=.038). The mutant allele (A) in rs1799931(G > A) had a protective effect for T2DM (OR 0.32, 95% CI 0.16-0.62; P=.001). Regression analysis showed that BMI, systolic BP and triglycerides are potential risk factors for T2DM. The genotypes as well as the individual alleles of rs1799931(G > A) differed significantly be.tween the case and control populations. The variation in the data reported so far suggest that polymorphism of the NAT gene may vary among different geographical areas. Environmental or dietary factors may also contribute to disease manifestation.

Lowering Risk for Type 2 Diabetes in High-Risk Youth

ERIC Educational Resources Information Center

Bobo, Nichole; Schantz, Shirley; Kaufman, Francine R.; Kollipara, Sobha

2009-01-01

Among children and youth who develop type 2 diabetes (T2DM) there are a number of genetic and environmental factors that lead to a combination of insulin resistance and relative-cell secretory failure of the pancreas. These factors include ethnicity (highest in American Indian youth), obesity, sedentary behavior, family history of T2DM, puberty,…

Lifestyle related risk factors of type 2 diabetes mellitus in Saudi Arabia.

PubMed

Midhet, Farid M; Al-Mohaimeed, Abdulrahman A; Sharaf, Fawzy K

2010-07-01

To assess the impact of diet and physical activity on the risk of type 2 diabetes mellitus (T2DM) in the Kingdom of Saudi Arabia (KSA) after adjusting for family history of diabetes. We conducted a case-control study in Al-Qassim, KSA to test the hypothesis that dietary practices and physical activity modify the risk of type 2 diabetes regardless of family history. Male and female Saudi citizens 30-70 years of age were eligible to participate. The sample included 283 cases (T2DM patients) and 215 non-diabetic controls randomly selected from patients visiting the primary health care centers from September to November 2009. We collected information on demographic variables, family history, dietary habits, and physical activity. Using logistic regression, we estimated adjusted odds ratios (AOR) for dietary habits and physical activity after controlling for the effects of gender, age, education, and family history of diabetes. There is strong association between diabetes and maternal history of diabetes, education, lack of exercise, and dietary habits. The AOR for regular eating of Kabsa was 5.5 (95% confidence limits [CL]: 2.3-13.5); for vegetables an AOR of 0.4 (95% CL: 0.2-0.7); for dates an AOR of 1.8 (95% CL: 1.0-3.3) ;and the AOR for sedentary lifestyle was 2.5 (95% CL: 1.2-5.0). Healthy diet and active lifestyle may significantly decrease the risk of T2DM in spite of having a family history of diabetes. Effective health education programs promoting healthy diet and regular exercise are needed to reduce the burden of diabetes in Saudi Arabia.

Risk of type 2 diabetes mellitus associated with plasma lipid levels: The rural Chinese cohort study.

PubMed

Zhang, Ming; Zhou, Junmei; Liu, Yu; Sun, Xizhuo; Luo, Xinping; Han, Chengyi; Zhang, Lu; Wang, Bingyuan; Ren, Yongcheng; Zhao, Yang; Zhang, Dongdong; Liu, Xuejiao; Hu, Dongsheng

2018-01-01

To investigate the association of type 2 diabetes mellitus (T2DM) risk and plasma lipid levels in rural Chinese. Each lipid variable was divided into quartiles and dichotomized by clinical cutoff points. Cox proportional-hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of T2DM risk and plasma lipid levels and explore the interaction between plasma lipid levels and other risk factors. 11,929 participants were included in the analysis. We documented 720 incident cases of T2DM over 70,720.84 person-years of follow-up, for an incidence of 10.18/1,000 person-years. In the multivariable-adjusted model, risk of T2DM was increased with the highest versus lowest quartiles of total cholesterol (TC) and triglycerides (TG) levels and TC/high-density lipoprotein-cholesterol (HDL-C) and TG/HDL-C ratios. The HRs (95% CIs) for the fourth quartiles, for example, were 1.34 (1.03-1.74), 2.32 (1.73-3.13), 1.66 (1.23-2.25), and 1.84 (1.38-2.45), respectively. In addition, risk of T2DM was increased with high TG level and TC/HDL-C and TG/HDL-C ratios by clinical cutoffs. The HRs (95% CIs) were 1.50 (1.25-1.80), 1.24 (1.03-1.48), and 1.44 (1.18-1.75), respectively. Risk of T2DM was associated with interactions between all lipid variables and age and BMI. TG level and TG/HDL-C ratio additionally interacted with gender (all P interaction  < 0.0001). Risk of T2DM was increased with elevated serum levels of TC and TG and TC/HDL-C and TG/HDL-C ratios and also with interactions between high TC and TG levels and TC/HDL-C and TG/HDL-C ratios and age and BMI in a rural Chinese population. Copyright © 2017 Elsevier B.V. All rights reserved.

Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.

PubMed

Walker, Celia G; Solis-Trapala, Ivonne; Holzapfel, Christina; Ambrosini, Gina L; Fuller, Nicholas R; Loos, Ruth J F; Hauner, Hans; Caterson, Ian D; Jebb, Susan A

2015-01-01

The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.

An after-school dance and lifestyle education program reduces risk factors for heart disease and diabetes in elementary school children

PubMed Central

Hogg, Jeannette; Diaz, Alejandro; Cid, Margareth Del; Mueller, Charles; Lipman, Elizabeth Grace; Cheruvu, Sunita; Chiu, Ya-lin; Vogiatzi, Maria; Nimkarn, Saroj

2013-01-01

Background Forty-three percent of New York City's (NYC) school-age children are overweight or obese, placing them at risk for heart disease and type 2 diabetes mellitus (T2DM). Objective The objective of this study was to determine if an intensive after-school dance and lifestyle education program would reduce risk factors for heart disease, T2DM, and improve lifestyle choices. Subjects Subject include 64 fourth- and fifth-grade students at an elementary school in NYC. Methods Students received freestyle dance and lifestyle classes for 16 weeks and were evaluated for changes in body composition, endurance, biochemical measurements, and lifestyle choices. Results Significant improvements in BMI percentiles were found among children in the overweight and obese categories as well as in endurance and biochemical measurements that reflect heart disease and diabetes risk. Improvement was also reported in lifestyle choices. Conclusion An intensive after-school dance and lifestyle education program can reduce risk factors for heart disease and T2DM and improve lifestyle choices among elementary school children. PMID:22876547

Type 2 Diabetes Mellitus Screening and Risk Factors Using Decision Tree: Results of Data Mining.

PubMed

Habibi, Shafi; Ahmadi, Maryam; Alizadeh, Somayeh

2015-03-18

The aim of this study was to examine a predictive model using features related to the diabetes type 2 risk factors. The data were obtained from a database in a diabetes control system in Tabriz, Iran. The data included all people referred for diabetes screening between 2009 and 2011. The features considered as "Inputs" were: age, sex, systolic and diastolic blood pressure, family history of diabetes, and body mass index (BMI). Moreover, we used diagnosis as "Class". We applied the "Decision Tree" technique and "J48" algorithm in the WEKA (3.6.10 version) software to develop the model. After data preprocessing and preparation, we used 22,398 records for data mining. The model precision to identify patients was 0.717. The age factor was placed in the root node of the tree as a result of higher information gain. The ROC curve indicates the model function in identification of patients and those individuals who are healthy. The curve indicates high capability of the model, especially in identification of the healthy persons. We developed a model using the decision tree for screening T2DM which did not require laboratory tests for T2DM diagnosis.

Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas.

PubMed

Iglay, Kristy; Qiu, Ying; Steve Fan, Chun-Po; Li, Zhiyi; Tang, Jackson; Laires, Pedro

2016-09-01

Sulfonylurea therapy among patients with type 2 diabetes mellitus (T2DM) can be disrupted due to adverse events, including hypoglycemia. A retrospective study using the MarketScan claims database quantified the frequency of sulfonylurea discontinuation or down-titration and identified associated risk factors. Adult patients with an index sulfonylurea prescription between 2008 and 2012 and 1 year continuous enrollment pre- and post-index were included. Therapy changes assessed over 1 year post-index included discontinuation and down-titration. Discontinuation occurred if the date of a fill was >90 days from the end date of the preceding fill. Down-titration occurred when a fill had a lower equivalent dose than the fill on the index date. Kaplan-Meier methods estimated the probability of either discontinuation or down-titration over 12 months, and Cox regression models identified associated risk factors. A total of 104,082 sulfonylurea users were included in the study and the probability of either discontinuation or down-titration at 3, 6 and 12 months was 23.2%, 38.9%, and 52.3%, respectively. Major risk factors associated with therapy changes included post-index hypoglycemia (discontinuation hazard ratio [HR] = 1.78 [1.68, 1.89]; down-titration HR =2.79 [2.40, 3.23]) and concomitant use of insulin (discontinuation HR =1.48 [1.40, 1.57]; down-titration HR =1.82 [1.56, 2.11]). Other risk factors included younger age, female gender, use of second generation sulfonylureas, prior cardiovascular comorbidity and liver disease. The study was not able to assess unreported, potentially mild cases of hypoglycemia, nor was it able to evaluate the association between changes in therapy and HbA1c levels or body weight. More than half of T2DM patients who initiated sulfonylurea therapy discontinued or down-titrated within 1 year. Insulin use and hypoglycemia were associated with sulfonylurea therapy change.

Accumulation of Major Life Events in Childhood and Adult Life and Risk of Type 2 Diabetes Mellitus

PubMed Central

Masters Pedersen, Jolene; Hulvej Rod, Naja; Andersen, Ingelise; Lange, Theis; Poulsen, Gry; Prescott, Eva; Lund, Rikke

2015-01-01

Background The aim of the study was to estimate the effect of the accumulation of major life events (MLE) in childhood and adulthood, in both the private and working domains, on risk of type 2 diabetes mellitus (T2DM). Furthermore, we aimed to test the possible interaction between childhood and adult MLE and to investigate modification of these associations by educational attainment. Methods The study was based on 4,761 participants from the Copenhagen City Heart Study free of diabetes at baseline and followed for 10 years. MLE were categorized as 0, 1, 2, 3 or more events. Multivariate logistic regression models adjusted for age, sex, education and family history of diabetes were used to estimate the association between MLE and T2DM. Results In childhood, experiencing 3 or more MLE was associated with a 69% higher risk of developing T2DM (Odds Ratio (OR) 1.69; 95% Confidence Interval (CI) 1.60, 3.27). The accumulation of MLE in adult private (p-trend = 0.016) and work life (p-trend = 0.049) was associated with risk of T2DM in a dose response manner. There was no evidence that experiencing MLE in both childhood and adult life was more strongly associated with T2DM than experiencing events at only one time point. There was some evidence that being simultaneously exposed to childhood MLE and short education (OR 2.28; 95% C.I. 1.45, 3.59) and work MLE and short education (OR 2.86; 95% C.I. 1.62, 5.03) was associated with higher risk of T2DM, as the joint effects were greater than the sum of their individual effects. Conclusions Findings from this study suggest that the accumulation of MLE in childhood, private adult life and work life, respectively, are risk factors for developing T2DM. PMID:26394040

Risk factors for mortality in patients undergoing hemodialysis: A systematic review and meta-analysis.

PubMed

Ma, Lijie; Zhao, Sumei

2017-07-01

No consensus exists regarding the factors influencing mortality in patients undergoing hemodialysis (HD). This meta-analysis aimed to evaluate the impact of various patient characteristics on the risk of mortality in such patients. PubMed, Embase, and Cochrane Central were searched for studies evaluating the risk factors for mortality in patients undergoing HD. The factors included age, gender, diabetes mellitus (DM), body mass index (BMI), previous cardiovascular disease (CVD), HD duration, hemoglobin, albumin, white blood cell, C-reactive protein (CRP), parathyroid hormone, total iron binding capacity (TIBC), iron, ln ferritin, adiponectin, apolipoprotein A1 (ApoA1), ApoA2, ApoA3, high-density lipoprotein (HDL), total cholesterol, hemoglobin A1c (HbA1c), serum phosphate, troponin T (TnT), and B-type natriuretic peptide (BNP). Relative risks with 95% confidence intervals were derived. Data were synthesized using the random-effects model. Age (per 1-year increment), DM, previous CVD, CRP (higher versus lower), ln ferritin, adiponectin (per 10.0μg/mL increment), HbA1c (higher versus lower), TnT, and BNP were associated with an increased risk of all-cause mortality. BMI (per 1kg/m 2 increment), hemoglobin (per 1d/dL increment), albumin (higher versus lower), TIBC, iron, ApoA2, and ApoA3 were associated with reduced risk of all-cause mortality. Age (per 1-year increment), gender (women versus men), DM, previous CVD, HD duration, ln ferritin, HDL, and HbA1c (higher versus lower) significantly increased the risk of cardiac death. Albumin (higher versus lower), TIBC, and ApoA2 had a beneficial impact on the risk of cardiac death. Multiple markers and factors influence the risk of mortality and cardiac death in patients undergoing HD. Copyright © 2017 Elsevier B.V. All rights reserved.

Size, density and cholesterol load of HDL predict microangiopathy, coronary artery disease and β-cell function in men with T2DM.

PubMed

Hermans, Michel P; Amoussou-Guenou, K Daniel; Bouenizabila, Evariste; Sadikot, Shaukat S; Ahn, Sylvie A; Rousseau, Michel F

The role of high-density lipoprotein cholesterol (HDL-C) as modifiable risk factor for cardiovascular (CV) disease is increasingly debated, notwithstanding the finding that small-dense and dysfunctional HDL are associated with the metabolic syndrome and T2DM. In order to better clarify the epidemiological risk related to HDL of different size/density, without resorting to direct measures, it would seem appropriate to adjust HDL-C to the level of its main apolipoprotein (apoA-I), thereby providing an [HDL-C/apoA-I] ratio. The latter allows not only to estimate an average size for HDLs, but also to derive indices on particle number, cholesterol load, and density. So far, the potential usefulness of this ratio in diabetes is barely addressed. To this end, we sorted 488 male patients with T2DM according to [HDL-C/apoA-I] quartiles (Q), to determine how the ratio relates to cardiometabolic risk, β-cell function, glycaemic control, and micro- and macrovascular complications. Five lipid parameters were derived from the combined determination of HDL-C and apoA-I, namely HDL size; particle number; cholesterol load/particle; apoA-I/particle; and particle density. An unfavorable cardiometabolic profile characterized patients from QI and QII, in which HDLs were pro-atherogenic, denser and apoA-I-depleted. By contrast, QIII patients had an [HDL-C/apoA-I] ratio close to that of non-diabetic controls. QIV patients had better than average HDL size and composition, and in those patients whose [HDL-C/apoA-I] ratio was above normal, a more favorable phenotype was observed regarding lifestyle, anthropometry, metabolic comorbidities, insulin sensitivity, MetS score/severity, glycaemic control, and target-organ damage pregalence in small or large vessels. In conclusion, [HDL-C/apoA-I] and the resulting indices of HDL composition and functionality predict macrovascular risk and β-cell function decline, as well as overall microangiopathic risk, suggesting that this ratio could serve

Glucagon gene polymorphism modifies the effects of smoking and physical activity on risk of type 2 diabetes mellitus in Han Chinese.

PubMed

Li, Linlin; Gao, Kaiping; Zhao, Jingzhi; Feng, Tianping; Yin, Lei; Wang, Jinjin; Wang, Chongjian; Li, Chunyang; Wang, Yan; Wang, Qian; Zhai, Yujia; You, Haifei; Ren, Yongcheng; Wang, Bingyuan; Hu, Dongsheng

2014-01-25

Few genome-wide association studies have considered interactions between multiple genetic variants and environmental factors associated with disease. The interaction was examined between a glucagon gene (GCG) polymorphism and smoking, alcohol consumption and physical activity and the association with risk of type 2 diabetes mellitus (T2DM) in a case-control study of Chinese Han subjects. The rs12104705 polymorphism of GCG and interactions with environmental variables were analyzed for 9619 participants by binary multiple logistic regression. Smoking with the C-C haplotype of rs12104705 was associated with increased risk of T2DM (OR=1.174, 95% CI=1.013-1.361). Moderate and high physical activity with the C-C genotype was associated with decreased risk of T2DM as compared with low physical activity with the genotype (OR=0.251, 95% CI=0.206-0.306 and OR=0.190, 95% CI=0.164-0.220). However, the interaction of drinking and genotype was not associated with risk of T2DM. Genetic polymorphism in rs12104705 of GCG may interact with smoking and physical activity to modify the risk of T2DM. © 2013.

Flavonoids intake and risk of type 2 diabetes mellitus: A meta-analysis of prospective cohort studies.

PubMed

Xu, Hui; Luo, Jia; Huang, Jia; Wen, Qian

2018-05-01

Epidemiological studies exploring the role of flavonoids intake in preventing type 2 diabetes mellitus (T2DM) showed inconsistent results. Therefore, we performed a meta-analysis of relevant studies to examine the relationship between flavonoids intake and risk of T2DM. We hypothesized that flavonoids intake may decrease the risk of developing T2DM.A systematical search in PubMed and Embase until September 2017 was performed to identify eligible prospective cohort studies. The summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models. Dose-response pattern between total flavonoids intake and T2DM risk was also estimated.Eight prospective studies were included with 312,015 participants, of whom 19,953 developed T2DM during the follow-up periods of 4 to 28 years. Compared with lower consumption, high intake of total flavonoids was associated with a decreased risk of T2DM (RR: 0.89, 95% CI: 0.82-0.96). Among flavonoid subclasses, inverse correlations with T2DM were achieved for intakes of anthocyanidins, flavan-3-ols, flavonols, and isoflavones. Dose-response meta-analysis indicated a curvilinear relationship between total flavonoids intake and incident T2DM (P for nonlinearity = .042), with a significant risk reduction at an intake of ≥550 mg/day. When assuming a linear pattern, the risk of T2DM was decreased by 5% for each 300-mg/day increment in total flavonoids intake (RR: 0.95, 95% CI: 0.93-0.97).Our study suggests that higher intakes of total flavonoids and subclasses (anthocyanidins, flavan-3-ols, flavonols, and isoflavones) are associated with lower risk of T2DM.

The MCP-1 Gene A-2518G Polymorphism Confers an Increased Risk of Vascular Complications in Type 2 Diabetes Mellitus Patients.

PubMed

Xu, Jin; Liao, Yun-Fei; Zhou, Wei-Ping; Ming, Hua-Li; Wang, Qing-Hai

2015-08-01

We aimed to evaluate the correlation of the monocyte chemoattractant protein 1 (MCP-1) A-2518G polymorphism with type 2 diabetes mellitus (T2DM) and vascular complications in T2DM, to aid in understanding its role in pathogenesis. A total of 150 T2DM patients and 50 healthy controls (group A) were enrolled. The T2DM patients were divided into three groups based on the absence of complications (group B) presence of microvascular disease (group C) or macrovascular disease (group D). DNA of all enrolled subjects was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the MCP-1 A-2518G polymorphism. Serum MCP-1 levels were measured by an enzyme-linked immunosorbent assay (ELISA). Participants in group D had increased serum MCP-1 levels relative to group B, group C, and group A (all p<0.01). Compared with group A, the frequencies of the MCP-1 A-2518G G/G genotype and G allele were significantly higher in group C and group D (all p<0.05). In contrast to group B, group C had higher frequencies of the G/G genotype and G allele, while group D had higher G allele frequencies (all p<0.05). Logistic regression analysis showed that lower body-mass index (BMI) and free cholesterol (FC), as well as higher high-density lipoprotein cholesterol (HDL-C) levels may be the protective factors for T2DM, while higher levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and G/G genotype frequency were independent risk factors for T2DM. Our data indicates a correlation between the MCP-1 A-2518G polymorphism with macrovascular complications in T2DM patients; lower BMI and FC, as well as higher HDL-C levels may be the protective factors for T2DM, while higher levels of TG, LDL-C, and G/G genotype frequency were independent risk factors for T2DM.

Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation – Description of a novel in vitro model

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

Ehnert, Sabrina, E-mail: sabrina.ehnert@gmail.com; Freude, Thomas, E-mail: tfreude@bgu-tuebingen.de; Ihle, Christoph, E-mail: cihle@bgu-tuebingen.de

Type 2 diabetes mellitus (T2DM) is one of the most frequent metabolic disorders in industrialized countries. Among other complications, T2DM patients have an increased fracture risk and delayed fracture healing. We have demonstrated that supraphysiological glucose and insulin levels inhibit primary human osteoblasts' maturation. We aimed at developing a more physiologically relevant in vitro model to analyze T2DM-mediated osteoblast changes. Therefore, SCP-1-immortalized pre-osteoblasts were differentiated with T2DM or control (non-obese and obese) sera. Between both control groups, no significant changes were observed. Proliferation was significantly increased (1.69-fold), while AP activity and matrix mineralization was significantly reduced in the T2DM group.more » Expression levels of osteogenic marker genes and transcription factors were altered, e.g. down-regulation of RUNX2 and SP-7 or up-regulation of STAT1, in the T2DM group. Active TGF-β levels were significantly increased (1.46-fold) in T2DM patients' sera. SCP-1 cells treated with these sera showed significantly increased TGF-β signaling (2.47-fold). Signaling inhibition effectively restored osteoblast maturation in the T2DM group. Summarizing our data, SCP-1 cells differentiated in the presence of T2DM patients' serum exhibit reduced osteoblast function. Thus, this model has a high physiological impact, as it can identify circulating factors in T2DM patients' blood that may affect bone function, e.g. TGF-β. - Highlights: • We present here a physiologically relevant in vitro model for diabetic osteopathy. • Blood of T2DM patients contains factors that affect osteoblasts' function. • The model developed here can be used to identify these factors, e.g. TGF-β. • Blocking TGF-β signaling partly rescues the osteoblasts' function in the T2DM group. • The model is useful to demonstrate the role of single factors in diabetic osteopathy.« less

Self-management levels of diet and metabolic risk factors according to disease duration in patients with type 2 diabetes.

PubMed

Cho, Sukyung; Kim, Minkyeong; Park, Kyong

2018-02-01

Metabolic risk factors should be managed effectively in patients with type 2 diabetes mellitus (T2DM) to prevent or delay diabetic complications. This study aimed to compare the self-management levels of diet and metabolic risk factors in patients with T2DM, according to the duration of illness, and to examine the trends in self-management levels during the recent decades. Data were collected from the Korea National Health and Nutrition Examination Surveys (KNHANES, 1998-2014). In our analysis, 4,148 patients with T2DM, aged ≥ 30 years, were categorized according to the duration of their illness (< 5 years, 5-9 years, and ≥ 10 years). Demographic and lifestyle information was assessed through self-administered questionnaires, and biomarker levels (e.g., fasting glucose level, blood pressure, or lipid level) were obtained from a health examination. Dietary intake was assessed by a 24-recall, and adherence level to dietary guidelines (meal patterns and intake levels of calories, carbohydrates, vegetable/seaweed, sodium, and alcohol) were assessed. Multivariable generalized linear regression and unconditional logistic regression models were used to compare the prevalence rates of hyperglycemia, dyslipidemia, and hypertension according to the duration of patients' illness, accounting for the complex survey design of the KNHANES. In the multivariable adjusted models, patients with a longer duration (≥ 10 years) of T2DM had a higher prevalence of hyperglycemia than those with a shorter duration of T2DM (< 5 years) (odds ratio 2.20, 95% confidence interval 1.61-3.01, P for trend < 0.001). We did not observe any associations of disease duration with the prevalence of hypertension and dyslipidemia. In addition, the adherence levels to dietary recommendations did not significantly differ according to disease duration, except adherence to moderate alcohol consumption. There were significant decreasing trends in the prevalence of hyperglycemia in patients with a duration

Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

USDA-ARS?s Scientific Manuscript database

Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasm...

Heart Disease Risk Factors You Can't Control

MedlinePlus

... Submit Heart disease risk factors you can't control Some factors you can't control, like pregnancy ... 2018. Heart disease risk factors you can't control Age and menopause As you get older, your ...

Adding Salt to Meals as a Risk Factor of Type 2 Diabetes Mellitus: A Case-Control Study.

PubMed

Radzeviciene, Lina; Ostrauskas, Rytas

2017-01-13

Type 2 diabetes mellitus (T2DM) is thought to arise from the complex interplay between genetic and environmental factors. It is important to identify modifiable risk factors that may help to reduce the risk of diabetes. Data on salt intake and the risk of type 2 diabetes are limited. The aim of this study was to assess the relationship between adding salt to prepared meals and the risk of type 2 diabetes. In a case-control study, we included 234 cases, all of whom were patients aged 35-86 years with a newly confirmed diagnosis of T2DM, and 468 controls that were free of the disease. Cases and controls (ratio 1:2) were matched by gender and age (±5 years). A questionnaire was used to collect information on possible risk factors for diabetes. Adding salt to prepared meals was assessed according to: Never, when there was not enough, or almost every time without tasting. The odds ratios (OR), and 95% confidence intervals (CI) for type 2 diabetes was calculated using a conditional logistic regression. The cases had a higher body mass index and a significantly lower education level compared to the controls. Variables such as waist circumference, body mass index, eating speed, smoking, family history of diabetes, arterial hypertension, plasma triglycerides, educational level, occupational status, morning exercise, marital status, daily urine sodium excretion, and daily energy intake were retained in the models as confounders. After adjusting for possible confounders, an approximately two-fold increased risk of type 2 diabetes was determined in subjects who add salt to prepared meals when "it is not enough" or "almost every time without tasting" (1.82; 95% CI 1.19-2.78; p = 0.006) compared with never adding salt. Presented data suggest the possible relationship between additional adding of salt to prepared meals and an increased risk of type 2 diabetes.

Factors Associated with Long-Term Control of Type 2 Diabetes Mellitus.

PubMed

Badedi, Mohammed; Solan, Yahiya; Darraj, Hussain; Sabai, Abdullah; Mahfouz, Mohamed; Alamodi, Saleh; Alsabaani, Abdullah

2016-01-01

Aims. This study assessed factors associated with glycemic control among Saudi patients with Type 2 diabetes mellitus (T2DM). Methods. We conducted an analytical cross-sectional study, which included a random sample of 288 patients with T2DM proportional to the diabetes population of each primary health care center in Jazan city, Kingdom of Saudi Arabia. Results. More than two-thirds (74%) of patients had poor glycemic control. Lack of education, polypharmacy, and duration of diabetes ≥ 7 years were significantly associated with higher glycated hemoglobin (HbA1c). Moreover, patients who were smoker or divorced were significantly more likely to have higher HbA1c. The patients who did not comply with diet or take their medications as prescribed had poor glycemic control. The study found lower HbA1c levels among patients who received family support or had close relationship with their physicians. Similarly, knowledgeable patients towards diabetes or those with greater confidence in ability to manage self-care behaviors had a lower HbA1c. In contrast, risk factors such as depression or stress were significantly correlated with poorer glycemic control. Conclusion. The majority of T2DM patients had poor glycemic control. The study identified several factors associated with glycemic control. Effective and tailored interventions are needed to mitigate exposure to these risk factors. This would improve glycemic control and reduce the risks inherent to diabetes complications.

Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus.

PubMed

Tang, W H Wilson; Wang, Zeneng; Li, Xinmin S; Fan, Yiying; Li, Daniel S; Wu, Yuping; Hazen, Stanley L

2017-01-01

Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a proatherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. We examined the relationship between fasting TMAO and 2 of its nutrient precursors, choline and betaine, vs 3-year major adverse cardiac events and 5-year mortality in 1216 stable patients with T2DM who underwent elective diagnostic coronary angiography. TMAO [4.4 μmol/L (interquartile range 2.8-7.7 μmol/L) vs 3.6 (2.3-5.7 μmol/L); P < 0.001] and choline concentrations were higher in individuals with T2DM vs healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac event risk (P < 0.001) and a 3.6-fold increased 5-year mortality risk (P < 0.001). Following adjustments for traditional risk factors and high-sensitivity C-reactive protein, glycohemoglobin, and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients [e.g., quartiles 4 vs 1, hazard ratio 2.05 (95% CI, 1.31-3.20), P < 0.001; and 2.07 (95% CI, 1.37-3.14), P < 0.001, respectively]. Fasting plasma concentrations of the proatherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control. © 2016 American Association for Clinical Chemistry.

Smoking and the risk of type 2 diabetes in Japan: A systematic review and meta-analysis.

PubMed

Akter, Shamima; Goto, Atsushi; Mizoue, Tetsuya

2017-12-01

Cigarette smoking is the leading avoidable cause of disease burden. Observational studies have suggested an association between smoking and risk of type 2 diabetes mellitus (T2DM). We conducted a meta-analysis of prospective observational studies to investigate the association of smoking status, smoking intensity, and smoking cessation with the risk of T2DM in Japan, where the prevalence of smoking has been decreasing but remains high. We systematically searched MEDLINE and the Ichushi database to December 2015 and identified 22 eligible articles, representing 343,573 subjects and 16,383 patients with T2DM. We estimated pooled relative risks (RRs) using a random-effects model and conducted subgroup analyses by participant and study characteristics. Compared with nonsmoking, the pooled RR of T2DM was 1.38 (95% confidence interval [CI], 1.28-1.49) for current smoking (19 studies) and 1.19 (95% CI, 1.09-1.31) for former smoking (15 studies). These associations persisted in all subgroup and sensitivity analyses. We found a linear dose-response relationship between cigarette consumption and T2DM risk; the risk of T2DM increased by 16% for each increment of 10 cigarettes smoked per day. The risk of T2DM remained high among those who quit during the preceding 5 years but decreased steadily with increasing duration of cessation, reaching a risk level comparable to that of never smokers after 10 years of smoking cessation. We estimated that 18.8% of T2DM cases in men and 5.4% of T2DM cases in women were attributable to smoking. The present findings suggest that cigarette smoking is associated with an increased risk of T2DM, so tobacco control programs to reduce smoking could have a substantial effect to decrease the burden of T2DM in Japan. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The effects of TLR3, TRIF and TRAF3 SNPs and interactions with environmental factors on type 2 diabetes mellitus and vascular complications in a Han Chinese population.

PubMed

Zhou, Zixing; Zeng, Chengli; Nie, Lihong; Huang, Shiqi; Guo, Congcong; Xiao, Di; Han, Yajing; Ye, Xiaohong; Ou, Meiling; Huang, Chuican; Ye, Xingguang; Wen, Zihao; Yang, Guang; Jing, Chunxia

2017-08-30

Toll-like receptor 3 (TLR3) is involved in type I interferon-β (IFN-β) via TIR-domain-containing adapter-inducing interferon-β (TRIF) and Tumor necrosis factor receptor-associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated. We identified a 21% increased risk of T2DM for the T allele of rs12435483 in the TRAF3 gene (OR: 1.21; 95% CI: 1.01-1.44; P=0.036). The GA genotype and GA+AA genotype of TRAF3 rs12147254 were found to increase the risk of coronary heart disease (CHD) among T2DM patients (GA vs. GG: OR=4.17, 95% CI: 1.04-16.79, P=0.045; GA+AA vs. GG: OR=3.97, 95% CI: 1.02-15.48, P=0.047). However, the GACGAC haplotype in TRAF3 had a protective effect on T2DM micro-macrovascular complications (OR=0.33, 95% CI: 0.13-0.85, P=0.017). Two-factor (TRAF3 rs12435483 and LDL) and three-factor (TRAF3 rs12435483, BMI and HDL) interactions of the risk of T2DM were identified. In conclusion, the genetic variants in the TLR3-TRIF-TRAF3-INF-β signaling pathway and interactions with some particular environmental factors (LDL, BMI and HDL) may contribute to susceptibility to T2DM and vascular complications in the Han Chinese population. Copyright © 2017. Published by Elsevier B.V.

Application of the integrated glucose–insulin model for cross‐study characterization of T2DM patients on metformin background treatment

PubMed Central

Hamrén, Bengt; Kjellsson, Maria C.; Skrtic, Stanko

2016-01-01

Aim The integrated glucose–insulin (IGI) model is a semi‐mechanistic physiological model which can describe the glucose–insulin homeostasis system following various glucose challenge settings. The aim of the present work was to apply the model to a large and diverse population of metformin‐only‐treated type 2 diabetes mellitus (T2DM) patients and identify patient‐specific covariates. Methods Data from four clinical studies were pooled, including glucose and insulin concentration–time profiles from T2DM patients on stable treatment with metformin alone following mixed‐meal tolerance tests. The data were collected from a wide range of patients with respect to the duration of diabetes and level of glycaemic control. Results The IGI model was expanded by four patient‐specific covariates. The level of glycaemic control, represented by baseline glycosylated haemoglobin was identified as a significant covariate for steady‐state glucose, insulin‐dependent glucose clearance and the magnitude of the incretin effect, while baseline body mass index was a significant covariate for steady‐state insulin levels. In addition, glucose dose was found to have an impact on glucose absorption rate. The developed model was used to simulate glucose and insulin profiles in different groups of T2DM patients, across a range of glycaemic control, and it was found accurately to characterize their response to the standard oral glucose challenge. Conclusions The IGI model was successfully applied to characterize differences between T2DM patients across a wide range of glycaemic control. The addition of patient‐specific covariates in the IGI model might be valuable for the future development of antidiabetic treatment and for the design and simulation of clinical studies. PMID:27450071

High prevalence of type 2 diabetes melitus and its risk factors among the rural population of Pondicherry, South India.

PubMed

Shrivastava, Saurabh RamBihariLal; Ghorpade, Arun Gangadhar

2014-01-01

We aimed to assess the prevalence of type-2 diabetes in rural Pondicherry and to study the determinants of Diabetes Mellitus (DM) in the rural population of Pondicherry, south Induia. It was a cross-sectional community-based study conducted from November 2010 to January 2012 in two of the field practice villages affiliated to a Medical College in Pondicherry. Sample size was calculated using open source software, Open Epi Version 2.3.10. The sampling frame comprised individuals aged above 25 years and single stage cluster random sampling was carried out. After obtaining the verbal informed consent each of the study participants were interviewed face-to-face using a pre-tested structured questionnaire. Data were analyzed using the SPSS version 16. The age of the study participants ranged from 25 to 98 years with mean of 42.6 (±13.7) and majority of the study participants 339 (32.5%) from the age-group of 30-39 years. The prevalence of diabetes was 19.8% (60-69 years), 17.1% (40-49 years), 16.8% (50-59 years), and 13.6% (>69 years) among study subjects. In univariate analysis, higher age, being educated, unemployed and poor was associated with higher risk of diabetes mellitus (DM). Furthermore, a high triglyceride level was significantly associated with increase in the risk of DM (adjusted odds ratio: 3.01; 95% CI: 1.86, 4.86). Type-2 diabetes mellitus (T2DM) is an important public health problem in the adults of rural Pondicherry. Among non-modifiable factors, higher age, better socio-educational background and positive family history of diabetes was significantly associated with T2DM.

A cross-sectional study to determine the prevalence of obesity and other risk factors for type 2 diabetes among school children in Trinidad, West Indies.

PubMed

Batson, Yvonne Ann; Teelucksingh, Surujpal; Maharaj, Rohan G; Cockburn, Brian N

2014-08-01

Our previous work has shown that type 2 diabetes mellitus is a problem in the school-aged population of Trinidad, West Indies. The current study evaluated the prevalence in this population of selected risk factors for diabetes, viz: obesity, family history of diabetes and acanthosis nigricans. To assess the prevalence of the following risk factors for type 2 diabetes (T2DM) in school children in Trinidad: obesity, family history of diabetes in first- or second-degree relatives and the presence of acanthosis nigricans (AN). A cross-sectional survey was performed among school children aged 7-18 years from September 2009 to June 2010. A convenience sample was selected from a random sample of 32 schools drawn from all educational districts. A self-administered questionnaire was employed to record family history, gender and ethnicity. AN was assessed and scored clinically at the neck and obesity was measured by anthropometry and bio-impedance. There were 2130 participants in the study. Fifteen per cent were obese and 17% were overweight. Primary school children had a higher prevalence of obesity (22·9% vs 11·0%) and overweight (20·0% vs 15·6%) than secondary school children (P<0·05). A greater proportion of males than females had combined overweight/obesity as measured by BMI for age (35·8 vs 29·4%, P<0·05). The overall prevalence of AN was 43·4%. However, just over 18% of all school children have a degree of AN greater than grade 2, which clinically is readily recognisable. Females displayed this physical sign more commonly than males (P<0·05). The prevalences of a family history of diabetes in first- and second-degrees relatives were 11·0% and 1·1%, respectively. Forty-three per cent had one risk factor for diabetes, 23·1% had two and 2·9% had three. Risk factors for T2DM are very common among school children in Trinidad. More than 40% had at least one risk factor. Strategies aimed at reducing risk factors for T2DM, especially obesity, among Trinidadian

Smoking and the risk of diabetic nephropathy in patients with type 1 and type 2 diabetes: a meta-analysis of observational studies.

PubMed

Jiang, Ning; Huang, Feng; Zhang, Xiurong

2017-11-03

Conflicting evidence exists for observational studies on whether tobacco smoking is a risk factor for diabetic nephropathy (DN) in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In this meta-analysis, we aimed to assess the effects of tobacco smoking on the development of DN. We searched MEDLINE and EMBASE databases from their inception to March 31 st , 2017 for cross-sectional, case-control, and prospective cohort studies. We screened reference lists of retrieved articles. Summary relative risks (SRRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. A total of nineteen observational studies (1 case-control, 8 cross-sectional and 10 prospective cohort studies) were identified, involving more than 78,000 participants and a total of 17,832 DN cases. Compared with never-smokers, there was an augmented SRR (95% CI) of DN in ever-smokers in patients with T1DM (1.31 [1.06-1.62]; P = 0.006) and T2DM (1.44 [1.24-1.67]; P < 0.001), respectively. In patients with T1DM, the SRR (95% CI) was 1.25 (0.86-1.83) for microalbuminuria only, 1.27 (1.10-1.48) for macroalbuminuria only, and 1.06 (0.97-1.15) for end-stage renal disease (ESRD). In patients with T2DM, the SRR (95% CI) associated with ever smoking was 1.46 (0.94-2.26) for microalbuminuria only, 1.72 (1.04-2.84) for macroalbuminuria only, and 1.10 (0.36-3.33) for ESRD. Our meta-analysis suggests evidence for cigarette smoking as an independent risk factor for the development of DN in patients with both T1DM and T2DM.

Differentials in Cardiovascular Risk Factors and Diabetes by Socioeconomic Status and Sex in Kalutara, Sri Lanka.

PubMed

Gamlath, Lakshman; Nandasena, Sumal; Hennadige Padmal de Silva, Sudirikku; Linhart, Christine; Ngo, Anh; Morrell, Stephen; Nathan, Sally; Sharpe, Albie; Taylor, Richard

2017-07-01

Since 1950, cardiovascular disease (CVD) has emerged as a leading cause of mortality in Sri Lanka, especially in men. In 2014, a survey in Kalutara to assess CVD and type 2 diabetes mellitus (T2DM) risk factors in adults aged 25 to 64 years (n = 1011), and associations with sex and socioeconomic status (SES), found similar CVD risk factors in both sexes, except for daily tobacco smoking at 19% in men and nil in women, and higher body mass index (BMI) in women than men. With increasing SES in men, there were significant linear increases in mean BMI, waist circumference, mean systolic and diastolic blood pressure, mean fasting plasma glucose, and T2DM prevalence, but decreases in tobacco smoking. Whereas in women higher SES was associated with a significant increase in mean BMI, but a significant decrease in hypertension prevalence. Tobacco smoking is the main risk factor explaining higher CVD mortality in men compared with women.

The FOXO1 Gene-Obesity Interaction Increases the Risk of Type 2 Diabetes Mellitus in a Chinese Han Population.

PubMed

Gong, Lilin; Li, Rong; Ren, Wei; Wang, Zengchan; Wang, Zhihong; Yang, Maosheng; Zhang, Suhua

2017-02-01

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178-3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404-4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037-1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156-13.675; P value from sign test [P(sign)] = 0.025; P value from permutation test [P(perm)] = 0.000-0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.

Forecasting the burden of type 2 diabetes mellitus in Qatar to 2050: A novel modeling approach.

PubMed

Awad, Susanne F; O'Flaherty, Martin; Critchley, Julia; Abu-Raddad, Laith J

2018-03-01

We developed and demonstrated a novel mathematical modeling approach to forecast the burden of type 2 diabetes mellitus (T2DM) and to investigate T2DM epidemiology for the purpose of informing public health policy and programming. A population-level compartmental mathematical model was constructed and applied to Qatar. The model was stratified according to sex, age group, risk factor status, and T2DM status, and was parameterized by nationally-representative data. T2DM prevalence increased from 16.7% in 2012 to at least 24.0% by 2050. The rise in T2DM was most prominent among 45-54 years old. T2DM health expenditure was estimated to increase by 200-600% and to account for up to 32% of total health expenditure by 2050. Prevalence of obesity, smoking, and physical inactivity was predicted to increase from 41.4% to 51.0%, from 16.4% to 19.4%, and from 45.9% to 53.0%, respectively. The proportion of T2DM incidence attributed to obesity, smoking and physical inactivity was estimated at 57.5%, 1.8%, and 5.4%, respectively in 2012, and 65.7%, 2.1%, and 6.0%, respectively in 2050. Exploring different scenarios for the trends in risk factors, T2DM prevalence reached up to 37.7% by 2050. Using our innovative approach, a rising T2DM epidemic is predicted to continue in the next decades, driven by population growth, ageing and adverse trends in risk factors. Obesity was the principal risk factor explaining two-thirds of T2DM incidence. T2DM must be a national priority addressed by preventive and therapeutic interventions targeting T2DM and its modifiable risk factors. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Increased Trimethylamine N-oxide (TMAO) Portends High Mortality Risk Independent of Glycemic Control in Patients with Type 2 Diabetes Mellitus

PubMed Central

Wilson Tang, W. H.; Wang, Zeneng; Li, Xinmin S.; Fan, Yiying; Li, Daniel S.; Wu, Yuping; Hazen, Stanley L.

2017-01-01

Background Recent studies show a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine and coronary artery disease pathogenesis. Concentrations of a pro-atherogenic gut microbe-generated metabolite, trimethylamine N-oxide (TMAO), predict increased incident cardiovascular disease risks in multiple cohorts. TMAO concentrations are increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic value and relation to glycemic control are unclear. Methods We examined the relationship between fasting TMAO and two of its nutrient precursors, choline and betaine, versus 3-year major adverse cardiac events and 5-year mortality in 1,216 stable patients with T2DM who underwent elective diagnostic coronary angiography. Results TMAO (4.4 µmol/L [interquartile range 2.8–7.7µmol/L] vs. 3.6[2.3–5.7µmol/L]; P<0.001) and choline concentrations were higher in individuals with T2DM versus healthy controls. Within T2DM patients, higher plasma TMAO was associated with a significant 3.0-fold increased 3-year major adverse cardiac events risk (P<0.001) and a 3.6-fold increased 5-year mortality risk (P<0.001). Following adjustments for traditional risk factors and high sensitivity C-reactive protein, glycated hemoglobin and estimated glomerular filtration rate, increased TMAO concentrations remained predictive of both major adverse cardiac events and mortality risks in T2DM patients (e.g. Quartiles 4 vs. 1, hazard ratio 2.05[95%CI 1.31–3.20], P<0.001; and 2.07[95%CI 1.37–3.14], P<0.001, respectively). Conclusion Fasting plasma concentrations of the pro-atherogenic gut microbe-generated metabolite TMAO are higher in diabetic patients and portend higher major adverse cardiac events and mortality risks independent of traditional risk factors, renal function, and relationship to glycemic control. PMID:27864387

A Prospective Evaluation of B-type Natriuretic Peptide Concentrations and the Risk of Type 2 Diabetes in Women

PubMed Central

Everett, Brendan M.; Cook, Nancy; Chasman, Daniel I.; Magnone, Maria C.; Bobadilla, Maria; Rifai, Nader; Ridker, Paul M; Pradhan, Aruna D.

2013-01-01

Background Animal data suggest that natriuretic peptides play an important role in energy metabolism, but prospective studies evaluating a relationship between these peptides and type 2 diabetes mellitus (T2DM) in humans are few and results are conflicting. Methods We used a prospective case-cohort approach (n=491 T2DM cases, n=561 reference subcohort) within the Women's Health Study to evaluate baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and the risk of incident T2DM. We also tested for associations between 4 common variants in the natriuretic peptide A and B genes (NPPA-NPPB) and NT-proBNP concentrations (n=458) and incident type 2 diabetes (n=1372 cases among 22607 women). Results Case subjects had higher median baseline body mass index (29.4 vs. 25.0 kg/m2, P<0.001) and lower baseline median (IQR) NT-proBNP concentrations [46.8 ng/L (26.1, 83.2) vs 66.7 ng/L (39.3, 124.7), P<0.001]. In proportional hazards models adjusting for established diabetes risk factors, women in the highest quartile of baseline NT-proBNP (≥117.4 ng/L) had a 49% reduction in risk of T2DM (HR 0.51, 0.30–0.86, P=0.01) relative to those in the lowest quartile. Two of the 4 tested variants in NPPA-NPPB (rs632793, rs198389) associated with increased NT-proBNP concentrations and reduced risk of T2DM. For example, each copy of the minor allele of rs632793 was associated with increased NT-proBNP (β (SE)=0.201 (0.063), P<0.01) and decreased T2DM risk (HR 0.91, 0.84–0.989, P=0.026). Conclusions NT-proBNP concentrations that are high, but still within the reference interval, associate with reduced risk of incident diabetes in women and support a favorable role for natriuretic peptides in the development of T2DM. PMID:23288489

Excess body iron and the risk of type 2 diabetes mellitus: a nested case-control in the PREDIMED (PREvention with MEDiterranean Diet) study.

PubMed

Arija, Victoria; Fernández-Cao, José C; Basora, Josep; Bulló, Mònica; Aranda, Nuria; Estruch, Ramón; Martínez-González, Miguel A; Salas-Salvadó, Jordi

2014-12-14

A prospective nested case-control study within the PREvention with MEDiterranean Diet (PREDIMED) was conducted to evaluate the relationship between excess body Fe (measured as serum ferritin (SF), soluble transferrin receptor (sTfR) and sTfR:ferritin ratio) and the risk of type 2 diabetes mellitus (T2DM) in a Mediterranean population at a high risk of CVD, without T2DM at the start of the study. The study contained 459 subjects, 153 with incident T2DM (cases) and 306 without incident T2DM (controls). The follow-up period was for 6.0 (interquartile range 3.9-6.5) years. For each incident diabetic subject, two subjects were selected as controls who were matched broadly for age as well as for sex, intervention group and BMI. We observed a relationship between SF values >257 μg/l in males and >139 μg/l in females and the risk of T2DM, following adjustment in the conditional logistic regression model for high-sensitivity C-reactive protein, fasting glucose and other components of the metabolic syndrome (OR 3.62, 95% CI 1.32, 19.95; P= 0.022). We also found an association between low sTfR:ferritin ratio levels and the incidence of T2DM (OR 3.02, 95% CI 1.09, 8.39; P= 0.042), but no association with sTfR (OR 1.29, 95% CI 0.51, 3.23; P= 0.722). Oxidative stress has been hypothesised to contribute to the development of insulin resistance and β-cell dysfunction, the two key events in the clinical development of T2DM. Following adjustment for other risk factors for T2DM, excess body Fe (measured as SF and sTfR:ferritin ratio) was associated with an increased risk of developing T2DM in a Mediterranean population at a high risk of CVD.

Work-related psychosocial stress and the risk of type 2 diabetes in later life.

PubMed

Pan, K-Y; Xu, W; Mangialasche, F; Fratiglioni, L; Wang, H-X

2017-06-01

Although work-related psychosocial stress and type 2 diabetes mellitus (T2DM) have been investigated, the association between lifelong work stress and T2DM in later life remains unclear. This study examined whether high work stress increased the risk of T2DM risk in later life, accounting also for other sources of stress outside work, such as burden from household chores. From the population-based prospective study SNAC-K, 2719 diabetes-free participants aged ≥60 years were identified and followed up for 6 years. T2DM was ascertained by glycated haemoglobin level, self-report, hypoglycaemic medication use and clinical records. Levels of job control and demands over the whole working life were assessed by a validated matrix. Household chores load was assessed by hours spent on such chores. Multivariate logistic regression models were used to estimate the association between job strain and T2DM. During the 6-year follow-up, 154 incident cases of T2DM were identified. High job strain was associated with T2DM occurrence amongst the 60-year-old cohort (OR = 3.14, 95% CI: 1.27-7.77), and only amongst women (OR = 6.18, 95% CI: 1.22-31.26), but not in men. When taking into account household chores load, a more pronounced risk of T2DM was associated with high job strain in combination with heavy household chores load in women aged 60 years at baseline (OR = 9.45, 95% CI: 1.17-76.53). Work-related psychosocial stress may increase the risk of T2DM only amongst women in their early 60s. The risk can be amplified by high household chores load. © 2017 The Association for the Publication of the Journal of Internal Medicine.

The effect of Liuwei Dihuang decoction on PI3K/Akt signaling pathway in liver of type 2 diabetes mellitus (T2DM) rats with insulin resistance.

PubMed

Dai, Bing; Wu, Qinxuan; Zeng, Chengxi; Zhang, Jiani; Cao, Luting; Xiao, Zizeng; Yang, Menglin

2016-11-04

Liuwei Dihaung decoction (LWDHT) is a well-known classic traditional Chinese medicine formula, consists of six herbs including Rehmannia glutinosa Libosch.(family: Scrophulariaceae), Cornus officinalis Sieb.(family: Cornaceae), Dioscorea opposite Thunb.(family: Dioscoreaceae), Alisma orientale(G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.) Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has been used in the treatment of many types of diseases with signs of deficiency of Yin in the kidneys in China clinically. This study is aimed at investigating the effect of Liuwei dihuang decoction on PI3K/Akt signaling pathway in liver of T2DM rats with insulin resistance. T2DM model was induced in male Sprague-Dawley (SD) rats by high sugar and high fat diets combined with small dose of streptozocin (STZ) injection. The successful T2DM rats were randomly allocated three group--vehicle group, positive control group and Liuwei Dihuang decoction group. After 12-weeks treatment with distilled water, rosiglitazone and LWDHT by intragastric administration respectively, the rats were put to death in batches. The variance of fasting blood glucose (FBG) and fasting insulin (FINS) in serum were determined, the pathological changes of each rats' liver were observed by hematoxylin-eosin (HE) staining, the expression of insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase (PI3K) and protein kinas B (Akt) involving the canonical PI3K/Akt signaling pathway were detected by Real-time fluorescent quantitative PCR (RT-PCR), and the expression level of IRS2, PI3K, Akt protein and phosphorylated IRS2, PI3K, Akt protein were evaluated by Western Blot. All the data were analyzed by SPSS 17.0. Four weeks of treatment with LWDHT could significantly decrease the level of FBG and FINS in serum, improve the cellular morphology of liver, kidney, pancreas tissue, and the expression of IRS2, PI3K, Akt mRNA and phosphorylated IRS2, PI3K, Akt

Risk factors for diabetes, but not for cardiovascular disease, are associated with family history of Type 2 diabetes in subjects from central Mexico.

PubMed

Zamora-Ginez, Irma; Pérez-Fuentes, Ricardo; Baez-Duarte, Blanca G; Revilla-Monsalve, Cristina; Brambila, Eduardo

2012-03-01

Independent of obesity, family history of type 2 diabetes mellitus (FHT2DM) is another important risk factor for developing diabetes. To establish the association among FHT2DM, risk factors for diabetes and cardiovascular disease in subjects from central Mexico. Clinical and biochemical studies were performed in 383 first-degree relatives of patients with type 2 diabetes and 270 subjects unrelated to patients with type 2 diabetes-all subjects were from the city of Puebla in central Mexico. Logistic regressions were used to assess the association between FHT2DM and metabolic parameters. Cardiovascular risk was classified by dyslipidemia and the Framingham Risk Score (FRS). FHT2DM was associated with risk factors for diabetes, such as increased fasting insulin levels (OR = 1.731, 95% CI = 1.041-2.877), decreased insulin sensitivity (OR = 1.951, 95% CI = 1.236-3.080) and pre-diabetes (OR = 1.63, 95% CI = 1.14-2.33). FHT2DH was not associated with risk factors for cardiovascular disease, such as dyslipidemia (OR = 1.12, 95% CI = 0.70-1.79) and FRS (OR = 0.74, 95% CI = 0.40-1.36) when adjusted for gender, age, smoking and obesity. Diabetic risk factors, but not cardiovascular disease risk factors, are associated with a positive family history of diabetes in subjects from central Mexico, independent of the presence of obesity.

T2DM Self-Management via Smartphone Applications: A Systematic Review and Meta-Analysis.

PubMed

Cui, Mingxuan; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2016-01-01

Mobile health interventions (mHealth) based on smartphone applications (apps) are promising tools to help improve diabetes care and self-management; however, more evidence on the efficacy of mHealth in diabetes care is needed. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of mHealth apps on changes in hemoglobin A1c (HbA1c), blood glucose, blood pressure, serum lipids, and body weight in type 2 diabetes mellitus (T2DM) patients. Two independent reviewers searched three online databases (PubMed, the Cochrane Library, and EMBASE) to identify relevant studies published between January 2005 and June 2016. Of the 2,596 articles retrieved, 13 RCTs were included. We used random effects model to estimate the pooled results. Thirteen studies were selected for the systematic review, six of which with data available containing 1,022 patients were included for the meta-analysis. There was a moderate effect on glycemic control after the mHealth app-based interventions. The overall effect on HbA1c shown as mean difference (MD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.11% [-7.54 to -1.20 mmol/mol]; p = 0.007) and standardized mean differences (SMD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.10% [-7.54 to -1.09 mmol/mol]; p = 0.008). A subgroup analysis showed a similar effect with -0.33% (-3.61 mmol/mol) (95% CI -0.59 to -0.06% [-6.45 to -0.66 mmol/mol]; p = 0.02) in MD and -0.38% (-4.15 mmol/mol) (95% CI -0.71 to -0.05% [-7.76 to -0.55 mmol/mol]; p = 0.02) in SMD in studies where patients' baseline HbA1c levels were less than 8.0%. No effects of mHealth app interventions were found on blood pressure, serum lipids, or weight. Assessment of overall study quality and publication bias demonstrated a low risk of bias among the six studies. Smartphone apps offered moderate benefits for T2DM self-management. However, more research with

T2DM Self-Management via Smartphone Applications: A Systematic Review and Meta-Analysis

PubMed Central

Cui, Mingxuan; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2016-01-01

Background Mobile health interventions (mHealth) based on smartphone applications (apps) are promising tools to help improve diabetes care and self-management; however, more evidence on the efficacy of mHealth in diabetes care is needed. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of mHealth apps on changes in hemoglobin A1c (HbA1c), blood glucose, blood pressure, serum lipids, and body weight in type 2 diabetes mellitus (T2DM) patients. Methods Two independent reviewers searched three online databases (PubMed, the Cochrane Library, and EMBASE) to identify relevant studies published between January 2005 and June 2016. Of the 2,596 articles retrieved, 13 RCTs were included. We used random effects model to estimate the pooled results. Results Thirteen studies were selected for the systematic review, six of which with data available containing 1,022 patients were included for the meta-analysis. There was a moderate effect on glycemic control after the mHealth app-based interventions. The overall effect on HbA1c shown as mean difference (MD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.11% [-7.54 to -1.20 mmol/mol]; p = 0.007) and standardized mean differences (SMD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.10% [-7.54 to -1.09 mmol/mol]; p = 0.008). A subgroup analysis showed a similar effect with -0.33% (-3.61 mmol/mol) (95% CI -0.59 to -0.06% [-6.45 to -0.66 mmol/mol]; p = 0.02) in MD and -0.38% (-4.15 mmol/mol) (95% CI -0.71 to -0.05% [-7.76 to -0.55 mmol/mol]; p = 0.02) in SMD in studies where patients’ baseline HbA1c levels were less than 8.0%. No effects of mHealth app interventions were found on blood pressure, serum lipids, or weight. Assessment of overall study quality and publication bias demonstrated a low risk of bias among the six studies. Conclusions Smartphone apps offered moderate benefits for T2DM self

Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study.

PubMed

Zaccardi, F; Webb, D R; Carter, P; Pitocco, D; Khunti, K; Davies, M J; Kurl, S; Laukkanen, J A

2015-06-01

Previous prospective studies showing a positive association between serum calcium and incidence of type 2 diabetes mellitus (T2DM) have relied on total calcium or an indirect estimate of active, ionized calcium (iCa). We aimed to assess this relationship using a direct measurement of iCa. iCa and cardiometabolic risk factors were measured in a population-based sample of 2350 men without a known history of T2DM at baseline. Associations between iCa levels and incident cases of T2DM (self-reported, ascertained with a glucose tolerance test, or determined by record linkage to national registers) were estimated using Cox regression analyses adjusted for potential confounders. At baseline, mean (standard deviation) age was 53 (5) years and mean iCa 1.18 (0.05) mmol/L. During a median follow-up of 23.1 years, 140 new cases of T2DM were recorded. In a multivariable analysis adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, there was no association comparing second (hazard ratio 0.84; 95% confidence interval 0.59-1.18), third (0.77; 0.52-1.14), or fourth (0.98; 0.69-1.39) vs first quartile of iCa (p for trend 0.538); further adjustment for C-reactive protein, physical activity level, and triglycerides did not change the estimates (p for trend 0.389). In this study, we did not find evidence of an association between direct measurement of active calcium and risk of T2DM. Further studies are needed to confirm our findings and define the relationship between factors influencing indirect calcium estimation and incident T2DM. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of temperate, subtropical, and tropical fruit consumption on risk of type 2 diabetes in an Asian population123

PubMed Central

Butler, Lesley M; Koh, Woon-Puay; Yuan, Jian-Min; van Dam, Rob M

2017-01-01

Background: Findings on the relation between fruit consumption and the risk of type 2 diabetes mellitus (T2DM) have been inconsistent. Objectives: We examined whether the consumption of total, temperate, subtropical, and tropical fruit is associated with T2DM risk and whether differences in the carbohydrate quality of fruit influence T2DM risk in Asians. Design: We included 45,411 participants in the Singapore Chinese Health Study who were 45–74 y old and had no diabetes, cancer, or cardiovascular disease at recruitment (1993–1998). Fruit intake was assessed with the use of a validated food-frequency questionnaire. Physician-diagnosed incident T2DM cases were reported at follow-up 1 (1999–2004) and follow-up 2 (2006–2010) interviews. Cox proportional hazards regression was used to estimate HRs and 95% CIs of diabetes risk. Results: In 494,741 person-years of follow-up, 5207 participants developed T2DM. After adjustment for lifestyle and dietary risk factors, high total fruit consumption was not consistently associated with lower T2DM risk [men: HR of 1.33 (95% CI: 1.04, 1.71) for ≥3 servings/d compared with <1 serving/wk (P-trend = 0.17); women: HR of 0.88 (95% CI: 0.71, 1.11) (P-trend = 0.008); P-interaction = 0.003]. The direct association in men was observed for higher–glycemic index (GI) fruit [HR: 1.51 (95% CI: 1.22, 1.86) for ≥1 serving/d compared with rarely consumed; P-trend = 0.001] but not for lower or moderate GI fruit. In women, the consumption of temperate fruit, but not of subtropical or tropical fruit, was associated with lower T2DM risk [HR: 0.79 (95% CI: 0.67, 0.92) for ≥1 serving/d compared with rarely; P-trend = 0.006]. Conclusions: The consumption of temperate fruit, such as apples, was associated with a lower risk of T2DM in women, whereas the consumption of higher-GI fruit, such as bananas, was associated with higher risk in men. The impact of fruit consumption on the risk of diabetes may differ by the type of fruit, which may

Genetic variants primarily associated with type 2 diabetes are related to coronary artery disease risk

PubMed Central

Jansen, Henning; Loley, Christina; Lieb, Wolfgang; Pencina, Michael J; Nelson, Christopher P; Kathiresan, Sekar; Peloso, Gina M; Voight, Benjamin F; Reilly, Muredach P; Assimes, Themistocles L; Boerwinkle, Eric; Hengstenberg, Christian; Laaksonen, Reijo; McPherson, Ruth; Roberts, Robert; Thorsteinsdottir, Unnur; Peters, Annette; Gieger, Christian; Rawal, Rajesh; Thompson, John R; König, Inke R; Vasan, Ramachandran S; Erdmann, Jeanette; Samani, Nilesh J; Schunkert, Heribert

2015-01-01

Background The mechanisms underlying the association between diabetes and coronary artery disease (CAD) risk are unclear. We aimed to assess this association by studying genetic variants that have been shown to associate with type 2 diabetes (T2DM). If the association between diabetes and CAD is causal, we expected to observe an association of these variants with CAD as well. Methods and Results We studied all genetic variants currently known to be associated with T2DM at a genome-wide significant level (p<5*10−8) in CARDIoGRAM, a genome-wide data-set of CAD including 22,233 CAD cases and 64,762 controls. Out of the 44 published T2DM SNPs 10 were significantly associated with CAD in CARDIoGRAM (OR>1, p<0.05), more than expected by chance (p=5.0*10−5). Considering all 44 SNPs, the average CAD risk observed per individual T2DM risk allele was 1.0076 (95% confidence interval (CI), 0.9973–1.0180). Such average risk increase was significantly lower than the increase expected based on i) the published effects of the SNPs on T2DM risk and ii) the effect of T2DM on CAD risk as observed in the Framingham Heart Study, which suggested a risk of 1.067 per allele (p=7.2*10−10 vs. the observed effect). Studying two risk scores based on risk alleles of the diabetes SNPs, one score using individual level data in 9856 subjects, and the second score on average effects of reported beta-coefficients from the entire CARDIoGRAM data-set, we again observed a significant - yet smaller than expected - association with CAD. Conclusions Our data indicate that an association between type 2 diabetes related SNPs and CAD exists. However, the effects on CAD risk appear to be by far lower than what would be expected based on the effects of risk alleles on T2DM and the effect of T2DM on CAD in the epidemiological setting. PMID:26074316

Determinants and prognostic implications of cardiac troponin T measured by a sensitive assay in type 2 diabetes mellitus.

PubMed

Hallén, Jonas; Johansen, Odd Erik; Birkeland, Kåre I; Gullestad, Lars; Aakhus, Svend; Endresen, Knut; Tjora, Solve; Jaffe, Allan S; Atar, Dan

2010-09-15

The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if available (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). One-hundred thirteen (90%) had detectable cTnT at baseline and of those, 22 (18% of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r=0.92, p>0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p=0.058). Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.

Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease

PubMed Central

2012-01-01

Background The most common apolipoprotein E (apoE) gene polymorphism has been found to influence plasma lipid concentration and its correlation with coronary artery disease (CAD) has been extensively investigated in the last decade. It is, however, unclear whether apoE gene polymorphism is also associated with increased risk of type 2 diabetes mellitus (T2DM). The knowledge of this study may provide the primary prevention for T2DM and CAD development before its initiation and progression. Therefore, this study was carried out to determine the association between apoE gene polymorphism and T2DM with and without CAD and its role in lipid metabolism. Methods The case-control study was carried out on a total of 451 samples including 149 normal control subjects, 155 subjects with T2DM, and 147 subjects with T2DM complicated with CAD. The apoE gene polymorphism was tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Univariable and multivariable logistic regression analyses were used to identify the possible risks of T2DM and CAD. Results A significantly increased frequency of E3/E4 genotype was observed only in T2DM with CAD group (p = 0.0004), whereas the ε4 allele was significantly higher in both T2DM (p = 0.047) and T2DM with CAD (p = 0.009) as compared with controls. E3/E4 genotype was also the independent risk in developing CAD after adjusting with established risk factors with adjusted odds ratio (OR) 2.52 (95%CI 1.28-4.97, p = 0.008). The independent predictor of individuals carrying ε4 allele still remained significantly associated with both CAD (adjusted OR 2.32, 95%CI 1.17-4.61, p = 0.016) and T2DM (adjusted OR 2.04, 95%CI 1.07-3.86, p = 0.029). After simultaneously examining the joint association of E3/E4 genotype combined with either obesity or smoking the risk increased to approximately 5-fold in T2DM (adjusted OR 4.93, 95%CI 1.74-13.98, p = 0.003) and 10-fold in CAD (adjusted OR 10.48, 95%CI 3.56-30.79, p < 0

Profiling of cardio-metabolic risk factors and medication utilisation among Type II diabetes patients in Ghana: a prospective cohort study.

PubMed

Adua, Eric; Roberts, Peter; Sakyi, Samuel Asamoah; Yeboah, Francis Agyemang; Dompreh, Albert; Frimpong, Kwasi; Anto, Enoch Odame; Wang, Wei

2017-09-07

Type II diabetes mellitus (T2DM) is complicated by multiple cardio-metabolic risk factors. Controlling these factors requires lifestyle modifications alongside utilisation of anti-diabetic medications. Different glucose lowering [(biguanides (BIGs), sulfonylureas (SUAs), thiazolidinediones (TNZ)], lipid lowering (statins), and anti-hypertensive medicines [angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs) and central acting drugs (CADs)] have been approved for controlling hyperglycaemia, dyslipidaemia and hypertension respectively. Here, we examined factors that characterise T2DM and explored the response to medication therapy among T2DM patients. This prospective cohort study recruited 241 T2DM patients reporting at a clinic in Ghana, from January through to August, 2016. Each patient's demographic, medications and anthropometric data was obtained while information on medication adherence was captured using Morisky adherence scale-8 (MMAS-8). Fasting blood samples were collected for biochemical analysis. The mean age of participants was 57.82 years for baseline and six-month follow-up. Physical activity differed at baseline and follow up (p < 0.05) but not body mass index (BMI). BIG alone, or in combination with SUA and TNZ did not improve glycaemic status at follow up (p > 0.05). Many participants using either ACEI or ARB were able to control their blood pressures. Among dyslipidaemia patients under statin treatment, there was an improved lipid profile at follow-up. Statin medications are effective for reducing dyslipidaemia in T2DM patients. However, control of modifiable risk factors, particularly blood glucose and to a lesser degree blood pressure is suboptimal. Addressing these will require concomitant interventions including education on medication adherence and correct dietary plans, lifestyle modifications and physical activity.

Risk factors and predictors of uncontrolled hyperglycemia and diabetic ketoacidosis in children and adolescents with type 1 diabetes mellitus in Jeddah, western Saudi Arabia.

PubMed

Sayed, Mohamed Hesham; Hegazi, Moustafa Abdelaal; Abdulwahed, Khairyah; Moussa, Khairya; El-Deek, Basem Salama; Gabel, Hala; Ragheb, Rana

2017-02-01

Little is known about levels of glycemic control and risk factors for uncontrolled hyperglycemia in Saudi children with type 1 diabetes mellitus (T1DM). The aim of the present study was to identify levels of glycemic control, risk factors and predictors of uncontrolled hyperglycemia (HG) and diabetic ketoacidosis (DKA) in children with T1DM. A retrospective study was performed on Saudi children and adolescents with confirmed T1DM who were followed at the Pediatric Endocrinology Clinic of the Maternity and Children Hospital, Jeddah, from 2000 to 2014. Data collection included all possible factors that may be associated with uncontrolled T1DM. Patients were classified according to American Diabetes Association guidelines for target HbA1c levels per age group. Comparisons were made between well-controlled (WC) patients, HG patients, and DKA patients. Calculation of odds ratios and logistic regression allowed for estimation of the role of each risk factor in uncontrolled T1DM. Only 31.2 % of children and adolescents with T1DM were well controlled. Better glycemic control was associated with age < 6 years, urban residence, and T1DM duration <5 years. Glycemic control was not affected by gender, insulin therapy, or comorbidities. The most significant independent predictors of hyperglycemia and DKA were poor compliance with a healthy lifestyle (adjusted hazards ratio [AHR] 28.94; 95 % confidence interval [CI] 8.37-100.04) and an excess intake of sweets (AHR 3.31; 95 % CI 1.54-7.11). The most significant independent predictor for poor glycemic control (particularly DKA rather than hyperglycemia) in Saudi children and adolescents was poor compliance with a healthy lifestyle with an excessive intake of sweets. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Dental caries-associated risk factors and type 1 diabetes mellitus.

PubMed

Sampaio, Norma; Mello, Sandra; Alves, Cresio

2011-01-01

Type 1 diabetes mellitus (T1DM) is associated with various oral complications. However there is no consensus regarding the association of T1DM and caries. Critical revision of dental caries-associated risk factors and type 1 diabetes mellitus. Search of the MEDLINE and LILACS databases from 2000 to 2010, using, in different combination, the key words "dental caries", "diabetes mellitus" and "type 1 diabetes mellitus". The association between T1DM and dental caries remains controversial. Although some studies demonstrate a higher prevalence of caries due to the increased concentration of salivary glucose, acidity of the oral cavity, salivary viscosity, reduced salivary flow rate, and salivary gland dysfunction; other studies report a reduction of caries levels, probably caused by decreased ucrose ingestion. Although patients with uncontrolled T1DM and poor oral hygiene may present increased prevalence of dental caries, the literature does not describe a consistent relationship between T1DM and dental caries. Further investigations are warranted. If a true association is substantiated, intervention studies to prevent or reduce the occurrence of caries in this population should follow.

Genetic Susceptible Locus in NOTCH2 Interacts with Arsenic in Drinking Water on Risk of Type 2 Diabetes

PubMed Central

Pan, Wen-Chi; Kile, Molly L.; Seow, Wei Jie; Lin, Xihong; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Lu, Quan; Christiani, David C.

2013-01-01

Background Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear. Objectives This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM. Methods In 2009–2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001–2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons. Results Median arsenic levels in 2001–2003 were higher among diabetic participants compared with non-diabetic ones (71.6 µg/L vs. 12.5 µg/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR)  = 2.30, 95% confidence interval (CI) 1.17–4.50; rs17070967, OR = 2.02, 95%CI 1.00–4.06; rs6766801, OR = 2.33, 95%CI 1.18–4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 µg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction  = 0.048; q-value = 0.004). Conclusions These findings suggest that genetic variation in NOTCH2 increased

Identifying Common Genetic Risk Factors of Diabetic Neuropathies

PubMed Central

Witzel, Ini-Isabée; Jelinek, Herbert F.; Khalaf, Kinda; Lee, Sungmun; Khandoker, Ahsan H.; Alsafar, Habiba

2015-01-01

Type 2 diabetes mellitus (T2DM) is a global public health problem of epidemic proportions, with 60–70% of affected individuals suffering from associated neurovascular complications that act on multiple organ systems. The most common and clinically significant neuropathies of T2DM include uremic neuropathy, peripheral neuropathy, and cardiac autonomic neuropathy. These conditions seriously impact an individual’s quality of life and significantly increase the risk of morbidity and mortality. Although advances in gene sequencing technologies have identified several genetic variants that may regulate the development and progression of T2DM, little is known about whether or not the variants are involved in disease progression and how these genetic variants are associated with diabetic neuropathy specifically. Significant missing heritability data and complex disease etiologies remain to be explained. This article is the first to provide a review of the genetic risk variants implicated in the diabetic neuropathies and to highlight potential commonalities. We thereby aim to contribute to the creation of a genetic-metabolic model that will help to elucidate the cause of diabetic neuropathies, evaluate a patient’s risk profile, and ultimately facilitate preventative and targeted treatment for the individual. PMID:26074879

Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus.

PubMed

Kautzky-Willer, Alexandra; Harreiter, Jürgen; Pacini, Giovanni

2016-06-01

The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM is more frequently diagnosed at lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Generally, large sex-ratio differences across countries are observed. Diversities in biology, culture, lifestyle, environment, and socioeconomic status impact differences between males and females in predisposition, development, and clinical presentation. Genetic effects and epigenetic mechanisms, nutritional factors and sedentary lifestyle affect risk and complications differently in both sexes. Furthermore, sex hormones have a great impact on energy metabolism, body composition, vascular function, and inflammatory responses. Thus, endocrine imbalances relate to unfavorable cardiometabolic traits, observable in women with androgen excess or men with hypogonadism. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome. Overall, psychosocial stress appears to have greater impact on women rather than on men. In addition, women have greater increases of cardiovascular risk, myocardial infarction, and stroke mortality than men, compared with nondiabetic subjects. However, when dialysis therapy is initiated, mortality is comparable in both males and females. Diabetes appears to attenuate the protective effect of the female sex in the development of cardiac diseases and nephropathy. Endocrine and behavioral factors are involved in gender inequalities and affect the outcome. More research regarding sex-dimorphic pathophysiological mechanisms of T2DM and its complications could contribute to more personalized diabetes care in the future and would thus promote more awareness in terms of sex- and gender-specific risk factors.

Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus

PubMed Central

Harreiter, Jürgen; Pacini, Giovanni

2016-01-01

The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM is more frequently diagnosed at lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Generally, large sex-ratio differences across countries are observed. Diversities in biology, culture, lifestyle, environment, and socioeconomic status impact differences between males and females in predisposition, development, and clinical presentation. Genetic effects and epigenetic mechanisms, nutritional factors and sedentary lifestyle affect risk and complications differently in both sexes. Furthermore, sex hormones have a great impact on energy metabolism, body composition, vascular function, and inflammatory responses. Thus, endocrine imbalances relate to unfavorable cardiometabolic traits, observable in women with androgen excess or men with hypogonadism. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome. Overall, psychosocial stress appears to have greater impact on women rather than on men. In addition, women have greater increases of cardiovascular risk, myocardial infarction, and stroke mortality than men, compared with nondiabetic subjects. However, when dialysis therapy is initiated, mortality is comparable in both males and females. Diabetes appears to attenuate the protective effect of the female sex in the development of cardiac diseases and nephropathy. Endocrine and behavioral factors are involved in gender inequalities and affect the outcome. More research regarding sex-dimorphic pathophysiological mechanisms of T2DM and its complications could contribute to more personalized diabetes care in the future and would thus promote more awareness in terms of sex- and gender-specific risk factors. PMID:27159875

Physical activity, smoking, and alcohol consumption in association with incidence of type 2 diabetes among middle-aged and elderly Chinese men.

PubMed

Shi, Liang; Shu, Xiao-Ou; Li, Honglan; Cai, Hui; Liu, Qiaolan; Zheng, Wei; Xiang, Yong-Bing; Villegas, Raquel

2013-01-01

Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease worldwide. The prevalence of T2DM is increasing rapidly in China. Understanding the contribution of modifiable lifestyle factors on T2DM risk is imperative to prevent the development of T2DM in China. We examined associations between lifestyle factors including physical activity, smoking and alcohol consumption with incidence of T2DM among middle-aged and elderly men in urban Shanghai. Information on socio-demographics, lifestyle habits, dietary habits, and disease history was collected via in-person interviews. Anthropometric measurements were taken. A total of 51 464 Chinese men aged 40-74 years free of T2DM, coronary heart disease (CHD), and stroke at baseline were included in the current study. Incident T2DM was identified through follow-up surveys conducted every 2-3 years. Cox proportional hazard analyses were conducted to evaluate associations between lifestyle risk factors and incidence of T2DM. We documented 1304 new cases of T2DM during 276 929 person-years of follow-up (average: 5.4 years). Physical activity was inversely associated with T2DM risk. Daily living, commuting, and total physical activity METs had inverse negative dose-response relationships with T2DM (P-trend = 0.0033, 0.0022, and <0.0001, respectively). Regular participation in exercise or sports reduced T2DM risk (HR = 0.86, 95%CI: 0.76-0.98). Moderate alcohol intake (1-3 drinks/day) was inversely related to T2DM risk (HR = 0.80, 95%CI: 0.67-0.94). Cigarette smoking, on the other hand, was associated with increased T2DM risk; HRs were 1.25 (95%CI: 1.00-1.56) for smoking more than 20 cigarettes per day and 1.28 (95%CI: 1.04-1.57) for smoking more than 40 pack-years. Physical activity and moderate alcohol intake are inversely associated with T2DM risk, whereas smoking was positively associated with T2DM risk among middle-age and elderly Chinese men. Preventive measures should be developed to focus on these modifiable lifestyle

Potassium measurements and risk of type 2 diabetes: a dose-response meta-analysis of prospective cohort studies

PubMed Central

Peng, Yang; Zhong, Guo-Chao; Mi, Qiao; Li, Kejia; Wang, Ao; Li, Ling; Liu, Hua; Yang, Gangyi

2017-01-01

Objective To clarify the relationship between serum, dietary, and urinary potassium and the risk of type 2 diabetes mellitus (T2DM). Materials and Methods We searched PubMed and EMBASE through January 6, 2017 for studies reporting risk estimates on the association of potassium measurements and the risk of T2DM. The summary risk estimates were obtained through a random-effects model. Dose-response analysis was conducted. Results Eight studies involving 5,053 cases and 119,993 individuals were included. A trend toward significance was found in the highest versus lowest meta-analysis on serum potassium and T2DM risk (RR = 0.79; 95% CI 0.60–1.04); moreover, the RR per 1 mmol/L increase in serum potassium was 0.83 (95% CI 0.73–0.95). A non-significant association of dietary potassium and T2DM risk was detected (RR for the highest versus lowest category: 0.93; 95% CI 0.81–1.06; RR for every 1000mg increase per day: 1.00, 95% CI 0.96–1.05). A similar non-significant association was found for urinary potassium and T2DM risk (RR for the highest versus lowest category: 0.83; 95% CI 0.39–1.75; RR per 10 mmol increase: 1.00; 95% CI 0.95–1.05). Evidence of a linear association between serum, dietary, and urinary potassium and the risk of T2DM was found (all Pnon-linearity > 0.05). Conclusions Low serum potassium increases the risk of T2DM in a linear dose-response manner; nevertheless, neither dietary potassium nor urinary potassium shows any association with the risk of T2DM. However, these findings should be interpreted with caution due to limited studies. PMID:29246005

Use of parenteral glucocorticoids and the risk of new onset type 2 diabetes mellitus: A case-control study.

PubMed

Keyany, Ala; Nielen, Johannes T H; Souverein, Patrick C; de Vries, Frank; van den Bemt, Bart

2018-05-01

Use of oral glucocorticoids (GCs) has been associated with hyperglycaemia and type 2 diabetes mellitus (T2DM). However, unlike oral GCs, there is minimal or no data on the effect of parenteral GC use on T2DM. To assess the association between use of parenteral GCs and the risk of receiving a first prescription of a non-insulin antidiabetic drug (NIAD) as a proxy for new onset of T2DM. A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 177,154) were defined as patients >18 years of age who had their first ever NIAD prescription between January 1987 and October 2013. Controls were matched by age, gender and general practitioner practice. Conditional logistic regression analyses were used to estimate the risk of NIAD prescription and use of parenteral GCs. Our analyses were statistically adjusted for lifestyle factors, comorbidities and concomitant drug use. Although this study confirmed that oral GCs increases the risk of receiving a first prescription of a NIAD (OR 2.63 [95% CI 2.53-2.73]), there was no association between the use of parenterally administered GCs and the risk of receiving a first prescription of a NIAD (OR 0.88 [95% CI 0.76-1.02]). The number of GC prescriptions was not associated with risk of new onset T2DM compared to no parenteral GCs use; neither the type of GC. Our study does not demonstrate an association between the use of parenteral GCs and the risk of new onset of T2DM. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of Low-Fat Diets Differing in Protein and Carbohydrate Content on Cardiometabolic Risk Factors during Weight Loss and Weight Maintenance in Obese Adults with Type 2 Diabetes

PubMed Central

Watson, Nerylee; Dyer, Kathryn; Buckley, Jonathan; Brinkworth, Grant; Coates, Alison; Parfitt, Gaynor; Howe, Peter; Noakes, Manny; Murphy, Karen

2016-01-01

Despite evidence for the benefits of higher-protein (HP) diets in weight loss, their role in type 2 diabetes mellitus (T2DM) management and weight maintenance is not clear. This randomised study compared the effects of a HP diet (38% carbohydrate, 30% protein, 29% fat) to a isocaloric higher-carbohydrate diet (HC: 53%:21%:23%) on cardiometabolic risk factors for 12 weeks in energy restriction (~30% reduction) followed by 12 weeks of energy balance whilst performing regular exercise. Outcomes were measured at baseline and the end of each phase. Sixty-one overweight/obese adults (BMI (body mass index) 34.3 ± 5.1 kg/m2, aged 55 ± 8 years) with T2DM who commenced the study were included in the intention-to-treat analysis including the 17 participants (HP n = 9, HC n = 8) who withdrew. Following weight loss (M ± SEM: −7.8 ± 0.6 kg), there were significant reductions in HbA1c (−1.4% ± 0.1%, p < 0.001) and several cardiometabolic health risk factors. Improvements were sustained for 12 weeks when weight was stabilised and weight loss maintained. Both the HP and HC dietary patterns with concurrent exercise may be effective strategies for weight loss and weight maintenance in T2DM although further studies are needed to determine the longer term effects of weight maintenance. PMID:27187457

Cardiorespiratory fitness and risk of type 2 diabetes mellitus: A 23-year cohort study and a meta-analysis of prospective studies.

PubMed

Zaccardi, Francesco; O'Donovan, Gary; Webb, David R; Yates, Thomas; Kurl, Sudhir; Khunti, Kamlesh; Davies, Melanie J; Laukkanen, Jari A

2015-11-01

To investigate the association between cardiorespiratory fitness (CRF) and type 2 diabetes mellitus (T2DM) in a cohort of middle-age Finnish men and to summarise the current evidence in a meta-analysis of prospective studies. CRF was measured at baseline in a random population-based sample of 2520 subjects by assessing oxygen uptake during maximal exercise. Cox regression analysis was used to estimate the association between CRF, expressed as metabolic equivalents (METs), and the risk of T2DM adjusted for potential confounders; this estimate was then pooled with the results of other prospective studies in a meta-analysis. Mean (SD) baseline age and CRF were 53 (5) years and 8.7 (2.1) METs, respectively. During 23 years of follow-up, 153 (6.1%) participants developed T2DM. The hazard ratio per 1-MET higher CRF, adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, was 0.93 (95% confidence interval (CI): 0.84, 1.02; p = 0.109); further adjustment for smoking, education, and socioeconomic status did not materially change the estimate. In a random-effects meta-analysis of eight studies (92,992 participants and 8564 T2DM cases) combining maximally adjusted estimates, the pooled risk ratio of T2DM per 1-MET higher CRF level was 0.95 (95% CI: 0.93, 0.98; p = 0.003; I(2) = 81%), corresponding to 23 fewer cases per 100,000 person-years based on the assumption of a causal link between CRF and T2DM. These data suggest that there is an inverse relationship between CRF and T2DM that is largely independent of other risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

T-cell receptor repertoire variation may be associated with type 2 diabetes mellitus in humans.

PubMed

Frankl, Joseph A; Thearle, Marie S; Desmarais, Cindy; Bogardus, Clifton; Krakoff, Jonathan

2016-03-01

Recent work in Pima Indians, a population with high rates of obesity and type 2 diabetes mellitus (T2DM), demonstrated that human leukocyte antigen haplotype DRB1*02 carriers have an increased acute insulin response and decreased risk for the development of T2DM, implicating loss of self-tolerance in the pathogenesis of T2DM. Advances in genomic sequencing have made T-cell receptor repertoire analysis a practical mode of investigation. High-throughput sequencing of T-cell receptor complementarity-determining region 3 was carried out in male Pima Indians with normal glucose regulation (n = 11; age = 31 ± 8 years; %fat = 30.2 ± 8.7%) and the protective DRB1*02 haplotype versus those with T2DM without DRB1*02 (n = 7; age = 34 ± 8 years; %fat = 31.2 ± 4.7%). Findings were partially replicated in another cohort by assessing the predictive ability of T-cell receptor variation on risk of T2DM in Pima Indian men (n = 27; age = 28.9 ± 7.1 years; %fat = 28.8 ± 7.1%) and women (n = 20; age = 29 ± 7.0 years; %fat = 37.1 ± 6.8%) with baseline normal glucose regulation but without the protective haplotype who were invited to follow-up examinations as frequently as every 2 years where diabetes status was assessed by a 75-g oral glucose tolerance test. Of these subjects, 13 developed diabetes. T-cell receptor complementarity-determining region 3 length was shorter in those with T2DM, and a one-nucleotide decrease in complementarity-determining region 3 length was associated with a nearly threefold increase in risk for future diabetes. The frequency of one variable gene, TRBV7-8, was higher in those with T2DM. A 1% increase in TRBV7-8 frequency was associated with a greater than threefold increase in diabetes risk. These results indicate that T-cell autoimmunity may be an important component in progression to T2DM in Pima Indians. Copyright © 2015 John Wiley & Sons, Ltd.

Risk of disseminated intravascular coagulation in patients with type 2 diabetes mellitus: retrospective cohort study

PubMed Central

Nogami, Kenichiro; Muraki, Isao; Imano, Hironori; Iso, Hiroyasu

2017-01-01

Objectives To determine quantitatively the association between type 2 diabetes mellitus (T2DM) and disseminated intravascular coagulation (DIC). Design Retrospective cohort study using a claims database. Setting Medical care institutions representing 9% of all secondary hospitals (acute care hospitals) in Japan. Participants In total, 797 324 admissions, comprising 435 354 patients aged 18–79 years at the time of admission, were enrolled between January 2010 and September 2014. All patients were diagnosed with diabetes or admitted to hospitals that provided laboratory data. Main outcome measures Incidence of DIC reported by physicians in claims data. Results Logistic regression analysis found that the risk of DIC was significantly higher in T2DM patients than in non-DM patients (fully adjusted OR: 1.39 (95% CI 1.32 to 1.45)), independent of age, sex, admission year and potential underlying diseases. The higher risk of DIC in T2DM patients was apparent in those who were treated with insulin within the 30-day period prior to admission (1.53 (1.37 to 1.72)). When stratified by the potential underlying diseases, the risk of DIC was higher in T2DM patients with non-septic severe infection (1.67 (1.41 to 1.97)) and with solid tumour (1.59 (1.47 to 1.72)) than in non-DM patients with those underlying diseases. The risk was similar between T2DM and non-DM patients with sepsis (0.98 (0.90 to 1.08)) and lower in T2DM patients with acute leukaemia (0.70 (0.59 to 0.84)). Conclusions T2DM was associated with a higher risk of DIC, particularly when recently treated with insulin, as well as among admissions with solid tumour or non-septic severe infection. PMID:28122835

Fetal overgrowth in women with type 1 and type 2 diabetes mellitus.

PubMed

Ladfors, Linnea; Shaat, Nael; Wiberg, Nana; Katasarou, Anastasia; Berntorp, Kerstin; Kristensen, Karl

2017-01-01

Despite improved glycemic control, the rate of large-for-gestational-age (LGA) infants remains high in pregnancies complicated by diabetes mellitus type 1 (T1DM) and type 2 (T2DM). Poor glycemic control, obesity, and excessive gestational weight gain are the main risk factors. The aim of this study was to determine the relative contribution of these risk factors for LGA in women with T1DM and T2DM, after controlling for important confounders such as age, smoking, and parity. In this retrospective chart review study, we analyzed the medical files of pregnant women with T1DM and T2DM who attended the antenatal care program at Skåne University Hospital during the years 2006 to 2016. HbA1c was used as a measure of glycemic control. Maternal weight in early pregnancy and at term was registered. LGA was defined as birth weight > 2 standard deviations of the mean. Univariable and multivariable logistic regression analysis was used to calculate odds ratios (OR's) and 95% confidence intervals (CIs) for LGA. Over the 11-year period, we identified 308 singleton pregnancies in 221 women with T1DM and in 87 women with T2DM. The rate of LGA was 50% in women with T1DM and 23% in women with T2DM. The multivariable regression model identified gestational weight gain and second-trimester HbA1c as risk factors for LGA in T1DM pregnancies (OR = 1.107, 95% CI: 1.044-1.17, and OR = 1.047, 95% CI: 1.015-1.080, respectively) and gestational weight gain as a risk factor in T2DM pregnancies (OR = 1.175, 95% CI: 1.048-1.318), independent of body mass index. Gestational weight gain was associated with LGA in women with T1DM and T2DM, independent of maternal body mass index. The findings suggest that monitoring and regulation of gestational weight gain is important in the clinical care of these women, to minimize the risk of fetal overgrowth.

Are falls prevention programs effective at reducing the risk factors for falls in people with type-2 diabetes mellitus and peripheral neuropathy: A systematic review with narrative synthesis.

PubMed

Gu, Yu; Dennis, Sarah M

2017-02-01

Diabetic peripheral neuropathy (DPN) is a common complication of type-2 diabetes mellitus (T2DM) that predisposes the elderly to a higher falls risk. Falls prevention programs with a component of weight-bearing exercises are effective in decreasing future falls in the elderly. However, weight-bearing exercise was only recently recommended in guidelines for exercise for people with T2DM and DPN. Since then, there have been an increasing number of studies to evaluate the effectiveness of falls prevention programs on this targeted population. A systematic literature review was undertaken to determine the effectiveness of falls prevention programs for people with T2DM and DPN. Nine published studies that investigated the effect of exercise training on falls risk among people with T2DM and DPN were included in the review. Interventions included lower limb strengthening, balance practice, aerobic exercise, walking programs, and Tai Chi. The preliminary evidence presented in this review suggests that people with T2DM and DPN can improve their balance and walking after a targeted multicomponent program without risk of serious adverse events. There is insufficient long-term follow-up data to determine whether the improvements in balance or strength resulted in a decrease falls risk in the community setting. Copyright © 2016 Elsevier Inc. All rights reserved.

A Systematic Review and Meta-Analysis of Proteomics Literature on the Response of Human Skeletal Muscle to Obesity/Type 2 Diabetes Mellitus (T2DM) Versus Exercise Training.

PubMed

Srisawat, Kanchana; Shepherd, Sam O; Lisboa, Paulo J; Burniston, Jatin G

2017-11-11

We performed a systematic review and meta-analysis of proteomics literature that reports human skeletal muscle responses in the context of either pathological decline associated with obesity/T2DM and physiological adaptations to exercise training. Literature was collected from PubMed and DOAJ databases following PRISMA guidelines using the search terms 'proteom*', and 'skeletal muscle' combined with either 'obesity, insulin resistance, diabetes, impaired glucose tolerance' or 'exercise, training'. Eleven studies were included in the systematic review, and meta-analysis was performed on a sub-set (four studies) of the reviewed literature that reported the necessary primary data. The majority of proteins ( n = 73) more abundant in the muscle of obese/T2DM individuals were unique to this group and not reported to be responsive to exercise training. The main response of skeletal muscle to exercise training was a greater abundance of proteins of the mitochondrial electron transport chain, tricarboxylic acid cycle and mitochondrial respiratory chain complex I assembly. In total, five proteins were less abundant in muscle of obese/T2DM individuals and were also reported to be more abundant in the muscle of endurance-trained individuals, suggesting one of the major mechanisms of exercise-induced protection against the deleterious effects of obesity/T2DM occurs at complex I of the electron transport chain.

A Systematic Review and Meta-Analysis of Proteomics Literature on the Response of Human Skeletal Muscle to Obesity/Type 2 Diabetes Mellitus (T2DM) Versus Exercise Training

PubMed Central

Srisawat, Kanchana; Shepherd, Sam O.; Lisboa, Paulo J.

2017-01-01

We performed a systematic review and meta-analysis of proteomics literature that reports human skeletal muscle responses in the context of either pathological decline associated with obesity/T2DM and physiological adaptations to exercise training. Literature was collected from PubMed and DOAJ databases following PRISMA guidelines using the search terms ‘proteom*’, and ‘skeletal muscle’ combined with either ‘obesity, insulin resistance, diabetes, impaired glucose tolerance’ or ‘exercise, training’. Eleven studies were included in the systematic review, and meta-analysis was performed on a sub-set (four studies) of the reviewed literature that reported the necessary primary data. The majority of proteins (n = 73) more abundant in the muscle of obese/T2DM individuals were unique to this group and not reported to be responsive to exercise training. The main response of skeletal muscle to exercise training was a greater abundance of proteins of the mitochondrial electron transport chain, tricarboxylic acid cycle and mitochondrial respiratory chain complex I assembly. In total, five proteins were less abundant in muscle of obese/T2DM individuals and were also reported to be more abundant in the muscle of endurance-trained individuals, suggesting one of the major mechanisms of exercise-induced protection against the deleterious effects of obesity/T2DM occurs at complex I of the electron transport chain. PMID:29137117

Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

PubMed Central

Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

2013-01-01

Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. PMID:23715661

Comparison of Accuracy of Diabetes Risk Score and Components of the Metabolic Syndrome in Assessing Risk of Incident Type 2 Diabetes in Inter99 Cohort

PubMed Central

Shafizadeh, Tracy B.; Moler, Edward J.; Kolberg, Janice A.; Nguyen, Uyen Thao; Hansen, Torben; Jorgensen, Torben; Pedersen, Oluf; Borch-Johnsen, Knut

2011-01-01

Background Given the increasing worldwide incidence of diabetes, methods to assess diabetes risk which would identify those at highest risk are needed. We compared two risk-stratification approaches for incident type 2 diabetes mellitus (T2DM); factors of metabolic syndrome (MetS) and a previously developed diabetes risk score, PreDx® Diabetes Risk Score (DRS). DRS assesses 5 yr risk of incident T2DM based on the measurement of 7 biomarkers in fasting blood. Methodology/Principal Findings DRS was evaluated in baseline serum samples from 4,128 non-diabetic subjects in the Inter99 cohort (Danes aged 30–60) for whom diabetes outcomes at 5 years were known. Subjects were classified as having MetS based on the presence of at least 3 MetS risk factors in baseline clinical data. The sensitivity and false positive rate for predicting diabetes using MetS was compared to DRS. When the sensitivity was fixed to match MetS, DRS had a significantly lower false positive rate. Similarly, when the false positive rate was fixed to match MetS, DRS had a significantly higher specificity. In further analyses, subjects were classified by presence of 0–2, 3 or 4–5 risk factors with matching proportions of subjects distributed among three DRS groups. Comparison between the two risk stratification schemes, MetS risk factors and DRS, were evaluated using Net Reclassification Improvement (NRI). Comparing risk stratification by DRS to MetS factors in the total population, the NRI was 0.146 (p = 0.008) demonstrating DRS provides significantly improved stratification. Additionally, the relative risk of T2DM differed by 15 fold between the low and high DRS risk groups, but only 8-fold between the low and high risk MetS groups. Conclusions/Significance DRS provides a more accurate assessment of risk for diabetes than MetS. This improved performance may allow clinicians to focus preventive strategies on those most in need of urgent intervention. PMID:21829540

Effects of Low-Fat Diets Differing in Protein and Carbohydrate Content on Cardiometabolic Risk Factors during Weight Loss and Weight Maintenance in Obese Adults with Type 2 Diabetes.

PubMed

Watson, Nerylee; Dyer, Kathryn; Buckley, Jonathan; Brinkworth, Grant; Coates, Alison; Parfitt, Gaynor; Howe, Peter; Noakes, Manny; Murphy, Karen

2016-05-12

Despite evidence for the benefits of higher-protein (HP) diets in weight loss, their role in type 2 diabetes mellitus (T2DM) management and weight maintenance is not clear. This randomised study compared the effects of a HP diet (38% carbohydrate, 30% protein, 29% fat) to a isocaloric higher-carbohydrate diet (HC: 53%:21%:23%) on cardiometabolic risk factors for 12 weeks in energy restriction (~30% reduction) followed by 12 weeks of energy balance whilst performing regular exercise. Outcomes were measured at baseline and the end of each phase. Sixty-one overweight/obese adults (BMI (body mass index) 34.3 ± 5.1 kg/m², aged 55 ± 8 years) with T2DM who commenced the study were included in the intention-to-treat analysis including the 17 participants (HP n = 9, HC n = 8) who withdrew. Following weight loss (M ± SEM: -7.8 ± 0.6 kg), there were significant reductions in HbA1c (-1.4% ± 0.1%, p < 0.001) and several cardiometabolic health risk factors. Improvements were sustained for 12 weeks when weight was stabilised and weight loss maintained. Both the HP and HC dietary patterns with concurrent exercise may be effective strategies for weight loss and weight maintenance in T2DM although further studies are needed to determine the longer term effects of weight maintenance.

Pregnancy complications, mental health-related problems and type 2 diabetes mellitus in Malaysian women.

PubMed

Hasan, Syed Shahzad; Thiruchelvam, Kaeshaelya; Ahmed, Syed Imran; Clavarino, Alexandra M; Mamun, Abdullah A; Kairuz, Therese

2013-01-01

The aim of this study was to investigate the association between pregnancy complications, mental health-related problems, and type 2 diabetes mellitus (T2DM) in Malaysian women. A case-control study of women with T2DM (n=160) matched by age range to controls without T2DM (n=160). Data were collected in the Negeri Sembilan and PutraJaya regions in Malaysia, from two hospital outpatient clinics, PutraJaya Hospital and Tuanku Jaa'far Hospital Seremban, and one health clinic at Seremban. Validated, interviewer-administered questionnaires were used to obtain the data. The unadjusted and adjusted estimates were calculated using the Mantel-Haenszel method. Neither depression (RR 0.74, 95% CI: 0.39-1.41) nor anxiety (RR 1.00, 95% CI: 0.53-1.88) symptoms increased the risk of T2DM significantly. However, gestational diabetes (RR 1.35, 95% CI: 1.02-1.79), and ≥3 pregnancies (RR 1.39, 95% CI: 1.08-1.79) were significant risk factors for the development of T2DM. T2DM was not a significant risk factor for either depression (RR 1.26, 95% CI: 0.91-1.74) or anxiety symptoms (RR 1.13, 95% CI: 0.59-2.19). In this study, T2DM is not a significant risk factor for depression and anxiety; similarly, neither are depression and anxiety significant risk factors for T2DM. Although prevalence of depression and anxiety is not alarming, the findings reported here should alert clinicians to screen and treat anxiety and depression in people with diabetes and also note the importance of monitoring women with complications in pregnancy for risk of later T2DM. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Extrahepatic Diseases and NAFLD: The Triangular Relationship between NAFLD, Type 2-Diabetes and Dysbiosis.

PubMed

Scorletti, Eleonora; Byrne, Christopher D

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases from simple steatosis with hepatic lipid accumulation to end-stage liver disease with decompensated cirrhosis, liver failure and hepatocellular carcinoma. Recent data from the USA showed that in 2013, NAFLD was the second most frequent indication for liver transplantation behind hepatitis C. Since there are now effective treatments for hepatitis C and there is currently no licensed treatment for NAFLD, it has been predicted that over the next 10-15 years, NAFLD will replace hepatitis C as the most frequent indication for liver transplantation. Besides, increasing the risk of hepatocellular carcinoma and end-stage liver disease, it has recently become clear that NAFLD also increases risk of extrahepatic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, cardiac diseases and chronic kidney disease, to name but a few. Of each of these extrahepatic diseases, the evidence to date suggests that NAFLD is a strong risk factor for T2DM. When NAFLD occurs in combination with obesity and insulin resistance (as it frequently does), there is a marked increase in risk of incident T2DM with possible synergism occurring between liver fat accumulation, insulin resistance and obesity to further increase risk of development of T2DM. Thus, there is a reciprocal relationship between NAFLD as a risk factor for T2DM, and T2DM as a risk factor for liver disease progression in NAFLD. Moreover, recent evidence now points to the importance of perturbation of the intestinal microbiota (dysbiosis) in both T2DM and NAFLD. Consequently, there is a triangular relationship between dysbiosis and T2DM and NAFLD. This review will focus on T2DM as a key extrahepatic complication of NAFLD and will describe and discuss the triangular relationship between dysbiosis and T2DM and NAFLD and the factors and potential mechanisms underpinning this relationship. © 2016 S. Karger AG, Basel.

Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2011 Patients.

PubMed

Pan, Jun; Xin, Lei; Wang, Dan; Liao, Zhuan; Lin, Jin-Huan; Li, Bai-Rong; Du, Ting-Ting; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Ji, Jun-Tao; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2016-04-01

Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP) and increases the mortality. The identification of risk factors for DM development may contribute to the early detection and potential risk reduction of DM in patients with CP.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of DM after the onset of CP were calculated by Kaplan-Meier method. Risk factors for DM development after the diagnosis of CP were identified by Cox proportional hazards regression model.A total of 2011 patients with CP were enrolled. During follow-up (median duration, 22.0 years), 564 patients developed DM. Cumulative rates of DM 20 and 50 years after the onset of CP were 45.8% (95% confidence interval [CI], 41.8%-50.0%) and 90.0% (95% CI, 75.4%-97.7%), respectively. Five risk factors for DM development after the diagnosis of CP were identified: male sex (hazard ratio [HR], 1.51; 95% CI, 1.08-2.11), alcohol abuse (HR, 2.00; 95% CI, 1.43-2.79), steatorrhea (HR, 1.46; 95% CI, 1.01-2.11), biliary stricture (HR, 2.25; 95% CI, 1.43-3.52), and distal pancreatectomy (HR, 3.41; 95% CI, 1.80-6.44).In conclusion, the risk of developing DM in patients with CP is not only influenced by the development of biliary stricture and steatorrhea indicating disease progression, and inherent nature of study subjects such as male sex, but also by modifiable factors including alcohol abuse and distal pancreatectomy .

Alterations in intervertebral disc composition, matrix homeostasis and biomechanical behavior in the UCD-T2DM rat model of type 2 diabetes

PubMed Central

Fields, Aaron J.; Berg-Johansen, Britta; Metz, Lionel N.; Miller, Stephanie; La, Brandan; Liebenberg, Ellen C.; Coughlin, Dezba G.; Graham, James L.; Stanhope, Kimber L.; Havel, Peter J.; Lotz, Jeffrey C.

2015-01-01

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis and biomechanical behavior. Coccygeal motion segments were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end-product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia-inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress and AGE/RAGE-mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. PMID:25641259

Interaction between β-hexachlorocyclohexane and ADIPOQ genotypes contributes to the risk of type 2 diabetes mellitus in East Chinese adults

NASA Astrophysics Data System (ADS)

Li, Shushu; Wang, Xichen; Yang, Lu; Yao, Shen; Zhang, Ruyang; Xiao, Xue; Zhang, Zhan; Wang, Li; Xu, Qiujin; Wang, Shou-Lin

2016-11-01

Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH interaction on T2DM risk remains unclear. Thus, a paired case-control study was conducted in an East Chinese community. A total of 1446 subjects, including 723 cases and 723 controls matched on age, gender and residence, were enrolled, and 4 types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally, 4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly increased with serum levels of β-HCH (P < 0.001). Furthermore, the synergistic interaction between β-HCH and rs182052 significantly increased T2DM risk (OR I-additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals carrying only rs182052 (A allele) with high levels of β-HCH had significant reduction in adiponectin levels (P = 0.016). These results indicate that the interaction between rs182052 and β-HCH might increase the risk of T2DM by jointly decreasing the adiponectin level and potentially trigger T2DM development.

[Association between sedentary life style and risks of metabolic syndrome and diabetes mellitus type 2].

PubMed

Ye, Ying; Zhong, Wenling; Lin, Xiuquan; Lin, Shuguang; Lin, Xi; Li, Xiaoqing; Chen, Tiehui

2014-11-01

To explore the association of sedentary life style with risk of metabolic syndrome (MS) and diabetes mellitus type 2(T2DM). A total of 6 016 local residents aged 18 years or older in Fujian province were recruited by multi-stage stratified cluster sampling method in 2010-2011. Data, including demographic information, physical activity and sedentary time were collected. Indices related to height, weight, waist circumference, blood pressure and blood lipid were determined while MS and T2DM were diagnosed by IDF (2005) and WHO (1999) criteria. Logistic regression was used to estimate the correlations between sedentary behavior and MS or T2DM. The prevalence rates of MS and T2DM were 19.0% and 8.0% respectively, in local residents aged 18 years or older, in Fujian province. The overall rate of sedentary behavior was 18.1%, with the mean sedentary time as 4.3 hours. Both data showed significantly differences (P < 0.001) among control group,MS without T2DM group,MS with T2DM group and T2DM without MS group. Compared with the group of sedentary time <2.0 h/d, 1) the group with 2.0-3.5 h/d was significantly correlated with MT group (OR = 1.44, 95% CI:1.03-2.03, P < 0.05), 2) groups of 3.5-6.0 h/d and ≥6.0 h/d were significantly correlated with M, T, MT group, respectively (OR:1.49-1.76 and 1.28-1.58 respectively, 95% CI:1.19-2.45 and 1.02-2.23 respectively, P < 0.05), and 3) sedentary behavior was independently associated with an increased risk of MT group (OR = 1.82, 95% CI: 1.33-2.48, P < 0.01) and M group (OR = 1.43, 95%CI:1.14-1.78, P < 0.01), after the adjustment for factors as age, sex, cigarette smoking, alcohol drinking,BMI, education, occupation, sedentary behavior/sedentary time. MS and T2DM were associated with sedentary lifestyle, but these findings should be confirmed through further longitudinal studies.

Body mass index and type 2 diabetes in Thai adults: defining risk thresholds and population impacts.

PubMed

Papier, Keren; D'Este, Catherine; Bain, Chris; Banwell, Cathy; Seubsman, Sam-Ang; Sleigh, Adrian; Jordan, Susan

2017-09-15

Body mass index (BMI) cut-off values (>25 and >30) that predict diabetes risk have been well validated in Caucasian populations but less so in Asian populations. We aimed to determine the BMI threshold associated with increased type 2 diabetes (T2DM) risk and to calculate the proportion of T2DM cases attributable to overweight and obesity in the Thai population. Participants were those from the Thai Cohort Study who were diabetes-free in 2005 and were followed-up in 2009 and 2013 (n = 39,021). We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the BMI-T2DM association. We modelled non-linear associations using restricted cubic splines. We estimated population attributable fractions (PAF) and the number of T2DM incident cases attributed to overweight and obesity. We also calculated the impact of reducing the prevalence of overweight and obesity on T2DM incidence in the Thai population. Non-linear modelling indicated that the points of inflection where the BMI-T2DM association became statistically significant compared to a reference of 20.00 kg/m 2 were 21.60 (OR = 1.27, 95% CI 1.00-1.61) and 20.03 (OR = 1.02, 95% CI 1.02-1.03) for men and women, respectively. Approximately two-thirds of T2DM cases in Thai adults could be attributed to overweight and obesity. Annually, if prevalent obesity was 5% lower, ~13,000 cases of T2DM might be prevented in the Thai population. A BMI cut-point of 22 kg/m 2 , one point lower than the current 23 kg/m 2 , would be justified for defining T2DM risk in Thai adults. Lowering obesity prevalence would greatly reduce T2DM incidence.

Delayed heart rate recovery after exercise as a risk factor of incident type 2 diabetes mellitus after adjusting for glycometabolic parameters in men.

PubMed

Yu, Tae Yang; Jee, Jae Hwan; Bae, Ji Cheol; Hong, Won-Jung; Jin, Sang-Man; Kim, Jae Hyeon; Lee, Moon-Kyu

2016-10-15

Some studies have reported that delayed heart rate recovery (HRR) after exercise is associated with incident type 2 diabetes mellitus (T2DM). This study aimed to investigate the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the development of T2DM including glucose-associated parameters as an adjusting factor in healthy Korean men. Analyses including fasting plasma glucose, HOMA-IR, HOMA-β, and HbA1c as confounding factors and known confounders were performed. HRR was calculated as peak heart rate minus heart rate after a 1-min rest (HRR 1). Cox proportional hazards model was used to quantify the independent association between HRR and incident T2DM. During 9082 person-years of follow-up between 2006 and 2012, there were 180 (10.1%) incident cases of T2DM. After adjustment for age, BMI, systolic BP, diastolic BP, smoking status, peak heart rate, peak oxygen uptake, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, HOMA-β, and HbA1c, the hazard ratios (HRs) [95% confidence interval (CI)] of incident T2DM comparing the second and third tertiles to the first tertile of HRR 1 were 0.867 (0.609-1.235) and 0.624 (0.426-0.915), respectively (p for trend=0.017). As a continuous variable, in the fully-adjusted model, the HR (95% CI) of incident T2DM associated with each 1 beat increase in HRR 1 was 0.980 (0.960-1.000) (p=0.048). This study demonstrated that delayed HRR after exercise predicts incident T2DM in men, even after adjusting for fasting glucose, HOMA-IR, HOMA-β, and HbA1c. However, only HRR 1 had clinical significance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Preferences for Type 2 Diabetes Health States among Adolescents With or at Risk of Type 2 Diabetes Mellitus

PubMed Central

Rhodes, Erinn T.; Prosser, Lisa A.; Lieu, Tracy A.; Songer, Thomas J.; Ludwig, David S.; Laffel, Lori M.

2015-01-01

Objective We evaluated how adolescents with or at risk of type 2 diabetes (T2DM) and their parent/guardians (parents) value health states associated with T2DM. Methods We interviewed overweight/obese (BMI≥85th percentile), 12–18 year-old adolescents with T2DM, prediabetes, or insulin resistance (IR) and a parent. The standard gamble (SG) method elicited preferences (utilities) for 7 hypothetical T2DM health states reported on a scale from 0 (dead) to 1 (perfect health). Adolescent’s current health was evaluated with the SG and Health Utilities Index (HUI). Results There were 70 adolescents and 69 parents. Adolescents were 67.1% female and 15.5±2.2 years old; 30% had T2DM, 30% prediabetes, and 40% IR. Almost half (48.6%) had a BMI>99th percentile. Parents (83% mothers) were 45.1±7.3 years old and 75% had at least some college/technical school education. Adolescents and parents rated T2DM with no complications treated with diet as most desirable (median [IQR]; adolescent 0.72 [0.54, 0.98]; parent 1.0 [0.88, 1.0]) and end stage renal disease as least desirable (adolescent 0.51 [0.31, 0.70]; parent 0.80 [0.65, 0.94]). However, adolescents’ utilities were significantly lower (p≤0.001) than parents for all health states assessed. Adolescents’ assessment of their current health with the SG and HUI were not correlated. Conclusions Adolescents with or at risk of T2DM rated treatments and sequelae of diabetes as significantly worse than their parents. These adolescent utilities should be considered in the evaluation of treatment strategies for youth with T2DM. Family-based programs for T2DM must also be prepared to address conflicting preferences in order to promote shared-decision making. PMID:21489091

Association of Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor gamma 2 (PPARγ2) Gene with Type 2 Diabetes Mellitus in Ethnic Kashmiri Population.

PubMed

Majid, Misbah; Masood, Akbar; Kadla, Showkat Ahmad; Hameed, Iqra; Ganai, Bashir A

2017-02-01

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia associated with insulin resistance and relative insulin deficiency. T2DM is believed to be attributable to the combined effect of genetic and environmental factors. Peroxisome proliferator-activated receptor gamma 2 (PPARγ2) is one of the main candidate genes that are implicated in T2DM. A common proline 12 alanine (Pro12Ala) polymorphism in PPARγ2 has been shown to be associated with T2DM. The aim of this work was to investigate the possible role of PPARγ2 gene polymorphism, as a genetic risk factor for T2DM. The study comprised 200 ethnic unrelated subjects (100 T2DM patients and 100 controls). PCR-RFLP technique was used for genotyping analysis. The frequency of the Pro allele was 79 and 91.5 % for controls and cases, respectively (P < 0.05; OR 3.2; 95 % CI 1.64-6.3). The Pro12Ala polymorphism was in Hardy-Weinberg equilibrium in both patients and controls (χ 2  = 0.13, P > 0.05). We found a significant association of Pro12Ala polymorphism of PPARγ2 gene with T2DM, however the genotypes showed statistically significant association only with few clinical parameters including body mass index, total cholesterol, and low-density lipoprotein (P < 0.05). The study signifies that Pro allele in PPARγ2 may be a genotypic risk factor that confers susceptibility to T2DM in ethnic Kashmiri population.

Rare sugar D-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats.

PubMed

Hossain, Akram; Yamaguchi, Fuminori; Hirose, Kayoko; Matsunaga, Toru; Sui, Li; Hirata, Yuko; Noguchi, Chisato; Katagi, Ayako; Kamitori, Kazuyo; Dong, Youyi; Tsukamoto, Ikuko; Tokuda, Masaaki

2015-01-01

The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects. Above mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic β-cells in OLETF rats. Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests. d-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic β-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue. Our findings suggest that the rare sugar d-psicose could be beneficial for the prevention and control of obesity and

Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly: A Study From the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO).

PubMed

Wallander, Märit; Axelsson, Kristian F; Nilsson, Anna G; Lundh, Dan; Lorentzon, Mattias

2017-03-01

Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 ± 8.2 years [mean ± SD], 58% women) from the Swedish registry "Senior Alert" and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM-I], 41% with oral antidiabetics [T2DM-O], and 14% with no antidiabetic treatment [T2DM-none]) and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]), and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (1.22 [1.16-1.29]) and T2DM-O (1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication. © 2016 American

Determinants and prognostic implications of Cardiac Troponin T measured by a sensitive assay in Type 2 Diabetes Mellitus

PubMed Central

2010-01-01

Background The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM. Methods cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if availabe (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk). Results One-hundred thirteen (90 %) had detectable cTnT at baseline and of those, 22 (18 % of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r = 0.92, p > 0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p = 0.058). Conclusions Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found. PMID:20843304