Incident T2DM Research Articles

Egg consumption and cardiovascular disease among diabetic individuals: a systematic review of the literature.

BackgroundThis study reviewed epidemiological and experimental evidence on the relationship between egg consumption and cardiovascular disease (CVD) risks among type II diabetes mellitus (T2DM) individuals, and T2DM risk in nondiabetic subjects.ResultsFour of the six studies that examined CVD and mortality and egg consumption among diabetics found a statistically significant association. Of the eight studies evaluating incident T2DM and egg consumption, four prospective studies found a statistically significant association. Lack of adjustment for dietary confounders was a common study limitation. A small number of experimental studies examined the relationship between egg intake and CVD risk biomarkers among diabetics or individuals with T2DM risk factors. Studies among healthy subjects found suggestive evidence that dietary interventions that include eggs may reduce the risk of T2DM and metabolic syndrome.ConclusionDifferences in study design, T2DM status, exposure measurement, subject age, control for confounders and follow-up time present significant challenges for conducting a meta-analysis. Conflicting results, coupled with small sample sizes, prevent broad interpretation. Given the study limitations, these findings need to be further investigated.

Long-term predictors of impaired fasting glucose and type 2 diabetes in subjects with family history of type 2 diabetes: A 12-years follow-up of the Brisighella Heart Study historical cohort

AimTo identify and quantify the role of different risk factors in the long-term development of IFG and T2DM in a rural Italian population sample with family history of T2DM. MethodsWe selected a sample of 1271 adult subjects from among those 1851 consecutively visited during four consecutive Brisighella Heart Study surveys (1996–2008), then selecting those ones with a family history of T2DM. Thus, we obtained a final sample including 545 subjects and for which a full clinical and ematochemistry data set was available. ResultsThe Cox-regression model better predicting the incident IFG and T2DM included age, gender, FPG, TG and SUA. The model best predicting the incident IFG status alone (without T2DM) is very similar to that predicting both IFG and T2DM, including the same predictors. Finally, the model best predicting T2DM (excluding IFG) simply includes FPG, BMI and ALT/AST ratio. Repeating the Cox-regression analysis using BMI as a covariate, TG appears to be also a significant predictor of T2DM (HR 1.018 95% CI 1.009–1.041, p=0.013). ConclusionIn a sample of subjects with a family history of diabetes the best long-term predictors of IFG are age, gender, FPG, TG and SUA, while those of T2DM are FPG and BMI.

Genetic Information and the Prediction of Incident Type 2 Diabetes in a High-Risk Multiethnic Population

OBJECTIVETo 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.RESEARCH DESIGN AND METHODSIn 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.RESULTSNine 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).CONCLUSIONST2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.

Correlates of Adverse Outcomes in Abdominally Obese Individuals: Findings from the Five-Year Followup of the Population-Based Study of Health in Pomerania

Background. Abdominal obesity is a major risk factor of cardiovascular disease (CVD), type 2 diabetes (T2DM), and premature death. However, it has not been resolved which factors predispose for the development of these adverse obesity-related outcomes in otherwise healthy individuals with abdominal obesity. Methods. We studied 1,506 abdominal obese individuals (waist-to-height ratio (WHtR) ≥ 0.5) free of CVD or T2DM from the population-based Study of Health in Pomerania and assessed the incidence of CVD or T2DM after a five-year followup. Logistic regression models were adjusted for major cardiovascular risk factors and liver, kidney diseases, and sociodemographic status. Results. During follow-up time, we observed 114 and 136 new T2DM and CVD cases, respectively. Regression models identified age, waist circumference, serum glucose, and liver disease as predictors of T2DM. Regarding CVD, only age, unemployment, and a divorced or widowed marital status were significantly associated with incident CVD. In this subgroup of obese individuals blood pressure, serum glucose, or lipids did not influence incidence of T2DM or CVD. Conclusion. We identified various factors associated with an increased risk of incident T2DM and CVD among abdominally obese individuals. These findings may improve the detection of high-risk individuals and help to advance prevention strategies in abdominal obesity.

The Influence of Type 1 and Type 2 Diabetes on Periodontal Disease Progression

OBJECTIVETo explore associations between diabetes etiology (type 1 diabetes mellitus [T1DM] vs. T2DM) and glycemic control in the prediction of 5-year periodontal status change.RESEARCH DESIGN AND METHODSThe Study of Health in Pomerania (SHIP) is a population-based stratified sample of German men and women. Healthy participants and those determined to have T2DM arose from the SHIP cohort, and T1DM participants were recruited from diabetes clinics in the catchment area that gave rise to SHIP. Dentate participants (n = 2,626; 53% women; 20–81 years of age) were included. Diabetes was determined via physician diagnosis and/or HbA1c ≥6.5% (uncontrolled diabetes >7.0%). Examiners blinded to diabetes status performed random half-mouth periodontal examinations, assessing probing depth (PD) and attachment loss (AL) (four sites/tooth) at baseline and follow-up. Participants were categorized into six groups as follows: 1) diabetes free (n = 2,280), 2) incident T2DM (n = 79), 3) controlled T2DM (n = 80), 4) uncontrolled T2DM (n = 72), 5) controlled T1DM (n = 43), and 6) uncontrolled T1DM (n = 72). In multivariable regressions, mean PD change (ΔMPD), mean AL change (ΔMAL), or incident tooth-loss values were regressed across the aforementioned diabetes categories.RESULTSMean (SD) ΔMPD and ΔMAL values among all participants were −0.08 ± 0.5 mm and 0.08 ± 1.03 mm, respectively, and 34% lost one or more teeth. Relative to diabetes-free participants, those with uncontrolled T2DM experienced greater ΔMPD ± SE (P < 0.05), whereas participants with either uncontrolled T1DM or uncontrolled T2DM realized greater ΔMAL (P < 0.05). Uncontrolled T1DM and T2DM were both associated with an increased risk of future tooth loss (P < 0.05).CONCLUSIONSDiabetes control, but not etiology, was associated with future tooth loss and accelerated AL progression.

Egg Consumption and Coronary Heart Disease among Diabetic Individuals: A Systematic Review of the Literature

This study reviews epidemiological and experimental evidence on the relationship between egg consumption and coronary heart disease (CHD) risks among type II diabetes mellitus (T2DM) individuals and T2DM risk in non‐diabetic subjects. Four of the six studies that examined cardiovascular disease and mortality and egg consumption among diabetics found a statistically significant association. Of the seven studies evaluating incident T2DM and egg consumption, three prospective studies found a statistically significant association. Lack of adjustment for dietary confounders was a common study limitation. Differences in study design, T2DM status, exposure measurement, subject age, control for confounders and follow‐up time limit the feasibility of a meta‐analysis. A small number of experimental studies examined the relationship between egg intake and CHD risk biomarkers among diabetics or individuals with T2DM risk factors. Conflicting results coupled with small sample sizes prevent broad interpretation. Studies among healthy subjects found suggestive evidence that dietary interventions including eggs may reduce the risk of T2DM and metabolic syndrome. Given the study limitations, these findings need to be further investigated.

Optimal body fat percentage cut‐offs for obesity in Chinese adults

Obesity results in an increased risk of metabolic syndrome (MetS) and Type 2 diabetes (T2DM). Body fat percentage (BF%) is a common index of body composition. The aim of the present study was to determine the optimal BF% cut-offs for obesity to predict MetS and T2DM in Chinese adults. The baseline study group comprised 3916 Chinese adults (age 30-70years of age); 2033 subjects without MetS or T2DM were followed up for a maximum of 5.5years. The BF% was estimated using bioelectrical impedance analysis. Optimal BF% cut-offs were analysed by receiver operating characteristic (ROC) curves. Binary logistic regression analysis was performed to measure the association between obesity at baseline defined by BF% and newly developed MetS and T2DM. Mean BF% levels were lower in men than in women (23.9±6.1% vs 33.5±7.1%, respectively; P<0.01). For men, the optimal BF% cut-offs for the prediction of MetS and T2DM were 25.45% and 26.65%, respectively; for women, the corresponding values were 34.95% and 36.55%. Subjects with high BF% (≥25% in men; ≥35% in women) had higher risks of incident MetS or T2DM than those with low BF% (<25% in men; <35% in women). The relative risks were 3.43 (95% confidence intervals (CI) 2.59-4.54) and 2.92 (95% CI 1.85-4.60), respectively. The optimal BF% cut-offs for obesity for the prediction of MetS and T2DM in Chinese men and women were around 25% and 35%, respectively.

Abstract P214: Adherence to Dietary Patterns after Gestational Diabetes Mellitus and Risk of Subsequent Type 2 Diabetes

Background: Adherence to healthful dietary patterns is associated with lower risk of type 2 diabetes (T2DM) in the general population. Women with a history of gestational diabetes mellitus (GDM) are at particularly high risk for future type 2 diabetes (T2DM), though relations of dietary patterns with incident T2DM in this population are unknown. Hypothesis: We hypothesize that adherence to healthful dietary patterns among women with prior GDM is inversely associated with incident T2DM. Methods: We evaluated 4,413 participants from the Nurses' Health Study II longitudinal cohort with a history of GDM in one or more pregnancies. GDM was ascertained by self-report of a physician's diagnosis and has been previously validated in a subsample with confirmation of over 90% by medical record review. Participants were free of chronic disease at baseline and followed from 1991 through 2007. Dietary pattern adherence scores were derived for the alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH), and the alternate Healthy Eating Index (aHEI) based on validated food frequency questionnaires assessed after GDM and updated every 4 years thereafter. Incident T2DM was assessed every 2 years through previously validated questionnaire responses. Multivariable Cox proportional hazards models estimated the relationship of each dietary pattern with incident T2DM, adjusting for age, total energy intake, parity, age at first birth, race/ethnicity, parental history of T2DM, oral contraceptive use, menopausal status, and smoking status. Body mass index (BMI) was included in a subsequent model. Results: There were 491 cases of incident T2DM over 52,743 person-years of observation. In multivariable analyses, the aMED, DASH, and aHEI dietary patterns were each inversely associated with incident T2DM. For each 1 standard deviation increase in score, the aMED pattern was associated with a 24% lower risk (HR=0.76 [95% CI: 0.67, 0.86] p&lt;0.0001), DASH with an 18% lower risk (HR=0.86 [95% CI: 0.73, 0.92] p=0.0005), and aHEI with a 30% lower risk (HR=0.70 [95% CI: 0.61, 0.79] p&lt;0.0001). Further adjustment for BMI moderately but not completely attenuated these findings: (aMED: HR=0.85 [95% CI: 0.75, 0.97] p=0.014; DASH: HR=0.91 [95% CI: 0.80, 1.02] p=0.11; aHEI: HR=0.84 [95% CI: 0.73, 0.96] p=0.009). Conclusions: Adherence to healthful dietary patterns is associated with a lower incidence of T2DM among women following a diagnosis of GDM, and may be partially mediated by BMI. These findings have implications for prevention efforts in this high-risk population.

Abstract 009: Plain Water and Total Beverage Intakes and Risk of Type 2 Diabetes in Young and Middle-aged Women

Introduction: Some caloric beverages (e.g., sugar-sweetened beverage and fruit juice) have been associated with an elevated risk of type 2 diabetes; therefore, substitution of these caloric beverages with non-caloric beverages such as plain water may be important for diabetes prevention. Few previous studies have examined the association between plain water or total beverage intake and risk of type 2 diabetes. Methods: We followed 82,900 women, aged 27-45 years and free of diabetes, cardiovascular disease and cancer at baseline, from 1991 to 2007. Diet, including various beverages, was assessed by food frequency questionnaires and updated every four years. Incident type 2 diabetes cases were confirmed by supplementary questionnaires. Cox proportional hazard models were used to calculate relative risks (RRs) and corresponding 95% confidence intervals (CIs), and we estimated the effect of “substituting” a serving of one beverage for another by including both as continuous variables in the same multivariable model. The difference in their beta coefficients and their variances and covariance were used to estimate the RR and 95% CI for the substitution effect. Results: During 1,294,196 person-years of follow-up, we documented 2,980 incident T2DM cases. After adjustment for age and body mass index, compared with the reference group (&lt;1 glass/d), the relative risks (RRs) and 95% confidence intervals (CIs) of type 2 diabetes according to categories of plain water consumption were 0.91 (0.81-1.02) for 1 glass/d, 0.91 (0.82-1.01) for 2-3 glasses/d, 0.98 (0.87-1.11) for 4-5 glasses/d, and 1.02 (0.89-1.18) for 6 or more glasses/d (P-for-trend=0.51). Further adjustment for other diabetes risk factors did not substantially alter the RRs. We estimated that substituting one serving/d of plain water for one serving/d of sugar-sweetened beverage or fruit juice was associated with a 10% (95% CI, 6%-13%) and 13% (95% CI, 7%-18%) lower risk of type 2 diabetes, respectively. In this cohort, no association was found for total beverage intake and risk of type 2 diabetes: compared with women who drank less than 6 servings/d of total beverage, the RRs (95% CIs) were 0.97 (0.87-1.09), 0.98 (0.88-1.10), 1.01 (0.89-11.5), and 0.99 (0.86-1.14) for women drank 6-8, 8-10, 10-12, and ≥12 servings/d of total beverages (P-for-trend=0.83). Conclusions: Increasing consumption of water per se was not associated with risk of type 2 diabetes, but substituting plain water for sugar-sweetened beverage or fruit juice was associated with a significantly lower risk of type 2 diabetes.

Work Stress, Obesity and the Risk of Type 2 Diabetes: Gender‐Specific Bidirectional Effect in the Whitehall II Study

Psychosocial work stress has been linked to higher risk of type 2 diabetes (T2DM), with the effect being consistently higher among women than men. Also, work stress has been linked to prospective weight gain among obese men but weight loss among lean men. Here, we aimed to examine the interaction between work stress and obesity in relation to T2DM risk in a gender-specific manner. We studied 5,568 white middle-aged men and women in the Whitehall II study, who were free from diabetes at analysis baseline (1993). After 1993, diabetes was ascertained at six consecutive phases by an oral glucose tolerance test supplemented by self-reports. Cox regression analysis was used to assess the association between job strain (high job demands/low job control) and 18-year incident T2DM stratifying by BMI (BMI <30kg/m(2) vs. BMI ≥30kg/m(2)). Overall, work stress was associated with incident T2DM among women (hazard ratio (HR) 1.41: 95% confidence intervals: 1.02; 1.95) but not among men (HR 0.87: 95% confidence interval 0.69; 1.11) (P(INTERACTION) = 0.017). Among men, work stress was associated with a lower risk of T2DM in nonobese (HR 0.70: 0.53; 0.93) but not in obese individuals (P(INTERACTION) = 0.17). Among women, work stress was associated with higher risk of T2DM in the obese (HR 2.01: 1.06; 3.92) but not in the nonobese (P(INTERACTION) = 0.005). Gender and body weight status play a critical role in determining the direction of the association between psychosocial stress and T2DM. The potential effect-modifying role of gender and obesity should not be ignored by future studies looking at stress-disease associations.

The Impact of Leptin and Adiponectin on Incident Type 2 Diabetes Is Modified by Sex and Insulin Resistance

Adiponectin and leptin and their ratio have been associated with incident type 2 diabetes (T2DM), although the data presented are conflicting and the populations studied have been small. In this large, prospective, nested, case referent study, we hypothesized that these associations are sex specific and may be modified by insulin resistance. Men and women aged 30-60 years with incident T2DM (n=640) and a prior health survey within the Västerbotten Intervention Programme (VIP) and matched referents (n=1564) were identified. Using conditional logistic regression analyses, we tested whether baseline plasma adiponectin and leptin levels and their ratio independently predicted incident T2DM, stratified for gender and insulin resistance. Adjusted for traditional risk factors, fourth-quartile levels of adiponectin were associated with a reduced risk of T2DM in men [odds ratio (OR) 0.55 (0.36-0.86)] and women [OR 0.47 (0.27-0.83)]. Quartile four of the leptin/adiponectin ratio predicted T2DM in both men [OR 3.08 (1.68-5.67)] and women [OR 3.31 (1.56-7.03)], whereas quartile-four levels of leptin predicted T2DM only in men [OR 2.30 (1.32-4.02)]. When stratified for insulin sensitivity and adjusted for body mass index (BMI), log(e)-transformed leptin predicted T2DM in insulin-sensitive men [OR 1.56 (1.13-2.17)] but not in insulin-resistant men [OR 1.03 (0.76-1.39)]. The effect of adiponectin and the leptin/adiponectin ratio was not influenced by the insulin sensitivity status. Leptin in men and adiponectin in both sexes were independent predictors of T2DM. The association was modified by the degree of insulin sensitivity. The leptin/adiponectin ratio may add predictive information beyond the separate hormones.

Discordant effects on central obesity, hepatic insulin resistance, and alanine aminotransferase of low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance

Alanine aminotransferase (ALT) predicts incident type 2 diabetes (T2DM), possibly reflecting early fatty liver and hepatic insulin resistance. Thiazolidinediones and metformin can improve fatty liver and hepatic insulin resistance, respectively. In the Canadian Normoglycemia Outcome Evaluation trial, rosiglitazone/metformin (Rosi/Met, 4/1000 mg) reduced incident T2DM by 66% in subjects with impaired glucose tolerance. For insight on the hepatic effects of this therapy in relation to T2DM, we evaluated the temporal changes in waist, hepatic insulin sensitivity (1/Homeostasis Model Assessment of Insulin Resistance) and ALT in the Rosi/Met (n = 103) and placebo (n = 104) arms over median of 3.9 years. Waist did not differ between the arms. Hepatic insulin sensitivity improved in the Rosi/Met arm in year 1, but deteriorated thereafter as in the placebo arm. In contrast, Rosi/Met lowered ALT in year 1 and maintained this effect throughout the trial. Thus, low-dose Rosi/Met had no effect on central obesity, a transient effect on hepatic insulin sensitivity, and a sustained effect on ALT.

Posters

Results: In the 8-year follow-up study for glycaemic progression involving 518 glycaemic progression cases and 998 persistent normal glucose tolerance (NGT) controls, the combined genetic risk score of these SNPs showed an odds ratio (OR) of 1.07 (P=1.3x10 -3 ) for each additional risk allele. Moreover, the CDKN2A/B rs10811661 was significantly associated with glycaemic progression (OR=1.19; P=0.026). Trends for associations with glycaemic progression were also observed in KCNJ11 rs5219 (OR=1.17; P=0.051) and IGF2BP2 rs11711477 (OR=1.17; P=0.086). In the 12-year follow-up study for T2DM development involving 200 incident T2DM cases and 903 persistent NGT controls, CDKN2A/B rs10811661 showed a significant association with incident T2DM (OR=1.42; P=2.3x10 -3 ) which persisted after adjustment for confounding factors. Conclusions: This study has demonstrated the combined genetic effect of the T2DM-associated SNPs, identified from GWA studies, on glycaemic progression in Southern Chinese. CDKN2A/B rs10811661 which showed an independent association with T2DM development warrants further investigation.

017 Socio-economic status, incidence of type 2 diabetes and relative mortality in Scotland 2001–2007

BackgroundRRs of mortality associated with type 2 diabetes (T2DM) have declined in recent years but are higher in women than men in many populations. The role of socio-economic status (SES)...

Leisure-time physical activity and risk of type 2 diabetes in patients with established vascular disease or poorly controlled vascular risk factors

Aim To investigate the effect of leisure-time physical activity on the incidence of type 2 diabetes (T2DM) in patients with manifest arterial disease, or poorly controlled risk factors. Methods We examined 3940 patients with manifest arterial disease, hypertension or hyperlipidemia, aged 55.2 ± 12.2 years. Leisure-time physical activity was measured by a questionnaire and metabolic equivalent (MET) hours per week (h/wk) were calculated. Incident T2DM was evaluated by a specific diabetes questionnaire. Results Most patients (65%) were physically inactive (0 MET h/wk), 12% were insufficiently physically active (0–10.5 MET h/wk) and 23% were sufficiently physically active (≥10.5 MET h/wk). During a mean follow-up of 4.7 years, 194 (5%) incident cases of T2DM occurred. Sufficiently physically active patients had a lower incidence of diabetes (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.37–0.83). Patients who were physically active and not-obese (BMI < 30 kg/m 2) were at the lowest risk for developing T2DM (HR 0.18, 95% CI 0.12–0.28) compared with patients who were physically inactive and obese. Conclusions Leisure-time physical activity is associated with a decreased risk of T2DM in patients with manifest arterial disease, or poorly controlled risk factors. The combination of physical activity and non-obesity is associated with an even lower risk of the development of type 2 diabetes than the sum of their independent, protective effect.

The Association of Endogenous Sex Hormones, Adiposity, and Insulin Resistance with Incident Diabetes in Postmenopausal Women

ABSTRACT Context: In postmenopausal women, endogenous bioavailable testosterone (T) and estradiol (E2) have been positively associated, and SHBG has been negatively associated, with incident type 2 diabetes (T2DM). Previous studies have not explored possible factors explaining these relationships. Objective: Our objective was to examine the association of endogenous sex hormones with incident T2DM in postmenopausal women and possible explanatory factors. Design, Setting, and Participants: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective study that included 1612 postmenopausal women aged 45–84 yr, followed between the years 2000-2006, who were not taking hormone replacement therapy, had no prevalent cardiovascular disease or diabetes, and had complete ascertainment of sex hormones. Main Outcome Measures: T2DM was defined based on fasting glucose and/or treatment for diabetes. Results: There were 116 incident cases of diabetes during follow-up. Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG, we found significantly greater hazards of developing incident T2DM (all P for trend ≤ 0.001). After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance, bioavailable T was no longer associated with incident T2DM. The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models (both P for trend &amp;lt; 0.02). Dehydroepiandrosterone had no relationship with incident T2DM. Conclusions: Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women.

The Association of Endogenous Sex Hormones, Adiposity, and Insulin Resistance with Incident Diabetes in Postmenopausal Women

In postmenopausal women, endogenous bioavailable testosterone (T) and estradiol (E2) have been positively associated, and SHBG has been negatively associated, with incident type 2 diabetes (T2DM). Previous studies have not explored possible factors explaining these relationships. Our objective was to examine the association of endogenous sex hormones with incident T2DM in postmenopausal women and possible explanatory factors. The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective study that included 1612 postmenopausal women aged 45-84 yr, followed between the years 2000-2006, who were not taking hormone replacement therapy, had no prevalent cardiovascular disease or diabetes, and had complete ascertainment of sex hormones. T2DM was defined based on fasting glucose and/or treatment for diabetes. There were 116 incident cases of diabetes during follow-up. Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG, we found significantly greater hazards of developing incident T2DM (all P for trend <or=0.001). After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance, bioavailable T was no longer associated with incident T2DM. The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models (both P for trend <0.02). Dehydroepiandrosterone had no relationship with incident T2DM. Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women.

Lack of Association between the Tagging SNP A+930→G of SOCS3 and Type 2 Diabetes Mellitus: Meta-Analysis of Four Independent Study Populations

BackgroundThe suppressor of cytokine signalling 3 (SOCS3) provides a link between cytokine action and their negative consequences on insulin signalling. Thus SOCS3 is a potential candidate gene for type 2 diabetes (T2DM).Methodology/Principal FindingsBased on HapMap we identified the polymorphism A+930→G (rs4969168) as a haplotype tagging SNP (htSNP) sufficiently covering the genetic variation of the whole gene. We therefore examined the association between rs4969168 within SOCS3 and T2DM in three independent study populations; one prospective case-cohort study and two cross-sectional study populations. Due to the low frequency of individuals being homozygous for the polymorphism a dominant model of inheritance was assumed. The case-cohort study with 2,957 individuals (764 of them with incident T2DM) showed no effect of the polymorphism on diabetes risk (hazard ratio (95%CI): 0.86 (0.66–1.13); p = 0.3). Within the MeSyBePo-study population 325 subjects had T2DM from a total of 1,897 individuals, while the second cross-sectional cohort included 851 cases of T2DM within a total of 1653 subjects. According to the results in the prospective study, no association with T2DM was found (odds ratio (95%CI): 0.78 (0.54–1.12) for MesyBepo and 1.13 (0.90–1.42) for the Leipzig study population). There was also no association with metabolic subtraits such as insulin sensitivity (p = 0.7), insulin secretion (p = 0.8) or the hyperbolic relation of both, the disposition index (p = 0.7). In addition, no evidence for interaction with BMI or sex was found. We subsequently performed a meta-analysis, additionally including the publicly available data from the T2DM-subcohort of the WTCCC (n = 4,855). The overall odds ratio within that meta-analysis was 0.96 (0.88–1.06).Conclusions/SignificanceThere is no strong effect of the common genetic variation within the SOCS3 gene on the development of T2DM.

Relative androgen deficiency in relation to obesity and metabolic status in older men

Although androgen deficiency in men has been linked with obesity and the metabolic syndrome, whether it predisposes to, or is a consequence of, type 2 diabetes mellitus (T2DM) is still unclear. To determine the relationship between plasma androgen levels, obesity, metabolic status and T2DM in men of 70 years or older. A sample of 195 men from the Australian Longitudinal Study of Ageing with a mean age of 76.2 +/- 0.3 years were followed up for 8 years. Total testosterone (TT), fasting plasma glucose (FPG), urate, serum creatinine, total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TG), blood pressure (BP), body mass index (BMI), waist circumference (WC) and diabetic status were assessed at baseline. Self-reported diabetic status was obtained after 8 years. Metabolic syndrome was diagnosed based on the Third National Cholesterol Education Program Adult Treatment Panel clinical criteria. TT levels were lower in diabetic men compared with non-diabetic men (12.1 +/- 0.7 vs. 14.2 +/- 0.4 nmol/l, p = 0.026). TT levels in healthy, non-diabetic men over 80 years of age were lower (11.9 +/- 0.8 vs. 15.0 +/- 0.5 nmol/l, p = 0.002) than TT levels in those aged 70-79 years, inversely related to BMI (r = -0.26, p = 0.001), WC (r = -0.30, p < 0.001) and TG (r = -0.22, p = 0.005) and positively related to LDL-C (r = 0.25, p = 0.002). Men with the metabolic syndrome had significantly lower levels of TT and HDL-C, and higher values of BP, FPG, TG, BMI and WC, compared with those without. However, no significant difference in plasma TT levels was noted between men with incident T2Dm and healthy men. Stepwise linear regression analysis revealed that only LDL-C and WC related significantly to the variance of TT. Multiple logistic regression revealed FPG to be the only independent predictor of incident diabetes (odds ratio = 60.2, p = 0.003). Testosterone levels continue to decline even in healthy men over the age of 80 years. Although TT levels were inversely related to visceral obesity and several components of the metabolic syndrome, our data do not support a predictive or causative role for decreasing TT levels in the development of incident T2Dm. Androgen deficiency is consequent upon, rather than a cause of, poor metabolic status.