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 <30 kg/m² vs. BMI ≥30 kg/m²). 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.     

How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

Background

High N-terminal pro-brain-type natriuretic peptide levels have been associated with a lower risk of type 2 diabetes mellitus (T2D). However, less is known about other cardiac stress biomarkers in this context. Here we evaluated the association of mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine vasopressin (copeptin), C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM) with incident T2D and changes in glucose metabolism.

Methods

We performed a prospective cohort study using data from the population-based KORA F4/FF4 study. 1773 participants (52.3% women) with MR-proANP measurements and 960 (52.7% women) with copeptin, CT-proET-1 and MR-proADM measurements were included. We examined associations of circulating plasma levels of MR-proANP, copeptin, CT-proET-1 and MR-proADM with incident T2D, the combined endpoint of incident prediabetes/T2D and with fasting and 2 h-glucose, fasting insulin, HOMA-IR, HOMA-B and HbA1c at follow-up. Logistic and linear regression models adjusted for age, sex, waist circumference, height, hypertension, total/HDL cholesterol ratio, triglycerides, smoking, physical activity and parental history of diabetes were used to compute effect estimates.

Results

During a median follow-up time of 6.4 years (25th and 75th percentiles: 6.0 and 6.6, respectively), 119 out of the 1773 participants and 72 out of the 960 participants developed T2D. MR-proANP was inversely associated with incident T2D (odds ratio [95% confidence interval]: 0.75 [0.58; 0.96] per 1-SD increase of log MR-proANP). Copeptin was positively associated with incident prediabetes/T2D (1.29 [1.02; 1.63] per 1-SD increase of log copeptin). Elevated levels of CT-proET-1 were associated with increased HOMA-B at follow-up, while elevated MR-proADM levels were associated with increased fasting insulin, HOMA-IR and HOMA-B at follow-up. These associations were independent of previously described diabetes risk factors.

Conclusions

High plasma concentrations of MR-proANP contributed to a lower risk of incident T2D, whereas high plasma concentrations of copeptin were associated with an increased risk of incident prediabetes/T2D. Furthermore, high plasma concentrations of CT-proET-1 and MR-proADM were associated with increased insulin resistance. Our study provides evidence that biomarkers implicated in cardiac stress are associated with incident T2D and changes in glucose metabolism.

     

HMGA2 expression in white adipose tissue linking cellular senescence with diabetes

There is a clear link between overweight, gain of white adipose tissue, and diabetes type 2 (T2D). The molecular mechanism of the gain of adipose tissue is linked with the expression of high mobility group protein AT-hook 2 (HMGA2), and recent studies revealed an association with a SNP near HMGA2. In this study, we investigated the gene expression of HMGA2, p14^Arf, CDKN1A, and BAX in human abdominal subcutaneous white adipose tissue from 157 patients. We found a significant higher HMGA2 expression in obese individuals than in non-obese patients. Furthermore, the HMGA2 expression in white adipose tissue in patient with type 2 diabetes was significantly higher than in nondiabetic patients. There is an association between the DNA-binding nonhistone protein HMGA2 and the risk of developing T2D that remains mechanistically unexplained so far. Likewise, p14^Arf, an inducer of cellular senescence, has been associated with the occurrence of T2D. The data of the present study provide evidence that both proteins act within the same network to drive proliferation of adipose tissue stem and precursor cells, senescence, and increased risk of T2D, respectively.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-013-0354-6) contains supplementary material, which is available to authorized users.     

Can Newer Therapies Delay the Progression of Type 2 Diabetes Mellitus?

ObjectiveTo review the multifactorial and progressive nature of type 2 diabetes mellitus (T2DM), the consequences of its progression, and the potential of traditional and newer therapies to delay the progression of this disease.MethodsThe relevant literature is reviewed, and the mechanisms of action of novel agents for treatment of T2DM are discussed.ResultsThe global prevalence of diabetes has been increasing in recent decades, reaching near-epidemic proportions, and is projected to more than double by 2030. More than 90% of cases of diabetes in most countries consist of T2DM, but many individuals remain undiagnosed or are diagnosed only after their disease has progressed considerably. Inadequate glycemic control in a majority of patients with T2DM is due to the progressive nature of the disease, delay in initiating pharmacotherapy, and failure to intensify treatment more quickly in patients who do not achieve glycemic targets. Traditional oral therapies are usually effective at lowering hyperglycemia initially but do not prevent disease progression; thus, many patients ultimately require insulin. Furthermore, because most antidiabetic therapies are associated with weight gain or risk of hypoglycemia (or both), patients may not adhere to treatment recommendations.ConclusionA new therapeutic approach focuses on the use of the incretin hormone glucagon-like peptide-1. Analogues of this hormone delay the progression of β-cell dysfunction and promote β-cell regeneration in animal models. In clinical trials, they have been shown to improve glycemic control by increasing glucose-stimulated insulin secretion and suppressing glucagon secretion. At high concentrations, they also slow gastric emptying and increase satiety, which often promotes weight loss. Another approach is to inhibit the enzyme dipeptidyl-peptidase 4, which rapidly inactivates glucagon-like peptide- 1 and glucose-dependent insulinotropic polypeptide, thereby increasing endogenous incretin levels. (Endocr Pract. 2008;14:625-638)     

Associations between Recreational and Commuter Cycling,Changes in Cycling,and Type 2 Diabetes Risk: A Cohort Study of Danish Men and Women

BackgroundCycling is a recreational activity and mode of commuting with substantial potential to improve public health in many countries around the world. The aim of this study was to examine prospective associations between recreational and commuter cycling, changes in cycling habits, and risk of type 2 diabetes (T2D) in Danish adults from the Diet, Cancer and Health cohort study.ConclusionsCommuter and recreational cycling was consistently associated with lower risk of T2D in Danish adults. Our results also provide evidence that late-in-life initiation of or continued engagement in cycling lowers risk of T2D.     

The Association of Maximum Body Weight on the Development of Type 2 Diabetes and Microvascular Complications: MAXWEL Study

Background

Obesity precedes the development of type 2 diabetes (T2D). However, the relationship between the magnitude and rate of weight gain to T2D development and complications, especially in non-White populations, has received less attention.

Methods and Findings

We determined the association of rate and magnitude of weight gain to age at T2D diagnosis (Age_T2D), HbA1c at T2D diagnosis (HbA1c_T2D), microalbuminuria, and diabetic retinopathy after adjusting for sex, BMI at age 20 years, lifestyles, family history of T2D and/or blood pressure and lipids in 2164 Korean subjects aged ≥30 years and newly diagnosed with diabetes. Body weight at age 20 years (Wt_20y) was obtained by recall or from participants’ medical, school, or military records. Participants recalled their maximum weight (Wt_max) prior to T2D diagnosis and age at maximum weight (Age_{max_wt}). The rate of weight gain (Rate_{max_wt}) was calculated from magnitude of weight gain (ΔWt = Wt_max–Wt_20y) divided by ΔTime (Age_{max_wt} –20 years). The mean Age_{max_wt} and Age_T2D were 41.5±10.9 years and 50.1±10.5 years, respectively. The Wt_20y and Wt_max were 59.9±10.5 kg and 72.9±11.4 kg, respectively. The Rate_{max_wt} was 0.56±0.50 kg/year. After adjusting for risk factors, greater ΔWt and higher Rate_{max_wt} were significantly associated with earlier Age_T2D, higher HbA1c_T2D after additional adjusting for Age_T2D, and microalbuminuria after further adjusting for HbA1c_T2D and lipid profiles. Greater ΔWt and higher Rate_{max_wt} were also significantly associated with diabetic retinopathy.

Conclusions

This finding supports public health recommendations to reduce the risk of T2D and its complications by preventing weight gain from early adulthood.     

Integrating polygenic risk scores in the prediction of type 2 diabetes risk and subtypes in British Pakistanis and Bangladeshis: A population-based cohort study

BackgroundType 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G&H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR). We then investigated whether the integration of a polygenic risk score (PRS) for T2D with an existing risk tool (QDiabetes) could improve prediction of incident disease and the characterisation of disease subtypes.Methods and findingsIn this observational cohort study, we assessed whether common genetic loci associated with T2D in EUR individuals were replicated in 22,490 BPB individuals in G&H. We replicated fewer loci in G&H (n = 76/338, 22%) than would be expected given power if all EUR-ascertained loci were transferable (n = 101, 30%; p = 0.001). Of the 27 transferable loci that were powered to interrogate this, only 9 showed evidence of shared causal variants. We constructed a T2D PRS and combined it with a clinical risk instrument (QDiabetes) in a novel, integrated risk tool (IRT) to assess risk of incident diabetes. To assess model performance, we compared categorical net reclassification index (NRI) versus QDiabetes alone. In 13,648 patients free from T2D followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval (CI): 2.0% to 4.4%). IRT performed best in reclassification of individuals aged less than 40 years deemed low risk by QDiabetes alone (NRI 5.6%, 95% CI 3.6% to 7.6%), who tended to be free from comorbidities and slim. After adjustment for QDiabetes score, PRS was independently associated with progression to T2D after gestational diabetes (hazard ratio (HR) per SD of PRS 1.23, 95% CI 1.05 to 1.42, p = 0.028). Using cluster analysis of clinical features at diabetes diagnosis, we replicated previously reported disease subgroups, including Mild Age-Related, Mild Obesity-related, and Insulin-Resistant Diabetes, and showed that PRS distribution differs between subgroups (p = 0.002). Integrating PRS in this cluster analysis revealed a Probable Severe Insulin Deficient Diabetes (pSIDD) subgroup, despite the absence of clinical measures of insulin secretion or resistance. We also observed differences in rates of progression to micro- and macrovascular complications between subgroups after adjustment for confounders. Study limitations include the absence of an external replication cohort and the potential biases arising from missing or incorrect routine health data.ConclusionsOur analysis of the transferability of T2D loci between EUR and BPB indicates the need for larger, multiancestry studies to better characterise the genetic contribution to disease and its varied aetiology. We show that a T2D PRS optimised for this high-risk BPB population has potential clinical application in BPB, improving the identification of T2D risk (especially in the young) on top of an established clinical risk algorithm and aiding identification of subgroups at diagnosis, which may help future efforts to stratify care and treatment of the disease.

Sam Hodgson and colleagues investigate whether the common genetic differences associated with type 2 diabetes in people of European ancestry can be transferred to people of British Pakistani and Bangladeshi ancestry, integrating a novel polygenic risk score with an established clinical risk score.     

Dietary Diversity,Diet Cost,and Incidence of Type 2 Diabetes in the United Kingdom: A Prospective Cohort Study

BackgroundDiet is a key modifiable risk factor for multiple chronic conditions, including type 2 diabetes (T2D). Consuming a range of foods from the five major food groups is advocated as critical to healthy eating, but the association of diversity across major food groups with T2D is not clear and the relationship of within-food-group diversity is unknown. In addition, there is a growing price gap between more and less healthy foods, which may limit the uptake of varied diets. The current study had two aims: first, to examine the association of reported diversity of intake of food groups as well as their subtypes with risk of developing T2D, and second, to estimate the monetary cost associated with dietary diversity.ConclusionsA diet characterized by regular consumption of all five food groups and by greater variety of dairy, fruit, and vegetable subtypes, appears important for a reduced risk of diabetes. However, such a diet is more expensive. Public health efforts to prevent diabetes should include food price policies to promote healthier, more varied diets.     

Obesity and the relation between joint exposure to ambient air pollutants and incident type 2 diabetes: A cohort study in UK Biobank

BackgroundAir pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship.Methods and findingsA total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m². Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 μm (PM_2.5), between 2.5 μm and 10 μm (PM_2.5–10), nitrogen dioxide (NO₂), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D (p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants.ConclusionsWe found that various air pollutants PM_2.5, PM_2.5–10, NO_2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity.

Xiang Li and co-workers study the potential influence of obesity on associations between air pollutants and incidence of type 2 diabetes.     

Revised Case Finding Protocol for Dysglycemia in Chile: A Call for Action in Other Populations

ObjectiveGuidelines recommend case finding for dysglycemia (prediabetes and type 2 diabetes [T2D]) in adults or youth older than 10 years with overweight/obesity, but increased adiposity has not been associated with dysglycemia in some Hispanic populations. This study aims to determine the prevalence of dysglycemia in this population using simplified criteria independent of body mass index and age to request an oral glucose tolerance test (OGTT).MethodsCross-sectional retrospective analysis of medical records from a clinical center in Chile (2000-2007). OGTT was obtained from any patient with 1 cardiometabolic risk factor (CMRF) independent of age and body mass index.ResultsIn total, 4969 adults (mean age ± SD) 45.7 ± 15.9 years and 509 youths 16.6 ± 3.0 years were included. The prevalence (%, 95% CI) of prediabetes doubled that of T2D in youths (14.1%, 1.4-17.4 vs 6.3%, 4.5-8.7) and tripled it in adults (36.0%, 34.7-37.4 vs 10.7%, 9.8-11.5). In underweight and normal-weight adults, 22% (12.0-36.7) and 29.2% (26.4-32.1) had prediabetes, whereas 4.9% (1.3-16.1) and 8.8% (7.2-10.7) had T2D, respectively. In normal weight youths, 10.5% (6.7-15.9) and 2.9% (1.2-6.6) had prediabetes and T2D, respectively. In adults, but not in youths, most dysglycemia categories were related to overweight/obesity.ConclusionThis study supports a public health policy to identify more people at risk for cardiovascular disease by implementing a revised case finding protocol for dysglycemia using OGTT in even normal weight patients over 6 years of age when there is at least 1 CMRF. Reanalysis of case finding protocols for cardiometabolic risk in other populations is warranted.     

Association of vitamin D receptor BsmI gene polymorphism with the risk of type 2 diabetes mellitus

Abstract

Relationship between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism and the type 2 diabetes mellitus (T2DM) susceptibility is still conflicting at present. This meta-analysis was conducted to assess the association between VDR BsmI gene polymorphism and the risk of T2DM. The association studies were identified from PubMed, and Cochrane Library on 1 January 2014, and eligible investigations were included and synthesized using meta-analysis method. Eleven reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with T2DM susceptibility. In overall populations, B allele, BB genotype and bb genotype were not associated with T2DM risk. VDR BsmI gene polymorphism was also not associated with the T2DM risk in Asians and Caucasians. In conclusion, VDR BsmI gene polymorphism was also not associated with T2DM risk in overall populations, Asians and Caucasians. However, more studies should be conducted to confirm it.     

“Metabolic” Surgery For Treatment Of Type 2 Diabetes Mellitus

ObjectiveTo discuss the potential contribution of “metabolic” surgery in providing optimal management of patients with type 2 diabetes mellitus (T2DM).MethodsA literature search was performed with use of PubMed, and the clinical experience of the authors was also considered.ResultsBariatric—or, more appropriately, metabolic—surgical procedures have been shown to provide dramatic improvement in blood glucose levels, blood pressure, and lipid control in obese patients with T2DM. In these patients, metabolic surgery involves a low risk of short-term mortality and a significant long-term survival advantage, whereas the diagnosis of diabetes is associated with significant long-term mortality. Experimental studies in animals and clinical trials suggest that gastrointestinal bypass procedures can control diabetes and associated metabolic alterations by mechanisms independent of weight loss. As a result, the use of bariatric surgery and experimental gastrointestinal manipulations to treat T2DM is increasing, even among less obese patients. Although body mass index (BMI) currently is the most important factor for identifying candidates for bariatric surgery, evidence shows that a specific cutoff BMI value cannot accurately predict successful surgical outcomes. Furthermore, BMI appears limited in defining the risk profile for patients with T2DM.ConclusionCurrent BMI-based criteria for performance of bariatric surgery are not adequate for determining eligibility for operative treatment in patients with diabetes. Large clinical trials, comparing bariatric surgery versus optimal medical care of patients with T2DM, should be given priority in order to define the role of surgery in the management of diabetes. Recognizing the need to work as a multidisciplinary team that includes endocrinologists and surgeons is an initial step in addressing the issues and opportunities that surgery offers to diabetes care and research. (Endocr Pract. 2009;15:624-631)     

Serum 25-hydroxyvitamin D levels are associated with carotid atherosclerosis in normotensive and euglycemic Chinese postmenopausal women: the Shanghai Changfeng study

Background

Obesity is associated with the onset of type 2 diabetes mellitus (T2D), but reports conflict regarding the association between obesity and macrovascular complications. In this study, we investigated associations between cardiovascular risk factors and body mass index (BMI) and glycemic control in non–insulin-treated patients with T2D.

Methods

Authors gathered cross-sectional data from five observational studies performed in Spain. Generalized logit models were used to analyze the relationship between cardiovascular risk factors (independent variables) and 5 BMI strata (<25 kg/m², 25 to <30 kg/m², 30 to <35 kg/m², 35 to <40 kg/m², ≥40 kg/m²) and 5 glycated hemoglobin (HbA1c) strata (≤6.5%, >6.5–7%, >7–8%, >8–9%, >9%) (dependent outcomes).

Results

In total, data from 6442 patients were analyzed. Patients generally had mean values of investigated cardiovascular risk factors outside recommended thresholds. Younger patients had higher BMI, triglyceride levels and HbA1c than their older counterparts. Diastolic blood pressure, systolic blood pressure and triglyceride levels were directly correlated with BMI strata, whereas an inverse correlation was observed between BMI strata and high-density lipoprotein cholesterol (HDL-C) levels, patient age, and duration of T2D. Increased duration of T2D and total cholesterol levels, and decreased HDL-C levels were associated with a higher HbA1c category. BMI and HbA1c levels were not associated with each other.

Conclusions

As insulin-naïve patients with T2D became more obese, cardiovascular risk factors became more pronounced. Higher BMI was associated with younger age and shorter duration of T2D, consistent with the notion that obesity at an early age may be key to the current T2D epidemic. Glycemic control was independent of BMI but associated with abnormal lipid levels. Further efforts should be done to improve modifiable cardiovascular risk factors.

     

Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data

BackgroundThe global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people’s diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex.Methods and findingsWe linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant’s home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual’s home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study’s key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere.ConclusionsOur results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.

Dian Kusuma and colleagues investigate the associations between exposure to the density and proximity of healthy and unhealthy food outlets and diabetes in Bangladesh and Sri Lanka.     

FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men

AimSeveral studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population.MethodsWe genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMI_max) before or at the time of diagnosis and 693 control individuals with information regarding their BMI_max.ResultsThe BMI_max showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMI_max and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMI_max and age.ConclusionsThese results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMI_max before or at the time of diagnosis.     

Higher Adiponectin Levels Predict Greater Weight Gain in Healthy Women in the Nurses' Health Study

Adiponectin and resistin's possible roles in weight regulation have received little attention. We tested the hypothesis that adipokine levels predict future weight gain in women in the Nurses' Health Study. Among women who provided blood samples in 1990, we studied 1,063 women who did not develop diabetes (“healthy”) and 984 women who subsequently developed diabetes. Total and high‐molecular‐weight (HMW) adiponectin and resistin levels were measured using enzyme‐linked immunosorbent assay. Women who did not developed diabetes had a mean BMI of 26.3 ± 6.0 kg/m² at baseline and gained 2.0 ± 6.1 kg over 4 years. Women who developed diabetes had a mean BMI of 30.1 ± 5.4 kg/m² at baseline, and gained 2.4 ± 7.1 kg over 4 years. In women who did not developed diabetes, higher baseline levels of total and HMW adiponectin were associated with significantly greater weight gain after adjustment for age, BMI, physical activity, diet, and other covariates: women in the highest quintile of total adiponectin gained 3.18 kg compared to women in the lowest quintile who gained 0.80 kg (fully adjusted; P for trend <0.0001). Adiponectin was not significantly associated with weight gain in women who subsequently developed diabetes. Resistin levels were not associated with weight gain in either women who did or did not develop diabetes during the follow‐up. We conclude that elevated adiponectin levels are associated with higher weight gain in healthy women, independent of confounding risk factors. High adiponectin production by adipocytes might be a sign of “healthy” adipose tissue with further capacity to store fat.     

Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study

BackgroundVitamin D deficiency has been associated with type 1 diabetes in observational studies, but evidence from randomized controlled trials (RCTs) is lacking. The aim of this study was to test whether genetically decreased vitamin D levels are causally associated with type 1 diabetes using Mendelian randomization (MR).Methods and findingsFor our two-sample MR study, we selected as instruments single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels in a large vitamin D genome-wide association study (GWAS) on 443,734 Europeans and obtained their corresponding effect estimates on type 1 diabetes risk from a large meta-analysis of 12 type 1 diabetes GWAS studies (Ntot = 24,063, 9,358 cases, and 15,705 controls). In addition to the main analysis using inverse variance weighted MR, we applied 3 additional methods to control for pleiotropy (MR-Egger, weighted median, and mode-based estimate) and compared the respective MR estimates. We also undertook sensitivity analyses excluding SNPs with potential pleiotropic effects. We identified 69 lead independent common SNPs to be genome-wide significant for 25OHD, explaining 3.1% of the variance in 25OHD levels. MR analyses suggested that a 1 standard deviation (SD) decrease in standardized natural log-transformed 25OHD (corresponding to a 29-nmol/l change in 25OHD levels in vitamin D–insufficient individuals) was not associated with an increase in type 1 diabetes risk (inverse-variance weighted (IVW) MR odds ratio (OR) = 1.09, 95% CI: 0.86 to 1.40, p = 0.48). We obtained similar results using the 3 pleiotropy robust MR methods and in sensitivity analyses excluding SNPs associated with serum lipid levels, body composition, blood traits, and type 2 diabetes. Our findings indicate that decreased vitamin D levels did not have a substantial impact on risk of type 1 diabetes in the populations studied. Study limitations include an inability to exclude the existence of smaller associations and a lack of evidence from non-European populations.ConclusionsOur findings suggest that 25OHD levels are unlikely to have a large effect on risk of type 1 diabetes, but larger MR studies or RCTs are needed to investigate small effects.

Despoina Manousaki and co-workers investigate vitamin D levels and risk of type I diabetes.     

Evaluation of the Effect of Vitamin D Supplementation on Anthropometric Indicators and Dietary Intake of Patients with Type 2 Diabetes

Background:Various studies have shown that diabetes and its complications are associated with vitamin D deficiency. Due to the possible role of vitamin D in reducing the complications of diabetes and the high prevalence of its deficiency in Iran, this study was designed to investigate the effect of vitamin D supplementation on anthropometric indices and dietary intake of patients with type 2 diabetes.Methods:This randomized clinical trial (RCT) study was performed on 74 patients with type 2 diabetes (T2DM). Patients randomly divided into two groups to receive vitamin D (VD) supplementation (100 μg or 4000 IU/day) or placebo for three months, randomization was based on the permutated-block method. Anthropometric indices including body weight (BW), body mass index (BMI) and waist circumference (WC) and physical activity, dietary intake were assessed by validated methods at the beginning and end of the trial.Results:VD supplementation had not any significant differences in anthropometric indices, dietary intake and physical activity between the two groups.Conclusion:Finally, it can be concluded, receiving 100 micrograms/day of VD for three months had no favourable effects on patients with T2DM.Key Words: Anthropometric indices, Diabetes Mellitus, Dietary intake, Vitamin D     

Genetic Effects on Longitudinal Changes from Healthy to Adverse Weight and Metabolic Status — The HUNT Study

IntroductionThe complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally.Subjects/MethodsTwenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995–97) and HUNT3 (2006–08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood.ResultsThe most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69–0.90, P = 3.9x10^-4, adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09–1.49, P = 3.0x10^-3, adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23–1.91, P = 1.8x10^-4, adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36–2.03, P = 5.7x10^-7, adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important.Conclusions DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.     

Weight Gain and Management Concerns in Patients on Insulin Therapy

Background: The benefits of tight glycemic control in preventing the onset and progression of microvascular complications in patients with type 2 diabetes mellitus (DM) are unarguable. The majority of patients with type 2 DM will eventually require insulin to achieve adequate glycemic control. Using insulin earlier rather than later in the course of type 2 DM may diminish the deleterious effects of hyperglycemia on β-cell function and therefore help prolong good glycemic control and prevent the occurrence of microvascular complications. However, weight gain is a potential adverse effect of insulin therapy.Objective: The goal of this article was to describe the benefit of insulin therapy early in the course of type 2 DM, review the association of weight gain with insulin therapy, and examine potential detrimental effects that insulin-associated weight gain could have in patients with type 2 DM.Methods: Materials used for this article were identified through a search of MEDLINE (1966–2006). English-language articles were chosen using the search terms diabetes mellitus type 2, insulin, and obesity.Results: Intensive insulin therapy is often associated with weight gain. Although there is concern that weight gain in patients with type 2 DM may have adverse effects on risk factors for cardiovascular disease, unfavorable changes in blood pressure and lipid levels have not been consistently observed in clinical trials. Furthermore, clinical evidence, including data from the United Kingdom Prospective Diabetes Study, supports the view that intensive insulin therapy does not increase the risk for cardiovascular disease.Conclusions: Early insulin therapy in patients with type 2 DM may be a strategy that will help patients achieve and maintain good glycemic control, thereby reducing the risk of developing microvascular complications. Although weight gain is commonly associated with insulin therapy, it does not appear to put these patients at greater risk for cardiovascular disease.