Increased Risk Of Type Research Articles

Abstract MP56: Intake of Ultra-Processed Foods is Associated With an Increase in Risk for Type Two Diabetes: Results From Three U.S. Cohort Studies and a Meta-Analysis

Introduction: There is limited evidence on the association between long-term consumption of ultra-processed foods (UPF) and the risk of type 2 diabetes (T2D), among the U.S population. The overall strength of this association has also not been established. Hypothesis: Higher intake of UPF is associated with a higher risk of T2D in U.S. adults. The pooled risk estimates from published literature reinforce the positive relationship between the UPF intakes and T2D. Methods: We first assessed this relationship among 71,871 women from the Nurses’ Health Study (NHS, 1984-2016), 87,918 women from NHSII (1991-2017), and 38,847 men from the Health Professionals Follow-up Study (HPFS, 1986-2016) who were all free of T2D at baseline. Diet was assessed using food frequency questionnaires, every 2-4 years. UPF were categorized according to the Nova classification. Information on incident cases of T2D was obtained through follow-up questionnaires every 2 years. The association between UPF intake and incident T2D was examined using Cox proportional hazards models. Second, after conducting a systematic review of prospective cohort studies, risk estimates from all included cohorts were pooled in a random-effects, dose-response, meta-analysis to assess nonlinearity of the association between total UPF intake and T2D risk. Finally, the strength of the meta-evidence was assessed using NutriGrade. Results: During 5,187,678 person-years of follow-up across the three cohorts, 19,503 T2D cases were documented. The pooled multivariable-adjusted hazard ratios (HRs) for T2D between the extreme quintiles of total UPF intake (% of grams/day), was 1.36 (95% confidence interval (CI): 1.29, 1.44; P trend <0.0001). This relationship was driven by intakes of ultra-processed animal-based products, ready-to-eat mixed dishes and artificially- and sugar-sweetened beverages. Ultra-processed cereals and ultra-processed dark breads and whole-grain breads were inversely associated with T2D risk. In the meta-analysis (7 risk estimates, 415,554 participants and 21,932 T2D cases), a significant positive dose-response association between total UPF intake and T2D was observed (P=0.90 for non-linearity): a 10% increase in total UPF intake (% grams from UPF/day) was associated with a 10% higher risk of T2D (95%CI: 8%, 12%; I 2 =23.1%; P heterogeneity =0.25). Per NutriGrade, the evidence supporting the positive relationship between total UPF intake and T2D was of high quality. Conclusions: High quality evidence shows that total UPF consumption is associated with higher risk of T2D, although not all individual foods classified as ultra-processed were associated with a higher risk in these U.S. cohorts.

Exploring the association between use of gonadotropin releasing hormones agonists and prostate cancer diagnosis per se and diabetes control in men with type 2 diabetes mellitus: a nationwide, population-based cohort study

BackgroundGonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM.MethodsNationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association.ResultsThere were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13–1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39–1.80), when we defined the worsening control of diabetes by combining all definitions above.ConclusionUse of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH.

130-OR: Statin Exposure Increases Star (Steroidogenic Acute Regulatory Protein) Expression in Islets: A Novel Mechanism for ß-Cell Dysfunction and Increased Diabetes Risk?

While statin therapy reduces plasma cholesterol, it also impairs β-cell function and increases the risk of developing diabetes. We have shown that the cholesterol transport protein STAR is synthesized in β cells and its upregulation results in increased β-cell mitochondrial cholesterol content, producing β-cell dysfunction. Given statins’ role in cholesterol metabolism, we determined whether statin exposure increased expression of islet STAR, decreased expression of the downstream cholesterol metabolizing enzyme CYP27A1 and inhibited β-cell function. Atorvastatin treatment of C57Bl/6 islets increased Star gene (4.51±1.12 vs. 1.00±0.19, n=5, p<0.05) and a 3.3-fold increase in relative protein levels (n=2, p<0.005) while decreasing expression of Cyp27a1 (0.55±0.14 vs. 1.00±0.18, n=5, p<0.05). As expected, inhibition of the enzyme HMG-CoA reductase (Hmgcr) with atorvastatin resulted in compensatory increases in expression of Hmgcr and the LDL receptor (Ldlr); (Hmgcr: 5.88±0.65 vs. 1.00±0.05; Ldlr: 3.22±0.58 vs. 1.00±0.12; n=5, p<0.05), and a 5.1-fold increase in relative LDLR protein (n=2, p<0.05). Atorvastatin decreased glucose-stimulated insulin secretion (fold insulin response to 20 mM over 2.8 mM glucose: 28.6±5.86 vs. 52.0±8.25, n=5, p<0.05), but did not change insulin content (51.0±5.64 vs. 47.2±3.51 pmol insulin/5 islets, n=5, p=0.90). In summary, exposure of islets to atorvastatin increased Star expression, decreased Cyp27a1 expression and reduced β-cell secretory function. These findings suggest that increased Star and impaired cholesterol metabolism, leading to increased cholesterol accumulation and mitochondrial dysfunction, may be a novel mechanism mediating the effects of statins to impair β-cell function and increase risk of type 2 diabetes. Disclosure M. F. Hogan: None. N. Esser: None. A. T. Templin: None. J. J. Castillo: None. R. Akter: None. R. L. Hull: None. S. E. Kahn: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc. S. Zraika: None. Funding American Diabetes Association (1-18-PDF-174 to M.F.H.); U.S. Department of Veterans Affairs (BX001060)

Increased risk of type 2 diabetes in antidepressant users: evidence from a 6-year longitudinal study in the E3N cohort.

To examine the association between antidepressant medication use and the risk of type 2 diabetes. Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire-based follow-up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional-hazard regression models were used, with drug exposure considered as a time-varying parameter. Of the 63999 women who were free of drug-treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6-year follow-up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non-users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine-type, 'other' or 'mixed' antidepressants had a 1.25-fold (95% CI 0.99, 1.57), 1.66-fold (95% CI 1.12, 2.46), 1.35-fold (95% CI 1.00, 1.84) and 1.82-fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non-users, respectively. Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).

Long-term effects of metabolically healthy obesity on the risks of diabetes, cardiovascular disease events and its mortality over 23 years in the China Daqing diabetes prevention study

Objective To investigate the long-term effects of metabolically healthy obesity on the risks of type 2 diabetes, cardiovascular disease events, and its mortality over a 23-year follow-up. Methods Based on the results of an oral glucose tolerance test, there were 519 participants with normal glucose tolerance and 630 with newly diagnosed type 2 diabetes enrolled in 1986 and then given to assess the long-term clinical outcomes during the 23-year follow-up in Daqing. Metabolically healthy obesity was defined as the overweight and obese individuals with no metabolic abnormalities (diabetes, hypertension, hyperlipidemia). Finally, we identified 682 participants (350 with normal glucose tolerance and 332 with newly diagnosed diabetes). They were divided into five groups: 211 individuals with metabolically healthy normal weight (MHNW group), 58 with metabolically healthy overweight and obesity (MHO group), 81, 109, 223 were metabolically unhealthy overweight and obesity with hypertension (MUHO group), type 2 diabetes (MUDO group), hypertension and diabetes (MUHDO group). Incidences of type 2 diabetes, morbidity and mortality of cardiovascular disease were compared among these groups. Results Over 23 years, instead of the morbidity and mortality of cardiovascular disease, the incidence of type 2 diabetes in MHO group was two times higher than in MHNW group ( 24.1%, 12.5/1 000 person years vs 10.9%, 5.2/1 000 person years, P=0.01), with an age, sex, and smoking history-adjusted hazard ratio (HR) of 2.42 (95% CI 1.24-4.74, P=0.01). The morbidity and mortality of cardiovascular disease in the groups of overweight and obesity with metabolically unhealthy were higher than in MHNW group, and increased across the subjects with MUHO, MUDO, MUHDO (P<0.05). Conclusion Compared with metabolically healthy normal weight participants, the metabolically healthy obese group was at increased risk of type 2 diabetes but not cardiovascular disease events and its mortality. On the contrary, the overweight and obese groups with metabolic abnormalities had significant higher incidence of type 2 diabetes, morbidity and mortality of cardiovascular diseases. Key words: Metabolically healthy obesity; Diabetes mellitus, type 2; Mortality; Cardiovascular disease events

Breakfast Skipping Is Associated with Increased Risk of Type 2 Diabetes among Adults: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Epidemiologic studies have indicated that breakfast skipping is associated with risk of type 2 diabetes. However, the shape of the dose-response relation and the influence of adiposity on this association have not been reported. We investigated the association between breakfast skipping and risk of type 2 diabetes by considering the influence of the body mass index (BMI). In this systematic review and meta-analysis, PubMed and Web of Science were searched up to August 2017. Prospective cohort studies on breakfast skipping and risk of type 2 diabetes in adults were included. Summary RRs and 95% CIs, without and with adjustment for BMI, were estimated with the use of a random-effects model in pairwise and dose-response meta-analyses. In total 6 studies, based on 96,175 participants and 4935 cases, were included. The summary RR for type 2 diabetes comparing ever with never skipping breakfast was 1.33 (95% CI: 1.22, 1.46, n=6 studies) without adjustment for BMI, and 1.22 (95% CI: 1.12, 1.34, n=4 studies) after adjustment for BMI. Nonlinear dose-response meta-analysis indicated that risk of type 2 diabetes increased with every additional day of breakfast skipping, but the curve reached a plateau at 4-5 d/wk, showing an increased risk of 55% (summary RR: 1.55; 95% CI: 1.41, 1.71). No further increase in risk of type 2 diabetes was observed after 5 d of breakfast skipping/wk (P for nonlinearity=0.08). This meta-analysis provides evidence that breakfast skipping is associated with an increased risk of type 2 diabetes, and the association is partly mediated by BMI.

Childhood BMI and Adult Type 2 Diabetes, Coronary Artery Diseases, Chronic Kidney Disease, and Cardiometabolic Traits: A Mendelian Randomization Analysis.

To test the causal effect of childhood BMI on adult cardiometabolic diseases using a Mendelian randomization analysis. We used 15 single nucleotide polymorphisms as instrumental variables for childhood BMI to test the causal effect of childhood BMI on cardiometabolic diseases using summary-level data from consortia. We found that a 1-SD increase in childhood BMI (kg/m2) was associated with an 83% increase in risk of type 2 diabetes (odds ratio [OR] 1.83 [95% CI 1.46, 2.30]; P = 2.5 × 10-7) and a 28% increase in risk of coronary artery disease (CAD) (OR 1.28 [95% CI 1.17, 1.39]; P = 2.1 × 10-8) at the Bonferroni-adjusted level of significance (P < 0.017) in adults. In addition, a 1-SD increase in childhood BMI was associated with a 0.587-SD increase in adulthood BMI (kg/m2), a 0.062-SD increase in hip circumference (cm), a 0.602-SD increase in waist circumference (cm), a 0.111 pmol/L increase in log fasting insulin, a 0.068 increase in log-transformed HOMA of ß-cell function (%), a 0.126 increase in log-transformed HOMA of insulin resistance (%), and a 0.109-SD increase in triglyceride (mg/dL) but a 0.138-SD decrease in HDL (mg/dL) in adults at the Bonferroni-adjusted level of significance (P < 0.0026). A genetic predisposition to higher childhood BMI was associated with increased risk of type 2 diabetes and CAD in adult life. These results provide evidence supportive of a causal association between childhood BMI and these outcomes.

Association between Transcription Factors 7-like 2 (rs7903146) Polymorphism and Some Renal Biomarkers with Type 2 Diabetic Nephropathy Complications

Diabetes mellitus as the most prevalent metabolic disease is a multifactorial disease which is infuenced by environmental and genetic factors. In this systematic review, we assessed the association between genetic variants and diabetes/its complications in studies with Iraqi populations Conducted in this study was to investigate the possible role TCF7L2 rs7903146 (C/G) variant on susceptibility of T2DM among Iraqi type 2 diabetic patients with nephropathy complications and its relations with some type of kidney biomarkers. This case-control study included 100 T2DM patients and 100 patient with kidney failure 100 healthy person (control group). The results confrm the association between the TCF7L2 rs7903146 polymorphism and increase risk for type 2 diabetes in Iraqi an populations.

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver.

Background and AimsNonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance.MethodsWe performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at‐risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population‐based Dallas Heart Study (DHS).ResultsHepatic fat was epidemiologically associated with liver damage, insulin resistance, dyslipidemia and hypertension. The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation. Genetically determined hepatic fat was associated with aminotransferases, and with inflammation, ballooning and fibrosis in the LBC. Furthermore, in the LBC, the causal association between hepatic fat and fibrosis was independent of disease activity, suggesting that a causal effect of long‐term liver fat accumulation on liver disease is independent of inflammation. Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS. However, this association was dependent on liver damage severity. Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available databases.ConclusionThese data suggest that long‐term hepatic fat accumulation plays a causal role in the development of chronic liver disease.

Gas6 gene rs8191974 and Ap3s2 gene rs2028299 are associated with type 2 diabetes in the northern Chinese Han population

Previous studies in other countries have shown that single nucleotide polymorphisms (SNPs) in the growth arrest-specific gene 6 (Gas6; rs8191974) and adapter-related protein complex 3 subunit sigma-2 (Ap3s2; rs2028299) were associated with an increasedrisk for type 2 diabetes mellitus (T2DM). However, the association of these loci with T2DM has not been examined in Chinese populations. We performed a replication study to investigate the association of these susceptibility loci with T2DM in the Chinese population.We genotyped 1968 Chinese participants (996 with T2DM and 972controls) for rs8191974 in Gas6 and rs2028299 near Ap3s2, and examined their association with T2DM using a logistic regression analysis. We also analyzed the correlation of genotypes and clinical phenotypes. The distribution of the T allele of SNP rs8191974 in the Gas6 gene was significantly different between T2DM cases and controls when compared with the C allele (P<0.05, OR: 0.80, 95% CI: 0.69-0.94). The occurrence of the CT genotype and the dominant model was also significantly less frequent in the T2DM cases vs. controls when compared with the CC genotype (CT vs. CC: P<0.05, OR: 0.75, 95% CI:0.62-0.90; TT+CT vs. CC: P<0.05, OR:0.75, 95% CI:0.63-0.90). In SNP rs2028299, the allele C showed no statistically significant differencein distribution between the control and T2DM groups when compared with allele A. However, in male populations, the dominant model was statistically more frequent when compared with genotype AA (CC+CA vs. AA: P<0.05, OR:1.29, 95% CI:1.02-1.64), and in obesity-stratified analysis, we also observed a significant difference in the distribution of the dominant model between the T2DM cases and controls in subjects with BMI≥24 kg/m2 and BMI<28kg/m2 (CC+CA vs. AA: P<0.05, OR: 6.33, 95% CI:4.17-9.61). In conclusion, our study shows that SNPsrs8191974 and rs2028299 are significantly associated with T2DM in the Chinese population.

Systolic Blood Pressure and Risk of Type 2 Diabetes: A Mendelian Randomization Study.

Observational studies have shown that elevated systolic blood pressure (SBP) is associated with future onset of type 2 diabetes, but whether this association is causal is not known. We applied the Mendelian randomization framework to evaluate the causal hypothesis that elevated SBP increases risk for type 2 diabetes. We used 28 genetic variants associated with SBP and evaluated their impact on type 2 diabetes using a European-centric meta-analysis comprising 37,293 case and 125,686 control subjects. We found that elevation of SBP levels by 1 mmHg due to our genetic score was associated with a 2% increase in risk of type 2 diabetes (odds ratio 1.02, 95% CI 1.01–1.03, P = 9.05 × 10−5). To limit confounding, we constructed a second score based on 13 variants exclusively associated with SBP and found a similar increase in type 2 diabetes risk per 1 mmHg of genetic elevation in SBP (odds ratio 1.02, 95% CI 1.01–1.03, P = 1.48 × 10−3). Sensitivity analyses using multiple, alternative causal inference measures and simulation studies demonstrated consistent association, suggesting robustness of our primary observation. In line with previous reports from observational studies, we found that genetically elevated SBP was associated with increased risk for type 2 diabetes. Further work will be required to elucidate the biological mechanism and translational implications.

Metabolic Health Declining Among the Obese

Metabolic Health Declining Among the Obese

Exposure to Antipsychotics May Increase Risk of Type 2 Diabetes in Youth

Exposure to Antipsychotics May Increase Risk of Type 2 Diabetes in Youth

A null mutation in ANGPTL8 does not associate with either plasma glucose or type 2 diabetes in humans.

BackgroundExperiments in mice initially suggested a role for the protein angiopoietin-like 8 (ANGPTL8) in glucose homeostasis. However, subsequent experiments in model systems have challenged this proposed role. We sought to better understand the importance of ANGPTL8 in human glucose homeostasis by examining the association of a null mutation in ANGPTL8 with fasting glucose levels and risk for type 2 diabetes.MethodsA naturally-occurring null mutation in human ANGPTL8 (rs145464906; c.361C > T; p.Q121X) is carried by ~1 in 1000 individuals of European ancestry and is associated with higher levels of plasma high-density lipoprotein cholesterol, suggesting that this mutation has functional significance. We examined the association of p.Q121X with fasting glucose levels and risk for type 2 diabetes in up to 95,558 individuals (14,824 type 2 diabetics and 80,734 controls).ResultsWe found no significant association of p.Q121X with either fasting glucose or type 2 diabetes (p-value = 0.90 and 0.65, respectively). Given our sample sizes, we had >98 % power to detect at least a 0.23 mmol/L effect on plasma glucose and >95 % power to detect a 70 % increase in risk for type 2 diabetes.ConclusionDisruption of ANGPTL8 function in humans does not seem to have a large effect on measures of glucose tolerance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-016-0088-8) contains supplementary material, which is available to authorized users.

Marginal structural models for the estimation of the risk of Diabetes Mellitus in the presence of elevated depressive symptoms and antidepressant medication use in the Women's Health Initiative observational and clinical trial cohorts.

BackgroundWe evaluate the combined effect of the presence of elevated depressive symptoms and antidepressant medication use with respect to risk of type 2 diabetes among approximately 120,000 women enrolled in the Women’s Health Initiative (WHI), and compare several different statistical models appropriate for causal inference in non-randomized settings.MethodsData were analyzed for 52,326 women in the Women’s Health Initiative Clinical Trials (CT) Cohort and 68,169 women in the Observational Study (OS) Cohort after exclusions. We included follow-up to 2005, resulting in a median duration of 7.6 years of follow up after enrollment. Results from three multivariable Cox models were compared to those from marginal structural models that included time varying measures of antidepressant medication use, presence of elevated depressive symptoms and BMI, while adjusting for potential confounders including age, ethnicity, education, minutes of recreational physical activity per week, total energy intake, hormone therapy use, family history of diabetes and smoking status.ResultsOur results are consistent with previous studies examining the relationship of antidepressant medication use and risk of type 2 diabetes. All models showed a significant increase in diabetes risk for those taking antidepressants. The Cox Proportional Hazards models using baseline covariates showed the lowest increase in risk , with hazard ratios of 1.19 (95 % CI 1.06 – 1.35) and 1.14 (95 % CI 1.01 – 1.30) in the OS and CT, respectively. Hazard ratios from marginal structural models comparing antidepressant users to non-users were 1.35 (95 % CI 1.21 – 1.51) and 1.27 (95 % CI 1.13 – 1.43) in the WHI OS and CT, respectively – however, differences among estimates from traditional Cox models and marginal structural models were not statistically significant in both cohorts. One explanation suggests that time-dependent confounding was not a substantial factor in these data, however other explanations exist. Unadjusted Cox Proportional Hazards models showed that women with elevated depressive symptoms had a significant increase in diabetes risk that remained after adjustment for confounders. However, this association missed the threshold for statistical significance in propensity score adjusted and marginal structural models.ConclusionsResults from the multiple approaches provide further evidence of an increase in risk of type 2 diabetes for those on antidepressants.

Prevalence of the rs1801282 single nucleotide polymorphism of the PPARG gene in patients with metabolic syndrome.

This study aimed to get the genotypic and allelic frequencies of rs1801282 in 179 volunteer donors and 154 patients with Metabolic syndrome (MetS) in Brasilia, Brazil and also examine the association with anthropometric, biochemical and hemodynamic variables in the latter group. MetS comprises a group of diseases resulting from insulin resistance, in-creased risk of type 2 diabetes and atherosclerotic cardiovascular disease. MetS is defined by the presence of increased visceral fat, atherogenic dyslipidemia (elevated triglycerides (TGL)), with decreased high density lipoprotein (HDL) and increased low density lipoprotein (LDL) levels, hypertension (BPH) and disturbances in glucose homeostasis representing a significant burden across the world due to the alarming increase in the incidence over the last decades besides their significant morbidity and mortality. Peroxisome proliferator activated receptor-gamma (PPARg) has been mentioned as a candidate gene for determining the risk of MetS. It is a member of the nuclear receptors superfamily and a ligand-activated transcription factor, which regulates the expression of genes involved in the network lipogenesis and adipogenesis, insulin sensitivity, energy balance, inflammation, angiogenesis and atherosclerosis. Among the PPARG genetic variants, single nucleotide polymorphism rs1801282 has been the most extensively studied one since it was first described by Yen and cols. in 1997. This polymorphism is characterized by the replacement of a proline (CCC) to an alanine (GCA) at codon 12 of exon B, due to the exchange of a cytosine with a guanine. The Ala allele frequency varies in different ethnic groups. DNA was extracted using Chelex-100 method and determinations of genotypes were performed by allele-specific chain reaction. The distribution of genotype frequency of the MetS group was not statistically different from the frequency in the donor population at large. In the first group, genotype frequency was CC to 0.869 and 0.103 for CG, while allelic frequencies were 0.948 for C and 0.052 for G allele. In the group of donors, the genotype and allele frequencies were 0.882 for CC, 0.117 to CG; and 0.941 to 0.059 for G and C, respectively. GG genotype was not found in any of the two groups. The genotype distribution and allele frequencies were in Hardy-Weinberg equilibrium. No marker could be detected from the analysis of anthropometric, biochemical and hemodynamic variables in the MetS group. Our data suggest that this polymorphism is not correlated with predisposition to MetS. The results obtained on a small sample of the population of Brasilia, corroborate the data reported in the literature on the prevalence of this polymorphism in PPAR in populations of different ethnic origins.

Anti-inflammatory cytokines and type 2 diabetes

Compared with proinflammatory processes in the development of type 2 diabetes, our knowledge on anti-inflammatory cytokines is rather limited. Anti-inflammatory cytokines such as adiponectin, interleukin 1 receptor antagonist(IL-1RA), transforming growth factor-β1(TGF-β1), growth differentiation factor-15(GDF-15), omentin, and secreted frizzled-related protein 5 (SFRP5) are strongly associated with increased risk of type 2 diabetes: Adiponectin and omentin levels decreased before type 2 diabetes, in contrast, concentrations of IL-1RA, TGF-β1, GDF-15 are increased. Change of SFRP5 levels in impaired glucose tolerance and type 2 diabetes remains controversial. This paper will summarize and recommend studies that investigated associations between circulating levels of anti-inflammatory cytokines and type 2 diabetes. (Chin J Endocrinol Metab, 2015, 31: 375-378) Key words: Anti-inflammatory cytokines; Inflammatory; Diabetic mellitus, type 2

N-3 Fatty acids attenuate the risk of diabetes associated with elevated serum nonesterified fatty acids: the multi-ethnic study of atherosclerosis.

OBJECTIVEChronically high nonesterified fatty acids (NEFAs) are a marker of metabolic dysfunction and likely increase risk of type 2 diabetes. By comparison, n-3 fatty acids (FAs) have been shown to have various health benefits and may protect against disease development. In 5,697 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we examined whether serum levels of NEFAs relate to risk of incident type 2 diabetes and further tested whether plasma n-3 FA levels may interact with this relation.RESEARCH DESIGN AND METHODSNEFAs were measured in fasting serum using an enzymatic colorimetric assay and phospholipid n-3 FAs eicosapentaenoic and docosahexaenoic acids were determined in plasma through gas chromatography-flame ionization detection in 5,697 MESA participants. Cox proportional hazards regression evaluated the association between NEFA levels and incident type 2 diabetes and whether plasma n-3 FAs modified this association adjusting for age, sex, race, education, field center, smoking, and alcohol use.RESULTSOver a mean 11.4 years of the study period, higher diabetes incidence was found across successive NEFA quartiles (Q) (hazard ratio [95% CI]): Q1, 1.0; Q2, 1.35 (1.07, 1.71); Q3, 1.58 (1.24, 2.00); and Q4, 1.86 (1.45, 2.38) (Ptrend < 0.001). A significant interaction of n-3 FAs on the relation between NEFAs and type 2 diabetes was also observed (Pinteraction = 0.03). For individuals with lower n-3 levels (<75th percentile), a higher risk of type 2 diabetes was observed across quartiles of NEFAs: Q1, 1.0; Q2, 1.41 (1.07, 1.84); Q3, 1.77 (1.35, 2.31); and Q4, 2.18 (1.65, 2.88) (Ptrend < 0.001). No significant associations were observed in those with n-3 FAs ≥75th percentile (Ptrend = 0.54).CONCLUSIONSNEFAs are a marker of type 2 diabetes and may have clinical utility for detecting risk of its development. The modifying influence of n-3 FAs suggests a protective effect against disease and/or metabolic dysfunction related to NEFAs and requires further study.

The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil.

The aim of this study was to investigate the association between the rs7903146 (C/T) polymorphism in the TCF7L2 gene and type 2 diabetes mellitus, in a Southern-Brazilian population. The TCF7L2 rs7903146 polymorphism was genotyped in 953 type 2 diabetic patients and 535 non-diabetic subjects. All subjects were white. The polymorphism was genotyped by Real-Time PCR using TaqMan MGB probes (Life Technologies). Odds ratios (OR) and 95% confidence intervals (CI) were calculated for additive, recessive and dominant inheritance models. Genotype and allele frequencies of the rs7903146 polymorphism differed significantly between type 2 diabetic patients and non-diabetic subjects (P = 0.001 and P = 0.0001, respectively). The frequency of the minor allele was 38% in type 2 diabetes group and 31% in non-diabetic subjects, and this allele was significantly associated with type 2 diabetes risk (OR = 1.42, 95% CI 1.15 - 1.76 for the dominant model of inheritance). Moreover, the T/T genotype was associated with a higher risk for type 2 diabetes (OR = 1.83, 95% CI 1.3-2.5) than the presence of only one copy of the T allele (OR = 1.31, 95% CI 1.1-1.6). Both results were adjusted for age and gender. Our results confirm the association between the TCF7L2 rs7903146 polymorphism and increase risk for type 2 diabetes in Southern-Brazil.

Lifelong patterns of BMI and cardiovascular phenotype in individuals aged 60–64 years in the 1946 British birth cohort study: an epidemiological study

Excess body fat is associated with an increase in risk of type 2 diabetes and hypertension in adulthood and these risks can adversely affect progression of arterial disease. We aimed to assess the impact of lifelong patterns of adiposity on cardiovascular risk factors and carotid intima media thickness (cIMT) in later life in participants in the 1946 British birth cohort study. The National Survey of Health and Development Study was a nationally representative sample of 5362 singleton births to married parents in England, Scotland, and Wales, stratified by social class, during 1 week in March 1946. Our present study is based on the 60% of participants still alive and with a known present address in England, Scotland, or Wales who attended a clinic assessment after invitation aged 60-64 years. We included participants with lifetime adiposity measures, cardiovascular risk factors, and cIMT measured at 60-64 years. Participants were classified as normal weight or overweight or obese at each age (36, 43, 53, and 60-64 years) in adulthood, and childhood overweight was defined. Patterns of BMI change were identified and we used BMI to define adiposity status. We used multivariable linear regression to establish the cross-sectional association of BMI category at age 60-64 years with cIMT, adjusted for various confounders. We included 1273 (45%) of 2856 participants eligible in 2006-10 (at age 60-64 years) in this study. Compared with normal weight, overweight and obesity were associated with higher cIMT (0·029 mm, 95% CI 0·014-0·043) and systolic blood pressure (7·95 mm Hg, 5·86-10·0). Increased cIMT, systolic blood pressure, leptin, prevalence of diabetes, and reduced adiponectin were all associated with duration of exposure to adult adiposity (p<0·0001 for all). We noted little additional effect of childhood overweight. Individuals who dropped a BMI category in adulthood had lower cIMT (-0·034 mm, -0·056 to -0·013) and leptin concentrations (-0·4 ng/mL, -0·47 to -0·32), even when this change was not maintained, than did those who never lost weight. Longer exposure to high adiposity in adulthood had a cumulative adverse effect on cardiovascular phenotype in later life. Reductions in BMI category, even if not sustained, were associated with decreases in cIMT and improvements in cardiovascular risk-factor profile, suggesting that weight loss, at any age in adulthood, is worthwhile because it might result in long-term cardiovascular benefit. Medical Research Council and the British Heart Foundation.