Risk Of To Type 2 Diabetes Mellitus Research Articles

Association of the C242T polymorphism in the NAD(P)H oxidase P22 phox gene with type 2 diabetes mellitus risk: a meta-analysis

Objectives:A number of epidemiological studies have explored the association between NAD(P)H oxidase P22 phox gene C242T (rs4673) polymorphism and susceptibility to type 2 diabetes mellitus (T2DM), but the results are still debatable. Therefore, we conducted a meta-analysis to assess the potential association between the NAD(P)H oxidase P22 phox gene C242T polymorphism and T2DM risk.Methods:Electronic literature searches of the PubMed, Embase, Web of Science, CBMdisc, CNKI and Google Scholar were performed up to June 15, 2013. Additionally, hand searching of the references of identified articles was performed. Data analyses were carried out by Stata 11.0.Results:Seven studies were included in the final meta-analysis, covering a total of 1661 T2DM cases and 1265 controls. The results showed evidence for significant association between the NAD(P)H oxidase P22 phox gene C242T polymorphism and T2DM risk (for T/T vs. T/C: OR = 1.61, 95% CI = 1.14–2.26, p = 0.007; for T/T vs. T/C + C/C: OR = 1.50, 95% CI = 1.10–2.05, p = 0.009). In the subgroup analysis, there was also evidence for significant association between the NAD(P)H oxidase P22 phox gene C242T polymorphism and T2DM risk, either for Asians (T/T vs. T/C + C/C: OR = 1.74, 95% CI = 1.15–2.64, p = 0.009) or for non-Asians (for T allele vs C allele: OR = 1.30, 95% CI = 1.04–1.61, p = 0.02).Conclusions:The present meta-analysis indicates that the NAD(P)H oxidase P22 phox gene 242 T allele might be associated with an increased T2DM risk.

Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies

Coffee and caffeine have been linked to type 2 diabetes mellitus (T2DM). A dose-response meta-analysis of prospective studies was conducted to assess the association between coffee and caffeine intake and T2DM incidence. Pertinent studies were identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled measure was selected based on between-study heterogeneity. Dose-response relationship was assessed by restricted cubic spline. Compared with the lowest level, the pooled relative risk (95 % CI) of T2DM was 0.71 (0.67-0.76) for the highest level of coffee intake (26 articles involving 50,595 T2DM cases and 1,096,647 participants), 0.79 (0.69-0.91) for the highest level of decaffeinated coffee intake (10 articles involving 29,165 T2DM cases and 491,485 participants) and 0.70 (0.65-0.75) for the highest level of caffeine intake (6 articles involving 9,302 T2DM cases and 321,960 participants). The association of coffee, decaffeinated coffee and caffeine intake with T2DM incidence was stronger for women than that for men. A stronger association of coffee intake with T2DM incidence was found for non-smokers and subjects with body mass index <25 kg/m(2). Dose-response analysis suggested that incidence of T2DM decreased by 12 % [0.88 (0.86-0.90)] for every 2 cups/day increment in coffee intake, 11 % [0.89 (0.82-0.98)] for every 2 cups/day increment in decaffeinated coffee intake and 14 % [0.86 (0.82-0.91)] for every 200 mg/day increment in caffeine intake. Coffee and caffeine intake might significantly reduce the incidence of T2DM.

The HindIII polymorphism in the lipoprotein lipase gene predicts type 2 diabetes risk among Chinese adults

Objective We aimed to investigate the polymorphism HindIII of the lipoprotein lipase (LPL) gene to explore whether it had a potential role in susceptibility to type 2 diabetes mellitus (T2DM) among Han Chinese, and whether this effect was influenced by regulating LPL or other risk factors. Methods Overall, 654 Han Chinese adults were selected from a community-based cross-sectional study using a stratified cluster random sampling. Genotyping was performed using the PCR–RFLP technique, and the metabolic variables were measured using standard methods. Results Individuals with the HindIII H−/H− genotype tended to have higher pre-heparin LPL (PrLPL) and lower triglyceride levels but an unexpected higher prevalence of T2DM compared with the H+/H+ genotype carriers. The association between the H−/H− genotype and T2DM risk remained unchanged across all subgroups of lipids/glucose-related RF. In a recessive model, the H−/H− genotype conferred a 2.12-fold increased risk [odds ratio (OR): 3.12; 95% confidence interval (CI): 1.18–8.27] for T2DM after controlling for age and sex, and increased further after additionally adjusting for traditional RFs, and PrLPL (OR = 4.45; 95% CI = 1.51–13.07). Conclusions This study indicated that Chinese adults with the LPL gene HindIII H−/H− genotype had a significantly increased risk of T2DM, even if they had favorable lipid profiles.

Coffee consumption is inversely associated with type 2 diabetes in Chinese

Coffee consumption has been shown to be inversely associated to type 2 diabetes mellitus (T2DM), but evidence in Chinese populations is limited. We investigated the relationship between coffee consumption and T2DM in a population-based cohort of middle-aged Chinese. We studied 2332 subjects who participated in the Taichung Community Health Study in Taiwan in 2004. The relationships between coffee consumption, T2DM and fasting glucose were assessed. The prevalence of T2DM was 14·0% and 10·4% in men and women. After adjustment for age, body mass index, blood pressure, smoking, alcohol drinking, betel nut chewing, physical activity, income, education level, fat%, protein%, carbohydrate% and magnesium, coffee intake was inversely associated with T2DM. Habitual coffee drinkers had 38-46% lower risk of T2DM than nondrinkers. Compared to nondrinkers, the adjusted odds ratios (ORs) for T2DM according to subjects with habitual coffee consumption (<1, 1-6, ≥7 times per week) were 0·77 (0·52-1·13), 0·46 (0·28-0·76) and 0·37 (0·16-0·83), respectively. The decreasing ORs indicate a dose-response effect of coffee consumption on the likelihood of having T2DM (P<0·001). A similar relationship was also evident in newly diagnosed T2DM (P<0·05). The adjusted mean fasting glucose levels gradually decreased as the frequency of coffee consumption increased (P<0·05). Coffee intake is inversely associated with T2DM in Chinese. Coffee may be a protective agent for T2DM in Chinese.

R1467H Variants of Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) are Associated with Type 2 Diabetes Mellitus in Koreans

BackgroundThe human Rho guanine nucleotide exchange factor 11 (ARHGEF11) functions as an activator of Rho GTPases and is thought to influence insulin signaling. The R1467H variant of ARHGEF11 has been reported to be associated with susceptibility to type 2 diabetes mellitus (T2DM) in Western populations.MethodsWe investigated the effects of the R1467H variant on susceptibility to T2DM as well as related traits in a Korean population. We genotyped the R1467H (rs945508) of ARHGEF11 in 689 unrelated T2DM patients and 249 non-diabetic individuals and compared the clinical and biochemical characteristics according to different alleles.ResultsThe H allele was significantly more frequent in T2DM cases than in controls (P = 0.037, 17.1% and 13.1%; respectively). H homozygocity was associated with a higher risk of T2DM compared to those with R/R or R/H genotype (odds ratio, 5.24; 95% confidence interval, 1.06 to 25.83; P = 0.042). The fasting plasma glucose, HbA1c, fasting insulin, HOMA2-IR and HOMA2-%β levels did not differ significantly between different genotypes.ConclusionOur study replicated associations of the ARHGEF11 polymorphism with increased risk of T2DM in a Korean population and thus supports previous data implicating a potential role of ARHGEF11 in the etiology of T2DM. Further studies revealing the underlying mechanism for this association are needed.

Joint analysis of individual participants’ data from 17 studies on the association of the IL6 variant -174G>C with circulating glucose levels, interleukin-6 levels, and body mass index

Background. Several studies have investigated associations between the -174G>C single nucleotide polymorphism (rs1800795) of the IL6 gene and phenotypes related to type 2 diabetes mellitus (T2DM) but presented inconsistent results.Aims. This joint analysis aimed to clarify whether IL6 -174G>C was associated with glucose and circulating interleukin-6 concentrations as well as body mass index (BMI).Methods. Individual-level data from all studies of the IL6-T2DM consortium on Caucasian subjects with available BMI were collected. As study-specific estimates did not show heterogeneity (P>0.1), they were combined by using the inverse-variance fixed-effect model.Results. The main analysis included 9440, 7398, 24,117, or 5659 non-diabetic and manifest T2DM subjects for fasting glucose, 2-hour glucose, BMI, or circulating interleukin-6 levels, respectively. IL6 -174 C-allele carriers had significantly lower fasting glucose (−0.091 mmol/L, P=0.014). There was no evidence for association between IL6 -174G>C and BMI or interleukin-6 levels, except in some subgroups.Conclusions. Our data suggest that C-allele carriers of the IL6 -174G>C polymorphism have lower fasting glucose levels on average, which substantiates previous findings of decreased T2DM risk of these subjects.

Association of calpain-10 polymorphisms with type 2 diabetes in the Tunisian population

Background Genome-wide analyses of the genetic predisposition to type 2 diabetes mellitus (T2DM) in different isolates and populations have identified regions of interest called non insulin-dependent diabetes mellitus (NIDDM) 1, 2, 3 and 4. At the NIDDM1 locus (2q37.3), calpain-10 ( CAPN10) encodes for a ubiquitously expressed protease implicated in the two fundamental pathophysiological aspects of T2DM. This is a report of the results of a study of the association of four CAPN10 polymorphisms with T2DM in the Tunisian population. Participants and methods A total of 222 T2DM patients with a diabetes duration of 10 years or more and 206 healthy controls were enrolled to analyze the frequency distribution of four CAPN10 polymorphisms (UCSNP-43, UCSNP-19, UCSNP-110 and UCSNP-63) using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) in the Tunisian population. We also investigated the association of T2DM with different haplotypes and haplotype combinations. Results Only the A allele of UCSNP-43 showed an association with T2DM (odds ratio, OR = 1.86). We also identified a novel combination of haplotypes (121/221) defined by three polymorphisms (UCNSP-43, -19 and -63) that is associated with an increased risk of T2DM (OR = 2.38). Conclusion In this study involving the Tunisian population, we identified genetic variants within CAPN10 that are linked with T2DM and a novel haplotype combination, 121/221, associated with an increased susceptibility to T2DM.

Low-glycaemic diets and health: implications for obesity

The present review considers the background to terminology that relates foods, glycaemia and health, including 'available carbohydrate', 'glycaemic index' (GI), 'glycaemic glucose equivalent', 'glycaemic response index' and 'net carbohydrate', and concludes that central to each of these terms is 'glycaemic load' (GL). GL represents the acute increase in exposure of tissue to glucose determined by foods; it is expressed in ingested glucose equivalents (per 100 g fresh weight or per serving), and is regarded as independent of the state of glucose metabolism from normal to type 2 diabetes mellitus (T2DM). Ad libitum studies in overweight or obese adults and children show that low-GL diets are associated with marked weight benefits, loss of adiposity and reduced food intake. Weight benefits appear on low-glycaemic v. high-glycaemic available carbohydrates, unavailable v. available carbohydrates and protein v. available carbohydrate. Energy intake immediately after lowering of meal GL via carbohydrate exchanges is apparent only after a threshold cumulative intake of >2000 MJ. Various epidemiological and interventional studies are discussed. A relationship between GL and the development of T2DM and CHD is evident. Studies that at first seem conflicting are actually consistent when data are overlaid, such that diets with a GL of >120 glucose equivalents/d would appear to be inadvisable. Whereas certain studies might place GI as being slightly stronger than GL in relation to T2DM risk, this situation appears to be associated with observations in a lower range of GL or when the range of GI is too narrow for accuracy; nevertheless, authors emphasise the importance of GL. Among the studies reviewed, GL offers a better or stronger explanation than GI in various observations including body weight, T2DM in nurses, CHD, plasma triacylglycerols, HDL-cholesterol, high-sensitivity C-reactive protein and protein glycation. Where information is available, the associations between risk factors and GL are either similar or stronger in the overweight or obese, as judged by BMI, and apply to both body weight and blood risk factors. The implications tend to favour a long-term benefit of reducing GL, for which further study is necessary to eliminate any possibility of publication bias and to establish results in clinical trials with overweight and obese patients.