Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study.
ABSTRACT The role of hyperhomocysteinemia as a risk factor for diabetic long-term complications has not been sufficiently evaluated in prospective studies, considering specific correlates of homocysteine (tHcy) concentration and traditional cardiovascular disease (CVD) risk factors. Fasting tHcy, vitamin B12 and folate plasma levels, the common methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, as well as clinical and lifestyle information were assessed in 216 type 2 diabetic patients attending two outpatient clinics, who had a follow-up evaluation at 65 ± 9 months for the incidence of macroangiopathy. At basal evaluation, mild hyperhomocysteinemia (tHcy ≥ 15 μmol/l) was diagnosed in 21.3% of participants. At follow-up, hyperhomocysteinemia and the distribution of MTHFR C677T genotype did not significantly differ according to the incidence of macroangiopathy. Multiple variables adjusted ORs (95% CI) for CVD associated with mild hyperhomocysteinemia were 1.01 (0.37-2.82); P > 0.05; those associated with MTHFR TT genotype were 0.46 (0.15-1.38); P > 0.05. Although the prevalence of hyperhomocysteinemia was higher in diabetic men (26.9%) than in women (16.1%; P > 0.05), similar results were also observed in a separate sex-analysis. At the multivariate analysis, including in the model other potential CVD risk factors, only creatinine clearance was a significant risk factor for the development of macroangiopathy. In this cohort of diabetic subjects, mild hyperhomocysteinemia and the MTHFR TT genotype are not significant risk factors for the development of macroangiopathy; impaired renal function was confirmed as a significant predictor of this complication.
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ABSTRACT: Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR = 0.78 (95% CI = 0.67-0.92), P = 0.003) and was also associated with 2 h postload plasma glucose (P = 0.04), high-density lipoprotein cholesterol (P = 0.004), and total cholesterol (P = 0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.Experimental Diabetes Research 01/2012; 2012:960318. · 3.54 Impact Factor
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ABSTRACT: Background The relationship between homocysteine (Hcy) and diabetic retinopathy (DR) remains unclear to date. Therefore, a systematic review and meta-analysis was performed on the relationship between Hcy level and DR.Methods Studies were identified by searching PubMed, Embase, and Web of Science databases until 5 May, 2014.ResultsA total of 31 studies involving 6,394 participants were included in the meta-analysis. After pooling the data from each included study, the blood Hcy concentration in the DR group was observed to be higher than that in the control group [WMD¿=¿2.55; 95% confidence interval (CI), 1.70¿3.40], and diabetes mellitus (DM) patients with hyperhomocysteinemia were at a risk for DR [odds ratio (OR)¿=¿1.93; 95% CI, 1.46¿2.53]. Considering the different DM types, hyperhomocysteinemia in T1DM (OR¿=¿1.83, 95% CI, 1.28¿2.62) was associated with DR rather than in T2DM (OR¿=¿1.59, 95% CI, 0.72¿3.51). Considerable statistical heterogeneity in the overall summary estimates was partly explained by the geographical differences.Conclusions Results from this current meta-analysis indicate that hyperhomocysteinemia is a risk factor for DR, especially proliferative DR. Differences between geographical regions were observed in the relationship between hyperhomocysteinemia with T1DM risk. Given the heterogeneous results, the relationship between high Hcy and DR needs further investigation.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_167.Diagnostic Pathology 09/2014; 9(1):167. · 2.41 Impact Factor
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ABSTRACT: We tested the hypothesis that elevated homocysteine (Hcy) level is causally associated with increased risk of type 2 diabetes mellitus (T2DM). The meta-analysis and Mendelian randomization analysis were performed among 4011 cases and 4303 controls. The absolute pooled mean Hcy concentration in subjects with MTHFR 677TT was 5.55 mumol/L (95% CI, 1.33 to 9.77) greater than that in subjects with MTHFR 677CC in T2DM. Overall, the T allele of the MTHFR 677 C > T conferred a greater risk for T2DM [Random effect (RE) OR = 1.31(1.17-1.64), I2 = 41.0%, p = 0.055]. The random effect (RE) pooled OR associated with T2DM for MTHFR 677TT relative to the 677CC was [RE OR = 1.38(1.18-1.62)]. The fixed-effect pooled OR of the association for the MTHFR 677 TT vs CT was 1.29 (95% CI, 1.09-1.51). MTHFR 677 TT showed a significantly higher risk for T2DM compared with MTHFR 677 CC + CT [Fixed effect (FE) OR = 1.32(1.14-1.54), I2 = 0.0%, p = 0.686]. The absolute pooled mean Hcy concentration in individuals with T2DM was 0.94 mumol/L (95% CI, 0.40-1.48) greater than that in control subjects. The estimated causal OR associated with T2DM was 1.29 for 5 mumol/L increment in Hcy. Our findings provided strong evidence on the causal association of Hcy level with the development of T2DM.BMC Genomics 12/2013; 14(1):867. · 4.04 Impact Factor