Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach

Abstract

BackgroundWe tested the hypothesis that elevated homocysteine (Hcy) level is causally associated with increased risk of type 2 diabetes mellitus (T2DM).ResultsThe 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 μmol/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 μmol/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 μmol/L increment in Hcy.ConclusionsOur findings provided strong evidence on the causal association of Hcy level with the development of T2DM.

Homocysteine, cysteine, folate and vitamin B12 status in type 2 diabetic patients with chronic kidney disease

“…Our study shows an increase of plasma tHcy in T2D-CKD patients. Our data support the recent meta-analysis and Mendelian randomization analysis performed among 4,011 cases and 4,303 controls, that revealed strong evidence for a causal association of Hcy level with the development of T2D [18]. Moreover, it has been reported that the status of plasma homocysteine is associated with both the risk and severity of nephropathy in T2D [19].…”

Sulfur amino acid metabolism in Zucker diabetic fatty rats

“…A recent meta-analysis and Mendelian randomization analysis performed among 4011 cases and 4303 controls provided a strong evidence for a causal association of homocysteine levels with the development of type 2 diabetes [3]. Homocysteine is an intermediate of the sulfur amino acid metabolic pathway.…”

Hyperhomocysteinaemia is associated with low plasma apolipoprotein AI levels in patients with impaired glucose tolerance

“…5 Patients with insulin resistance or type 2 diabetes often have HHcy. 6 Animal studies have shown that Hcy suppresses hepatic apoAI synthesis, and Hcy levels are negatively correlated with apoAI levels in male patients with coronary artery disease. 7 However, the associations between Hcy and apoAI levels in early-stage insulin resistance conditions, such as IGT, have not been well-characterized.…”