Insulin sensitivity and plasma homocysteine concentrations in non-diabetic obese and normal weight subjects

Objective: To determine whether plasma homocysteine (tHcy) levels were related to insulin resistance and obesity in subjects without diabetes or vascular disease. Research design and methods: We studied correlates of plasma tHcy in 26 subjects covering a wide spectrum of obesity and insulin sensitivity (S_I). The measurement of in vivo insulin sensitivity was performed using the minimal model analysis of the frequently sampled intravenous glucose tolerance test (FSIVGTT). Results: There was no relationship between tHcy and body mass index. There was a significant relationship between plasma tHcy and S_I (r=0.53, P=0.006), demonstrating that the more insulin sensitive subjects had higher levels of tHcy. On log transformation of the plasma insulin values, log insulin correlated negatively with plasma tHcy (r=-0.47; P=0.02). None of the subjects were deficient in vitamin B₁₂ and folate. Plasma vitamin B₁₂ was significantly related to plasma tHcy (r=-0.44, P=0.017), although we found no significant relationship between plasma folate and tHcy (r=-0.21, P=0.27). S_I correlated significantly with vitamin B₁₂ (r=0.4, P=0.045) whereas, we found no significant relationship between S_I and plasma folate (r=0.27, P=0.2). On multiple linear regression using tHcy as the dependent variable, S_I and vitamin B₁₂ remained significant predictors of plasma tHcy, whereas, age and plasma folate were not predictors of tHcy. Conclusions: We conclude that in vitamin replete lean and obese individuals, insulin sensitivity correlates significantly with plasma tHcy. This relationship may need to be considered when evaluating the role of plasma homocysteine as a risk factor in patients with obesity and type 2 diabetes.