Plasma Homocysteine Concentrations in Young Individuals at Increased Risk of Type 2 Diabetes are Associated with Subtle Differences in Glomerular Filtration Rate but Not with Insulin Resistance

Introduction

Plasma homocysteine levels are elevated in type 2 diabetics ([Araki et al., 1993]; [Buysschaert et al., 2000]; [Emoto et al., 2001]) and it is believed that this factor contributes to the increase of cardiovascular risk and mortality in these patients ([Hoogeveen et al., 2000]; [Kark et al., 1999]), that is already 2 to 4 times higher than in nondiabetic subjects ([Panzram, 1987]).

Several studies suggest a positive association between insulin resistance, a principal underlying defect in the development of type 2 diabetes ([Reaven, 1984]), and hyperhomocysteinemia. In animal studies, induced hyperinsulinemia or insulin resistance led to increased homocysteine levels ([Fonseca et al., 2000]). However, in humans, the data on the correlation between homocysteine concentrations and insulin sensitivity is conflicting ([Giltay et al., 1998]; [Fonseca et al., 2003]; [Abbasi et al., 1999]; [Godsland et al., 2001]).

To analyze the association between hyperhomocysteinemia and insulin resistance, we performed a cross sectional study with a total of 839 subjects with an increased risk for type 2 diabetes due to a positive family history of diabetes, a history of gestational diabetes, or overweight (BMI > 25 kg/m²). To differentiate from effects induced by hyperglycemia itself we excluded subjects with type 2 diabetes and furthermore, individuals with preexisting kidney disease from the study.

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1 * These authors contributed equally to this article.