Abstract
BackgroundPlasma total homocysteine (tHcy) is commonly elevated in persons with diabetes. This may be due to effects of insulin and/or glucose and/or metabolic control on the metabolism or plasma levels of tHcy. This study examined the effects of fasting plasma glucose status on fasting tHcy levels among adults without diabetes, and diabetes per se among adults with a self-report history of diabetes.MethodsAnalysis of data on adults (≥ 20y) who had fasted at least 8 hours, from the National Health and Nutrition Examination Survey (1999–2000 and 2001–2002). Subjects with no self-report history of diabetes were grouped according to fasting plasma glucose status as normal (< 100 mg/dL = NFG, n = 2,244), impaired (≥ 100 < 126 mg/dL = IFG, n = 1,108), or a provisional diagnosis of diabetes (≥ 126 mg/dL = DFG, n = 133). Subjects with a self-report history of diabetes (n = 275) were examined separately.ResultsFasting tHcy was higher (Ps < 0.01) among non-diabetic subjects with DFG and IFG, compared to NFG (median [95% confidence interval] = 8.6 [8.0–9.2], 8.3 [8.1–8.5], and 7.4 [7.3–7.5] μmol/L, respectively). Diabetic subjects had levels similar to non-diabetic subjects with DFG and IFG (8.3 [7.9–8.6] μmol/L). Age and estimated creatinine clearance were strong correlates of fasting tHcy among non-diabetic subjects (r = 0.38 to 0.44 and r = -0.35 to -0.46, respectively) and diabetic subjects (r = 0.41 and r = -0.46, respectively) (Ps < 0.001), while fasting glucose and glycohemoglobin (HbA1c) were weaker (but still significant) correlates of tHcy in non-diabetic and diabetic subjects. Fasting glucose status was not a significant independent predictor of fasting tHcy levels in non-diabetic subjects, and HbA1c was not a significant independent predictor of tHcy in diabetic subjects (Ps > 0.05).ConclusionFasting tHcy levels are elevated among non-diabetic adults with elevated fasting glucose levels, compared to persons with normal fasting glucose levels, and among diabetic adults. However, elevations in fasting tHcy appear to be mediated primarily by age and kidney function, and not by measures of glucose metabolism.
Highlights
Plasma total homocysteine is commonly elevated in persons with diabetes
In an early meta-analysis assessing the relationship between plasma total homocysteine and cardiovascular disease (CVD) [6], it was reported that elevated tHcy was strongly and independently related to several manifestations of CVD in the general population
In a large cohort of 50–75y men from the Netherlands [9], the risk for any CVD was increased with a parallel elevation in tHcy across subjects stratified by glucose tolerance – from normal glucose tolerance to impaired glucose tolerance to type 2 diabetes – even after adjustment for traditional CVD risk factors and serum creatinine
Summary
Plasma total homocysteine (tHcy) is commonly elevated in persons with diabetes. This may be due to effects of insulin and/or glucose and/or metabolic control on the metabolism or plasma levels of tHcy. In an early meta-analysis assessing the relationship between plasma total homocysteine (tHcy) and CVD [6], it was reported that elevated tHcy was strongly and independently related to several manifestations of CVD in the general population. In a prospective analysis of this cohort, elevated tHcy was related to 5-year mortality [10] and coronary events [11] in subjects with type 2 diabetes, independent of other CVD risk factors. In these studies, elevated tHcy was a stronger risk factor for CVD in diabetic than in nondiabetic individuals
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