Correlates of total homocysteine plasma concentration in type 2 diabetes.
ABSTRACT Although well-defined in the general population, correlates of total homocysteine (tHcy) plasma concentration have not been sufficiently evaluated in diabetes. We investigated factors potentially associated with tHcy concentration in a cohort of type 2 diabetic subjects.
The common methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism, fasting tHcy, vitamin B12 and folate plasma levels were assessed in 312 diabetic subjects, whose clinical, metabolic and lifestyle information was also available.
The MTHFR genotype distribution was comparable to the Hardy-Weinberg equilibrium, with an overall TT homozygous frequency of 22%. Fasting tHcy concentration was significantly higher in men than in women (P < 0.001). Multivariate-adjusted tHcy concentration was significantly different across the quartiles of age (P < 0.001), folate (P = 0.01), vitamin B12 (P = 0.03), creatinine concentrations (P = 0.001) and smoking (P = 0.02). Overall, significant trends were noted for creatinine clearance (P for trend = 0.02) and systolic blood pressure (BP) (unadjusted P for trend = 0.01), whereas no differences were noted according to BMI, diastolic BP, presence of hypertension, and diabetes-related variables, such as diabetes duration, fasting glucose and glycated haemoglobin concentrations, current treatment and diabetes long-term complications. Total homocysteine levels significantly correlated with age, systolic BP, vitamin B12, creatinine and creatinine clearance, but only age, creatinine, folate and vitamin B12 levels were independently associated with tHcy concentration in stepwise regression analysis.
Age, creatinine, folate, vitamin B12, and to a minor extent, sex, smoking, TT genotype and systolic BP were significantly associated with Hcy plasma concentration in type 2 diabetes, whereas no significant associations were noted with diabetes-related variables.
Article: Hyperhomocysteinemia and elevated ox-LDL in Tunisian type 2 diabetic patients: role of genetic and dietary factors.[show abstract] [hide abstract]
ABSTRACT: Total plasma homocysteine (tHcy) is an emerging risk factor for the development of atherosclerosis. However, its relationship with diabetes is still unclear. We evaluated the association between tHcy levels and methylenetetrahydrofolate reductase (MTHFR) 677C-->T genotype in a type 2 diabetes mellitus (DM) population and their relationship with oxidized LDL (ox-LDL) according to dietary habits and vascular complications. Eighty-six DM patients were compared to 120 healthy volunteers. Associated higher tHcy levels and significantly higher ox-LDL levels (p<0.001) were found in DM patients compared to healthy subjects. Homozygosity for the T allele of MTHFR was more frequent in diabetics than in healthy subjects (12.8% vs. 7.2%) and it was associated with higher tHcy levels. Moreover, this elevated level was associated with significantly higher ox-LDL levels in DM patients with hypertension (p<0.05). Improving folate and vitamin C intakes could have beneficial effects on lowering the tHcy and ox-LDL levels. The interplay of genetic and dietary factors modulates the effect of homocysteine on cardiovascular risk factors.Clinical Biochemistry 10/2007; 40(13-14):1007-14. · 2.08 Impact Factor
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ABSTRACT: Previous studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes. This observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B12 status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 micromol/L (9.9 micromol/L; 15.9 micromol/L) versus 11.7 micromol/L (9.6 micromol/L; 14.5 micromol/L), P=0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 micromol/L (10.5 micromol/L; 16.7 micromol/L) in patients with diabetes versus 12.2 micromol/L (10.1 micromol/L; 15.2 micromol/L) in patients without diabetes, P=0.006] but not in those with a glomerular filtration rate > or = 90 mL/min [10.1 micromol/L (8.1 micromol/L; 12.4 micromol/L) versus 10.2 micromol/L (8.8 micromol/L; 12.3 micromol/L), P=0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P=0.342). Circulating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.Nutrition, metabolism, and cardiovascular diseases: NMCD 01/2008; 18(1):66-73. · 3.52 Impact Factor
Article: Age and kidney function are the primary correlates of fasting plasma total homocysteine levels in non-diabetic and diabetic adults. Results from the 1999-2002 National Health and Nutrition Examination Survey.[show abstract] [hide abstract]
ABSTRACT: 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. 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. Analysis of data on adults (> or = 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 (> or = 100 < 126 mg/dL = IFG, n = 1,108), or a provisional diagnosis of diabetes (> or = 126 mg/dL = DFG, n = 133). Subjects with a self-report history of diabetes (n = 275) were examined separately. Fasting 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] micromol/L, respectively). Diabetic subjects had levels similar to non-diabetic subjects with DFG and IFG (8.3 [7.9-8.6] micromol/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). Fasting 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.Nutrition & Metabolism 06/2005; 2:13. · 2.88 Impact Factor