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© 2003 by the American Diabetes Association, Inc.
Letters: Observations |
Homocysteinemia Is Not Changed by 3-Day Insulin-Induced Normoglycemia in Type 2 Diabetic Subjects
1 Laboratoire de Biochimie, Hôpital Haut-Lévêque, Pessac, France
2 Service de Nutrition et Diabétologie, Hôpital Haut-Lévêque, Pessac, France
Address correspondence to Marie-Christine Beauvieux, Laboratoire de Biochimie, Hôpital Haut-Lévêque, Avenue de Magellan, 33604 Pessac, France. E-mail: marie-christine.beauvieux{at}chu-bordeaux.fr
Diabetic patients have a two- to sixfold increase in the prevalence of cardiovascular diseases (CVDs) (1). Homocysteinemia is an independent risk factor for CVD (2). Genetic, age- and sex-related, nutritional, and hormonal factors leading to the abnormal regulation of homocysteinemia in diabetes play a role in CVD (3). The relation between homocysteinemia and cardiovascular morbidity remains unclear (4). Type 2 diabetes is the result of insulin resistance paired with a progressive loss of insulin secretion, and the resulting chronic hyperglycemia is associated with long-term CVD. In type 2 diabetes, a 3-day insulin-induced strict normoglycemia improves 1) postprandial carbohydrate oxidation evaluated by indirect calorimetry (5) and 2) parameters of erythrocytic lipoperoxidation, such as malondialdehyde and vitamin E (6). Few studies have analyzed the relation between type 2 diabetes and homocysteinemia in regard to metabolic control. We studied the effect of a short period of normoglycemia (72 h), induced by an adapted infusion of insulin, on homocysteinemia.
With informed consent, the study included 12 (7 men and 5 women; aged 58.10 ± 3.20 years and BMI 29.71 ± 0.97 kg/m2) poorly controlled (HbA1c 10.1 ± 0.5%) type 2 diabetic subjects without renal insufficiency (creatinemia 85.80 ± 4.20 µmol/l). Oral antidiabetic treatment was continued. No vitamin supplements were taken. The intravenous insulin infusion rate (by electric syringe) was adapted every 2 h to capillary glucose assessment (our objective was 5.5 mmol/l). Venous blood was collected for biochemical assays. Glycemia was 6.7 ± 0.5, 6.0 ± 0.6, and 5.5 ± 0.5 mmol/l after 24, 48, and 72 h insulin infusion, respectively. Plasma total homocysteinemia was measured by competitive immunoassay coupled with chemiluminescence (DPC-France, La-Garenne-Colombes, France) on blood centrifuged at 4°C without delay. An unpaired t test was performed between control and diabetic subjects; paired t test and a two-tailed test were used for values before and after the infusion (P < 0.05). At t = 0, homocysteinemia was 9.26 ± 1.46 µmol/l in diabetic subjects, which was not significantly different versus that of the control group at 6.77 ± 1.13 µmol/l (n = 7; aged 47 ± 3 years and BMI 23.0 ± 1.3 kg/m2). Homocysteinemia was also inversely correlated (r = 0.65) to glomerular filtration rate (Cockroft formula 97.10 ± 7.50 ml/min), as previously reported (7). At t = 0, no correlation was found between homocysteinemia and HbA1c (r = 0.24) or insulin resistance (r = 0.37) evaluated by homeostasis model assessment (8). The 3-day treatment decreased triglyceridemia (-0.5 mmol/l). The major finding is that homocysteinemia, when measured 24 h after the end of insulin infusion (with insulinemia returned to the initial value), was statistically unchanged versus that at t = 0 (10.26 ± 1.90 µmol/l).
Improved glucose control with similar insulin levels did not modify homocysteinemia in our study. Homocysteinemia could be unchanged because the period of strict normoglycemia was too short compared with several weeks in rats, in which insulin induced an increase in the activities of enzymes implicated in the conversion of homocysteinemia (9). However, this 72-h normoglycemia induces a significant effect on carbohydrate metabolism (5), and it leads to better glucose control after 3.5 years in 45% of a type 2 diabetic population (10). On the other hand, 3-h hyperinsulinemia decreases homocysteinemia in normal subjects but not in insulin-resistant diabetic subjects under a euglycemic clamp (11), suggesting that this is the contribution of insulin resistance rather than hyperglycemia. No correlation between homocysteinemia and the degree of metabolic control was reported (12). Therefore, our results mainly suggest that homocysteinemia is highly independent of glycemic control in type 2 diabetes.
References
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- Nehler MR, Taylor LM, Porter JM: Homocysteinemia as a risk factor for atherosclerosis: a review. Cardiovasc Surg 5:559–567, 1997[Medline]
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- Yeromenko Y, Lavie L, Levy Y: Homocysteine and cardiovascular risk in patients with diabetes mellitus. Nutr Metab Cardiovasc Dis 2:108–116, 2001
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- Peuchant E, Delmas-Beauvieux MC, Couchouron A, Dubourg L, Thomas MJ, Perromat A, Clerc M, Gin H: Short-term insulin therapy and normoglycemia: effects on erythrocytes lipid peroxidation in NIDDM patients. Diabetes Care 20:202–207, 1997[Abstract]
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[Abstract/Free Full Text]
- Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419, 1985[Medline]
- Gursu MF, Baydas G, Cikim G, Canatan H: Insulin increases homocysteine levels in a dose-dependent manner in diabetic rats. Arch Med Res 33:305–307, 2002[Medline]
- Dupuy O, Mayaudon H, Palou M, Sarret D, Bordier L, Bauduceau B: Optimized transient insulin infusion in uncontrolled type 2 diabetes: evaluation of a pragmatic attitude. Diabetes Metab 26:371–375, 2000[Medline]
- Fonseca VA, Mudaliar S, Schmidt B, Fink LM, Kern PA, Henry RR: Plasma homocysteine concentrations are regulated by acute hyperinsulinemia in nondiabetic but not type 2 diabetic subjects. Metabolism 47:686–689, 1998[Medline]
- Hoogeven EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CDA: Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol 18:133–138, 1998
[Abstract/Free Full Text]
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