Metabolism. 2003 Jun;52(6):720-3.

Seghieri G, Breschi MC, Anichini R, De Bellis A, Alviggi L, Maida I, Franconi F. Department of Internal Medicine, Spedali Riuniti, Pistoia, Italy.

Serum homocysteine (sHcy) has been found to be elevated in patients with type 2 diabetes mellitus, as well as in other clinical conditions associated with insulin resistance and/or vascular diseases. The aims of this study were to measure the relationship between sHcy with biohumoral markers of insulin resistance in pregnant women affected with gestational diabetes mellitus (GDM).

We studied 2 groups of pregnant women categorized, after a 100-g, 3-hour oral glucose tolerance test (OGTT) as nondiabetic (n = 78) or affected with GDM (n = 15), by measuring sHcy, serum folate, albumin, vitamin B(12), uric acid, and lipids.

In both groups, peripheral insulin sensitivity was measured by using the OGTT-derived index of Matsuda and DeFronzo (ISI(OGTT)). Serum homocysteine was significantly higher in the group with GDM compared with nondiabetic women (5.88 +/- 2.26 micromol/L v 4.45 +/- 1.52 micromol/L; P =.003); was inversely related to serum folate (r = -.48; P =.0001), and was significantly related to serum albumin (r =.27; P =.009), 2-hour plasma glucose (r =.25; P =.01), as well as to serum uric acid (r =.23; P =.03). No relationship was observed between sHcy and serum vitamin B(12), serum triglycerides, total, or high-density lipoprotein (HDL) cholesterol, mean blood pressure and ISI(OGTT). Vitamin B(12) was correlated with ISI(OGTT) (r =.36; P =.0005) and inversely with mean blood pressure (r = -.24; P =.02). GDM remained significantly associated with higher sHcy concentrations also after adjusting for age, serum folate, albumin, uric acid, ISI(OGTT), and vitamin B(12) (P =.006).

In conclusion, we found that sHcy is significantly increased in women with GDM, independently of other confounding variables, is significantly related to 2-hour OGTT plasma glucose, and seems unrelated to insulin resistance in these subjects.

17. Variations in the lipid profile of patients with chronic renal failure, treated with folic acid.

Int J Vitam Nutr Res. 2003 May;73(3):215-20. de Gomez Dumm NT, Giammona AM, Touceda LA. Instituto de Investigaciones Bioquimicas de La Plata (INIBIOLP-CONICET-UNLP), Universidad Nacional de La Plata, 60 y 120, 1900, La Plata, Argentina. tacconi@atlas.med.unlp.edu.ar

Dyslipidemia and increases in plasma homocysteine usually occur at end-stage renal disease; both are recognized as risk factors for atherosclerosis. Folate administration reduces homocysteine concentration.

In this study we determined the effect of a high dose of folic acid (40 mg intravenous injection three times a week) on plasma and red blood cell lipid profiles in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (baseline) and after 21, 42, and 64 days of treatment.

Folic acid supplementation decreased plasma homocysteine. Plasma triglyceride levels decreased whereas polyunsaturated fatty acid values increased after 21 days; then they returned to baseline levels at the end of treatment. Total cholesterol and low-density lipoprotein (LDL) cholesterol were higher than those of the baseline during all the study, whereas high-density lipoprotein (HDL) cholesterol was reduced. In erythrocyte membranes, folic acid therapy enhanced cholesterol/phospholipid ratios and the fluorescence anisotropy of diphenyl-hexatriene.

We conclude that large doses of folic acid produce a favorable effect, reducing plasma homocysteine levels and protecting patients from atherosclerosis.

However, as this therapy induces significant alterations in both plasma and erythrocyte membrane lipid profiles, plasma lipid values should be controlled throughout the treatment of patients with renal failure.

18. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial.

Diabetologia. 2004 Jul 14 [Epub ahead of print]

Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, Bassford T, Burke G, Torrens J, Howard BV. Hennepin County Medical Center, Minneapolis, Minnesota, USA.

AIMS/HYPOTHESIS. Studies examining the effect of postmenopausal hormone therapy on concentrations of glucose, insulin and diabetes incidence have been inconclusive, in part because many of the studies were too small. We examined the effect of oestrogen plus progestin on diabetes incidence and insulin resistance.

METHODS. The study was a randomised, double-blind trial comparing the effect of daily 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up. The participants were 15,641 postmenopausal women enrolled in the Women's Health Initiative Hormone Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were measured in a random sample at baseline and at 1 and 3 years.

RESULTS. The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2% in the placebo group (hazard ratio 0.79, 95% CI 0.67-0.93, p=0.004). There was little change in the hazard ratio after adjustment for changes in BMI and waist circumference. During the first year of follow-up, changes in fasting glucose and insulin indicated a significant fall in insulin resistance in actively treated women compared to the control subjects (Year 1 to baseline between-group difference -0.22+/-0.10, p=0.03).

INTERPRETATIONS/CONCLUSION. These data suggest that combined therapy with oestrogen and progestin reduces the incidence of diabetes, possibly mediated by a decrease in insulin resistance unrelated to body size. Future studies of alternative postmenopausal hormone therapy regimens and selective oestrogen agonists and/or antagonists should consider the effects of these regimens on insulin resistance and diabetes.

19. Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebo-controlled trial.

Ann Intern Med. 2003 Jan 7;138(1):1-9.

Comment in: ACP J Club. 2003 Sep-Oct;139(2):39. Ann Intern Med. 2003 Dec 16;139(12):1043-4; author reply 1044. Ann Intern Med. 2003 Dec 16;139(12):1043; author reply 1044. Ann Intern Med. 2003 Dec 16;139(12):1043; author reply 1044. Ann Intern Med. 2003 Jan 7;138(1):69-70. Summary for patients in: Ann Intern Med. 2003 Jan 7;138(1):I10.

Kanaya AM, Herrington D, Vittinghoff E, Lin F, Grady D, Bittner V, Cauley JA, Barrett-Connor E; Heart and Estrogen/progestin Replacement Study. Division of General Internal Medicine, University of California, San Francisco, 1701 Divisadero Street, Suite 536, San Francisco, CA 94143-1732, USA. alkak@itsa.ucsf.edu

BACKGROUND: Randomized trials of postmenopausal hormone therapy have found differing effects on fasting glucose levels. No trial has evaluated the effect of hormone therapy on diabetes incidence.

OBJECTIVE: To evaluate the effect of hormone therapy on fasting glucose level and incident diabetes. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 20 U.S. clinical centers.

PARTICIPANTS: 2763 postmenopausal women with coronary heart disease who were followed for 4.1 years. At baseline, 734 women had diabetes, 218 women had impaired fasting glucose, and 1811 women were normoglycemic; the 2029 women without diabetes were followed for incident diabetes. INTERVENTION: 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate daily, or placebo.

MEASUREMENTS: Fasting glucose level was measured at baseline, at year 1, and at the end of the trial. Incident diabetes was defined by self-report of diabetes or disease complication, fasting glucose level of 6.9 mmol/L or greater (> or =126 mg/dL), or initiation of therapy with diabetes medication.

RESULTS: Fasting glucose levels increased significantly among women assigned to placebo but did not change among women receiving hormone therapy. The incidence of diabetes was 6.2% in the hormone therapy group and 9.5% in the placebo group (relative hazard, 0.65 [95% CI, 0.48 to 0.89]; P = 0.006). The number needed to treat for benefit to prevent one case of diabetes was 30 (CI, 18 to 103). Changes in weight and waist circumference did not mediate this effect.