The pendulum swings from fear to understanding
Fasting glucose was reduced in the EPT part of WHI, as in the Postmenopausal Estrogen Progestin Intervention (PEPI) trial. But 2-hour glucose levels were elevated by hormone treatment in PEPI, and were not measured in the WHI. Many studies have shown that postprandial or post-challenge glucose is a stronger risk factor for cardiovascular disease than fasting hyperglycemia.
Could an elevated post-challenge glucose have played a role in the unexpected excess cardiovascular disease observed with hormone therapy in healthy women in WHI and with hormone therapy in women with documented coronary heart disease in the Heart and Estrogen/progestin Replacement Study (HERS)?
Will transdermal estrogen reduce both fasting and post-challenge glucose? These and other questions remain. (EBC)
Lifestyle changes work best
- This report raises the possibility but does not justify prescribing EPT for diabetes prevention.
Postmenopausal women randomized to EPT had a lower incidence of treated diabetes, by self-report, than women assigned to placebo: a 21% relative risk reduction over 3 years. At 1 year, a comparison of changes from baseline in estimated insulin resistance (HOMA model) in a subgroup indicated a significant reduction with EPT compared with placebo group, but no significant difference at 3 years.
Because of the far-reaching morbidity and mortality due to Type 2 diabetes, particularly from cardiovascular disease, prevention would have major benefits, but the authors acknowledge that this report does not justify prescribing this therapy for this purpose, given hazards previously reported in the WHI.
Still, we can bear in mind other means of reducing risk for diabetes. In the Diabetes Prevention Program,1metformin reduced type 2 diabetes risk by 31%, and a diet plus exercise program reduced it even more: by 58% over approximately 3 years of follow-up in high-risk persons. People at risk for diabetes should be counseled to make lifestyle changes that can reduce this risk far more, and more safely, than might EPT. (CGS)
Consider diabetes implications
- EPT can reduce the incidence of diabetes to the same degree as medications used for cardiovascular disease prevention.2
Growing evidence indicates that reducing insulin resistance in women can prevent onset of diabetes,3and that improving insulin resistance can slow the progression of atherosclerosis.4 Observational studies5—the Heart and Estrogen/progestin Replacement Study (HERS),6 and now the WHI—strongly indicate that EPT reduces the incidence of diabetes in postmenopausal women. Notably, HERS and WHI findings were with continuous-combined estrogen with progestin, the latter often viewed as antagonistic to the beneficial effects of estrogen on carbohydrate metabolism.) Diabetes is much more devastating in women, and more likely to strike. The risk (3,000 of 10,000) in postmenopausal women equals or exceeds that of postmenopausal breast cancer, coronary disease, or hip fracture.7The time has come to consider health and cost implications of long-term HT, especially in women with diabetes risk factors: age, obesity, high systolic BP, high nonfasting glucose, antihypertensive drug use, low HDL, or Hispanic or African-American ethnicity. Clinical trials confirming HT’s benefit add to the totality of evidence that the benefits outweigh the risks.8Since long-term effects (>10 years) reflect only observational data, we urgently need studies designed to understand long-term benefits and risks. (HNH)
1. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
2. Pepine CJ, Cooper-Dehoff RM. Cardiovascular therapies and risk for development of diabetes. J Am Coll Cardiol. 2004;44:509-512.
3. Buchanan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance inhigh risk Hispanic women. Diabetes. 2002;51:2796-2803.
4. Xiang AH, Peters RK, Kjos SL, et al. Effect of thiazolidinedione treatment on progression of subclinical atherosclerosis in premenopausal women at high risk for type 2 diabetes. J Clin Endocrinol Metab. 2005;90:1986-1991.
5. Manson JE, Rimm EB, Colditz GA, et al. A prospective study of postmenopausal estrogen therapy and subsequent incidence of non-insulin-dependent diabetes mellitus. Ann Epidemiol. 1992;2:665-673.
6. Kanaya AM, Herrington D, et al. Glycemic effects of postmenopausal hormone therapy: Heart and Estrogen/progestin Replacement Study. Randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138:1-9.
7. Narayan KMV, Boyle JP, et al. Lifetime risk for diabetes mellitus in the US. JAMA 2003;290:1884-1890.
