Overt non-insulin-dependent diabetes mellitus (NIDDM) is the end of a continuum in metabolic insulin resistance with decreasing compensation by insulin production from the beta cell [1]. Risk factors for ischaemic heart disease, the most importance cause of death and disability in elderly patients with diabetes, like carbohydrate intolerance or manifest diabetes, visceral obesity, hypertriglyceridaemia [2], low HDL-cholesterol content in plasma [3] and hypertension [2] are often clustered in a more or less complete profile of interdependent metabolic abnormalities, called the insulin resistance syndrome [4]. The balance between coagulation and fibrinolysis is intimately linked with this profile [5][6][7]. In patients with NIDDM the cardiovascular risk is increased 2 Diabetologia (1997) b -estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA 1c ), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA 1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol-and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL 2 -cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary. [Diabetologia (1997) 40: 843-849] Keywords Oestrogen therapy, non-insulin-dependent diabetes mellitus, glucose regulation, insulin sensitivity, hepatic glucose production, lipoprotein profiles, coagulation factors, fibrinolysis.Received: 12 November 1996 and in revised form: 21 March 1997Corresponding author: H. E. Brussaard, M. D., Virga Jesse Hospital, Stadsomvaart 11, B-3500 Hasselt, Belgium Abbreviations: Apo A1 and apo B, Apolipoprotein A1 and B; ERT, oestrogen replacement therapy; FSH, follicle stimulating hormone; HDL-chol, high density cholesterol; HGP 1 and HGP 2 , hepatic glucose production basal (first step) and second step; HGP suppr , suppression of HGP from the first to the second step; LDL-chol, low-density cholesterol; LH, luteinising hormone; NEFA, non-esterified fatty acids; NEFA suppr , percentage suppression of NEFA from the first to the second step; t-PA-ag, tissue type plasminogen activator antigen; PAI-1, plasminogen activator inhibitor; VLDL-TG, very low density ...

In type II diabetes mellitus the altered hormonal state after menopause may represent an additional cardiovascular risk factor. Estrogen replacement therapy (ERT) is associated with a decreased cardiovascular risk, at least in nondiabetic postmenopausal women. We studied the effect of ERT on plasma lipids and lipoproteins and on LDL oxidation in 40 postmenopausal women with type II diabetes but with minimal vascular complications in a randomized placebo-controlled trial. Twenty patients were treated orally with 2 mg/d micronized 17 beta-estradiol and 20 patients with placebo for 6 weeks. Plasma total cholesterol (-6%, P = .04), LDL cholesterol (-16%, P = .0001), and apoB (-11%, P = .001) levels decreased and HDL cholesterol (20%, P = .0001) and apoA-I (14%, P = .0001) levels increased after ERT compared with placebo. Glycated hemoglobin (HbA1c) decreased significantly after ERT (-3%, P = .03), the cholesterol content of the LDL particles decreased (-5%, P = .006), triglyceride content increased (16%, P = .01), and LDL particle size did not change significantly. ERT had no effect on parameters of LDL oxidation. We conclude that plasma levels of HDL cholesterol, apoA-I, LDL cholesterol, apoB, and glycated hemoglobin are improved in postmenopausal women with type II diabetes mellitus after treatment with 17 beta-estradiol, indicative of a better metabolic control, and that ERT has no effect on LDL oxidizability.

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