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With a prevalence of 5-10% the polycystic ovary syndrome (PCOS) is a common disorder of premenopausal women. According to prospective studies abnormal glucose tolerance and diabetes mellitus present in about 10.0% and 35.0% of adult women with PCOS, respectively. PCOS patients have a higher prevalence of cardiovascular risk factors such as hypertension and dyslipidaemia. The rate of spontaneous abortions as well as the risk of developing gestational diabetes is increased in PCOS. Therefore, PCOS is not only a reproductive problem, but a complex endocrine disease with important health implications. The role of glucose metabolism in PCOS, the health consequences and possible interventions are reviewed in this article.

Type 2 diabetes mellitus is a major health problem associated with excess morbidity and mortality. Defects in the action and/or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes. The natural history of type 2 diabetes includes a preceding period of impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) which provides an opportunity for targeted intervention within large communities. As the prevalence of this metabolic disorder is rapidly increasing and current treatment fails to stabilise the disease in most patients, prevention should be considered as a key objective in the near future. Lifestyle intervention studies have consistently shown that quite modest changes can reduce the progression from IGT to diabetes by 50-60%. The Diabetes Prevention Program (DPP) randomised trial has shown that a combined program of weight loss, improvement of diet and increase of physical exercise lowers the risk for development of type 2 diabetes by 58% compared with placebo. It may, however, not be possible to translate these successful findings to larger cohorts or maintain the lifestyle changes longer term. This has lead to consideration of pharmacotherapy. Benefits have been found for metformin, acarbose and troglitazone. Treatment with metformin was less effective than lifestyle modifications, resulting in an average reduction of risk for development of type 2 diabetes by 31% compared with placebo. Similarly, acarbose in the STOP-NIDDM trial reduced the risk of developing type 2 diabetes in patients with IGT by 25%. Remarkably, cardiovascular event rates, in particular myocardial infarction, were significantly reduced when acarbose was used instead of placebo in subjects with glucose intolerance. The ACE inhibitors captopril (CAPPP) or ramipril (HOPE) and the Angiotensin-II receptor antagonist losartan (LIFE) have been shown to reduce the appearance of diabetes by one third when given to patients with hypertension. Since many hypertensive patients are insulin-resistant and have an increased risk in developing type 2 diabetes, the protective effect of these classes of antihypertensive drugs might be explained by their antiinsulin-resistance effects.

Peroxisome proliferator-activated receptor alpha and gamma (PPAR alpha, PPAR gamma) are nuclear transcription factors regulating gene expression in response to their ligands. Initially, PPARs were identified as regulators of gene expression in lipid metabolism and adipogenesis, but recent work has demonstrated PPAR expression in vascular cells and suggests antiinflammatory properties in the vasculature. Since PPAR alpha activators include lipid-lowering fibric acid derivatives and since PPAR gamma can be activated by antidiabetic thiazolidinediones, activation of these receptors might be an intriguing tool to influence atherogenesis in patients with vascular disease. However, there is also evidence that PPAR activators might furnish lesion development under certain circumstances. The following review will focus on these aspects of potential anti- or proatherogenic effects in the vessel wall and discuss potential clinical implications of these findings.

Dyslipoproteinemia associated with type 2 diabetes comprises hypertriglyceridemia caused by reduced insulin sensitivity, and consequently, low HDL levels and an increase in the proportion of small dense LDL particles. In addition, in both type 1 and 2 diabetes glycated LDL is formed in the presence of high plasma glucose levels. These lipoprotein disorders are all atherogenic and are responsible for the distinctly increased risk for cardiovascular disease in diabetics. Intensive glucose-lowering measures result in lower rates of micro- and macro-angiopathies in both types of diabetes. The benefit of additional lipid-lowering measures has not yet been confirmed by appropriate investigations. However, subgroup analyses from two large intervention trials do demonstrate that mortality from coronary heart disease may be substantially reduced. LDL cholesterol levels in diabetics should not exceed 115 mg/dl (3 mmol/l), and fasting triglycerides should be lower than 180 mg/dL (2 mmol/l).

The glitazones, also known as insulin sensitizers, represent a new concept in the treatment of type 2 diabetes. While previously available antidiabetics have no influence on an existing insulin resistance, the glitazones act directly on the receptors in the muscles, fatty tissue and liver, and in this way reduce insulin resistance. To date, three members of this group of substances are known: troglitazone, rosiglitazone and pioglitazone. In a study done to investigate pioglitazone, fasting blood sugar and HbA1c achieved virtually normal values, and lipid metabolism also improved. On the basis of the results of studies done to date, the tolerability of both pioglitazone and rosiglitazone is good. In contrast to troglitazone, no evidence has been found for a hepatotoxic effect. Insulin sensitizers do not cause hypoglycemia, since they do not stimulate the pancreas. They are suitable both for monotherapy and combination treatment with metformin, sulfonylureas and insulin.