Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis*. ANDREA DUNAIF. Pennsylvania State University ...Since the report by Burghen et al. (7) in 1980 that PCOS was associated with hyperinsulinemia, it has become clear that the syndrome has major metabolic as well as reproductive morbidities. The recognition of this association has also instigated extensive investigation of the relationship between insulin and gonadal function (1, 8 –11). This review will summarize our current understanding of insulin action in PCOS, address areas of controversy, and propose several hypotheses for this association. Abnormalities of steroidogenesis and gonadotropin release will not be discussed in detail; these changes have been reviewed recently by Erhmann and colleagues (12) and by Crowley (13), respectively. The association between a disorder of carbohydrate metabolism and hyperandrogenism was first described in 1921 by Achard and Thiers (14) and was called “the diabetes of bearded women (diabete des femmes a barbe).” The skin lesion, acanthosis nigricans, was reported to occur frequently in women with hyperandrogenism and diabetes mellitus by Kierland et al. (15) in 1947. Brown and Winkelmann (16) noted in 1968 that it was insulin-resistant diabetes mellitus, and a genetic basis was suggested by reports of affected sisters (17), including a pair of identical twins who also had acromegaloid features (18). Several additional syndromes with distinctive phenotypic features, acanthosis nigricans, hyperandrogenism, and insulin-resistant diabetes mellitus have been identified (Table 1)....

Insulin resistance is a condition that increases your chances of developing type 2 diabetes and heart disease. When you have insulin resistance, your body has problems responding to insulin. Eventually, your blood glucose (sugar) levels rise above normal. The good news is that cutting calories, adding physical activity to your daily routine, and losing weight can reverse insulin resistance and lessen your chances of getting type 2 diabetes and heart disease....Insulin’s job is to help the body use glucose for energy. It’s a hormone, one of the chemicals your body makes to help trigger or regulate processes in the body. Insulin is made by the pancreas, an organ located behind the lower part of the stomach. Your pancreas usually makes just the right amount of insulin to match the food you eat. Insulin acts as the doorman at the entrance to your cell. Food arrives at the door of a cell in the form of blood glucose. When your insulin is working effectively, it opens the door, just like a doorman. Then blood glucose enters the cell where it is used for energy....

Insulin Resistance and the. Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis1. Andrea Dunaif. Pennsylvania State University College ...Its etiology remains unknown. Although there have been no specific populationbased studies, a 5–10% prevalence of this disorder in women of reproductive age is probably a reasonable conservative estimate. This is based as an upper limit on studies of the prevalence of polycystic ovaries, which found that 20% of self-selected normal women had polycystic ovary morphology on ovarian ultrasound (3). Many of these women had subtle endocrine abnormalities (3). The lower estimate is based on the reported 3% prevalence rate of secondary amenorrhea for 3 or more months (4) and the fact that up to 75% of women with secondary amenorrhea will fulfill diagnostic criteria for PCOS (5). PCOS women can also have less profound disturbances in menstrual function (1, 3, 6). Since the report by Burghen et al. (7) in 1980 that PCOS was associated with hyperinsulinemia, it has become clear that the syndrome has major metabolic as well as reproductive morbidities. The recognition of this association has also instigated extensive investigation of the relationship between insulin and gonadal function (1, 8, 9, 10, 11). This review will summarize our current understanding of insulin action in PCOS, address areas of controversy, and propose several hypotheses for this association. Abnormalities of steroidogenesis and gonadotropin release will not be discussed in detail; these changes have been reviewed recently by Erhmann and colleagues (12) and by Crowley (13), respectively....

Insulin Resistance and Depressive Symptoms in Young Adult Males: Findings. From Finnish Military Conscripts. MARKKU TIMONEN, MD, PHD, ILKKA ...To investigate whether the association between insulin resistance (IR) and depressive symptoms is present already in young adult males. The association between IR and depression has been poorly studied, although the existence of a connection of Type II diabetes with depression is well established. We previously demonstrated at epidemiological level in two groups of men aged 31 years and 61 to 63 years that IR is linked with depressive symptoms. Methods: In a cross-sectional study, involving 1054 healthy Finnish male military conscripts of about 19 years of age, IR was defined through homeostasis model assessment (HOMA-IR). The severity of the depressive symptoms was evaluated through a Finnish modification of the 13-item Beck Depression Inventory (R-BDI). Moderate-to-severe depressive symptoms were said to be present, if the R-BDI score was Ն8, and mild depressive symptoms were present if the R-BDI score was 5 to 7. Results: After adjusting for confounders, moderate-to-severe depressive symptoms increased the risk for IR, as defined by the highest decile of the HOMA-IR, up to 2.8-fold (odds ratio ϭ 2.8; 1.2– 6.5). Mild depressive symptoms were not significantly associated with IR. ...

Insulin resistance has been proposed as a mediator of the association between risk factors for cardiovascular disease in the population. The clinical syndrome of glucocorticoid excess (Cushing’s syndrome) is associated with glucose intolerance, obesity and hypertension. By opposing the actions of insulin, glucocorticoids could contribute to insulin resistance and its association with other cardiovascular risk factors. In this review, we describe briefly the known mechanisms of insulin resistance and highlight the potential mechanisms for the effect of glucocorticoids. We then discuss factors which modulate the influence of glucocorticoids on insulin sensitivity ; this highlights a novel therapeutic strategy to manipulate glucocorticoid action which may prove to be a useful tool in treating subjects with insulin resistance. Finally, we describe evidence from human studies that glucocorticoids make an important contribution to the pathophysiology of insulin resistance in the population....