Hyperandrogenism, Insulin Resistance and Hyperinsulinemia as Cardiovascular Risk Factors in Diabetes Mellitus

Abstract

The polycystic ovary syndrome (PCOS) and hyperandrogenism are some of the most common endocrine disorders in women of fertile age. Insulin resistance is present in a significant proportion of hyperandrogenic patients, yet also, impaired beta-cell function, even in absence of clinically evident glucose intolerance, is a frequent finding, especially in patients with familial history of type 2 diabetes mellitus. Therefore, it is not surprising that hyperandrogenism, PCOS, and disorders of carbohydrate metabolism are associated frequently. This association was first reported 75 years ago and, although the mechanisms responsible are not precisely understood, insulin resistance plays an important role in the development of both disorders. PCOS patients develop type 2 diabetes mellitus more frequently than non-hyperandrogenic women and, conversely, women with type 2 diabetes have a greater risk of having PCOS compared with the normal population. Although type 1 diabetes mellitus is a disease characterized by complete abolition of endogenous insulin secretion, a certain degree of hyperinsulinism may exist, resulting from the relatively excessive insulin doses needed to maintain a strict metabolic control. This exogenous hyperinsulinism may increase ovarian androgen secretion, and it has been reported that there is an increased prevalence of hyperandrogenic disorders in type 1 diabetic women. Considering that insulin resistance, hyperinsulinemia and androgen excess may collaborate in increasing the risk for CVD in these women, the identification of hyperandrogenic symptoms in diabetic women, and the identification of disorders of glucose tolerance in hyperandrogenic patients, may have important consequences for the correct management of these women.

Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review

“…In this review, all five studies reporting total daily insulin showed clinically significant reductions with a low-carbohydrate diet [ 8 , 10 , 22 , 24 , 26 ]. The excessive use of insulin that is often required to achieve glycaemic control in type 1 diabetes increases susceptibility to severe hypoglycaemia and may lead to some measure of hyperinsulinemia [ 29 ]. Hyperinsulinemia is associated with; excessive weight gain [ 30 ], development of the metabolic syndrome [ 31 ], inflammation and atherosclerosis [ 32 ], Alzheimer’s Disease [ 33 ] and cancer [ 34 ].…”

Increased mean glucose levels in patients with polycystic ovary syndrome and hyperandrogenemia as determined by continuous glucose monitoring

“…However, women with PCOS have more severe IR than weight‐matched women without PCOS, suggesting that factors in addition to obesity may be involved in the development of IR (15). In addition to genetic factors, hyperandrogenemia (HA), which is observed in up to 74.2% of Chinese PCOS patients (16), may also be associated with the development of T2DM in PCOS patients (17). Glucose metabolic disorders, such as IR, have been found in PCOS patients with HA (18).…”

Type 1 Diabetes Treatment beyond Insulin: Role of GLP-1 Analogs

“…1 There are several shortcomings of the current treatment strategies for type 1 diabetes. These are the following: (1) only one of the underlying disease processes (insulin deficiency) is addressed, whereas other pathophysiologic contributors, such as excess glucagon, are not; (2) the most “rapid”-acting insulin currently available still peak in activity too late to perfectly match the postprandial glycemic peak, so every meal consumed leads to postprandial glucose spikes; (3) the doses of exogenous insulin needed to maintain metabolic control are supraphysiologic and lead to systemic hyperinsulinemia, which can contribute to low-grade inflammation (IL-6 and tumor necrosis factor α), obesity, vascular dysfunction, and possibly malignancy 2–4 ; and (4) obesity is an increasing problem in type 1 diabetes, which insulin only propagates. 5,6 Currently, the only noninsulin medication approved for use in type 1 diabetes is pramlintide, which delays gastric emptying and reduces postprandial glucagon secretion.…”