Obesity related insulin Resistance

 

Q .1 Most common cause Causes of anovulation in PCO : High insulin and high LH spoils the cyclicity of menstruation & ovulation

Patients with PCOS frequently exhibit insulin resistance and hyperinsulinemia. Insulin resistance and hyperinsulinemia participate in the ovarian steroidogenic dysfunction of PCOS. Insulin alters ovarian steroidogenesis independent of godadotropin secretion in PCOS. Insulin and insulin-like growth factor I (IGF-I) receptors are present I the ovarian stromal cells.

 

Q.2: How does insulin resistance put its teeth and nails in a cell ?  A specific defect in the early steps of insulin receptor-mediated signaling (diminished autophosphorylation) was identified in 50% of women with PCOS .Insulin has direct and indirect roles in the pathogenesis of hyperandrogenism in PCOS.

 

1.  Insulin in collaboration with LH enhances the androgen production of theca cells. Insulin inhibits the hepatic synthesis of sex hormone-binding globulin, the main circulating protein that binds to testosterone, thus increasing the proportion of unbound or bioavailable testosterone.

 

Q.3: What may be endocrine changes noticed after  6 months  metformin or Rosiglitazone therapy?? Ans : On subfertile women after  Met Ry or Rosiglitazone therapy suprisgly there is no significant changes in fasting plasma glucose or HbA (1C) or IGFBP-3 values. However, in both groups, fasting serum insulin, total T, free T, LH, DHEA-S, delta4A, and IGF-1 levels decreased significantly, and SHBG and IGFBP-1 exhibited significant increases.

 

Why insulin resistance occurs? Ill effects of obesity The most common cause of insulin resistance and compensatory hyperinsulinemia is obesity, but despite its frequent occurrence in PCOS, obesity alone does not explain this important association The insulin resistance associated with PCOS is not solely the result of hyperandrogenism based on the following:

Hyperinsulinemia is not a characteristic of hyperandrogenism in general but is uniquely associated with PCOS .

 

Q.5: Relation of  Obesity with IR? In obese women with PCOS, 30% to 45% have glucose intolerance or frank diabetes mellitus, whereas ovulatory hyperandrogenic women have normal insulin levels and glucose tolerance.

It seems that the associations between PCOS and obesity on the action of insulin are synergistic.

Suppression of ovarian steroidogenesis in women with PCOS with long-acting GnRH analogues does not change insulin levels or insulin resistance.

Oophoectomy in patients with hyperthecosis accompanied by hyperinsulinemia and hyperanodrogenemia does not change insulin resistance, despite a decrease in androgen levels .

Q. 8: What is acanthosis nigricans?? Acanthosis nigricans is a reliable marker of insulin resistance in hirsute women. This thickened, pigmented, velvety skin lesion is most often found in the vulva and may be present on the axilla, over nape of the neck, below the breast, and on the inner thigh The HAIR-AN syndrome consists of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) . These patients often have high testosterone levels (>150 ng/dL), fasting insulin levels of greater than 25 μIU/mL (normal <20 to 24 μIU/mL), and maximal serum insulin responses to glucose load (75 gm) exceeding 300 μIU/mL (normal is <160 μIU/m: at 2 hours postglucose load).