Familial Diabetes in Obese PCOS Predisposes Individuals to Compensatory Hyperinsulinemia and Insulin Resistance (IR) Also for Reduced Hepatic Insulin Extraction (HIE)

Abstract

Background: Polycystic ovary syndrome (PCOS) is a frequent reproductive disease characterized by hyperandrogenism, oligo /anovulation, and polycystic aspects at ultrasound. In these last years, a body of evidence disclosed the frequent occurrence in PCOS patients of insulin resistance (IR) and compensatory hyperinsulinemia. Aim: To evaluate whether any relationship exists between IR, compensatory hyperinsulinemia and familial predisposition to diabetes. Methods: A group of overweight/obese PCOS patients (n = 84) was selected from our Clinic database according to the Rotterdam criteria and the following parameters were extracted from the database: insulin, C Peptide, aspartate amino transferase (AST), alanine amino transferase (ALT), HOMA (Homeostasis Model Assessment) index, total cholesterol, LDL (Low Density Lypoprotein), HDL (High Density Lypoprotein), and body mass index (BMI). The presence and absence of diabetes among first grade relatives (parents and/or grandparents) were also considered. The Hepatic Insulin Extraction (HIE) index was computed as a ratio between insulin and C-Peptide plasma levels. Results: PCOS patients with familial diabetes showed higher levels of ALT, AST, HOMA index, and HIE. Baseline insulin levels above 12 μU/mL were more frequently observed in PCOS with familial diabetes. HIE index, ALT, and AST were higher in these latter PCOS patients than in PCOS without diabetic first grade relatives, sustaining the hypothesis of an impaired liver clearance of insulin in the case of familial diabetes. Conclusions: According to our study, the presence of anamnestic evidence of familial diabetes together with baseline levels of insulin higher that 12 µIU/mL and elevated transaminase levels should be considered as a consistent clinical suspect of liver impairment that might trigger compensatory hyperinsulinemia and lead to NAFLD and liver steatosis.

Polycystic Ovary Syndrome as Metabolic Disease: New Insights on Insulin Resistance

“…84 In addition, patients with PCOS with familial diabetes also showed ALT and AST plasma levels at the upper limit of normality and higher than in patients with PCOS without familial diabetes. 85 These data let us infer that a specific impairment might be induced by a familial predisposition to diabetes affecting hepatocyte functions. Indeed, patients with PCOS with familial diabetes showed a higher IR than patients with PCOS without familial diabetes when undergoing OGTT.…”

“…84 , 85 Recently, our group evaluated the hepatic insulin extraction (HIE) index in patients with PCOS who are overweight or obese and found that this index indicated impairment, specifically when familial diabetes was present in at least one first-degree relative (parents and/or grandparents). 84 , 85 …”

“…Consequently, several reports have demonstrated that insulin clearance is impaired in patients who are overweight or obese, 83 similarly to patients with PCOS who are overweight or obese. 84,85 Recently, our group evaluated the hepatic insulin extraction (HIE) index in patients with PCOS who are overweight or obese and found that this index indicated impairment, specifically when familial diabetes was present in at least one first-degree relative (parents and/or grandparents). 84,85 HIE can be computed with various algorithms, 73,86 of which the computation of the ratio between insulin and C-peptide plasma levels is the simplest.…”

“…84,85 Recently, our group evaluated the hepatic insulin extraction (HIE) index in patients with PCOS who are overweight or obese and found that this index indicated impairment, specifically when familial diabetes was present in at least one first-degree relative (parents and/or grandparents). 84,85 HIE can be computed with various algorithms, 73,86 of which the computation of the ratio between insulin and C-peptide plasma levels is the simplest. 86 Recent studies reported that reduced liver function and the ability to clear insulin participate in improving IR.…”

“…parents and/or grandparents). 85 Figure 3: Insulin secretion and removal from the general circulation depend on pancreatic activity and from the clearance exerted by various organs: liver (-50%), kidney (-30%), muscles (-15 to -35%) Insulin secretion from β cells of Langherhans islets of the pancreas derives from cleavage of pro-insulin into insulin and C-peptide, and the these products are secreted into the portal vein. The blood passes through the liver, which extracts about 50% of the newly secreted insulin.…”