Metabolic characteristics of glucose intolerance: The critical role of obesity

Introduction: Obesity enhances insulin secretion and resistance. We investigated its importance in linking insulin metabolism to glucose intolerance. Material and Methods: We studied 700 subjects referred by general practitioners for possible metabolic abnormalities. Plasma glucose was measured before (FPG) and after (2h-PG) OGTT, together with insulin. Insulin resistance was estimated by HOMA-IR, insulin sensitivity using ISI(gly) and ISI(Stumvoll) indexes, insulin secretion by first (1stPH_est) and second phase (2ndPH_est) estimates. Results: Sixty three subjects had impaired glucose tolerance (IGT), 132 impaired fasting glucose (IFG), 63 a mixed disorder (IFG/IGT). Insulin resistance was present only in IGT and IFG/IGT. IFG subjects had inappropriately low insulin secretion exclusively during fasting. In a stepwise logistic regression analysis BMI≥27, female sex and hypertension were associated to an altered 2h-PG during OGTT, while hypertension and age were linked to alterations in FPG. While overweight prevalence (BMI≥27) was higher in all glucose intolerance groups, obesity (BMI≥30) was typical of IGT. Overweight and obesity were related to higher insulin concentration, secretion and resistance. Obese normal glucose tolerant subjects were more insulin resistant than lean IFG patients. Discussion: OGTT is essential to correctly establish the metabolic derangement of glucose intolerance. Obesity is significantly connected with the impairment of insulin metabolism even in subjects with normal FPG. Considering that both obesity and insulin resistance are independently associated to an increased cardiovascular risk, all overweight subjects, even with normal FPG, should be referred for OGTT evaluation to define glucose tolerance status in order to enforce adequate preventive actions.