The dysfunction of the β cells plays an important role in the development and the progression of the impaired glucose tolerance towards Type 2 Diabetes Mellitus (TD2M), above all in the phase in which an effective secretory capacity of the pancreatic cells would be extremely opportune in order to tackle the insulin-resistance. In the natural history of TD2M the β cells secretory capacity is precociously impaired, with the typical reduction of the early-phase insulin release. In particular, subjects with isolated Impaired Fasting Glucose (IFG) manifest a decrease in early-phase insulin response to oral glucose tolerance test (OGTT). However, late-phase plasma insulin response during OGTT is less severely impaired than in Impaired Glucose Tolerance (IGT). Subjects with IGT have severe defects in both early- and late-phase insulin responses to oral glucose. Thus, reduced insulinogenic index (ΔI 0-30/ΔG 0-30) is a consistent finding in subjects with IGT and IFG, indicating an impaired early insulin secretory response to OGTT. Both IGT and IFG are also insulin-resistant states (they have a significantly elevated HOMA-IR, that is a surrogate measure of insulin sensitivity) but they differ in site of insulin resistance. Subjects with IFG predominantly have hepatic insulin resistance and normal muscle insulin sensitivity, while individuals with IGT have normal to slightly reduced hepatic insulin sensitivity and moderate to severe muscle insulin resistance. The functional modifications reflect the histological modifications observed in the pancreatic islets where, as consequence of a reduction of the β cells and the expansion of the α cells a functional endocrine umbalance develops. The reduction of the β cells is due to an increase in the apoptosis, a condition which has been supposed to be enhanced by gluco- and lipotoxicity related mechanisms. Therefore, in the T2DM a vicious circle, in which the initial pancreatic secretion defect contributes to the progressive metabolic deterioration which, in turn, reduces either the β cells mass or its functionality, is hypothesized. Therefore, the pathogenetic mechanisms of the T2DM are very heterogeneous and involve different defects of both insulin secretion and tissue insulin sensitivity, which account for different clinical phenotypes of the disease. Selecting subjects with HOMA-IR higher than the 75° percentile but with normal insulinogenic index (insulin-resistant phenotype) and subjects with an insulinogenic index lower than the 25° percentile (reduced insulin-secretion phenotype), the 36% of the patients with IGR belongs to the first phenotypes and 16% to the second, while the 58% is simultaneously included in both categories. The respective phenotypes are indeed associated to several metabolic profiles which in turn characterize different risk class of complications. From the comparison of the clinical and metabolic parameters of the two groups, distinguished on the basis of the glycemic and insulinemic responses to the OGTT, the subjects with insulin-resistant phenotype present higher levels of total cholesterol and triglycerides, lower cholesterol-HDL concentrations and higher values of arterial systolic and diastolic pressure. A careful investigation obtained by the study of the OGTT, could therefore, not only allow a more careful stratification of the risk, but above all could address the pharmacological treatment in the conviction that a therapy tailored on the preponderant pathogenetic cause can contribute to a better and lasting metabolic control.
|Titolo:||Il carico orale di glucosio:cosa si aspetta il clinico|
|Data di pubblicazione:||2007|
|Appare nelle tipologie:||1.1 Articolo in rivista|