Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese

Abstract

InsulIn resistance and impaired insulin secretion are considered the primary pathophysiological factors in the development of type 2 diabetes [1]. Although hyperglycemic and euglycemic clamp studies are wellestablished methods of assessing insulin secretion and insulin sensitivity [2,3], the oral glucose tolerance test (OGTT) is a simpler and less expensive method that provides estimates of both factors. As a measure of insulin secretion, insulinogenic index is highly correlated with the acute insulin response (AIR) on the intravenous glucose tolerance test (IVGTT) in nondiabetic subjects [4,5], and it has been widely used as an index of early-phase insulin secretion in clinical Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese Abstract. The aim of this study was to assess the changes in insulin secretion and insulin sensitivity in relation to fasting and 2-hour plasma glucose (PG) levels and to assess the independent contributions of their impairments to non-diabetic hyperglycemia. A total of 2157 Japanese workers (mean age 52.6±7.3 years and mean BMI 23.9±3.2 kg/m 2 ) underwent an oral glucose tolerance test (OGTT). Of these subjects, 1125 had normal glucose tolerance (NGT), 525 subjects had isolated impaired fasting glucose (IFG), 159 subjects had isolated impaired glucose tolerance (IGT), 263 subjects had combined IFG and IGT, and 85 subjects had newly diagnosed type 2 diabetes. Insulinogenic index and Matsuda insulin sensitivity index (ISI) were significantly attenuated in subjects with normal but slightly elevated fasting PG, or in subjects with normal but slightly elevated 2-hour PG. Whereas, InsAUC 120 /GluAUC 120 was not significantly decreased in those subjects, and significant decrease of it was observed exclusively in subjects with abnormal fasting PG (≥ 106 mg/dL) or abnormal 2-hour PG (≥ 221 mg/dL). Using multiple regression analyses, both Matsuda ISI and insulinogenic index were independently correlated with PG concentrations in subjects with IFG and/or IGT, while Matsuda ISI alone was independently correlated with fasting PG concentrations in normoglycemic subjects. In conclusion, both insulinogenic index and Matsuda ISI were significantly attenuated in subjects with normal but slightly elevated PG. Lowering of Matsuda ISI was likely to be a strong contributor to 'elevation of fasting PG within the normal range' in this population.

The evolution of non-diabetic hyperglycemia: a longitudinal study

“…Data from consecutive 2,264 individuals who received the checkup including a 75 g OGTT with immunoreactive insulin (IRI) measurement between April 2006 and March 2010 [18] without a history of DM or gastrectomy and not taking glucocorticoid or anticancer drugs were used. Among them, the number of subjects with the ADA-defined NGT [19] was 1,209.…”

“…After an overnight fast, a standard 75 g OGTT was performed as previously described [18]. Plasma glucose (PG) was analyzed by the glucose oxidase method (Automatic Glucose Analyzer ADAMS Glucose GA-1160, Arkray, Kyoto) and immunoreactive insulin (IRI) by the chemiluminescence method (ADVIA Centaur, Siemens Medical Solutions).…”

Impaired β-cell function and decreased insulin sensitivity in subjects with normal oral glucose tolerance but isolated high glycosylated hemoglobin

“…Similarly, in a study of overweight/obese adolescents, subjects with HbA1c 5.7 to <6.5% had significantly lower insulin sensitivity and β-cell function versus those with normal HbA1c [25]. Previous studies had demonstrated that impairment of insulin secretion and insulin sensitivity starts from the NGT range of 2-h plasma glucose, and minimally elevated glucose may indicate the onset of insulin sensitivity and β-cell function impairment [26]. Our study demonstrated that after adjustment for various confounding factors including FPG and 2h-β-cell function and isolated high HbA1c PG, the OR of insulin resistance (IR-Matsuda ISI) and impaired early β-cell response to insulin sensitivity (IB-DI30) remained significant.…”

Impaired Glucose Tolerance, Obesity and Inflammatory Mediators

“…Subjects with IGT have impaired late-phase insulin secretion and increased insulin resistance (IR) in skeletal muscle. In contrasts, subjects with IFG have impaired early -phase insulin secretion and increased IR in liver [6][7][8]. Similarly there are some discrepancies between the clinical features of IFG and IGT.…”

“…Similarly there are some discrepancies between the clinical features of IFG and IGT. Subjects with isolated IFG are more insulin resistant, and subjects with isolated IGT exhibits a more severe deficit in insulin secretion [8]. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability [5].…”