Associations of Glucose Control with Insulin Sensitivity and Pancreatic β-Cell Responsiveness in Newly Presenting Type 2 Diabetes

• Published in: The journal of clinical endocrinology and metabolism 2002-01, Vol.87 (1), p.198-203
• Main Authors: Albarrak, Ahmed I., Luzio, Stephen D., Chassin, Ludovic J., Playle, Rebecca A., Owens, David R., Hovorka, Roman
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Glucose - analysis; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glucose Tolerance Test; Glycated Hemoglobin A - analysis; Hormones. Régulation; Humans; Insulin - blood; Insulin - metabolism; Insulin Resistance; Islets of Langerhans - metabolism; Male; Medical sciences; Middle Aged; Postprandial Period; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.87.1.8152

We examined the ability of indices of insulin sensitivity and pancreatic β-cell responsiveness to explain interindividual variability of clinical measures of glucose control in newly presenting type 2 diabetes. Subjects with newly presenting type 2 diabetes (n = 65; 53 males and 12 females; age, 54 ± 1 yr; body mass index, 30.5 ± 0.7 kg/m2; mean ± se) underwent an insulin-modified iv glucose tolerance test to determine minimal model-derived insulin sensitivity (SI), glucose effectiveness, first-phase insulin secretion, and disposition index. Subjects also underwent a standard meal tolerance test (MTT) to measure fasting/basal (M0) and postprandial (MI) pancreatic β-cell responsiveness. Stepwise linear regression used these indices to explain interindividual variability of fasting and postprandial plasma glucose and insulin concentrations and glycated hemoglobin (HbA1C). All measures of pancreatic β-cell responsiveness (M0, MI, and first-phase insulin secretion) were negatively correlated with fasting plasma glucose (P < 0.01) and positively correlated with fasting plasma insulin (FPI) and insulin responses to MTT (P < 0.05). SI demonstrated negative correlation with FPI (P < 0.001) but failed to correlate with any glucose variable. MI followed by disposition index (composite index of insulin sensitivity and pancreatic β-cell responsiveness) were most informative in explaining interindividual variability. It was possible to explain 70–80% interindividual variability of fasting plasma glucose, FPI, HbA1C, and insulin responses to MTT, and only 25–40% interindividual variability of postprandial glucose. In conclusion, postprandial insulin deficiency is the most powerful explanatory factor of deteriorating glucose control in newly presenting type 2 diabetes. Indices of insulin sensitivity and pancreatic β-cell responsiveness explain fasting glucose and HbA1C well but fail to explain postprandial glucose.