BACKGROUND: This study aimed to compare the metabolic and insulin secretory responses to dexamethasone with the metabolic responses observed at 10 years in normoglycaemic relatives of type 2 diabetic and healthy control subjects. METHODS: Twenty relatives and 20 matched control subjects were studied twice at 0 year (pre- and post-dexamethasone) and at 10 years, employing a 75-g oral glucose tolerance test (OGTT), with serial measurements of glucose and insulin, for determination of glucose tolerance and calculations of acute insulin release (ΔI30 /ΔG30 ; insulinogenic index) and insulin sensitivity (SIHOMA ). RESULTS: Following dexamethasone, the relatives group developed varying degrees of glucose intolerance, associated with reduced insulin sensitivity and insulinogenic index. By 10 years, fasting glucose and 2-h OGTT glucose were raised in the relatives group, especially in the relatives most metabolically affected by dexamethasone, including a reduced insulinogenic index. Multiple regression analysis of the data in relatives demonstrated that the 2-h OGTT glucose and fasting glucose values at 10 years depended on the 0-year post-dexamethasone 2-h OGTT glucose, post-dexamethasone fasting glucose and post-dexamethasone insulin sensitivity, r(2) adj = 56% (p < 0.001) and r(2) adj = 60% (p < 0.0001), respectively. No pre-dexamethasone metabolic or insulin secretory responses entered these models. CONCLUSIONS: In relatives, fasting and 2-h OGTT glucose concentrations and β-cell responses to acute dexamethasone-induced insulin resistance are similar to those observed at 10 years, especially in relatives who develop the most disturbed dexamethasone-induced glucose intolerance and impaired acute insulin secretion. The combined 0-year, post-dexamethasone fasting and 2-h OGTT glucose concentrations and insulin resistance, measured as SIHOMA , are the best predictors in relatives of future dysglycaemia.
BACKGROUND: This study aimed to compare the metabolic and insulin secretory responses to dexamethasone with the metabolic responses observed at 10 years in normoglycaemic relatives of type 2 diabetic and healthy control subjects. METHODS: Twenty relatives and 20 matched control subjects were studied twice at 0 year (pre- and post-dexamethasone) and at 10 years, employing a 75-g oral glucose tolerance test (OGTT), with serial measurements of glucose and insulin, for determination of glucose tolerance and calculations of acute insulin release (ΔI30 /ΔG30 ; insulinogenic index) and insulin sensitivity (SIHOMA ). RESULTS: Following dexamethasone, the relatives group developed varying degrees of glucose intolerance, associated with reduced insulin sensitivity and insulinogenic index. By 10 years, fasting glucose and 2-h OGTT glucose were raised in the relatives group, especially in the relatives most metabolically affected by dexamethasone, including a reduced insulinogenic index. Multiple regression analysis of the data in relatives demonstrated that the 2-h OGTT glucose and fasting glucose values at 10 years depended on the 0-year post-dexamethasone 2-h OGTT glucose, post-dexamethasone fasting glucose and post-dexamethasone insulin sensitivity, r(2) adj = 56% (p < 0.001) and r(2) adj = 60% (p < 0.0001), respectively. No pre-dexamethasone metabolic or insulin secretory responses entered these models. CONCLUSIONS: In relatives, fasting and 2-h OGTT glucose concentrations and β-cell responses to acute dexamethasone-induced insulin resistance are similar to those observed at 10 years, especially in relatives who develop the most disturbed dexamethasone-induced glucose intolerance and impaired acute insulin secretion. The combined 0-year, post-dexamethasone fasting and 2-h OGTT glucose concentrations and insulin resistance, measured as SIHOMA , are the best predictors in relatives of future dysglycaemia.