| Insulin resistance and insulin secretion dysfunction are the main pathophys-iologic mechanism of type 2 diabetes mellitus ( DM ). It has been debated, however, about which lesion is primary and their relative contribution to hypergly-caemia. Great disagreement exists in the studies from different countries, and the difference in ethnic characteristics and study methods are thought to be two;major reasons for this disagreement. Therefore, we performed this cross - section study in use of hyperinsulin - euglycemic clamp which is the internationally accepted as " golden standard" to determine insulin resistance and intraveneous glucose tolerance test (IVGTT) which is regarded as the more liable index than those derived from OGTT data to evaluate early disturbance in insulin secretion. In this way we managed to investigate the characterization of insulin resistance and insulin secretion abnormalities in Chinese subjects with impaired glucose tolerance (IGT) subjects in Shenyang, in order to deduce the relative role of insulin resistance and beta - cell dysfunction in the progression of type 2 diabetes.Subjects1. Normal glucose tolerance (NGT) and IGT group26 subjects (15 males and 11 females, aged 48. 5 + 16. 1 yr) who are of Chinese Han nationality living in Shenyang were recruited from the outpatient department of our hospital and from the communities nearby. They were classified into different stages of glucose tolerance ( NGT, n = 12; IGT, n = 14) by a75 - g OGTT after a 12 - 14h fast with measurement of fasting plasma glucose concentration (FPG) and 2 -h plasma glucose concentration (2 - h PG) according to WHO 1999 diagnostic criteria.2. DM group8 individuals with known type 2 diabetes (4 males and 4 females, aged 42. 3 + 15. 5 yr) were invited from our outpatient department to participate in our study. Their mean course of disease was 2. 9 +0. 5 years and hemoglobin Ale ( HbA1c) concentration was 9.7 +0. 8%.MethodsThe insulin clamp and IVGTT were respectively performed in NGT and IGT subjects (intervals between the two tests are one week at least). DM group only received the clamp.1. The hyperinsulin - euglycemic clampAfter a 10 - h fast, the subjects were given a continuous infusion of insulin ( Novolin R, Denmark) at a constant speed of 40mU/m2 ( body surface area ) and a variable infusion rate of a 25% solution of glucose adjusted according to the plasma glucose level at the same time. During the period of the experiment, blood samples were taken at 5 -10 min intervals for immediate determination of glucose concentration by a glucose oxidase analyzer ( BIOSEN, 5030, Germany) . The plasma glucose concentration was maintained at approximately 5mmol/ 1 by the periodic adjustment of the infusion of the glucose solution according to the plasma glucose level. When getting into the steady - state conditions of glucose infusion and constant euglycemia, the glucose infusion rate (GIR) was calculated as the quantitative index of insulin resistance.2. The intraveneous glucose tolerance testFollowing a 10 - 12h overnight fast, a 25% solution of glucose was infused intravenously at a precise rate of 0. 5g/kg ( body weight) in three minutes. Plasma samples for determination of plasma glucose and insulin level were taken before initiating the infusion and at 1, 3, 5, 10, 30, 60, 120 min after the infusion was finished. Plasma glucose level was measured by the same method as a-bove. Serum insulin samples were determined by radio - immunoassay ( Chinese atomicenergic institute). Fasting insulin ( FINS) is used to assess the basal secretory function of beta cell. Sum up the amount of insulin secretion at 1 -lOmin as the first - phase insulin secretion (1st PH) to determine acute insulin response to glucose ( AIR) , and 30 - 120min as the second - phase insulin secretion (2nd PH).Statistical analysisDifferences between the groups were tested by the Students test and with A-nalysis of Variance ( ANOVA) after adjustment for age, sex and other confounding factors. Corr...
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