Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study

doi:10.1016/0140-6736(92)92814-V

The Lancet

Volume 340, Issue 8825, 17 October 1992, Pages 925-929

https://doi.org/10.1016/0140-6736(92)92814-V Get rights and content

Abstract

Type 2 diabetes mellitus is characterised by resistance of peripheral tissues to insulin and a relative deficiency of insulin secretion. To find out which is the earliest or primary determinant of disease, we used a minimum model of glucose disposal and insulin secretion based on intravenous glucose tolerance tests to estimate insulin sensitivity (S_I), glucose effectiveness (ie, insulin-independent glucose removal rate, S_G), and first-phase and second-phase beta-cell responsiveness in normoglycaemic offspring of couples who both had type 2 diabetes. 155 subjects from 86 families were followed-up for 6-25 years. More than 10 years before the development of diabetes, subjects who developed the disease had lower values of both S_I (mean 3·2 [SD 2·4] vs 8·1 [6·7] 10^-3 I min^-1 pmol^-1 insulin; p<0·0001) and S_G (1·6 [0·9] vs 2·3 [1·2] 10^-2 min^-1, p<0·0001) than did those who remained normoglycaemic). For the subjects with both S_I and S_G below the group median, the cumulative incidence of type 2 diabetes during the 25 years was 76% (95% confidence interval 54-99). By contrast, no subject with both S_I and S_G above the median developed the disease. Subjects with low S_I/high S_G or high S_I/low S_G had intermediate risks. Insulin secretion, especially first phase, tended to be increased rather than decreased in this prediabetic phase and was appropriate for the level of insulin resistance. The development of type 2 diabetes is preceded by and predicted by defects in both insulin-dependent and insulin-independent glucose uptake; the defects are detectable when the patients are normoglycaemic and in most cases more than a decade before diagnosis of disease.

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ORIGINAL ARTICLESRole of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study

Abstract

J Biol Chem

Mapping genes in diabetes

Diabetes

Role of insulin resistance in human disease

Diabetes

The triumvirate: beta-cell, muscle, liver: a collusion responsible for NIDDM

Diabetes

Hyperproinsulinemia and amyloid in NIDDM

Diabetes

Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis

Diabetes/Metab Rev

Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese-American men

Diabetes

Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity and body-fat distribution

Diabetes

Slow glucose-removal rate and hyperinsulinaemia precede the development of type II diabetes in offspring with diabetic parents

Ann Intern Med

Toward physiological understanding of glucose tolerance: minimal model approach

Diabetes

Physiologic evaluation of factors controlling glucose tolerance in man

J Clin Invest

Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp

J Clin Invest

Classification and diagnosis of diabetes mellitus and other categories of glucose tolerance

Diabetes

A new and rapid method for the determination of glucose by measurement of rate of oxygen consumption

Clin Chem

Critical variables in the radioimmunoassay of serum insulin using the double antibody technique

Diabetes

ORIGINAL ARTICLES
Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study