Insulin Resistance and Insulin Secretory Dysfunction as Precursors of Non-Insulin-Dependent Diabetes Mellitus: Prospective Studies of Pima Indians

Lillioja, Stephen; Mott, David M.; Spraul, Maximilian; Ferraro, R T; Foley, James E.; Ravussin, Éric; Knowler, William C.; Bennett, Peter H.; Bogardus, Clifton

doi:10.1056/nejm199312303292703

Cited by 1,381 publications

(1,038 citation statements)

References 27 publications

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“…However, impaired pancreatic beta cell function is an essential element in the development of abnormal glucose tolerance. Indeed, altered beta cell function is a known predisposing factor for type 2 diabetes [4][5][6][7][8], while other studies have found that insulin insensitivity and abnormal beta cell function are independent predictors [9][10][11]. A major problem until now has been the lack of detailed information about the specific abnormalities of beta cell function that predispose to diabetes.…”

Section: Introductionmentioning

confidence: 99%

Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects

et al. 2005

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Aims/hypothesis: The aim of this prospective study was to investigate predictors of deteriorating glucose tolerance in subjects of British extraction. Methods: A total of 156 non-diabetic subjects (86 with a family history of type 2 diabetes) underwent a 75-g OGTT and anthropometric assessment at baseline and 5 years later. Pancreatic beta cell function and whole-body insulin sensitivity were studied by model assessment. Subjects were classified as progressors if glucose tolerance moved one or more steps from normal, impaired fasting glucose, impaired glucose tolerance and diabetes over the follow-up period. Results: At baseline, the progressors (n=22) had increased adiposity and a higher proportion of familial diabetes and abnormal glucose tolerance than non-progressors. Baseline pancreatic beta cell sensitivity to changes in glucose (p<0.02) and whole-body insulin sensitivity (p<0.0001) were decreased in the progressors. Logistic regression revealed that baseline and follow-up changes in beta cell glucose sensitivity and insulin sensitivity, rather than the classical clinical predictors (adiposity, familial diabetes and glucose levels), were the key independent predictors of progression (explaining over 50% of the progression). Conclusions/ interpretation: Impaired pancreatic beta cell glucose sensing and whole-body insulin sensitivity predict progression to hyperglycaemia. Strikingly, these pathophysiological changes override the importance of the clinical risk factors and highlight potential metabolic targets for prevention strategies.

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Section: Introductionmentioning

confidence: 99%

Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects

et al. 2005

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“…Insulin resistance is a well-established risk factor for the development of T2DM [21]. Obesity increases insulin resistance and is associated with elevated cardiovascular risk factors [22].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of type 2 diabetes among women with a previous history of gestational diabetes mellitus

Lee

Jang

Park³

et al. 2008

Diabetes Research and Clinical Practice

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“…Plasma glucose and insulin concentrations were measured in blood samples drawn before glucose ingestion and at 30, 60, 120 and 180 min thereafter. Insulin action was measured at physiologic and supraphysiologic insulin concentrations during a two-step hyperinsulinaemic-euglycaemic glucose clamp [2]. After an overnight fast, a primed continuous intravenous insulin infusion was administered for 100 min at a constant rate of 40 mU·m -2 body surface area·minute -1 (low dose), followed by a second insulin infusion for 100 min at 400 mU·m -2 ·minute -1 (high dose).…”

Section: Methodsmentioning

confidence: 99%

“…Insulin resistance, characterized as decreased insulin action on glucose uptake and metabolism, is a major predictor of Type II diabetes independent of obesity in Pima Indians of Arizona [2] who have a high prevalence of the disease [3]. Under physiological conditions, insulin-stimulated glucose metabolism occurs mainly in skeletal muscle (>80%) and adipose (~5-10%) tissues [4].…”

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confidence: 99%

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

et al. 2002

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Aims/hypothesis. We carried out global transcript profiling to identify differentially expressed skeletal muscle genes in insulin resistance, a major risk factor for Type II (non-insulin-dependent) diabetes mellitus. This approach also complemented the ongoing genomic linkage analyses to identify genes linked to insulin resistance and diabetes in Pima Indians. Methods. We compared gene expression profiles of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally obese, non-diabetic Pima Indians using oligonucleotide arrays consisting of about 40,600 transcripts of known genes and expressed sequence tags, and analysed the results with the Wilcoxon rank sum test. We verified the mRNA expression of ten differentially (best-ranked) and ten similarly (worst-ranked) genes using quantitative Real Time PCR.Results. There were 185 differentially expressed transcripts by the rank sum test. The differential expressions of two out of the ten best-ranked genes were confirmed and the similar expressions of all ten worstranked genes were reproduced. Conclusion/interpretation. Of the 185 differentially expressed transcripts, 20 per cent were true positives and some could generate new hypotheses about the aetiology or pathophysiology of insulin resistance. Furthermore, differentially expressed genes in chromosomal regions with linkage to diabetes and insulin resistance serve as new diabetes susceptibility genes. [Diabetologia (2002[Diabetologia ( ) 45:1584[Diabetologia ( -1593

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Insulin Resistance and Insulin Secretory Dysfunction as Precursors of Non-Insulin-Dependent Diabetes Mellitus: Prospective Studies of Pima Indians

Abstract: Insulin resistance is a major risk factor for the development of NIDDM: A low acute insulin response to glucose is an additional but weaker risk factor.

Cited by 1,381 publications

References 27 publications

Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects

Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects

Prevalence of type 2 diabetes among women with a previous history of gestational diabetes mellitus

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

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