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

Martin, B.C.; Warram, James H.; Królewski, Andrzej S.; Soeldner, J S; Kahn, C. Ronald; Bergman, Richard N.

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

Cited by 1,067 publications

(684 citation statements)

References 29 publications

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“…Adiponectin, a relatively novel serum protein produced uniquely by adipocytes, has been studied in a variety of contexts in vivo and in vitro and is proposed to have anti-diabetic, antiinflammatory and anti-atherogenic properties. Thus, we evaluated the role of total and %HMW adiponectin in vascular function in offspring whose parents both had type 2 diabetes, a group at high risk of developing diabetes [29,30]. The study cohort was highly enriched for progression to diabetes, as half of subjects had early glucose intolerance to provocative testing in addition to low insulin sensitivity and glucose effectiveness.…”

Section: Discussionmentioning

confidence: 99%

“…A 100-g glucose load was administered to maximise glucose and insulin excursion, and glucose and insulin levels were measured prior to and 30, 60, 90 and 120 min after glucose was administered. Each subject was considered non-diabetic based on the National Diabetes Data Group criteria for a 75-g load [29,33].…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

“…Thus, we sought to evaluate the relationship between total and high-molecular-weight adiponectin and measures of vascular function in offspring whose parents both had type 2 diabetes. This group is at risk of diabetes [29,30] and may have early atherosclerotic disease manifested as abnormal endothelial function [31,32].…”

Section: Introductionmentioning

confidence: 99%

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The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

et al. 2005

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Aims/hypothesis: Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. We studied the role played by total adiponectin and by the bioactive high-molecular-weight (HMW) oligomeric complexes of adiponectin in vascular function in offspring whose parents both had type 2 diabetes, a population at high risk of diabetes and atherosclerosis. Methods: Total and %HMW adiponectin, the cytokines C-reactive protein, interleukin-6 and plasminogen activator inhibitor-1 (PAI-1), as well as lipid profiles were assayed in 19 offspring, each with two type 2 diabetic parents. Subjects underwent OGTTs and IVGTTs. Endothelium-dependent vasodilation (EDV) was assessed by brachial artery ultrasonography. Results: There was a significant relationship between %HMW and total adiponectin levels (r=0.72, p=0.001). Despite an expected strong positive correlation between HDL-cholesterol and adiponectin levels (r=0.52, p=0.04), as well as HDL-cholesterol and EDV (r=0.56, p<0.02), there was no significant relationship between either total adiponectin or % HMW adiponectin and EDV. Adiponectin was inversely associated with PAI-1 (r=0.50, p=0.05), but did not correlate with the inflammatory markers C-reactive protein or interleukin-6. Conclusions/interpretation: In offspring of diabetic parents, a population at high risk of diabetes and atherosclerotic disease, there is no relationship between total or %HMW adiponectin and endotheliumdependent vasodilation. However, low adiponectin was associated with impaired fibrinolysis as manifested by increased levels of plasminogen activator inhibitor-1.

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Section: Discussionmentioning

confidence: 99%

Section: Subjects Materials and Methodsmentioning

confidence: 99%

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The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

et al. 2005

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“…Insulin resistance is believed to precede the development of diabetes. Low insulin sensitivity has been found in normoglycaemic relatives of Type 2 diabetic patients [1,2] and to predict the development of clinically overt hyperglycaemia [3]. Loss of compensatory hypersecretion of insulin has been indicated as the turning point for the development of diabetes [4].…”

Section: [Suppl1]:m2-m8]mentioning

confidence: 99%

Loss of early insulin secretion leads to postprandial hyperglycaemia

2003

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Aims/Hypothesis. A loss of early-phase insulin response is common in Type 2 diabetic patients and in people with impaired glucose metabolism. It is hypothesized that this alteration is not simply a marker for the risk of developing diabetes, rather it is a an important pathogenetic mechanism causing excessive postprandial hyperglycaemia. Methods. Relevant literature on the epidemiology, physiopathology, and therapeutic intervention related to loss of early insulin secretion and postprandial hyperglycaemia has been analysed. Results. In response to intravenous glucose, insulin secretion is biphasic. This behaviour translates as a rapid release of insulin into the blood stream in response to the ingestion of carbohydrates or a mixed meal. The rapid increase in portal insulin concentration and the avid binding of the hormone to its receptor on liver cell membranes, account for a prompt suppression of endogenous glucose production and reduction of the rate of increase in plasma glucose concentrations. This has been supported by experimental studies carried out in both animals and humans: the selective abolition of early insulin secretion in healthy subjects results in impaired glucose tolerance, excessive glucose excursions, and possible hampering of the thermic effects of ingested carbohydrates. In nondiabetic subjects, the loss of early insulin secretion is a determinant for developing diabetes. The critical role of the early-phase insulin response in determining postprandial hyperglycaemia, is supported by an amelioration of glucose tolerance by restoring the acute rise in plasma insulin concentrations after the ingestion of both glucose and a mixed meal. This amelioration in plasma glucose profile can prevent late hyperglycaemia and hyperinsulinaemia. Conclusion/interpretation. Therapeutic approaches aimed at restoring a physiological pattern of insulin secretion could prove effective in reducing postprandial glucose excursions particularly in the early stage of Type 2 diabetes. [Diabetologia (2003)

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“…[Diabetologia (2002) Type II (non-insulin-dependent) diabetes mellitus is associated with a reduced insulin-stimulated glucose disposal in skeletal muscle and other tissues [1]. Because insulin resistance is also observed in non-diabetic first-degree relatives of diabetic subjects [2,3,4,5], and because it seems to precede the development of frank diabetes [6], an inherited basis of at least a part of the diabetes-associated insulin resistance has been proposed [7]. On the other hand metabolic abnormalities in the diabetic state itself such as hyper-…”

Section: Introductionmentioning

confidence: 99%

Insulin signalling in skeletal muscle of subjects with or without Type II-diabetes and first degree relatives of patients with the disease

et al. 2002

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Aims/hypothesis. Alterations in insulin signalling could contribute to insulin resistance in Type II (non-insulindependent) diabetes mellitus. Some of these alterations could be secondary to the diabetic state, ie. the hyperglycaemia or increased NEFA concentrations. We sought to exclude such secondary factors and to investigate whether Type II diabetes in itself is associated with altered insulin signalling in skeletal muscle. Methods. Hyperinsulinaemic-euglycaemic clamps were performed in 10 obese Type II diabetic patients whose glucose concentrations had been normalised for 8 h by plasma glucose-adapted insulin infusion, 10 BMImatched first-degree relatives of Type II diabetic patients, and 10 BMI-matched non-diabetic subjects. Muscle biopsies were obtained before and at the end of the clamps, and insulin receptor kinase activity, phosphatidylinositol-3′-kinase activity, Akt-Thr 308 -phosphorylation, and glycogen synthase activity determined. Results. At similar steady-state clamp insulin concentrations (~400 pmol/l) similar receptor kinase activities, phosphatidylinositol-3′-kinase activities, AktThr 308 -phosphorylation, and glycogen synthase activities were found in all subject groups although glucose disposal was reduced in the diabetic subjects and relatives. Pre-clamp signalling levels were different between subject groups, most likely due to different preclamp insulin concentrations. Conclusion/interpretation. Our results in subjects at risk for the development of diabetes and Type II diabetic patients with normalized glucose concentrations suggest that Type II diabetes in itself is not associated with reduced signalling intensity at the studied signalling molecules, at least not at the chosen clamp insulin concentration and under the chosen conditions. Alterations responsible for the reduced glucose disposal could be located downstream of the investigated steps or in alternative insulin signalling pathways. A different spatial organisation of the investigated signalling molecules can also not be excluded. [Diabetologia (2002) Type II (non-insulin-dependent) diabetes mellitus is associated with a reduced insulin-stimulated glucose disposal in skeletal muscle and other tissues [1]. Because insulin resistance is also observed in non-diabetic first-degree relatives of diabetic subjects [2,3,4,5], and because it seems to precede the development of frank diabetes [6], an inherited basis of at least a part of the diabetes-associated insulin resistance has been proposed [7]. On the other hand metabolic abnormalities in the diabetic state itself such as hyper-

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

Cited by 1,067 publications

References 29 publications

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

Loss of early insulin secretion leads to postprandial hyperglycaemia

Insulin signalling in skeletal muscle of subjects with or without Type II-diabetes and first degree relatives of patients with the disease

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