Hyperbolic Relationship Between Insulin Secretion and Sensitivity on Oral Glucose Tolerance Test

Retnakaran, Ravi; Shen, Shih-Chieh; Hanley, Anthony J.; Vuksan, Vladimir; Hamilton, Jill; Zinman, Bernard

doi:10.1038/oby.2008.307

Cited by 304 publications

(347 citation statements)

References 35 publications

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“…glucose tolerance tests (6). Recently, the hyperbolic relationship of b-cell function and insulin sensitivity has also been demonstrated with data obtained from OGTT results in nonpregnant individuals (17,18), and this relationship has not been tested in pregnancy. In pregnant women in late gestation (weeks [24][25][26][27][28], b-cell function adjusted for insulin sensitivity deteriorated markedly when impaired glucose tolerance (IGT) and GDM individuals were compared with normal glucose tolerance (NGT) individuals, and most so in GDM (19).…”

Section: Introductionmentioning

confidence: 93%

“…an oral DI, was recently done in NGT and GDM women post partum (17). In this cohort, only the combination of IS ogtt and AUC ins/glc fit the strict hyperbolic criteria in both NGT and IGT subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Early onset of GDM (weeks [16][17][18][19][20] was found in 40% of subjects with GDM and normal BMI when tested with 75 g OGTT (4). In the early-onset group, significant reductions in b-cell function were found, as well as decreases in insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…We found a hyperbolic relationship after plotting the ratio of AUC insulin to AUC glucose (AUC ins/glc ) against the IS ogtt index, and subsequently calculated an oral (DI o ZAUC ins/glc !IS ogtt ) to adjust b-cell function for the effect of decreasing insulin sensitivity (17).…”

Section: Outcome Variablesmentioning

confidence: 99%

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Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

Qvigstad

Voldner²,

Godang³

et al. 2010

European Journal of Endocrinology

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Objective: To monitor b-cell function and insulin sensitivity longitudinally in a large cohort of pregnant women to elucidate mechanisms that influence glycemic control in pregnancy. Design and methods: Five hundred and fifty-three pregnant Scandinavian women underwent 75 g oral glucose tolerance test (OGTT) at weeks 14-16 and 30-32. Insulin sensitivity (Matsuda index) and b-cell function (ratio of AUC insulin to AUC glucose , AUC ins/glc ) were calculated from 520 complete tests, and subsequently b-cell function was adjusted for insulin sensitivity, rendering an oral disposition index (DI o ). Results: Eleven women (2.1%) had gestational diabetes mellitus (GDM1) at weeks 14-16, and 49 (9.4%) at weeks 30-32 (GDM2), which is higher than that previously reported in this region. In the subdivision of OGTT, more overweight (body mass indexO25) was found in glucose-intolerant groups (glucose-tolerant women (normal glucose tolerance, NGT) 38 versus GDM2 women 58 and GDM1 women 82%, P!0.005). In early pregnancy, insulin sensitivity was lowest in GDM1, intermediate in GDM2, and highest in NGT. In late pregnancy, insulin sensitivity decreased in all groups, most in gestational diabetes. b-cell function demonstrated minor shifts during pregnancy, but when adjusted for decreasing insulin sensitivity, DI o levels fell by 40% (P!0.001). DI o was significantly attenuated relative to glucose intolerance (GDM1 25% and GDM2 53%) during pregnancy. In overweight women, DI o levels were lower throughout pregnancy (P!0.001 versus normal weight women), this reduction was significant (P!0.01) in both NGT (21-25%) and GDM2 subjects (26-49%). Conclusion: b-cell function adjusted for insulin sensitivity (DI o ) deteriorated during pregnancy in both glucose-tolerant and glucose-intolerant women. The failure to compensate the decrease in insulin sensitivity was accentuated in overweight women.

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Section: Introductionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Outcome Variablesmentioning

confidence: 99%

See 2 more Smart Citations

Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

Qvigstad

Voldner²,

Godang³

et al. 2010

European Journal of Endocrinology

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“…(iAUC insulin /iAUC glucose )× Matsuda index), assuming the existence of an inverse hyperbolic relationship between insulin secretion and action. To evaluate this, we performed weighted least-squares linear regression analysis [33] with log beta cell glucose sensitivity as the dependent and log Matsuda index as the independent variable, and also between log iAUC ISR /iAUC Glucose…”

Section: Methodsmentioning

confidence: 99%

Steroid-induced insulin resistance and impaired glucose tolerance are both associated with a progressive decline of incretin effect in first-degree relatives of patients with type 2 diabetes

et al. 2012

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Aims/hypothesis The aim of this study was to evaluate the separate impact of insulin resistance and impaired glucose tolerance (IGT) on the incretin effect. Methods Twenty-one healthy glucose-tolerant first-degree relatives of patients with type 2 diabetes underwent a 75 g OGTT, an isoglycaemic i.v. glucose test and a mixed meal to evaluate the incretin effect before and after treatment with dexamethasone to increase insulin resistance. Beta cell glucose sensitivity, beta cell index and fasting proinsulin were measured as indices of beta cell function.Results After dexamethasone, ten individuals had increased insulin resistance but normal glucose tolerance (NGT), while 11 individuals with an equal increase in insulin resistance developed IGT. In the NGT and IGT groups, the incretin effects were 71±3.2% and 67±4.6% (p00.4) before treatment, but decreased significantly in both groups to 58±5.2% and 32±8.8% (p<0.05 between groups) after treatment. Dexamethasone increased total glucagon-like peptide-1 and glucose-dependent insulinotropic peptide responses to the OGTT. The impaired incretin effect in NGT was observed in the absence of reductions in beta cell glucose sensitivity and beta cell index during i.v. glucose, corrected for insulin resistance, but in parallel with increased proinsulin/C-peptide ratio. Conclusion/interpretation Insulin resistance and IGT, representing two stages in the path towards diabetes, are associated with differential reductions in the incretin effect seen before the development of IGT and overt type 2 diabetes. The reduction is unrelated to secretion of incretin hormones, but is related to insulin resistance and subtle beta cell defects, and is further aggravated on development of IGT.Trial registration: ClinicalTrials.gov NCT00784745.

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Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training

Roberts

Hevener

Barnard

2013

Comprehensive Physiology

451

425

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Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity.

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Hyperbolic Relationship Between Insulin Secretion and Sensitivity on Oral Glucose Tolerance Test

Cited by 304 publications

References 35 publications

Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

Overweight is associated with impaired β-cell function during pregnancy: a longitudinal study of 553 normal pregnancies

Steroid-induced insulin resistance and impaired glucose tolerance are both associated with a progressive decline of incretin effect in first-degree relatives of patients with type 2 diabetes

Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training

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