Muscle and Liver Insulin Resistance Indexes Derived From the Oral Glucose Tolerance Test

Abdul‐Ghani, Muhammad; Matsuda, Masafumi; Balas, Bogdana; DeFronzo, Ralph A.

doi:10.2337/dc06-1519

Cited by 444 publications

(414 citation statements)

References 26 publications

(30 reference statements)

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Section: Discussionmentioning

confidence: 99%

“…ISI 0,120 includes 2 h post-OGTT plasma glucose and serum insulin concentrations in the calculation, and it mainly reflects peripheral or whole-body insulin sensitivity [37]. By contrast, the HOMA-IS model is based on fasting plasma glucose and serum insulin concentrations and therefore primarily reflects hepatic insulin sensitivity [37]. The findings of associations of PAEE and CRF with peripheral insulin sensitivity are consistent with previous findings using objectively measured PAEE [38,39], including previous analyses on participants in the ADDITION-PRO cohort [22].…”

Section: Discussionmentioning

confidence: 99%

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Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

et al. 2015

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Aim/hypothesis Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test the hypothesis that CRF modifies the association between PAEE and glucose metabolism. Methods We analysed cross-sectional data from 755 adults from the Danish ADDITION-PRO study. On the basis of OGTT results, participants without known diabetes were classified as having normal glucose tolerance, isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG + IGT or screen-detected diabetes mellitus. Markers of insulin sensitivity and beta cell function were determined. PAEE was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake) was estimated using a submaximal 8 min step test. The associations were examined by linear regression analysis. Results were adjusted for relevant confounders. Results PAEE and CRF were reduced in individuals with i-IGT, combined IFG + IGT and screen-detected diabetes mellitus, but were not significantly different in individuals with i-IFG compared with those with normal glucose tolerance. When adjusting CRF for PAEE and vice versa, PAEE and CRF were both associated with lower fasting and 2 h insulin and higher peripheral insulin sensitivity. CRF was additionally associated with lower fasting and 2 h glucose and higher insulin sensitivity and beta cell function. There was no interaction between CRF and PAEE for any markers of glucose metabolism. Conclusions/interpretation Only CRF, not PAEE, appears to be independently associated with plasma glucose levels and beta cell function, suggesting that CRF may be particularly important for glycaemic control.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

et al. 2015

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“…Skeletal muscle insulin sensitivity can be calculated as the rate of decline in plasma glucose concentration divided by plasma insulin concentration, as follows. Muscle insulin sensitivity index=dG/dt/mean plasma insulin concentration, where dG /dt is the rate of decline in plasma glucose concentration and is calculated as the slope of the least square fit to the decline in plasma glucose concentration from peak to nadir [20]. See the electronic supplementary material (ESM) for further details.…”

Section: Methodsmentioning

confidence: 99%

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

et al. 2014

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Aims/hypothesis The cholesterol absorption inhibitor ezetimibe has been shown to ameliorate non-alcoholic fatty liver disease (NAFLD) pathology in a single-armed clinical study and in experimental animal models. In this study, we investigated the efficacy of ezetimibe on NAFLD pathology in an open-label randomised controlled clinical trial. Methods We had planned to enrol 80 patients in the trial, as we had estimated that, with this sample size, the study would have 90% power. The study intervention and enrolment were discontinued because of the higher proportion of adverse events (significant elevation in HbA 1c ) in the ezetimibe group than in the control group. Thirty-two patients with NAFLD were enrolled and randomised (allocation by computer program). Ezetimibe (10 mg/day) was given to 17 patients with NAFLD for 6 months. The primary endpoint was change in serum aminotransferase level. Secondary outcomes were change in liver histology (12 control and 16 ezetimibe patients), insulin sensitivity including a hyperinsulinaemic-euglycaemic clamp study (ten control and 13 ezetimibe patients) and hepatic fatty acid composition (six control and nine ezetimibe patients). Hepatic gene expression profiling was completed in 15 patients using an Affymetrix gene chip. Patients and the physician in charge knew to which group the patient had been allocated, but people carrying out measurements or examinations were blinded to group. Results Serum total cholesterol was significantly decreased in the ezetimibe group. The fibrosis stage and ballooning score were also significantly improved with ezetimibe treatment. However, ezetimibe treatment significantly increased HbA 1c and was associated with a significant increase in hepatic longchain fatty acids. Hepatic gene expression analysis showed coordinate downregulation of genes involved in skeletal muscle development and cell adhesion molecules in the ezetimibe treatment group, suggesting a suppression of stellate cell development into myofibroblasts. Genes involved in the L-carnitine pathway were coordinately downregulated by ezetimibe treatment and those in the steroid metabolism pathway upregulated, suggestive of impaired oxidation of long-chain fatty acids. Conclusions/interpretation Ezetimibe improved hepatic fibrosis but increased hepatic long-chain fatty acids and HbA 1c in patients with NAFLD. These findings shed light on previously unrecognised actions of ezetimibe that should be examined further in future studies.

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“…Definition of IIS and IR AUCs for type 2 diabetes (FPG ≥7.0 mmol/l and/or 2 h post-load PG ≥11.1 mmol/l) were calculated relative to insulin secretion and IR indices derived from the OGTT in 3,916 participants who were not receiving medical treatment for diabetes at baseline [17][18][19][20][21][22][23][24]. The AUCs of these indices, shown in Table 1, were crosssectionally evaluated using receiver operating characteristic (ROC) curves.…”

Section: Methodsmentioning

confidence: 99%

Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study

et al. 2013

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Aims/hypothesis To assess the impact of impaired insulin secretion (IIS) and insulin resistance (IR) on type 2 diabetes incidence in a Japanese population. Methods This 4 year cohort study included 3,059 participants aged 30-69 without diabetes at baseline who underwent comprehensive medical check-ups between April 2006 and March 2007 at Saku Central Hospital. Based on their insulinogenic index and HOMA-IR values, participants were classified by the criteria of the Japan Diabetes Society into four categories: normal; isolated IIS (i-IIS); isolated IR (i-IR); and IIS plus IR. They were followed up until March 2011. The incidence of type 2 diabetes was determined from fasting and 2 h post-load plasma glucose concentrations and from receiving medical treatment for diabetes. Results At baseline, 1,550 individuals (50.7%) were classified as normal, 900 (29.4%) i-IIS, 505 (16.5%) i-IR, and 104 (3.4%) IIS plus IR. During 10,553 person-years of follow-up, 219 individuals developed type 2 diabetes, with 126 (57.5%) having i-IIS at baseline. Relative to the normal group, the multivariable-adjusted HRs for type 2 diabetes in the i-IIS, i-IR and IIS plus IR groups were 8.27 (95% CI 5.33, 12.83), 4.90 (95% CI 2. 94, 8.17) and 16.93 (95% CI 9.80, 29.25), respectively. The population-attributable fractions of type 2 diabetes onset due to i-IIS, i-IR, and IIS plus IR were 50.6% (95% CI 46.7%, 53.0%), 14.2% (95% CI 11.8%, 15.6%) and 12.9% (95% CI 12.3%, 13.2%), respectively. Conclusions/interpretation Compared with IR, IIS had a greater impact on the incidence of type 2 diabetes in a Japanese population.

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Muscle and Liver Insulin Resistance Indexes Derived From the Oral Glucose Tolerance Test

Cited by 444 publications

References 26 publications

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study

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