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Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques.

ABSTRACT: We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6 ± 1.0 years, BMI 31.5 ± 0.4 kg/m(2); 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6-6(2)H(2)] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39-56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r(2) = 27-32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations.

SUBMITTER: Hattersley JG

PROVIDER: S-EPMC3382235 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques.

Hattersley John G JG Möhlig Matthias M Roden Michael M Arafat Ayman M AM Loeffelholz Christian V CV Nowotny Peter P Machann Jürgen J Hierholzer Johannes J Osterhoff Martin M Khan Michael M Pfeiffer Andreas F H AF Weickert Martin O MO

PloS one 20120622 6

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6 ± 1.0 years, BMI 31.5 ± 0.4 kg/m(2); 30 males). HEP-IR was defined by measuring endogenous-glucose-production ( ...[more]

PMID: 22761721

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Project description:Unlabelled♦BackgroundInsulin resistance (IR) is common in maintenance dialysis patients and is associated with excess mortality. Hyperinsulinemic euglycemic glucose clamp (HEGC) is the gold standard for measuring IR. There are limited studies using HEGC for comparison to other indirect indices of IR in peritoneal dialysis (PD) patients, nor have there been direct comparisons between patients receiving PD and those on maintenance hemodialysis (MHD) with regard to severity of IR, methods of measurement, or factors associated with the development of IR. ♦MethodsThis is a cross-sectional, single-center study performed in 10 prevalent PD patients of median age 48 years (range 41 - 54); 50% were female and 60% were African American. Insulin resistance was assessed by HEGC (glucose disposal rate [GDR]), homeostatic model assessment of IR (HOMA-IR), HOMA-IR corrected by adiponectin (HOMA-AD), leptin adiponectin ratio (LAR), quantitative insulin sensitivity check index (QUICKI), McAuley's index, and oral glucose tolerance test (OGTT) at each time point for a total of 18 studies. Retrospective analysis compared this cohort to 12 hemodialysis patients who had previously undergone similar testing. ♦ResultsThe median GDR was 6.4 mg/kg/min (interquartile range [IQR] 6.0, 7.8) in the PD cohort compared with the MHD group, which was 5.7 mg/kg/min (IQR 4.3, 6.6). For both the PD and MHD cohorts, the best predictors of GDR by HEGC after adjusting for age, gender, and body mass index (BMI), were HOMA-AD (PD: r = -0.69, p = 0.01; MHD: r = -0.78, p = 0.03) and LAR (PD: r = -0.68, p < 0.001; MHD: r = -0.65, p = 0.04). In both groups, HOMA-IR and QUICKI failed to have strong predictive value. Eight of 10 PD patients had at least 1 abnormal OGTT, demonstrating impaired glucose tolerance. ♦ConclusionsInsulin resistance is highly prevalent in PD patients. The adipokine based formulas, HOMA-AD and LAR, correlated well in both the PD and MHD populations in predicting GDR by HEGC, outperforming HOMA-IR. The use of these novel markers could be considered for large-scale, epidemiological outcome studies.

Project description:The mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.We investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided.Insulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; P(trend) = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P(trend) = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (P(trend) = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile.Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.

Dataset Information

Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques.

Publications

Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques.

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