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Early Insulin Response and Insulin Sensitivity are Equally Important as Predictors of Glucose Tolerance after Correction for Measurement Errors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin diabetes och metabolism)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
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2009 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 86, no 3, 219-224 p.Article in journal (Refereed) Published
Abstract [en]

Aims: We estimated measurement error (ME) corrected effects of   insulin sensitivity (M/I), from euglycaemic insulin clamp, and insulin   secretion, measured as early insulin response (EIR) from oral glucose   tolerance test (OGTT), on fasting plasma glucose, HbA1c and type 2   diabetes longitudinally and cross-sectional.   Methods: : In a population-based study (n = 1128 men) 17 men made   replicate measurements to estimate ME at age 71 years. Effect of 1 SD   decrease of predictors M/I and EIR on longitudinal response variables   fasting plasma glucose (FPG) and HbA1c at follow-ups up to 11 years,   were estimated using uncorrected and ME-corrected (with the regression   calibration method) regression models.   Results: : Uncorrected effect on FPG at age 77 years was larger for M/I   than for EIR (effect difference 0.10 mmol/l, 95% CI 0.00;0.21), while   ME-corrected effects were similar (0.02 mmol/l, 95% CI -0.13;0.15   mmol/l). EIR had greater ME-corrected impact than M/I on HbA1c at age   82 years (-0.11%, -0.28; -0.01%).   Conclusions: : Due to higher ME effect of EIR on glycaemia is   underestimated as compared with M/I. By correcting for ME valid   estimates of relative contributions of insulin secretion and insulin   sensitivity on glycaemia are obtained.

Place, publisher, year, edition, pages
2009. Vol. 86, no 3, 219-224 p.
National Category
Medical and Health Sciences
Research subject
Geriatrics
Identifiers
URN: urn:nbn:se:uu:diva-99497DOI: 10.1016/j.diabres.2009.09.016ISI: 000272521800010PubMedID: 19811847OAI: oai:DiVA.org:uu-99497DiVA: diva2:208021
Available from: 2009-03-18 Created: 2009-03-15 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Measurement Variability Related to Insulin Secretion and Sensitivity: Assessment and Implications in Epidemiological Studies
Open this publication in new window or tab >>Measurement Variability Related to Insulin Secretion and Sensitivity: Assessment and Implications in Epidemiological Studies
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is a growing interest in random measurement variability of biological variables. In regression models, such variability of the predictors yields biased estimators of coefficients (regression dilution bias). The objectives of this thesis were to develop an efficient method to correct for such bias, to reveal the relative importance of insulin sensitivity and insulin secretion, corrected for regression dilution bias, on glucose tolerance, and to explore the seasonal nature of the variability of insulin sensitivity.

A reliability study is often designed to randomly select subjects from the main study. Our idea was to collect replicates for subjects with extreme values on their first measurement. The extreme selection design, in combination with maximum likelihood estimation, resulted in an efficient estimator of a corrected regression coefficient in a simple linear regression model. Results were presented theoretically and with an application: The relation between insulin sensitivity and fasting insulin in Uppsala Longitudinal Study of Adult Men (ULSAM) where the extreme selection design decreased the standard error of the estimated regression coefficient with 28 per cent compared with the random sampling design.

We estimated the partial longitudinal effects of the predictors insulin sensitivity and insulin secretion, corrected for regression dilution bias, on glucose tolerance in ULSAM. The effects of the predictors, when corrected, were similar.

Insulin sensitivity in ULSAM increased during summer and decreased during winter and insulin secretion exposed opposite variation keeping glucose homeostasis nearly constant. Insulin sensitivity was related to outdoor temperature.

In summary, we developed a cost-efficient reliability design for correction for regression dilution bias. Insulin sensitivity and insulin secretion had similar longitudinal effects on glucose tolerance, which implies that interventions aimed at these targets are equally important. Further, we revealed the seasonal nature of variations of insulin sensitivity and insulin secretion. This result has implications on glycaemic control in diabetic patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 440
National Category
Geriatrics
Research subject
Geriatrics
Identifiers
urn:nbn:se:uu:diva-99636 (URN)978-91-554-7469-0 (ISBN)
Public defence
2009-04-29, Enghoffsalen, Akademiska sjukhuset, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2009-04-07 Created: 2009-03-18 Last updated: 2012-07-26Bibliographically approved

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Berglund, LarsBerne, Christian

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