Within-subject variability of measures of beta cell function derived from a 2 h OGTT: implications for research studies

Utzschneider, Kristina M.; Prigeon, Ronald L.; Tong, Jenny; Gerchman, Fernando; Carr, Darcy B.; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Montgomery, Brenda; Mari, Andrea

doi:10.1007/s00125-007-0819-5

Cited by 97 publications

(96 citation statements)

References 22 publications

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“…The regression method we used corrects this bias by incorporation of a factor computed as the ratio of the variances of the error in the y to x variables (16). The error estimates for these measurements (57.1% for ⌬I 0 -30 /⌬G 0 -30 , 24.9% for incAUC ins/glu , 16.6% for 1/fasting insulin, and 16.4% for HOMA-S) were based on the day-to-day coefficients of variation in a group of subjects with various glucose tolerance (11). A hyperbolic relationship was presumed if the 95% CI of the slope included Ϫ1.…”

Section: Discussionmentioning

confidence: 99%

Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

et al. 2009

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OBJECTIVE -We sought to determine whether an oral disposition index (DI O ) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DI O by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and ␤-cell function.RESEARCH DESIGN AND METHODS -A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g oral glucose tolerance test (OGTT) at baseline, 5 years, and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response was estimated as the change in insulin divided by change in glucose from 0 to 30 min (⌬I 0 -30 /⌬G 0 -30 ).RESULTS -⌬I 0 -30 /⌬G 0 -30 demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the log e -transformed estimates included Ϫ1 for ⌬I 0 -30 /⌬G 0 -30 versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included Ϫ1 only for subjects with normal glucose tolerance (NGT) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of ⌬I 0 -30 /⌬G 0 -30 and 1/fasting insulin was calculated (DI O ) and decreased from NGT to IFG/IGT to diabetes (P Ͻ 0.001). Among nondiabetic subjects at baseline, baseline DI O predicted cumulative diabetes at 10 years (P Ͻ 0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations.CONCLUSIONS -The DI O provides a measure of ␤-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.

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Section: Discussionmentioning

confidence: 99%

Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

et al. 2009

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“…Several limitations of this study should be considered. First, insulinogenic index has been characterized by marked within-subject variability in previous studies [32]. InsAUC 30 /GluAUC 30, rather than insulinogenic index, has been reported to have a stronger correlation with the AIR measured by the IVGTT [12].…”

Section: Discussionmentioning

confidence: 94%

Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese

et al. 2012

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InsulIn resistance and impaired insulin secretion are considered the primary pathophysiological factors in the development of type 2 diabetes [1]. Although hyperglycemic and euglycemic clamp studies are wellestablished methods of assessing insulin secretion and insulin sensitivity [2,3], the oral glucose tolerance test (OGTT) is a simpler and less expensive method that provides estimates of both factors. As a measure of insulin secretion, insulinogenic index is highly correlated with the acute insulin response (AIR) on the intravenous glucose tolerance test (IVGTT) in nondiabetic subjects [4,5], and it has been widely used as an index of early-phase insulin secretion in clinical Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese Abstract. The aim of this study was to assess the changes in insulin secretion and insulin sensitivity in relation to fasting and 2-hour plasma glucose (PG) levels and to assess the independent contributions of their impairments to non-diabetic hyperglycemia. A total of 2157 Japanese workers (mean age 52.6±7.3 years and mean BMI 23.9±3.2 kg/m 2 ) underwent an oral glucose tolerance test (OGTT). Of these subjects, 1125 had normal glucose tolerance (NGT), 525 subjects had isolated impaired fasting glucose (IFG), 159 subjects had isolated impaired glucose tolerance (IGT), 263 subjects had combined IFG and IGT, and 85 subjects had newly diagnosed type 2 diabetes. Insulinogenic index and Matsuda insulin sensitivity index (ISI) were significantly attenuated in subjects with normal but slightly elevated fasting PG, or in subjects with normal but slightly elevated 2-hour PG. Whereas, InsAUC 120 /GluAUC 120 was not significantly decreased in those subjects, and significant decrease of it was observed exclusively in subjects with abnormal fasting PG (≥ 106 mg/dL) or abnormal 2-hour PG (≥ 221 mg/dL). Using multiple regression analyses, both Matsuda ISI and insulinogenic index were independently correlated with PG concentrations in subjects with IFG and/or IGT, while Matsuda ISI alone was independently correlated with fasting PG concentrations in normoglycemic subjects. In conclusion, both insulinogenic index and Matsuda ISI were significantly attenuated in subjects with normal but slightly elevated PG. Lowering of Matsuda ISI was likely to be a strong contributor to 'elevation of fasting PG within the normal range' in this population.

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“…35 The insulinogenic index, a measure of the early insulin response to oral glucose, was calculated as the difference in insulin concentration divided by the difference in glucose concentration from fasting to 30 minutes. 36 Glucose AUC was calculated as a measure of glucose tolerance. 37 …”

Section: Measurements Of Glucose and Insulin Homeostasismentioning

confidence: 99%

Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD

Zelnick

Afkarian

Ayers

et al. 2016

JASN

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Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m 2 ) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemiceuglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per mU/ml; P,0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P,0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P,0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, 20.7; 95% confidence interval, 21.4 to 0.0 mg/min per mU/ml) and insulin clearance (adjusted difference, 285; 95% confidence interval, 2160 to 210 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.

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Within-subject variability of measures of beta cell function derived from a 2 h OGTT: implications for research studies

Cited by 97 publications

References 22 publications

Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese

Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD

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