Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes.

Buchanan, Thomas A.; Xiang, Anny H.; Peters, Ruth; Kjos, Siri L.; Berkowitz, Kathleen M.; Marroquin, Aura; Goico, Jose; Ochoa, César; Azen, Stanley P.

doi:10.2337/diabetes.49.5.782

Cited by 99 publications

(68 citation statements)

References 26 publications

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“…Differences in results between our study and that by Retnakaran et al could be due to differences in error estimates, as the slopes are quite sensitive to changes in error estimates. Of note, our results are consistent with the slope estimates for the log-relationship between the acute insulin response to glucose and the insulin sensitivity index (S I ) derived from a frequently sampled intravenous glucose tolerance test (slope ϭ Ϫ0.97) (3) or between ⌬I 0 -30 /⌬G 0 -30 and S I (slope ϭ Ϫ0.86) (10).…”

Section: Discussionsupporting

confidence: 77%

“…This hyperbolic relationship has been demonstrated between measures of insulin sensitivity and response derived from intravenous tests (3) as well as between the early insulin response during an oral glucose tolerance test (OGTT) and insulin sensitivity derived from intravenous testing (10). However, intravenous tests are time-consuming, expensive, and not practical for large studies.…”

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confidence: 99%

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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: Discussionsupporting

confidence: 77%

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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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“…IVGTT glucose and insulin data were analyzed by minimal model (MINMOD Millennium version 5.18). The disposition index (DI), a measure of ␤-cell compensation for insulin resistance, was computed as the product of the insulin sensitivity index (S I ) and early insulin response (DI ϭ S I ϫ AIR from the IVGTT [11,12]; DI30 ϭ S I ϫ 30 min ⌬insulin from the OGTT [13]). …”

Section: Methodsmentioning

confidence: 99%

Transcription Factor 7-Like 2 (TCF7L2) Is Associated With Gestational Diabetes Mellitus and Interacts With Adiposity to Alter Insulin Secretion in Mexican Americans

et al. 2007

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OBJECTIVE-Variation in transcription factor 7-like 2 (TCF7L2) gene has been shown to be associated with type 2 diabetes and diabetes-related quantitative traits. We examined variation in a 0.1-Mb region surrounding marker DG10S478 for association with diabetes-related quantitative traits in 132 Mexican-American families of a proband with previous gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS-Study participantswere phenotyped by an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test and by a dual-energy X-ray absorptiometry scan for percentage of body fat. Of the 42 tag single nucleotide polymorphisms (SNPs) genotyped, 15 were identified.RESULTS-On univariate analysis, none of the SNPs showed association with diabetes-related quantitative traits. However, rs12255372 showed association with 30Ј ⌬insulin (OGTT 30Ј min fasting insulin) in an interaction with percentage of body fat (Bonferroni-corrected P ϭ 0.027). The effect of adiposity to increase 30Ј ⌬insulin was greater in subjects with the T allele. This interaction was not associated with acute insulin response to intravenous glucose. rs12255372 also showed an association with ␤-cell compensation for insulin resistance based on 30Ј ⌬insulin in an interaction with percentage of body fat (Bonferroni-corrected P ϭ 0.014). rs12255372 was also associated with GDM (odds ratio [OR] 2.49 [95% CI 1.17-5.31]; P ϭ 0.018) in our case-control sample.CONCLUSIONS-We conclude that variation in TCF7L2 is associated with GDM and interacts with adiposity to alter insulin secretion in Mexican Americans. Our observations partly explain the increased ORs observed in previous associated studies when analyses were restricted to lean subjects and the variability in quantitative trait association results.

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“…Pregnancy, due to placental hormone action, is characterized by a physiological increase of insulin resistance (IR), which has the aim to promote the use of nutrients by the fetus, especially in the second and third trimesters of pregnancy (2), however, this physiological mechanism could lead to the onset of GDM (3).…”

Section: Introductionmentioning

confidence: 99%

The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance

et al. 2017

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Abstract. The aim of the present study was to demonstrate that the use of inositol and folic acid from the first trimester of pregnancy, counteracts the onset of gestational diabetes mellitus (GDM) in women at risk, preserving the infants from macrosomia, hypoglycemia and preterm delivery. The authors collected data from the pregnant women at the laboratory (Unit of Cytogenic and Molecular Genetics), from January 2014 to April 2016, all with first trimester fasting plasma glucose (FPG) >92 mg/dl. A total of 40 women were treated with 250 mg/day D-chiro-inositol, 1.75 g/day D-myo-inositol, 12.5 mg/day zinc, 10 mg/day methylsulfonylmethane, 400 µg/day 5-methyltetrahydrofolic acid. The other 43 women (control group) were treated with only 400 µg/day folic acid. The primary outcome measure was the incidence of maternal GDM. The secondary outcome measures were the incidence of fetal macrosomia, preterm delivery and neonatal hypoglycemia. At the 24th week of pregnancy, the incidence of maternal GDM was recorded in 18 women in the control group and in 5 women in the treated group [relative risk (RR)=3.35; 95% confidence interval (CI)=1.37-8.17; P=0.0028). A significant difference was observed between treated and control groups in terms of risk of macrosomia. A total of seven infants in the control group, and two in the treated group, weighed >4,000 g (RR=5,12; 95% CI=1.21-21.68; P=0.0099). No significant difference was identified between two groups, regarding the other two secondary outcomes, neonatal hypoglycemia (RR=4.650; 95% CI= 0.57-38.11; P= 0.1086) and preterm delivery (RR=1.74; 95% CI=0.83-3.66; P=0.1301). The current study demonstrated the potential benefit of supplementation with the association of D-chiro-inositol and D-myo-inositol in pregnant 'at risk' women, with first trimester FPG >92 mg/dl, in preventing the onset of maternal GDM and macrosomia in newborns.

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Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes.

Cited by 99 publications

References 26 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

Transcription Factor 7-Like 2 (TCF7L2) Is Associated With Gestational Diabetes Mellitus and Interacts With Adiposity to Alter Insulin Secretion in Mexican Americans

The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance

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