Oral minimal model-based estimates of insulin sensitivity in obese youth depend on oral glucose tolerance test protocol duration

Bartlette, Kai; Carreau, Anne‐Marie; Xie, Danielle; Garcia‐Reyes, Yesenia; Rahat, Haseeb; Pyle, Laura; Nadeau, Kristen J.; Cree-Green, Melanie; Behn, Cecilia Diniz

doi:10.1016/j.metop.2021.100078

Cited by 11 publications

(16 citation statements)

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“…Future studies aiming to assess the relationship between pancreatic fat and postprandial insulin response may want to use longer OGTT protocols. Bartlette et al described duration dependence in OMM Si (32). In order to rule out an effect of duration dependence in the relationship between OMM Si and PFF in this study, we examined a subgroup of girls who completed a 6‐hour OGTT to determine whether the 6‐hour OMM Si would be related to PFF.…”

Section: Discussionmentioning

confidence: 99%

“…For APPLE and PLUM, 2‐hour OMM Si included time points 0, 10, 30, 60, 90, and 120 minutes, whereas AIRS included 0, 15, 30, 60, 90, and 120 minutes. A 6‐hour OMM Si was also calculated for APPLE and PLUM to account for potential method dependence in OMM Si estimates in this cohort ( n = 56) (32). The insulinogenic index was calculated to measure first‐phase insulin secretion during the OGTT ([Insulin 30 − Insulin 0 ]/[Glucose 30 − Glucose 0 ]) (30).…”

Section: Methodsmentioning

confidence: 99%

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Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity

Ware

Kaar

Behn

et al. 2021

Obesity

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Objective: Adolescents with polycystic ovary syndrome (PCOS) and obesity can have insulin resistance, dysglycemia, and hepatic steatosis. Excess pancreatic fat may disturb insulin secretion and relate to hepatic fat. Associations between pancreatic fat fraction (PFF) and metabolic measures in PCOS were unknown. Methods:This secondary analysis included 113 sedentary, nondiabetic adolescent girls (age = 15.4 [1.9] years), with or without PCOS and BMI ≥ 90th percentile.Participants underwent fasting labs, oral glucose tolerance tests, and magnetic resonance imaging for hepatic fat fraction (HFF) and PFF. Groups were categorized by PFF (above or below the median of 2.18%) and compared.Results: Visceral fat and HFF were elevated in individuals with PCOS versus control individuals, but PFF was similar. PFF did not correlate with serum androgens. Higher and lower PFF groups had similar HFF, with no correlation between PFF and HFF, although hepatic steatosis was more common in those with higher PFF (≥5.0% HFF; 60% vs. 36%; p = 0.014). The higher PFF group had higher fasting insulin (p = 0.026), fasting insulin resistance (homeostatic model assessment of insulin resistance, p = 0.032; 1/fasting insulin, p = 0.028), free fatty acids (p = 0.034), and triglycerides (p = 0.004) compared with those with lower PFF. β-Cell function and insulin sensitivity were similar between groups. Conclusions:Neither PCOS status nor androgens related to PFF. However, fasting insulin and postprandial lipids were worse with higher PFF.Data are presented as mean ± SD or median and interquartile range (25th, 75th). Impaired fasting glucose is >90 mg/dL. Impaired glucose tolerance is ≥140 mg/dL at 2 hours post glucose load in the OGTT. Prediabetes is HbA1c between 5.7% and 6.4% or impaired fasting glucose (glucose > 90 mg/dL) or impaired glucose tolerance (glucose ≥ 140 mg/dL at 2 hours post glucose load in the OGTT).Abbreviations: HbA1c, hemoglobin A1c; HOMA-IR, homeostatic model assessment of insulin resistance; ISSI-2, insulin secretion-sensitivity index-2; OMM, oral minimal model; PFF, pancreatic fat fraction; Si, insulin sensitivity; WBISI, whole-body insulin sensitivity index. a Excludes participants taking exenatide (n = 8).b n = 66.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity

Ware

Kaar

Behn

et al. 2021

Obesity

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“…The limited number of samples were contributed to fit the Ra curve. For another reason, different groups have varying Ra curves—for example, the Ra curves of obese adolescents have more peaks ( 34 ). Additionally, tracer approaches have also been used to determine the Ra experimentally.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl-Peptidase-IV Inhibitors, Imigliptin and Alogliptin, Improve Beta-Cell Function in Type 2 Diabetes

Liu

et al. 2021

Front. Endocrinol.

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ObjectsImigliptin is a novel dipeptidyl peptidase-4 inhibitor. In the present study, we aimed to evaluate the effects of imigliptin and alogliptin on insulin resistance and beta-cell function in Chinese patients with type-2 diabetes mellitus (T2DM).MethodsA total of 37 Chinese T2DM patients were randomized to receive 25 mg imigliptin, 50 mg imigliptin, placebo, and 25 mg alogliptin (positive drug) for 13 days. Oral glucose tolerance tests were conducted at baseline and on day 13, followed by the oral minimal model (OMM).ResultsImigliptin or alogliptin treatment, compared with their baseline or placebo, was associated with higher beta-cell function parameters (φs and φtot) and lower glucose area under the curve (AUC) and postprandial glucose levels. The changes in the AUC for the glucose appearance rate between 0 and 120 min also showed a decrease in imigliptin or alogliptin groups. However, the insulin resistance parameter, fasting glucose, was not changed. For the homeostatic model assessment (HOMA-β and HOMA-IR) parameters or secretory units of islets in transplantation index (SUIT), no statistically significant changes were found both within treatments and between treatments.ConclusionsAfter 13 days of treatment, imigliptin and alogliptin could decrease glycemic levels by improving beta-cell function. By comparing OMM with HOMA or SUIT results, glucose stimulation might be more sensitive for detecting changes in beta-cell function.

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“…This formula was also used to calculate a “free 11-oxyandrogen index” for each of the 3 metabolites. Measures of insulin sensitivity included the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) calculated as fasting plasma glucose [mg/dL] × fasting plasma insulin [mg/dL]/405 [ 13 ], the Matsuda index as 10 000/(sqrt(fasting glucose*fasting insulin*mean glucose*mean insulin) [ 20 ], and the oral minimal model calculated with a 2-hour exponential model using SAAM II software (SAAM II software v 2.2, The Epsilon Group) [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome

Taylor

Ware

Breslow

et al. 2022

Journal of the Endocrine Society

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Background/context Polycystic ovary syndrome (PCOS) is common and diagnosis requires an elevated testosterone. The clinical importance of adrenal 11-oxyandrogens in PCOS is unclear. We sought to determine if 11-oxyandrogens: 1) better identify PCOS diagnosis compared to testosterone 2) predict clinical comorbidities of PCOS, 3) are altered with combined oral contraceptive pill (COCP) or metformin therapy. Methods Data from 200 adolescent females aged 12-21 years, most with obesity, enrolled across 6 studies in pediatric endocrinology were included: 70 non-PCOS controls, 115 untreated PCOS, 9 PCOS+obesity treated with COCP, 6 PCOS+obesity treated with metformin. 11-hydroxyandrostenedione (11OHA4), 11-hydroxytestosterone (1-OHT), 11-ketotestosterone (11KT) and testosterone were measured with LC/MSMS. Data between 1) untreated PCOS and controls and 2) untreated PCOS and the 2 treatment groups were compared. Results Untreated girls with PCOS had higher 11OHA4 (p=0.003) and 11OHT (p=0.005) compared to controls, but not 11KT (p=0.745). Elevated 11OHA4 remained significant after controlling for obesity. Testosterone better predicted PCOS status compared to 11-oxyandrogens (ROC analysis: 11OHA4 AUC=0.620, 11OHT AUC=0.638; testosterone AUC=0.840). Among untreated PCOS, all three 11-oxyandrogens correlated with hirsutism severity. 11KT (p=0.039) and testosterone (p<0.006) was lower in those on COCP treatment compared to untreated PCOS). Metformin treatment had no effect on 11-oxyandrogens, although testosterone was lower (p=0.01). Conclusions/Relevance While 11-oxyandrogens do not aid in the diagnosis of PCOS, they relate to excess hair growth. COCP treatment may related to 11-KT, however, further work is needed to determine causality, relationship with metabolic outcomes, and the clinical utility of measuring these androgens in PCOS.

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Oral minimal model-based estimates of insulin sensitivity in obese youth depend on oral glucose tolerance test protocol duration

Cited by 11 publications

References 51 publications

Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity

Pancreatic fat relates to fasting insulin and postprandial lipids but not polycystic ovary syndrome in adolescents with obesity

Dipeptidyl-Peptidase-IV Inhibitors, Imigliptin and Alogliptin, Improve Beta-Cell Function in Type 2 Diabetes

11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome

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