Utility of early insulin response and proinsulin to assess insulin resistance
Amy M Jean, Abeer Hassoun, Jennifer Hughes, Christy Pomeranz, Ilene Fennoy, Donald J McMahon, Sharon E Oberfield, Amy M Jean, Abeer Hassoun, Jennifer Hughes, Christy Pomeranz, Ilene Fennoy, Donald J McMahon, Sharon E Oberfield
Abstract
Objective: To determine whether obesity and premature adrenarche are additive events increasing the risk of insulin resistance and beta-cell failure, using early insulin response (EIR) or the insulinogenic index and proinsulin (PI) as markers.
Study design: This was a prospective case-control study conducted at a tertiary care academic medical center involving 81 prepubertal, predominantly Hispanic children (34 males, 47 females), classified as lean controls (4 males, 6 females; mean age, 6.5 +/- 1.2 years; mean body mass index [BMI] z-score, 0.08 +/- 0.6), obese controls (20 males, 10 females; mean age, 7.2 +/- 1.5 years; mean BMI z-score, 2.5 +/- 0.5), lean premature adrenarche (3 males, 11 females; mean age, 7.1 +/- 1.2 years; mean BMI z-score, 0.09 +/- 0.6), and obese premature adrenarche (7 males, 20 females; mean age, 7.3 +/- 1.0; mean BMI z-score, 2.2 +/- 0.4). Fasting glucose (G(0)), insulin (I(0)), PI(0), androgen levels, insulin-like growth factor 1, insulin-like growth factor binding protein 1, and lipid levels were obtained. An oral glucose tolerance test was performed. EIR was calculated as (I(30) - I(0))/(G(30) - G(0)). Between-group differences were assessed by 2-way analysis of variance, with interactions and associations explored with correlation/regression.
Results: EIR was greater in the obese subjects with and without premature adrenarche. Combined analysis of the independent variables obesity and premature adrenarche showed that the obese premature adrenarche group had the highest EIR. The obese subjects with premature adrenarche had greater fasting PI levels than their lean counterparts. The differences in fasting PI/I ratio among the groups were not statistically significant.
Conclusions: Using EIR and PI as markers to assess the risk of insulin resistance and impaired insulin secretion indicates that obese children with premature adrenarche may be at greater risk for the development of prediabetes and type 2 diabetes mellitus compared with their lean counterparts.
Figures
![Figure 1. Glucose, Insulin, Proinsulin OGTT Results](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2823814/bin/nihms123343f1.jpg)
Figure 2. Markers of Insulin Sensitivity
Δ…
Figure 2. Markers of Insulin Sensitivity
Δ = lean premature adrenarche vs lean controls, †…
- Body mass index at the presentation of premature adrenarche is associated with components of metabolic syndrome at puberty.Kaya G, Yavas Abali Z, Bas F, Poyrazoglu S, Darendeliler F. Kaya G, et al. Eur J Pediatr. 2018 Nov;177(11):1593-1601. doi: 10.1007/s00431-018-3211-1. Epub 2018 Jul 28. Eur J Pediatr. 2018. PMID: 30056577
- Prediction models for insulin resistance in girls with premature adrenarche. The premature adrenarche insulin resistance score: PAIR score.Vuguin P, Grinstein G, Freeman K, Saenger P, DiMartino Nardi J. Vuguin P, et al. Horm Res. 2006;65(4):185-91. doi: 10.1159/000092103. Epub 2006 Mar 17. Horm Res. 2006. PMID: 16549934
- The roles of insulin sensitivity, insulin-like growth factor I (IGF-I), and IGF-binding protein-1 and -3 in the hyperandrogenism of African-American and Caribbean Hispanic girls with premature adrenarche.Vuguin P, Linder B, Rosenfeld RG, Saenger P, DiMartino-Nardi J. Vuguin P, et al. J Clin Endocrinol Metab. 1999 Jun;84(6):2037-42. doi: 10.1210/jcem.84.6.5722. J Clin Endocrinol Metab. 1999. PMID: 10372707
- Insulin sensitivity and the insulin-like growth factor system in prepubertal boys with premature adrenarche.Denburg MR, Silfen ME, Manibo AM, Chin D, Levine LS, Ferin M, McMahon DJ, Go C, Oberfield SE. Denburg MR, et al. J Clin Endocrinol Metab. 2002 Dec;87(12):5604-9. doi: 10.1210/jc.2002-020896. J Clin Endocrinol Metab. 2002. PMID: 12466359
- Pre- and postpuberal findings in premature adrenarche.DiMartino-Nardi J. DiMartino-Nardi J. J Pediatr Endocrinol Metab. 2000;13 Suppl 5:1265-9. J Pediatr Endocrinol Metab. 2000. PMID: 11117667 Review.
- The Unique Role of 11-Oxygenated C19 Steroids in Both Premature Adrenarche and Premature Pubarche.Wise-Oringer BK, Burghard AC, O'Day P, Hassoun A, Sopher AB, Fennoy I, Williams KM, Vuguin PM, Nandakumar R, McMahon DJ, Auchus RJ, Oberfield SE. Wise-Oringer BK, et al. Horm Res Paediatr. 2020;93(7-8):460-469. doi: 10.1159/000513236. Epub 2021 Feb 2. Horm Res Paediatr. 2020. PMID: 33530089 Free PMC article.
- The Relationship of Metabolic Syndrome and Body Composition in Children with Premature Adrenarche: Is It Age Related?Williams KM, Oberfield SE, Zhang C, McMahon DJ, Sopher AB. Williams KM, et al. Horm Res Paediatr. 2015;84(6):401-7. doi: 10.1159/000441498. Epub 2015 Oct 30. Horm Res Paediatr. 2015. PMID: 26513727 Free PMC article.
- Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 y in Chilean children of normal birth weight.Corvalán C, Uauy R, Mericq V. Corvalán C, et al. Am J Clin Nutr. 2013 Feb;97(2):318-25. doi: 10.3945/ajcn.112.037325. Epub 2013 Jan 2. Am J Clin Nutr. 2013. PMID: 23283497 Free PMC article.
- Bone age advancement in prepubertal children with obesity and premature adrenarche: possible potentiating factors.Sopher AB, Jean AM, Zwany SK, Winston DM, Pomeranz CB, Bell JJ, McMahon DJ, Hassoun A, Fennoy I, Oberfield SE. Sopher AB, et al. Obesity (Silver Spring). 2011 Jun;19(6):1259-64. doi: 10.1038/oby.2010.305. Epub 2011 Feb 10. Obesity (Silver Spring). 2011. PMID: 21311512 Free PMC article.
- Research Support, N.I.H., Extramural
- Adrenarche / metabolism*
- Blood Glucose / metabolism
- Body Mass Index
- Case-Control Studies
- Child
- Child, Preschool
- Cohort Studies
- Female
- Humans
- Insulin Resistance / physiology*
- Male
- Obesity / complications
- Obesity / metabolism*
- Proinsulin / metabolism*
- Puberty, Precocious / complications
- Puberty, Precocious / metabolism*
- Reproducibility of Results
- Risk Factors
- Blood Glucose
- Proinsulin
- Full Text Sources
- Medical
- Research Materials
- Miscellaneous
![Figure 2. Markers of Insulin Sensitivity](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2823814/bin/nihms123343f2.jpg)
Source: PubMed