Increased insulin secretion in puberty: A compensatory response to reductions in insulin sensitivity

Caprio, Sonia; Plewe, G.; Diamond, Michael P.; Simonson, Donald C.; Boulware, Susan D.; Sherwin, Robert S.; Tamborlane, William V.

doi:10.1016/s0022-3476(89)80438-x

Cited by 296 publications

(194 citation statements)

References 13 publications

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“…12,34 Pubertal insulin resistance has been well documented in several cross-sectional studies. 8,35 Pubertal development is associated with an approximately 25-30% reduction in insulin sensitivity, with a peak reduction at Tanner stage III, followed by recovery by Tanner stage V. 8 This drop may be driven by the transient increase in growth hormone levels during puberty. Growth hormone may also contribute to insulin resistance via its effect on increasing lipolysis and free fatty acid concentrations.…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

et al. 2005

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OBJECTIVE:To establish the prevalence of insulin resistance and impaired glucose tolerance (IGT) and their determinants in a cohort of obese children and adolescents. METHODS: A retrospective design was used. The study group included 234 patients with a body mass index (BMI) greater than the 95th percentile for age and gender and 22 patients with a BMI between the 85th and 95th percentile for age and gender referred for evaluation to a major tertiary-care center in Israel. Ages ranged from 5 to 22 y. Estimates of insulin resistance (homeostatic model assessment (HOMA-IR)); insulin sensitivity (ratio of fasting glucose (GF) to fasting insulin (IF) (GF/IF), the quantitative insulin sensitivity check index (QUICKI)), and pancreatic b-cell function (HOMA-derived b-cell function (HOMA %B)) were derived from fasting measurements. An oral glucose tolerance test (OGTT) was performed in 192 patients to determine the presence of IGT. RESULTS: Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. Only two patients with IGT also had impaired fasting glucose (IFG). The prevalence of IGT was higher in adolescents than prepubertal children (14.7 vs 8.6%). GF/IF and QUICKI decreased significantly during puberty (Po0.005), whereas HOMA-IR and HOMA %B did not. Insulin resistance and insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or family history of type 2 diabetes. Patients with obesity complications had lower insulin sensitivity indexes than those without (P ¼ 0.05). Compared with subjects with normal glucose tolerance (NGT), patients with IGT had significantly higher fasting blood glucose (85.976.5 vs 89.2710.6 mg/dl, Po0.05), higher 2-h post-OGGT insulin levels (101.2774.0 vs 207.67129.7 mU/ml, Po0.001), a lower QUICKI (0.32370.031 vs 0.30970.022, Po0.05), and higher fasting triglyceride levels (117.4753.1 vs 156.9768.9, P ¼ 0.002). However, several of the fasting indexes except QUICKI failed to predict IGT. There was no difference between the group with IGT and the group with NGT in fasting insulin, HOMA-IR, HOMA %B or the male-to-female ratio, age, BMI-SDS, presence of acanthosis nigricans, ethnicity, and family history of type 2 diabetes. CONCLUSIONS: Insulin resistance is highly prevalent in obese children and adolescents. The onset of IGT is associated with the development of severe hyperinsulinemia as there are no predictive cutpoint values of insulin resistance or insulin sensitivity indexes for IGT, and neither fasting blood glucose nor insulin levels nor HOMA-IR or HOMA %B are effective screening tools; an OGTT is required in all subjects at high risk. Longitudinal studies are needed to identify the metabolic precursors and the natural history of the development of type 2 diabetes in these patients.

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Section: Discussionmentioning

confidence: 99%

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

et al. 2005

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“…The transient insulin resistance of puberty [44] that is associated with a compensatory increase in insulin secretion [45] might accelerate progression of beta cell failure because of the additional stress on insulin-producing cells during crucial periods of growth and development, but the mechanism(s) contributing to the resistance has not been clearly determined. The hypothesis that reduced insulin sensitivity is driven by transient changes in growth hormone levels during puberty [46] is attractive, since growth hormone and IGF-1 levels are transiently higher in mid-puberty and mirror the changes in insulin sensitivity [47].…”

Section: Puberty and Adolescencementioning

confidence: 99%

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mezza

Kulkarni

2014

Diabetologia

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Regeneration of mature cells that produce functional insulin represents a major focus and a challenge of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes, as well as in ageing. The capacity to adapt to diverse physiological states during life and the consequent ability to cope with increased metabolic demands in the normal regulation of glucose homeostasis is a distinctive feature of the endocrine pancreas in mammals. Both beta and alpha cells, and presumably other islet cells, are dynamically regulated via nutrient, neural and/or hormonal activation of growth factor signalling and the post-transcriptional modification of a variety of genes or via the microbiome to continually maintain a balance between regeneration (e.g. proliferation, neogenesis) and apoptosis. Here we review key regulators that determine islet cell mass at different ages in mammals. Understanding the chronobiology and the dynamics and agedependent processes that regulate the relationship between the different cell types in the overall maintenance of an optimally functional islet cell mass could provide important insights into planning therapeutic approaches to counter and/or prevent the development of diabetes.

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“…[1][2][3][4] In Caucasian children, decreased SI during puberty is accompanied by increased insulin secretion that normalizes as insulin resistance improves near the end of puberty. 5 Cross-sectionally, Moran et al 3 showed that SI (measured using the euglycemic-hyperinsulinemic clamp) was highest in Tanner stage I, lowest in Tanner stage III (B20% lower than stage I), and near prepubertal levels in Tanner stage V. Using a longitudinal design, Goran and Gower 2 observed that the pubertal transition from Tanner stage I to III was associated with a 32% reduction in SI (measured by the intravenous glucose tolerance test and minimal modeling) in Caucasian and African-Americans which was consistent across a range of body fatness. Our research group has previously demonstrated that Hispanic and African-American children have lower SI in relation to Caucasians, and while Hispanics compensate for their lower SI by increasing insulin secretion, African-Americans exhibit reduced insulin clearance to help maintain normoglycemia.…”

Section: Introductionmentioning

confidence: 99%

Insulin sensitivity, insulin secretion and β-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes

et al. 2005

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OBJECTIVE:To examine cross-sectional differences in insulin sensitivity, insulin secretion and b-cell function during puberty in overweight Hispanic boys and girls with a family history of type 2 diabetes. STUDY DESIGN AND PARTICIPANTS: This cross-sectional, observational study included 214 8-13-y-old Hispanic children with a BMI percentile Z85th percentile and family history of type 2 diabetes. METHODS AND ANALYSES: Participants underwent a physical examination, body composition measures, oral glucose tolerance test (OGTT), and frequently-sampled intravenous glucose tolerance test. Unadjusted and adjusted general linear models (GLM) tested whether insulin/glucose dynamics differed by Tanner stage and gender. RESULTS: Unadjusted group comparisons showed that fasting insulin increased whereas insulin sensitivity (SI) and the disposition index (DI) (a measure of pancreatic b-cell function) decreased across Tanner stage groups (all Po0.05). No differences in the acute insulin response to glucose (AIRg), fasting glucose or 2-h glucose were found. After adjusting for covariates, there was no independent effect of Tanner stage on SI (P ¼ 0.9) or AIRg (P ¼ 0.2), but DI was slightly lower in later Tanner stages suggesting decreased b-cell function in the more mature groups (P ¼ 0.10). CONCLUSIONS: Overweight Hispanic children with a family history of type 2 diabetes may represent a unique population given that pubertal insulin resistance was not evident once analyses controlled for body composition. Longitudinal analyses are required to determine whether the slightly diminished b-cell function in later Tanner stages plays a role in the development of type 2 diabetes.

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Increased insulin secretion in puberty: A compensatory response to reductions in insulin sensitivity

Cited by 296 publications

References 13 publications

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Insulin sensitivity, insulin secretion and β-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes

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