β-Cell Function, Insulin Sensitivity, and Glucose Tolerance in Obese Diabetic and Nondiabetic Adolescents and Young Adults

Elder, Deborah A.; Prigeon, Ronald L.; Wadwa, R. Paul; Dolan, Lawrence M.; D’Alessio, David A.

doi:10.1210/jc.2005-0853

Cited by 74 publications

(83 citation statements)

References 37 publications

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“…Recent studies from a group in Ohio, USA, used OGTT and IVGTT to show that adolescents with type 2 diabetes have significant insulin resistance, even compared with non-diabetic subjects of similar obesity and body fatness, and impaired insulin secretion relative to their degree of insulin resistance [28]. In contrast to our findings, the diabetic subjects in those studies retained a first-phase insulin response to glucose that was comparable with lean control subjects.…”

Section: Discussioncontrasting

confidence: 96%

Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training

et al. 2007

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Aims/hypothesis Early-onset type 2 diabetes is associated with marked visceral obesity and extreme insulin resistance, but its pathogenesis and response to treatment are not completely understood. We studied physical fitness, wholebody and hepatic glucose turnover, and insulin secretion in young obese Irish subjects before and after 3 months of aerobic exercise training. We hypothesised that exercise alone, with stable diet, should improve insulin sensitivity. Materials and methods Anthropometric parameters and maximum volume of oxygen utilisation (VO 2max ) were measured in 13 subjects with type 2 diabetes and 18 nondiabetic control subjects, matched for age and BMI. Insulin sensitivity and hepatic glucose turnover were measured using the hyperinsulinaemic-euglycaemic clamp. Insulin secretion was assessed from an OGTT and a modified intravenous glucose tolerance test. Some subjects (seven type 2 diabetic, 14 non-diabetic control subjects) then completed a 12-week supervised aerobic exercise programme. All measurements were repeated on completion of the exercise programme. Results Type 2 diabetic subjects had higher WHR, systolic blood pressure and triacylglycerols than non-diabetic control subjects. They were significantly more insulinresistant as measured both by the clamp and oral glucose insulin sensitivity. They also displayed marked defects in insulin secretion in response to oral and intravenous glucose challenges. Exercise intervention had no significant effect on whole-body or hepatic insulin sensitivity or insulin secretion. VO 2max increased significantly in the non-diabetic control subjects, but not in the type 2 diabetic subjects after exercise training. Conclusions/interpretation Young obese subjects with type 2 diabetes are severely insulin-resistant with marked loss of beta cell function compared with control subjects matched for age and obesity. Neither group responded metabolically to aerobic exercise intervention.

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Section: Discussioncontrasting

confidence: 96%

Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training

et al. 2007

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“…Accordingly, β cell function, assessed as total meal-induced insulin secretion in relationship to insulin sensitivity (i.e., DI), increased approximately 75% in both surgical groups. These data suggest the deterioration in β cell function that occurs as obese people progress from normal glucose homeostasis to T2DM (14) can be prevented by weight loss induced by either LAGB or RYGB surgery.…”

Section: Discussionmentioning

confidence: 85%

Gastric bypass and banding equally improve insulin sensitivity and β cell function

Bradley¹,

Conte²,

et al. 2012

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Bariatric surgery in obese patients is a highly effective method of preventing or resolving type 2 diabetes mellitus (T2DM); however, the remission rate is not the same among different surgical procedures. We compared the effects of 20% weight loss induced by laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery on the metabolic response to a mixed meal, insulin sensitivity, and β cell function in nondiabetic obese adults. The metabolic response to meal ingestion was markedly different after RYGB than after LAGB surgery, manifested by rapid delivery of ingested glucose into the systemic circulation, by an increase in the dynamic insulin secretion rate, and by large, early postprandial increases in plasma glucose, insulin, and glucagon-like peptide-1 concentrations in the RYGB group. However, the improvement in oral glucose tolerance, insulin sensitivity, and overall β cell function after weight loss were not different between surgical groups. Additionally, both surgical procedures resulted in a similar decrease in adipose tissue markers of inflammation. We conclude that marked weight loss itself is primarily responsible for the therapeutic effects of RYGB and LAGB on insulin sensitivity, β cell function, and oral glucose tolerance in nondiabetic obese adults.

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“…Plasma concentration of fructosamine indicates the amount of glycated protein and is considered a good index of glucose levels over a preceding period of 2-3 weeks; in our particular case of suckling piglets, this parameter may be even more reliable that a single-point glucose determination. Thus, these results would indicate a certain impairment of glucose regulation, possibly related to increases in fat-content because adiposity increases insulin resistance in human young individuals (Elder et al 2006, Scheen 2010.…”

Section: Discussionmentioning

confidence: 91%

Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance

González-Bulnes¹,

Astiz²,

Óvilo³

et al. 2014

Journal of Endocrinology

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Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre-and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity.

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β-Cell Function, Insulin Sensitivity, and Glucose Tolerance in Obese Diabetic and Nondiabetic Adolescents and Young Adults

Cited by 74 publications

References 37 publications

Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training

Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training

Gastric bypass and banding equally improve insulin sensitivity and β cell function

Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance

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