Insulin dynamics predict body mass index and z-score response to insulin suppression or sensitization pharmacotherapy in obese children

Published: The Journal of Pediatrics
Date:
Authors: Robert H Lustig 1 , Michele L Mietus-Snyder, Peter Bacchetti, Ann A Lazar, Pedro A Velasquez-Mieyer, Michael L Christensen
Abstract:
To assess the use of oral glucose tolerance testing (OGTT) to predict efficacy of insulin sensitization (metformin) or suppression (octreotide) because insulin resistance and insulin hypersecretion may impact pharmacotherapeutic efficacy in obese children.

Single- and multiple-dose pharmacokinetics of pioglitazone in adolescents with type 2 diabetes

Published: The Journal of Clinical Pharmacology
Date:
Authors: Michael L Christensen 1 , Bernd Meibohm, Edmund V Capparelli, Pedro Velasquez-Mieyer, George A Burghen, William V Tamborlane
Abstract:
This study assessed the single- and multiple-dose pharmacokinetics of 3 doses (15 mg, 30 mg, and 45 mg) of pioglitazone in 36 adolescents with type 2 diabetes.

Obesity, leptin resistance, and the effects of insulin reduction

Published: International journal of obesity and related metabolic disorders
Date:
Authors: R H Lustig 1 , S Sen, J E Soberman, P A Velasquez-Mieyer
Abstract:
Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity.

Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults

Published: International journal of obesity and related metabolic disorders
Date:
Authors: P A Velasquez-Mieyer 1 , G E Umpierrez, R H Lustig, A K Cashion, P A Cowan, M Christensen, K A Spencer, G A Burghen
Abstract:
This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR Depot; Novartis) on the enteroinsular axis in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct beta-cell effect and through mediating a glucagon-like peptide 1 (GLP-1) response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations.

Type 2 diabetes mellitus in children and adolescents: the new challenge

Published: Journal of Pediatric Pharmacology and Therapeutics
Date:
Authors: Michael L Christensen 1 , Sahar M Rashed, Julie Sinclair, Patricia A Cowan, Pedro Velasquez-Mieyer, George A Burghen
Abstract:
The epidemic increase in the incidence of type 2 diabetes mellitus (T2DM) in children and adolescents is presenting enormous challenges to the medical profession. The combination of factors such as obesity, ethnicity, puberty, and genetic predisposition has contributed to the development of T2DM in younger ages.

Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects

Published: International journal of obesity and related metabolic disorders
Date:
Authors: P A Velasquez-Mieyer 1 , P A Cowan, G E Umpierrez, R H Lustig, A K Cashion, G A Burghen
Abstract:
Obese African-American (AA) subjects have higher resting and stimulated insulin concentrations than obese Caucasians (C), which could not be explained by the severity of obesity or the degree of insulin sensitivity. We investigated whether differences in glucagon-like peptide-1 (GLP-1), the most potent incretin that regulates insulin secretion, might explain racial differences in insulin response.

Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults

Published: International journal of obesity and related metabolic disorders
Date:
Authors: P A Velasquez-Mieyer 1 , P A Cowan, K L Arheart, C K Buffington, K A Spencer, B E Connelly, G W Cowan, R H Lustig
Abstract:
Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults.

Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist

Published: The Journal of Pediatrics
Date:
Authors: R H Lustig 1 , S R Rose, G A Burghen, P Velasquez-Mieyer, D C Broome, K Smith, H Li, M M Hudson, R L Heideman, L E Kun
Abstract:
Hypothalamic obesity is a rare sequela of cranial insult, for which pathogenesis and treatment remain obscure. In rodents ventromedial hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin resistance. Reduction of insulin secretion in humans may attenuate weight gain.