Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Published: The New England Journal of Medicine
Date:
Authors: Vlado Perkovic 1 , Meg J Jardine 1 , Bruce Neal 1 , Severine Bompoint 1 , Hiddo J L Heerspink 1 , David M Charytan 1 , Robert Edwards 1 , Rajiv Agarwal 1 , George Bakris 1 , Scott Bull 1 , Christopher P Cannon 1 , George Capuano 1 , Pei-Ling Chu 1 , Dick de Zeeuw 1 , Tom Greene 1 , Adeera Levin 1 , Carol Pollock 1 , David C Wheeler 1 , Yshai Yavin 1 , Hong Zhang 1 , Bernard Zinman 1 , Gary Meininger 1 , Barry M Brenner 1 , Kenneth W Mahaffey 1 , CREDENCE Trial Investigators
Abstract:
Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.

The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics

Published: American Journal of Nephrology
Date:
Authors: Meg J Jardine 1 2 , Kenneth W Mahaffey 3 , Bruce Neal 1 4 5 6 , Rajiv Agarwal 7 , George L Bakris 8 , Barry M Brenner 9 , Scott Bull 10 , Christopher P Cannon 11 , David M Charytan 12 , Dick de Zeeuw 13 , Robert Edwards 10 , Tom Greene 14 , Hiddo J L Heerspink 13 , Adeera Levin 15 , Carol Pollock 16 , David C Wheeler 17 , John Xie 10 , Hong Zhang 18 , Bernard Zinman 19 , Mehul Desai 10 , Vlado Perkovic 1 , CREDENCE study investigators
Abstract:
People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitors lower plasma glucose by reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion.

Racial disparity in glucagon-like peptide 1 and inflammation markers among severely obese adolescents

Published: Diabetes Care
Date:
Authors: Pedro A Velásquez-Mieyer 1 , Patricia A Cowan, Sylvia Pérez-Faustinelli, Ramfis Nieto-Martínez, Cesar Villegas-Barreto, Elizabeth A Tolley, Robert H Lustig, Bruce S Alpert
Abstract:
Compared with Caucasians, obese African-American adolescents have a higher risk for type 2 diabetes. Subclinical inflammation and reduced glucagon-like peptide 1 (GLP-1) concentration are linked to the pathogenesis of the disease.

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.

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.