Silva Arslanian1,2, Joon Young Kim1, Alexis Nasr1, Fida Bacha3, Hala Tfayli4, SoJung Lee1, Frederico G S Toledo5. 1. Division of Weight Management and Wellness, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. 2. Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. 3. Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas. 4. Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon. 5. Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
OBJECTIVE: Youth type 2 diabetes mellitus (T2DM) occurs decades earlier than adult T2DM and is characterized by high therapeutic failure rates and decreased response to insulin sensitizers suggesting a more severe disease process than in adults. To explain these observations, we hypothesized that insulin resistance is worse in obese youth than adults with impaired glucose tolerance (IGT), a state of high-risk for T2DM. As proof-of-concept, we compared insulin sensitivity between BMI-, sex-, and race-matched obese youth vs adults with IGT. METHODS: This retrospective analysis of IGT youth and adults included 34 obese adolescents matched (2:1) for BMI, sex, and race to 17 adults. Hepatic and peripheral insulin sensitivity were measured by [6,6-2 H2 ]glucose and hyperinsulinemic-euglycemic clamp. Body composition (DEXA) and serum lipid profile were examined. RESULTS: Despite similar percent body fat, obese adolescents had 2-fold higher fasting insulin concentration, lower hepatic (~53%) and peripheral (~42%) insulin sensitivity and lower HDL compared with adults (all P < .01). Surrogate estimate of insulin sensitivity, 1/fasting insulin was lower and HOMA-IR was higher in adolescents vs adults. Adults had a more atherogenic lipid profile with higher total-, LDL-, and non-HDL cholesterol. CONCLUSIONS: Obese youth and adults with IGT differ in that youth are more insulin resistant than adults in spite of similar adiposity. This could potentially explain the earlier onset of T2DM in youth through an early and amplified burden on a β-cell destined to decompensate, and explicate their lower therapeutic response to insulin sensitizers.
OBJECTIVE: Youth type 2 diabetes mellitus (T2DM) occurs decades earlier than adult T2DM and is characterized by high therapeutic failure rates and decreased response to insulin sensitizers suggesting a more severe disease process than in adults. To explain these observations, we hypothesized that insulin resistance is worse in obese youth than adults with impaired glucose tolerance (IGT), a state of high-risk for T2DM. As proof-of-concept, we compared insulin sensitivity between BMI-, sex-, and race-matched obese youth vs adults with IGT. METHODS: This retrospective analysis of IGT youth and adults included 34 obese adolescents matched (2:1) for BMI, sex, and race to 17 adults. Hepatic and peripheral insulin sensitivity were measured by [6,6-2 H2 ]glucose and hyperinsulinemic-euglycemic clamp. Body composition (DEXA) and serum lipid profile were examined. RESULTS: Despite similar percent body fat, obese adolescents had 2-fold higher fasting insulin concentration, lower hepatic (~53%) and peripheral (~42%) insulin sensitivity and lower HDL compared with adults (all P < .01). Surrogate estimate of insulin sensitivity, 1/fasting insulin was lower and HOMA-IR was higher in adolescents vs adults. Adults had a more atherogenic lipid profile with higher total-, LDL-, and non-HDL cholesterol. CONCLUSIONS:Obese youth and adults with IGT differ in that youth are more insulin resistant than adults in spite of similar adiposity. This could potentially explain the earlier onset of T2DM in youth through an early and amplified burden on a β-cell destined to decompensate, and explicate their lower therapeutic response to insulin sensitizers.
Authors: Fida Bacha; Laure El Ghormli; Silva Arslanian; Philip Zeitler; Lori M Laffel; Lorraine E Levitt Katz; Rachelle Gandica; Nancy T Chang; Jennifer E Sprague; Sarah A Macleish Journal: Pediatr Diabetes Date: 2019-08-27 Impact factor: 4.866
Authors: Janey S A Pratt; Allen Browne; Nancy T Browne; Matias Bruzoni; Megan Cohen; Ashish Desai; Thomas Inge; Bradley C Linden; Samer G Mattar; Marc Michalsky; David Podkameni; Kirk W Reichard; Fatima Cody Stanford; Meg H Zeller; Jeffrey Zitsman Journal: Surg Obes Relat Dis Date: 2018-03-23 Impact factor: 4.734
Authors: Joon Young Kim; Fida Bacha; Hala Tfayli; Sara F Michaliszyn; Shahwar Yousuf; Silva Arslanian Journal: Diabetes Care Date: 2018-11-19 Impact factor: 19.112
Authors: Silva A Arslanian; Laure El Ghormli; Joon Young Kim; Ashley H Tjaden; Elena Barengolts; Sonia Caprio; Tamara S Hannon; Kieren J Mather; Kristen J Nadeau; Kristina M Utzschneider; Steven E Kahn Journal: Diabetes Care Date: 2021-01-12 Impact factor: 19.112