CONTEXT: Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control. OBJECTIVE: We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration. DESIGN, PATIENTS, AND METHODS: Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 ± 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Glucose metabolism was quantified using an infusion of [6,6-(2)H(2)]glucose. Hepatic insulin sensitivity was measured using the insulin IC(50) for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose. RESULTS: Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8- and 40-mU/m(2) · min stages. CONCLUSION: Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia.
CONTEXT: Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control. OBJECTIVE: We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration. DESIGN, PATIENTS, AND METHODS: Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 ± 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Glucose metabolism was quantified using an infusion of [6,6-(2)H(2)]glucose. Hepatic insulin sensitivity was measured using the insulin IC(50) for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose. RESULTS: Throughout the study, glucoseRa was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucoseRa was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8- and 40-mU/m(2) · min stages. CONCLUSION:Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia.
Authors: Irene E Schauer; Janet K Snell-Bergeon; Bryan C Bergman; David M Maahs; Adam Kretowski; Robert H Eckel; Marian Rewers Journal: Diabetes Date: 2010-10-26 Impact factor: 9.461
Authors: Melanie Cree-Green; Bryan C Bergman; Eda Cengiz; Larry A Fox; Tamara S Hannon; Kellee Miller; Brandon Nathan; Laura Pyle; Darcy Kahn; Michael Tansey; Eileen Tichy; Eva Tsalikian; Ingrid Libman; Kristen J Nadeau Journal: J Clin Endocrinol Metab Date: 2019-08-01 Impact factor: 5.958
Authors: Sonali S Patel; Uyen Truong; Martina King; Annie Ferland; Kerrie L Moreau; Jennifer Dorosz; John E Hokanson; Hong Wang; Gregory L Kinney; David M Maahs; Robert H Eckel; Kristen J Nadeau; Melanie Cree-Green Journal: Vasc Med Date: 2017-01-17 Impact factor: 3.239
Authors: Sarah Sczelecki; Aurèle Besse-Patin; Alexandra Abboud; Sandra Kleiner; Dina Laznik-Bogoslavski; Christiane D Wrann; Jorge L Ruas; Benjamin Haibe-Kains; Jennifer L Estall Journal: Am J Physiol Endocrinol Metab Date: 2013-11-26 Impact factor: 4.310
Authors: Petter Bjornstad; Janet K Snell-Bergeon; Kimberly McFann; R Paul Wadwa; Marian Rewers; Christopher J Rivard; Diana Jalal; Michel B Chonchol; Richard J Johnson; David M Maahs Journal: J Diabetes Complications Date: 2013-12-27 Impact factor: 2.852
Authors: Bryan C Bergman; David Howard; Irene E Schauer; David M Maahs; Janet K Snell-Bergeon; Timothy W Clement; Robert H Eckel; Leigh Perreault; Marian Rewers Journal: J Clin Endocrinol Metab Date: 2012-11-12 Impact factor: 5.958