Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 97; no. 5; pp. 1663 - 1672
• Main Authors: Bergman, Bryan C, Howard, David, Schauer, Irene E, Maahs, David M, Snell-Bergeon, Janet K, Eckel, Robert H, Perreault, Leigh, Rewers, Marian
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-05-2012; Copyright by The Endocrine Society
• Subjects: Adiposity; Adult; Biological and medical sciences; Blood Glucose - metabolism; Body Mass Index; Diabetes Mellitus, Type 1 - metabolism; Diabetes. Impaired glucose tolerance; Diet; Endocrine pancreas. Apud cells (diseases); Endocrine Research; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Glucose Clamp Technique; Humans; Insulin - pharmacology; Insulin Resistance - physiology; Liver - metabolism; Male; Medical sciences; Middle Aged; Muscle, Skeletal - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Immunopathology; Obesity; Pancreatic hormone; Nutrition; Digestive system; Liver; Nutrition disorder; Autoimmune disease; Metabolic diseases; Striated muscle; Insulin; Target tissue resistance; Type 1 diabetes; Insulin resistance; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-3172

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/m2 · min. Glucose metabolism was quantified using an infusion of [6,6-2H2]glucose. Hepatic insulin sensitivity was measured using the insulin IC50 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/m2 · 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.