title: Insulin resistance in type 1 diabetes mellitus.
abstract: For long the presence of insulin resistance in type 1 diabetes has been questioned. Detailed metabolic analyses revealed 12%-61% and up to 20% lower whole-body (skeletal muscle) and hepatic insulin sensitivity in type 1 diabetes, depending on the population studied. Type 1 diabetes patients feature impaired muscle adenosine triphosphate (ATP) synthesis and enhanced oxidative stress, predominantly relating to hyperglycemia. They may also exhibit abnormal fasting and postprandial glycogen metabolism in liver, while the role of hepatic energy metabolism for insulin resistance remains uncertain. Recent rodent studies point to tissue-specific differences in the mechanisms underlying insulin resistance. In non-obese diabetic mice, increased lipid availability contributes to muscle insulin resistance via diacylglycerol/protein kinase C isoforms. Furthermore, humans with type 1 diabetes respond to lifestyle modifications or metformin by 20%-60% increased whole-body insulin sensitivity, likely through improvement in both glycemic control and oxidative phosphorylation. Intensive insulin treatment and islet transplantation also increase but fail to completely restore whole-body and hepatic insulin sensitivity. In conclusion, insulin resistance is a feature of type 1 diabetes, but more controlled trials are needed to address its contribution to disease progression, which might help to optimize treatment and reduce comorbidities.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Germany; German Center of Diabetes Research Partner, Düsseldorf, Germany.
authors.forename: Kirti
authors.initials: K
authors.lastname: Kaul
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Germany; German Center of Diabetes Research Partner, Düsseldorf, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Apostolopoulou
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University Düsseldorf, Germany; German Center of Diabetes Research Partner, Düsseldorf, Germany; Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. Electronic address: michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress
keywords: Glucotoxicity; Insulin sensitivity; Lipotoxicity; Mitochondria; Type 1 diabetes mellitus