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Rottenkolber, M. ; Gar, C. ; Then, C. ; Wanger, L.* ; Sacco, V. ; Banning, F. ; Potzel, A. ; Kern-Matschilles, S. ; Nevinny-Stickel-Hinzpeter, C.* ; Grallert, H. ; Hesse, N.* ; Seissler, J. ; Lechner, A.

A pathophysiology of type 2 diabetes unrelated to metabolic syndrome.

J. Clin. Endocrinol. Metab. 106, 1460-1471 (2021)
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OBJECTIVE: Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we reevaluated this hypothesis. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis of 138 women from the monocenter, post gestational diabetes study PPSDiab, 73 of which had incident prediabetes or T2DM. Additionally, we examined all the 412 incident cases of T2DM in phases 3-9 of the Whitehall II Study in comparison to healthy controls. Our analysis included a medical history, anthropometrics, oral glucose tolerance testing, and laboratory chemistry in both studies. Additional analyses from the PPSDiab Study consisted of cardiopulmonary exercise testing, magnetic resonance imaging, auto-antibody testing, and the exclusion of glucokinase maturity-onset diabetes of the young. RESULTS: We found that 33 (45%) of the women with prediabetes or T2DM in the PPSDiab Study displayed no components of metabolic syndrome. They reached no point for metabolic syndrome in the NCEP ATP3 score other than hyperglycemia and, moreover, had levels of liver fat content, plasma triglycerides, hdl cholesterol, c-reactive protein, and blood pressure that were comparable to healthy controls. In the Whitehall II Study, 62 (15%) of the incident T2DM cases fulfilled the same criteria. In both studies, these cases without metabolic syndrome revealed insulin resistance and inadequately low insulin secretion. CONCLUSIONS: Our results contradict the hypothesis that components of metabolic syndrome are central to all cases of T2DM. Instead, they suggest the common occurrence of a second, unrelated pathophysiology.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Insulin Resistance ; Metabolic Syndrome ; Type 2 Diabetes ; Insulin Secretion ; Subclassifications ; Subtypes; Insulin Sensitivity; Adipose-tissue; Resistance; Phenotype; Women; Fat; Individuals; Secretion; Mellitus
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Journal Journal of Clinical Endocrinology & Metabolism, The
Quellenangaben Volume: 106, Issue: 5, Pages: 1460-1471 Article Number: , Supplement: ,
Publisher Endocrine Society
Publishing Place Bethesda, Md.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Biomarker for the subclassification of T2DM (KKG-KDB)
Institute of Epidemiology II (EPI2)
Grants US National Institutes of Health
British Heart Foundation
German Center for Diabetes Research
Helmholtz Zentrum München
LMU Klinikum