Increased Intramyocellular Lipid Concentration Identifies Impaired Glucose Metabolism in Women With Previous Gestational Diabetes

Increased Intramyocellular Lipid Concentration Identifies Impaired Glucose Metabolism in Women With Previous Gestational Diabetes Alexandra Kautzky-Willer 1 , Martin Krssak 1 , Christine Winzer 1 , Giovanni Pacini 2 , Andrea Tura 2 , Serdar Farhan 1 , Oswald Wagner 3 , Georg Brabant 4 , Rüdiger Horn 4 , Harald Stingl 1 , Barbara Schneider 5 , Werner Waldhäusl 1 and Michael Roden 1 1 Department of Internal Medicine III, Division of Endocrinology and Metabolism, University of Vienna, Vienna, Austria 2 Metabolic Unit, Institute of Biomedical Engineering, National Research Council (ISIB-CNR), Padova, Italy 3 Institute for Medical Laboratory Diagnostics, University of Vienna, Vienna, Austria 4 Division of Endocrinology, University of Hannover, Hannover, Germany 5 Institute of Biostatistics, University of Vienna, Vienna, Austria Abstract Women with previous gestational diabetes (pGDM) are frequently insulin-resistant, which could relate to intramyocellular lipid content (IMCL). IMCL were measured with 1 H nuclear magnetic resonance spectroscopy in soleus (IMCL-S) and tibialis-anterior muscles (IMCL-T) of 39 pGDM (32 ± 2 years, waist-to-hip ratio 0.81 ± 0.01) and 22 women with normal glucose tolerance (NGT; 31 ± 1 years, 0.76 ± 0.02) at 4–6 months after delivery. Body fat mass (BFM) was assessed from bioimpedance analysis, insulin sensitivity index (S I ), and glucose effectiveness (S G ) from insulin-modified frequently sampled glucose tolerance tests. pGDM exhibited 45% increased BFM, 35% reduced S I and S G ( P < 0.05), and 40% ( P < 0.05) and 55% ( P < 0.005) higher IMCL-S and IMCL-T, respectively. IMCL related to body fat (BFM P < 0.005, leptin P < 0.03), but only IMCL-T correlated ( P < 0.03) with S I and glucose tolerance index independent of BMI. Insulin-resistant pGDM ( n = 17) had higher IMCL-S (+66%) and IMCL-T (+86%) than NGT and insulin-sensitive pGDM (+28%). IMCL were also higher ( P < 0.005, P = 0.05) in insulin-sensitive pGDM requiring insulin treatment during pregnancy and inversely related to the gestational week of GDM diagnosis. Thus, IMCL-T reflects insulin sensitivity, whereas IMCL-S relates to obesity. IMCL could serve as an additional parameter of increased diabetes risk because it identifies insulin-resistant pGDM and those who were diagnosed earlier and/or required insulin during pregnancy. Footnotes Address correspondence and reprint requests to Michael Roden, MD, Division of Endocrinology and Metabolism, Department of Internal Medicine