Increased intramyocellular lipid concentration identifies impaired glucose metabolism in women with previous gestational diabetes.

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.

[1]  A. Lammert,et al.  Soluble leptin receptor represents the main leptin binding activity in human blood. , 2001, Biochemical and biophysical research communications.

[2]  E. Boyko,et al.  Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans. , 1999, Diabetes care.

[3]  J. Halter,et al.  Insulin Resistance and Impaired Insulin Secretion in Subjects with Histories of Gestational Diabetes Mellitus , 1985, Diabetes.

[4]  T. Buchanan,et al.  TRIPOD (TRoglitazone In the Prevention Of Diabetes): a randomized, placebo-controlled trial of troglitazone in women with prior gestational diabetes mellitus. , 1998, Controlled clinical trials.

[5]  L. Mandarino,et al.  Fuel selection in human skeletal muscle in insulin resistance: a reexamination. , 2000, Diabetes.

[6]  R. DeFronzo,et al.  Non-insulin-dependent diabetes mellitus and gestational diabetes mellitus: Same disease, another name? , 1995 .

[7]  G. Pacini,et al.  Pronounced Insulin Resistance and Inadequate β-cell Secretion Characterize Lean Gestational Diabetes During and After Pregnancy , 1997, Diabetes Care.

[8]  B. Goodpaster,et al.  Subcutaneous Abdominal Fat and Thigh Muscle Composition Predict Insulin Sensitivity Independently of Visceral Fat , 1997, Diabetes.

[9]  F. Schick,et al.  Fast elevation of the intramyocellular lipid content in the presence of circulating free fatty acids and hyperinsulinemia: A dynamic 1H‐MRS study , 2001, Magnetic resonance in medicine.

[10]  T. Buchanan,et al.  Gestational diabetes mellitus. , 2005, The Journal of clinical investigation.

[11]  A. von zur Mühlen,et al.  Free and protein bound leptin are distinct and independently controlled factors in energy regulation , 2000, Diabetologia.

[12]  B. Saltin,et al.  Evidence of an Increased Number of Type IIb Muscle Fibers in Insulin-Resistant First-Degree Relatives of Patients with NIDDM , 1997, Diabetes.

[13]  G. Medley,et al.  Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies. , 1999, The Journal of clinical endocrinology and metabolism.

[14]  R. Bergman,et al.  Quantification of the Relationship Between Insulin Sensitivity and β-Cell Function in Human Subjects: Evidence for a Hyperbolic Function , 1993, Diabetes.

[15]  Andrea Mari,et al.  A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test , 2001 .

[16]  E. Kraegen,et al.  Diet-Induced Muscle Insulin Resistance in Rats Is Ameliorated by Acute Dietary Lipid Withdrawal or a Single Bout of Exercise: Parallel Relationship Between Insulin Stimulation of Glucose Uptake and Suppression of Long-Chain Fatty Acyl-CoA , 1997, Diabetes.

[17]  B. Metzger,et al.  Prepregnancy Weight and Antepartum Insulin Secretion Predict Glucose Tolerance Five Years After Gestational Diabetes Mellitus , 1993, Diabetes Care.

[18]  B. Goodpaster,et al.  An aspect of regional adiposity and insulin resistance , 2001 .

[19]  G. Dohm,et al.  Skeletal muscle fiber composition is related to adiposity and in vitro glucose transport rate in humans. , 1995, The American journal of physiology.

[20]  S. Lillioja,et al.  Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action , 1997, Diabetes.

[21]  B. Fielding,et al.  Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects. , 1996, Metabolism: clinical and experimental.

[22]  J. Simoneau,et al.  Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  S. Lemieux,et al.  Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects. , 2001, Diabetes.

[24]  Giovanni Pacini,et al.  Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT. , 1998, American journal of physiology. Endocrinology and metabolism.

[25]  C Boesch,et al.  In vivo determination of intra‐myocellular lipids in human muscle by means of localized 1H‐MR‐spectroscopy , 1997, Magnetic resonance in medicine.

[26]  E. Kraegen,et al.  Influence of Dietary Fat Composition on Development of Insulin Resistance in Rats: Relationship to Muscle Triglyceride and ω-3 Fatty Acids in Muscle Phospholipid , 1991, Diabetes.

[27]  L. DiPietro,et al.  Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study , 1999, Diabetologia.

[28]  F. Schick,et al.  Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. , 1999, Diabetes.

[29]  Zhuowei Wang,et al.  Modulation of Circulating Leptin Levels by Its Soluble Receptor* , 2001, The Journal of Biological Chemistry.

[30]  D. Zheng,et al.  The insulin action-fiber type relationship in humans is muscle group specific. , 1995, The American journal of physiology.

[31]  M. Roden Non-invasive studies of glycogen metabolism in human skeletal muscle using nuclear magnetic resonance spectroscopy , 2001, Current opinion in clinical nutrition and metabolic care.

[32]  K Thomaseth,et al.  Integrated mathematical model to assess beta-cell activity during the oral glucose test. , 1996, The American journal of physiology.

[33]  M. Roden,et al.  The effects of free fatty acids on glucose transport and phosphorylation in human skeletal muscle , 2000 .

[34]  M. Manns,et al.  Elevated bound leptin correlates with energy expenditure in cirrhotics. , 2000, Gastroenterology.

[35]  P. Scifo,et al.  Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. , 1999, Diabetes.

[36]  A. Tremblay,et al.  Elevated intramyocellular lipid concentration in obese subjects is not reduced after diet and exercise training. , 2001, American journal of physiology. Endocrinology and metabolism.

[37]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[38]  G. Cooney,et al.  Mechanisms of Liver and Muscle Insulin Resistance Induced by Chronic High-Fat Feeding , 1997, Diabetes.

[39]  C. Ricordi,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1999 by The Endocrine Society Leptin Suppression of Insulin Secretion and Gene Expression in Human Pancreatic Islets: Implications for the Development of Adipogenic Diabetes Me , 2022 .

[40]  G. Shulman,et al.  On Diabetes: Insulin Resistance Cellular Mechanisms of Insulin Resistance , 2022 .

[41]  T. Buchanan,et al.  Gestational Diabetes: Antepartum Characteristics That Predict Postpartum Glucose Intolerance and Type 2 Diabetes in Latino Women , 1998, Diabetes.

[42]  B. Goodpaster,et al.  Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance. , 2001, Diabetes care.

[43]  M. Roden,et al.  Free fatty acids inhibit the glucose-stimulated increase of intramuscular glucose-6-phosphate concentration in humans. , 2001, The Journal of clinical endocrinology and metabolism.

[44]  T. Stein,et al.  Plasma leptin influences gestational weight gain and postpartum weight retention. , 1998, The American journal of clinical nutrition.

[45]  A. Tura,et al.  Increased plasma leptin in gestational diabetes , 2001, Diabetologia.

[46]  M. Johnson,et al.  Data on the distribution of fibre types in thirty-six human muscles. An autopsy study. , 1973, Journal of the neurological sciences.

[47]  E. Richter,et al.  Functional differences in lipid metabolism in resting skeletal muscle of various fiber types. , 1997, The American journal of physiology.

[48]  G. Cooney,et al.  Peroxisome Proliferator—Activated Receptor (PPAR)-α Activation Lowers Muscle Lipids and Improves Insulin Sensitivity in High Fat—Fed Rats Comparison With PPAR-γ Activation , 2001 .

[49]  P. Damm,et al.  Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus. , 1992 .

[50]  H. Beck-Nielsen,et al.  GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease? , 2001, Diabetes.

[51]  G. Cooney,et al.  Peroxisome proliferator-activated receptor (PPAR)-alpha activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats: comparison with PPAR-gamma activation. , 2001, Diabetes.

[52]  G. Frühbeck,et al.  Relation between leptin and the regulation of glucose metabolism , 2000, Diabetologia.