This Article Full Text Full Text (PDF) All Versions of this Article: 90/10/5559    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bernroider, E. Articles by Roden, M. Search for Related Content PubMed PubMed Citation Articles by Bernroider, E. Articles by Roden, M. Related Collections Diabetes and Insulin Metabolism Lipid

The Role of Intramyocellular Lipids during Hypoglycemia in Patients with Intensively Treated Type 1 Diabetes

Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna (E.B., A.B., M.K., C.A., M.R.), A-1090 Vienna, Austria; Institute of Biomedical Engineering, University of Technology (Z.T.), A-8020 Graz, Austria; Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine (G.C., G.I.S.), New Haven, Connecticut 06536-8012; and First Medical Department, Hanusch Hospital (M.R.), A-1140 Vienna, Austria

Address all correspondence and requests for reprints to: Dr. Michael Roden, First Medical Department, Hanusch Hospital, Heinrich Collin Strasse 30, A-1140 Vienna, Austria. E-mail: michael.roden{at}meduniwien.ac.at.

Context: Endocrine defensive mechanisms provide for energy supply during hypoglycemia. Intramyocellular lipids (IMCL) were recently shown to contribute to energy supply during exercise.

Objective: The objective of this study was to assess the contribution of IMCL compared with lipolysis and endogenous glucose production (EGP) to insulin-mediated hypoglycemia counterregulation in patients with type 1 diabetes mellitus (T1DM).

Design and Setting: This was a prospective explorative study preformed in a university research facility.

Participants: Six well-controlled T1DM (age, 29 ± 4 yr; body mass index, 23.4 ± 1.0 kg/m²; hemoglobin A_1c, 6.3 ± 0.1%) and six nondiabetic humans (controls; age, 28 ± 2 yr; body mass index, 23.4 ± 1.0 kg/m²; hemoglobin A_1c, 5.1 ± 0.1%) were studied.

Interventions: We performed 240-min hypoglycemic (3 mM)-hyperinsulinemic (0.8 mU/kg·min) clamps on separate days to measure: 1) systemic lipolysis ([²H₅]glycerol turnover), EGP ([6,6-²H₂]glucose), and local lipolysis in abdominal sc adipose tissue and gastrocnemius muscle (microdialysis); and 2) IMCL (by ¹H nuclear magnetic resonance spectroscopy) in soleus and tibialis anterior muscle.

Main Outcome Measures: The main outcome measures were changes in IMCL during prolonged hypoglycemia.

Results: At baseline, EGP, glycerol turnover, and IMCL were not different between the groups. During hypoglycemia, hormonal counterregulation was blunted in T1DM (peak: glucagon, 68 ± 4 vs. 170 ± 37 pg/ml; cortisol, 16 ± 2 vs. 24 ± 2 µg/dl; epinephrine, 274 ± 84 vs. 597 ± 212 pg/ml; all P < 0.05 vs. control). T1DM had approximately 50% lower EGP (4.6 ± 0.6 vs. 10.9 ± 0.5 µmol/kg·min; P < 0.005), but approximately 40% higher glycerol turnover (374 ± 21 vs. 272 ± 19 µmol/kg·min; P < 0.01). Glycerol concentrations in muscle (T1DM, 302 ± 22 control, 346 ± 17 µmol/liter) and adipose tissue (264 ± 25 vs. 318 ± 25 µmol/liter) did not differ between groups. IMCL in soleus and tibialis anterior muscle did not change from baseline during hypoglycemia.

Conclusions: In well-controlled T1DM, impaired hypoglycemia counterregulation is associated with decreased glucose production and augmented whole body lipolysis, which cannot be explained by either hydrolysis of muscle triglycerides or increased abdominal sc adipose tissue lipolysis.