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Submitted on September 2, 2004
Accepted on June 28, 2005
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Institute of Biomedical Engineering; Univ. of Technology, Graz, Austria; Howard Hughes Medical Institute, Department of Internal Medicine, Yale University School of Medicine, Connecticut, USA; 1. Medical Department, Hanusch Hospital, Vienna, Austria
* To whom correspondence should be addressed. 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. To assess the contribution of IMCL compared with lipolysis and endogenous glucose production (EGP) to insulin-mediated hypoglycemia counterregulation in type 1 diabetic patients (T1DM).
Design and Setting. Prospective explorative study in a University research facility.
Participants. Six well controlled T1DM (29 ± 4 a, BMI: 23.4 ± 1.0 kg/m2, HbA1c: 6.3 ± 0.1%) and six nondiabetic humans (CON: 28 ± 2 a, 23.4 ± 1.0 kg/m2, 5.1 ± 0.1%).
Interventions. 240-min hypoglycemic (
3 mM)-hyperinsulinemic (0.8 mU•kg-1•min-1) clamps on separate days to measure: (i) systemic lipolysis ([2H5]glycerol turnover), EGP ([6,6-2H2]glucose) and local lipolysis in abdominal sc adipose tissue and gastrocnemius muscle (microdialysis), (ii) IMCL [1H nuclear magnetic resonance spectroscopy, NMRS] in soleus and tibialis anterior muscle (IMCL-S, -TA).
Main outcome measure. 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. CON). T1DM featured 50% lower EGP (4.6 ± 0.6 vs. 10.9 ± 0.5 µmol•kg-1•min-1; P < 0.005) but 40% higher glycerol turnover (374 ± 21 vs. 272 ± 19 µmol•min-1; P < 0.01). Glycerol concentrations in muscle (T1DM: 302 ± 22 vs. CON: 346 ± 17 µmol/l) and adipose tissue (264 ± 25 vs. 318 ± 25 µmol/l) did not differ between groups. IMCL-S and IMCL-TA, did not change from baseline during hypoglyemia.
Conclusions. In well controlled T1DM impaired hypoglycemia counterregulation is associated with decreased glucose production and augmented whole body lipolysis which can neither be explained by hydrolysis of muscle triglycerides nor by increased abdominal sc adipose tissue lipolysis.
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