The role of intramyocellular lipids during hypoglycemia in patients with intensively treated type 1 diabetes.
BACKGROUND
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).


METHODS
This was a prospective explorative study performed in a university research facility.


METHODS
Six well-controlled T1DM (age, 29 +/- 4 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 6.3 +/- 0.1%) and six nondiabetic humans (controls; age, 28 +/- 2 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 5.1 +/- 0.1%) were studied.


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


METHODS
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 microg/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 micromol/kg x min; P < 0.005), but approximately 40% higher glycerol turnover (374 +/- 21 vs. 272 +/- 19 micromol/kg x min; P < 0.01). Glycerol concentrations in muscle (T1DM, 302 +/- 22 control, 346 +/- 17 micromol/liter) and adipose tissue (264 +/- 25 vs. 318 +/- 25 micromol/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 s.c. adipose tissue lipolysis.
Bernroider
Elisabeth
E
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Austria.
Brehm
Attila
A
Krssak
Martin
M
Anderwald
Christian
C
Trajanoski
Zlatko
Z
Cline
Gary
G
Shulman
Gerald I
GI
Roden
Michael
M
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000188:drug therapy* / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D007700:Kinetics; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D032342:Muscle Cells / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D005934:Glucagon; D005947:Glucose; D005990:Glycerol; D006854:Hydrocortisone; D004837:Epinephrine