The role of intramyocellular lipids during hypoglycemia in patients with intensively treated type 1 diabetes
E Bernroider, A Brehm, M Krssak… - The Journal of …, 2005 - academic.oup.com
The Journal of Clinical Endocrinology & Metabolism, 2005•academic.oup.com
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 …
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 …
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 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.
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.
Oxford University Press