ECE2007 Oral Communications Diabetes (7 abstracts)
Hypoglycemia and cerebral ATP synthesis in Type 1 Diabetes
Martina Mandl 1 , Stefan Zbyn 1 , Vladimir Mlynarik 2 , Miriam Promintzer 1 , Anton Luger 1 , Michael Krebs 1 , Christian Anderwald 1 & Martin G. Bischof 1
1Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; 2MR Center of Excellence, Medical University of Vienna, Vienna, Austria.
The mechanisms responsible for the progressive failure of hypoglycemia counter-regulation in type-1 diabetes (T1DM) are poorly understood. Alterations of brain energy metabolism could influence glucose sensing by the brain and, thus contribute to hypoglycemia associated autonomic failure. Thus, we measured intraneuronal kinetics of total ATP-synthesis from PCr (kfor) in T1DM patients and effects of hypo/hyperglycemia on this brain energy metabolism. Healthy nondiabetic humans (CON; 5 m/1f, BMI=23.5±1.0 kg/m2, age=25±1 yr, HbA1c=5.1±0.1%), T1DM patients with good (T1DMgood; 5 m/1f, BMI=25.5±0.4 kg/m2, age=24±2 yr, HbA1c=6.8±0,1%) and poor (T1DMpoor; 5 m/1f, BMI=24.9±1.6 kg/m2, age=25±2 yr, HbA1c=8.9±0.3%) glycemic control were examined before, during and after hyperinsulinemic-(1.5 mU·kg−1·min−1)-hypoglycemic-(∼50 mg/dl) or –hyperglycemic-(∼250 mg/dl)-clamp tests. kfor in the occipital lobe was measured by 31P-nuclear-magnetic-resoance spectroscopy (3T) using saturation transfer, and calculated with McConnell equations. In T1DMpoor, kfor was increased during hypoglycemia (0.58±0.07 s−1), when compared to CON (0.36±0.03 s−1; P=0.006), T1DMgood (0.41±0.02 s−1; P=0.03), and baseline (0.43±0.05 s−1; P=0.03). During post-hypoglycemic recovery, T1DMpoor showed higher kfor (0.57±0.07 s−1), when compared to CON (0.40±0.05 s−1, P<0.05), and T1DMgood (0.37±0.01 s−1, P=0.03). HbA1c-levels were positively correlated with kfor during hypoglycemia (r=0.47, P=0.02), but not at baseline (r=0.20, P=0.37) or during recovery (r=0.39, P=0.07).
Conclusion: 31P NMRS with saturation transfer can be used for non-invasively measurement of cerebral ATP-synthesis during hypoglycemia in vivo. The positive correlation of HbA1c levels and kfor during hypoglycemia hints at an involvement of the CK system in the pathogenesis of hypoglycemia associated autonomic failure.
Volume 14
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