49-OR: Changes in Regional Cerebral Blood Flow during Hypoglycemia in T1DM

Abstract

Regulation of cerebral blood flow (CBF) during hypoglycemia (HYPO) is critical for maintaining adequate glucose delivery to the brain; however, specific changes in regional CBF during HYPO are not well defined. We measured CBF in 14 T1DM (mean ± SD age 31 ± 7 yrs, DM duration 16 ± 5 yrs, A1c 7.2 ± 1.0 %) and 13 healthy controls (CON; age 35 ± 11 yrs, A1c 5.2 ± 0.5 %) using 3.0 T MRI continuous arterial spin labeling during fasting baseline (BAS), a hyperinsulinemic (2 mU/kg/min) euglycemic clamp (EUG; 90 mg/dl), followed by a hypoglycemic clamp (HYPO; 50 mg/dl). Global and regional changes in CBF were measured in 15 regions of interest (ROI). At BAS, gray matter CBF was similar in CON and T1DM (58 ± 16 vs. 61 ± 11 ml/100 gm brain/min). No significant changes in CBF were observed from BAS to EUG in any brain region in either CON or T1DM. However, during HYPO in T1DM, CBF increased by 10% in gray matter and 16% in brainstem, both p <0.05. CBF also increased by 10% - 18% in specific ROIs involved in awareness of internal states, reward and emotion (orbitofrontal cortex, insula, anterior cingulate cortex, thalamus, and substantia nigra; p<0.01 to p<0.05). Minimal increases in CBF (1% - 6%) were observed in regions primarily involved in sensory or motor function, (occipital cortex, motor cortex, cerebellum, caudate, putamen) or in the posterior cingulate (all p > 0.30). In CON, no significant global or regional changes in CBF occurred during HYPO. In all subjects, higher A1c correlated with greater increases in CBF during HYPO (p<0.05). Conclusions: 1) Hyperinsulinemia per se does not alter CBF in T1DM or CON, 2) During HYPO, brain blood flow increases more in T1DM vs. CON, especially in regions involved in integration of internal awareness, reward and emotion, compared to sensory or motor function, and 3) Greater increases in CBF in subjects with higher A1c suggest that compensatory physiologic mechanisms enable subjects with chronic exposure to hyperglycemia to maintain adequate cerebral glucose supply when plasma glucose levels are suddenly reduced. Disclosure D. C. Simonson: Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. N. R. Bolo: None. J. Theberge: None. G. Musen: None. A. M. Jacobson: None. Funding National Institutes of Health (DK073843)