In this study, we sought to determine by 3T MRI the cerebral blood flow (CBF) responses to hypoglycemia (HG) in nondiabetic controls exposed to either two euglycemic or two hypoglycemic clamps on the day before the MRI (EU- or HYPO-preconditioning, respectively). Under the belief that HYPO-preconditioning induces hypoglycemia-associated autonomic failure (HAAF) with blunting of the counter-regulatory hormone and symptom responses to HG (Arbelaez et al, 2008), we hypothesized that CBF responses after HYPO-preconditioning would resemble those reported in T1D subjects with impaired awareness of hypoglycemia (IAH) (Weigers et al, 2017). CBF was measured by arterial spin labeling during a 2-step hyperinsulinemic clamp [step 1 = 95 mg/dL normoglycemia (NG), step 2 = 50 mg/dL (HG)]. Symptom and counter-regulatory hormone were also measured. Full CBF datasets were obtained from 10 participants who underwent EU-preconditioning (7F/3M, age 37 ± 14 years, BMI 27.2 ± 3.7 kg/m2) and 9 who underwent HYPO-preconditioning (5F/4M, age 40 ± 14 years, BMI 26.2 ± 2.6 kg/m2). In contrast with our assumption, the HYPO-preconditioning did not induce blunting of symptom or counter-regulatory hormone responses to HG other than for glucagon (33 ± 19 and 14 ± 21 pg/mL for EU- and HYPO-preconditioning, respectively, p=0.04 uncorr). CBF responses did not differ between the two pre-conditionings, and resembled those reported in the literature in naïve nondiabetic controls (Weigers et al, 2017). In particular, the cortical grey matter CBF did not change during HG vs. NG for either the EU- or HYPO-preconditioning settings (1 ± 10% and 2 ± 10%, respectively), while thalamic CBF increased in both settings (21 ± 20%, p=0.012 corr, and 27 ± 30%, p=0.06 corr, respectively). We conclude that the preconditioning protocols should be used with caution in nondiabetic controls for investigating IAH, as the mechanisms of HAAF in T1D patients may be specific to their disease condition.


A. Canna: None. H. Grohn: None. D. Mascali: None. P. Filip: None. A. Moheet: None. A. Kumar: None. X. Li: None. E.A. Olawsky: None. L.E. Eberly: None. F. Esposito: None. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company, Zucara Therapeutics Inc. Consultant; Self; 360 Consulting, MannKind Corporation. Research Support; Self; Eli Lilly and Company, JDRF, National Institutes of Health. Other Relationship; Self; American Diabetes Association, Sanofi, WebMD. S. Mangia: None.


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