Shonkwiler, Cheryl

Carotid bodies (CB) are desensitized by hyperoxia/hyperglycemia and sensitized by hypoxia/hypoglycemia. We have reported in healthy humans that CB chemoreceptors secrete counterregulatory hormones in response to normoxia and hypoglycemia. While the role of central nervous system in glucose counterregulation is known, it is unknown whether alteration in CB response to glucose contributes to the pathogenesis of hypoglycema in T1D. We hypothesized that glucose counterregulation is impaired in T1D due to reduced sensitization of CB. 10 T1D and 12 healthy subjects (ND), matched for BMI (23 ± 3 vs 26 ± 5 kg/m 2 ) underwent a 180 min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic clamp (~3.3mM) under normoxic conditions (SpO2 98 ± 1%). T1D subjects did not report autonomic symptoms. [3‐ 3 H] glucose was infused to measure glucose turnover. Results were compared using means of last forty minutes of clamp data. Statistical analyses were done using unpaired t‐tests and p<0.05 was considered significant. In the presence of matched glucose (3.3±0.1 vs.3.3±0.1 mM) and insulin concentrations (783±106 vs. 812±185 pM;p=0.66), counterregulatory hormonal responses epinephrine (274 ± 165 vs. 742 ± 279 pg/ml) and glucagon (30 ± 11 vs 105 ± 31pg/ml) to hypoglycemia were significantly lower (p<0.001) in T1D vs. ND respectively. The glucose infusion rate required to maintain hypoglycemia was significantly higher (36 ± 1 vs.28 ± 0 µmol/kg/min, p <0.001) and endogenous glucose production was significantly lower (10 ± 3 vs.14 ± 4 µmol/kg/min, p<0.05) in T1D vs. ND with unchanged insulin stimulated glucose uptake. We conclude that in T1D the CB sensitivity to hypoglycemia is impaired and may contribute to increased risk of hypoglycemia in these individuals. Future studies are required to evaluate CB response in hypoglycemia unaware individuals with T1D. Grant Funding Source : DK90541