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Abstract Context Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality. Objective The objective of this work is to investigate the role of the adrenocorticotropin (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1–24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day. Design A double-blind, placebo-controlled, random-order, cross-over study was conducted. Setting This study took place in a clinical research center. Participants Participants included healthy men and women. Interventions Interventions included an intravenous infusion of cosyntropin (70 μg/hour for 2.5 hours in the morning and again in the early afternoon) vs normal saline placebo. Main Outcome Measures Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions. Results Cosyntropin infusion attenuated BRS (mm Hg/ms) as compared to placebo (baseline 17.8 ± 1.38 vs 17.0 ± 2.07; during 14.4 ± 1.43 vs 17.3 ± 1.65; and next day 14.8 ± 1.42 vs 18.9 ± 2.04; P < .05, time by treatment, analysis of variance). BRS was decreased during the final 30 minutes of the morning cosyntropin infusion as compared to baseline (P < .01) and remained suppressed the next day (16 hours after afternoon infusion) (P < .025). Placebo infusion did not significantly change BRS. Corrected QT interval was not affected. Conclusions ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.

Background: In patients with type 2 diabetes mellitus, the development of diabetic retinopathy (DR) correlates positively with elevated serum chemerin levels. This study was aimed at investigating the probable association between the serum chemerin level and the development of DR in patients with type 1 diabetes mellitus (T1DM). Methods: In this cross-sectional study, we included Egyptians and classified them into four groups: group 1, including healthy individuals; group 2, including patients with T1DM without DR; group 3, including patients with T1DM with non-proliferative DR (NPDR); and group 4, including patients with T1DM with proliferative DR (PDR). The assessment included best-corrected distance visual acuity assessment, slit-lamp biomicroscopy, funduscopy, fundus fluorescein angiography, and macular ocular coherence tomography. Fasting blood samples were obtained from all participants to measure serum chemerin, glycated hemoglobin (HbA1c), total cholesterol, triglyceride, and creatinine levels. Serum chemerin levels were compared among the groups, and their correlations with age, duration of diabetes, HbA1c, total cholesterol, triglyceride, and creatinine levels were analyzed. Results: We recruited 209 participants, including 46 healthy individuals in group 1, 52 patients (T1DM and no DR) in group 2, 61 patients (T1DM and NPDR) in group 3, and 50 patients (T1DM and PDR) in group 4, with comparable mean ages and sex ratios among groups. The diabetes duration, body mass index, HbA1c, total cholesterol, triglyceride, and serum chemerin levels differed significantly among the groups (all P < 0.001), whereas the creatinine level did not (P > 0.05). The serum chemerin level was significantly higher in group 4 than in groups 3 and 2, in group 3 than in group 2, and in groups 3 and 4 than in group 1 (all P < 0.001). However, it was comparable between groups 1 and 2 (P > 0.05). It correlated with the duration of T1DM and HbA1c, total cholesterol, triglyceride, and creatinine levels but not with age. Conclusions: Patients with T1DM with DR showed higher serum chemerin levels than those with T1DM without DR or healthy individuals. Serum chemerin levels were higher in those with PDR than in those with NPDR. Thus, serum chemerin levels are a potential biomarker of the development and severity of DR in patients with T1DM. Nevertheless, future diagnostic accuracy studies are required to confirm these potential applications.