Autonomic dysfunction and insulin resistance in type 2 diabetes mellitus with hypoglycemia unawareness: an observational study.

Purpose: To evaluate the association between hypoglycemia unawareness, cardiac autonomic function, and insulin resistance in individuals with type2 diabetes, and explore potential correlations between autonomic dysfunction and metabolic parameters. Methods: 50 individuals with type2 diabetes (age 50-65 years, duration >5 years) were recruited and classified into two groups using Clarke's Hypoglycemia Awareness Questionnaire: hypoglycemia unawareness group (n = 25) and controls (n = 25). Standardized cardiovascular autonomic function tests (AFTs) and short-term heart rate variability (HRV) analyses were performed. Autonomic dysfunction was graded using Ewing's, Bellavere's, and All India Institute of Medical Sciences AFT Lab criteria. Results: The hypoglycemia unawareness group exhibited significantly lower Valsalva ratio (1.49 ± 0.31) vs. the control group (1.80 ± 0.42) (P = 0.004), and reduced diastolic blood pressure (BP) response during the cold pressor test (10.92 ± 9.81 mmHg) vs. the control group (18.36 ± 8.50 mmHg) (P = 0.001). A greater fall in systolic BP during postural change was also noted (11.08 ± 6.38 mmHg) vs. the control group (7.64 ± 3.53 mmHg) (P = 0.037). HRV indices like SD of all N-N intervals and total power were reduced in hypoglycemia-unawareness individuals, indicating impaired sympatho-vagal modulation. Fasting glucose was significantly higher in hypoglycemia-unawareness individuals (114.36 ± 11.81) vs. the control group (106.44 ± 13.11) (P = 0.021), but no significant difference in homeostatic model assessment for insulin resistance was observed. Serum insulin levels showed negative correlations with sympathetic function measures. Conclusion: Hypoglycemia unawareness in T2DM is associated with combined sympathetic and parasympathetic dysfunction and reduced HRV, consistent with a hypoglycemia-associated autonomic failure cycle. Routine autonomic assessment may aid in early detection, risk stratification, and prevention of adverse cardiovascular outcomes in this high-risk subgroup.