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.