Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes Is Not Associated With Autonomic Dysfunction or Peripheral Neuropathy

Abstract

OBJECTIVEImpaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in people with insulin-treated diabetes; autonomic neuropathy has been suggested to underlie its development. The aim was to evaluate a putative association between IAH and autonomic dysfunction using novel and sensitive measures of autonomic neural function. RESEARCH DESIGN AND METHODSSixty-six adults with type 1 diabetes were studied, 33 with IAH and 33 with normal awareness of hypoglycemia (NAH), confirmed by formal testing. Participants were matched for age, sex, and diabetes duration. Clinical and laboratory evaluations included extensive autonomic function testing, peripheral nerve conduction studies, and quantitative sensory testing. Composite abnormality Z scores were used for group comparisons. RESULTSThe IAH and NAH group had similar median (interquartile range) age of 48 (14.5) vs. 47 (14.5) years, diabetes duration of 30 (13.5) vs. 31 (13.5) years, and mean 6 SD HbA 1c 7.8 6 2.2% vs. 8.1 6 1.9%, respectively. The autonomic composite Z score did not differ between the two groups (mean difference 20.15, 95% CI 20.46, 0.16; P = 0.33), nor did the thermal detection (mean difference 0.15, 95% CI 20.31, 0.61; P = 0.51) or nerve conduction scores (mean difference 0.03, 95% CI 20.43, 0.49; P = 0.89). CONCLUSIONSIn adults with type 1 diabetes, IAH was not associated with autonomic dysfunction or peripheral neuropathy.Impaired awareness of hypoglycemia (IAH), defined as a diminished ability to perceive the onset of hypoglycemia, is associated with an increased risk of severe hypoglycemia in people with insulin-treated diabetes (1-3). Elucidation of the pathogenesis of IAH may help to minimize the risk of severe hypoglycemia.The glycemic thresholds for counterregulatory responses, generation of symptoms, and cognitive impairment are reset at lower levels of blood glucose in people who have developed IAH (4). This cerebral adaptation appears to be induced by

Cardiovascular Autonomic Neuropathy and Glucose Variability in Patients With Type 1 Diabetes: Is There an Association?

“…Most of patients in our study had only a moderate AN. Moreover, in adults with type 1 diabetes in another study no relationship was found between hypoglycemia unawareness and autonomic dysfunction similarly with our observations ( 29 , 40 ). A study on type 1 diabetic patients, however, had conflicting data with our findings in which autonomic function characterized with heart rate variability correlated with low blood glucose index and area under the curve for hypoglycemia of CGM measures ( 41 ).…”

The current status of treatment-related severe hypoglycemia in Japanese patients with diabetes mellitus: a report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society

“…Given that low BMI value was identified as a factor associated with hypoglycemia unawareness in the survey, partly because type 1 diabetic patients tend to have low BMI values and also because type 2 diabetic patients with low BMI values are thought likely to be associated with worsening of hypoglycemia, further detailed study is required to clarify the association between BMI, worsening of hypoglycemia, and hypoglycemia unawareness. Again, while the association between neuropathy and asymptomatic hypoglycemia remains controversial [28,29], our survey results demonstrated that peripheral neuropathy is more strongly associated with asymptomatic hypoglycemia than autonomic neuropathy or autonomic failure. Since our survey employed no consistent or quantitative criteria for diagnosis of autonomic neuropathy, peripheral neuropathy, a factor that is readily amenable to early diagnosis in clinical settings, was chosen as an explanatory factor for asymptomatic hypoglycemia.…”

The current status of treatment‐related severe hypoglycemia in Japanese patients with diabetes mellitus: A report from the committee on a survey of severe hypoglycemia in the Japan Diabetes Society

“…Given that low BMI value was identified as a factor associated with hypoglycemia unawareness in the survey, partly because type 1 diabetic patients tend to have low BMI values but also because type 2 diabetic patients with low BMI values are thought likely to be associated with worsening of hypoglycemia, further detailed study is required to clarify the association between BMI, worsening of hypoglycemia, and hypoglycemia unawareness. Again, while the association between neuropathy and asymptomatic hypoglycemia remains controversial, our survey results demonstrated that peripheral neuropathy is more strongly associated with asymptomatic hypoglycemia than autonomic neuropathy or autonomic failure. Since our survey employed no consistent or quantitative criteria for diagnosis of autonomic neuropathy, peripheral neuropathy, a factor that is readily amenable to early diagnosis in clinical settings, was chosen as an explanatory factor for asymptomatic hypoglycemia.…”