Neuropathy Drives Hypoglycemia Cluelessness in T1D

Researchers published the study covered in this summary on as a preprint that has not yet been peer reviewed.

Key Takeaways

  • In Japanese adults with type 1 diabetes insulin-pump treatment (continuous subcutaneous insulin infusion) and higher problem-solving perception appear protective against impaired awareness of hypoglycemia (IAH), while diabetic peripheral neuropathy (DPN) is associated with increased risk.

  • Diabetes distress and fear of hypoglycemia are common in people with IAH.

Why This Matters

  • Adults with type 1 diabetes and IAH have a reduced ability to perceive hypoglycemic symptoms and are at risk of severe hypoglycemic events because they are unable to take immediate corrective action.

  • This is the first study to identify protective factors and risk factors of IAH in Japanese adults with type 1 diabetes.

  • People with IAH may plan to loosen tight glucose management and intentionally omit insulin injection to prevent severe hypoglycemia.

  • The information in this report may help improve the management of people with problematic hypoglycemia, the authors suggested. Treatment with an insulin pump and structured education aimed at improving problem-solving skills may be useful interventions for adults with type 1 diabetes and IAH, they suggested.

Study Design

  • The study involved a cross-sectional analysis of 288 Japanese adults with type 1 diabetes who averaged 50 years old, had diabetes for an average of about 18 years, had an average A1c at baseline of 7.7%, and included about 37% men and 63% women.

  • The cohort included 55 people with IAH (19%) and 233 with no impairment of their hypoglycemia awareness, based on their score on the Clarke questionnaire.

Key Results

  • DPN was significantly more prevalent in the IAH group than in the control group (12.0% vs 26.5%). A logistic regression analysis showed that the odds ratio for DPN was 2.63-fold higher among people with IAH compared with those without IAH, but there were no differences in other complications or by A1c levels.

  • Treatment with continuous subcutaneous insulin therapy (an insulin pump) was significantly less prevalent in the IAH group compared with those without IAH (23.6% vs 39.5%), with an adjusted odds ratio of 0.48. The two subgroups showed no differences in use of continuous glucose monitoring, used by 56% of the people in each of the two subgroups.

  • The two subgroups showed no differences in their healthy lifestyle score, sleep debt, or rates of excessive drinking.

  • Mean autonomic symptom scores for both sweating and shaking were significantly reduced in the IAH group, but no between-group differences appeared for palpations or hunger.

  • All mean neuroglycopenic symptom scores were significantly lower in those without IAH, including confusion and speech difficulty.

  • Scores for measures of diabetes distress and for the worry component of the fear-of-hypoglycemia were significantly higher in the IAH group, but there were no differences in other psychological measures.

  • Higher hypoglycemia problem-solving perception scores were significantly associated with decreased IAH risk with a calculated odds ratio of 0.54, but other aspects of hypoglycemia problem-solving such as detection control, goal setting, and strategy evaluation showed no significant links.


  • The study used a cross-sectional design, which is not suited to making causal inferences.

  • The authors characterized DPN as either present or absent. They did not evaluate or analyze the severity of peripheral neuropathy.

  • The authors evaluated diabetic cardiac autonomic neuropathy (DCAN) by a person’s coefficient of variation of R-R intervals, and definitive diagnosis of DCAN required at least two positive results on a cardiac autonomic test. More vigorous evaluation using a more definitive assessment of DCAN is needed to relate DCAN and IAH status.


  • The study received no commercial funding

  • The authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross- sectional analysis of baseline data from the PR-IAH study,” written by researchers at several hospitals in Japan, all affiliated with the National Hospital Organization, on Research Square brought to you by Medscape. The study has not yet been peer-reviewed. The full text of the study can be found on

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