Association of impaired awareness of hypoglycemia and real-time continuous glucose monitoring with the occurrence and frequency of severe hypoglycemia in adults with type 1 diabetes mellitus: a real-world panel data analysis from the PR-IAH study.

Background: Patients with long-standing type 1 diabetes mellitus (T1DM) often experience severe hypoglycemia (SH); however, the protective and risk factors that influence its occurrence and frequency in the era of advanced diabetes technology remain unclear. This study aimed to investigate the association of impaired awareness of hypoglycemia (IAH) and real-time continuous glucose monitoring (rtCGM) with the incidence and frequency of SH in adults with T1DM. Methods: This prospective, observational study recruited 311 adults with T1DM (mean age: 50.6 ± 14.7 years; male: 37.9%; diabetes duration: 17.9 ± 11.3 years; mean HbA1c: 7.7 ± 1.0%) from seven diabetes centers across Japan. All participants were aged ≥ 20 years and had been diagnosed with type 1 diabetes for at least 1 year. The primary outcomes were the incidence and frequency of SH, defined as an episode of hypoglycemia necessitating assistance from others. Logistic and Poisson fixed- or random-effects models were selected using the Hausman test and were applied to analyze the data. Data are presented as coefficients with 95% confidence intervals (CIs). Results: The prevalence of SH was 5.4 (95% CI 3.6-7.7)/100 person-years during the 2-year follow-up period. The logit random-effects model for predicting the occurrence of SH revealed that diabetic peripheral neuropathy (DPN) tended to be associated with an increased risk (coefficient: 2.01, 95% CI - 0.02 to 4.04; P = 0.053), whereas IAH (coefficient: 1.08, 95% CI 0.49 to 1.66; P < 0.001) exhibited a significant association with an increased risk. rtCGM (coefficient: - 1.75, 95% CI - 2.49 to - 1.00; P < 0.001) was associated with a reduced risk. The Poisson random-effects model for predicting the frequency of SH revealed that DPN and the IAH score (coefficient: 0.21, 95% CI 0.06 to 0.35; P = 0.006) exhibited positive associations with an increased frequency of SH, whereas rtCGM (coefficient: - 1.60, 95% CI - 2.84 to - 0.37; P = 0.011) was associated with a reduced frequency of SH. Conclusion: This panel data analysis demonstrated that IAH was associated with an increased incidence and frequency of SH, whereas rtCGM was associated with a decreased incidence and frequency of SH. Trial registration: University Hospital Medical Information Network (UMIN) Center: UMIN000039475), approval date: February 13, 2020.