Aims/Introduction: Although the epidemiological relationship between hypoglycemia and increased risk of acute coronary syndrome (ACS) has been well established, the time period for increased risk of ACS after a severe hypoglycemic episode remains unknown. The present study aimed to determine the ACS risk after a severe hypoglycemic episode.Materials and Methods: We carried out a retrospective population‐based cohort study based on national claims data in Japan. We retrieved data of diabetes patients aged ≥35 years collected from April 2014 to March 2016. The absolute risk of ACS was defined as the occurrence of an emergency percutaneous coronary intervention after a severe hypoglycemic episode.Results: In total, data of 7,909,626 patients were included in the analysis. The absolute risk of ACS was 2.9 out of 1,000 person‐years in all patients. ACS risk in patients with severe hypoglycemic episodes was 3.0 out of 1,000 person‐years. Severe hypoglycemic episodes increased the absolute risk of ACS in patients aged ≥70 years, but not in patients aged <70 years. The absolute risk of ACS was 10.6 out of 1,000 person‐years within 10 days of a severe hypoglycemic episode. There was a significant trend between shorter duration after an episode and higher ACS risk.Conclusions: Severe hypoglycemia was associated with an increased risk of ACS in elderly diabetes patients. ACS risk increased with a shorter period after a severe hypoglycemic episode, suggesting that severe hypoglycemia leads to an increased risk of ACS in diabetes patients. These findings show that it is important to avoid severe hypoglycemia while treating diabetes, particularly in elderly patients.

Aim: This study aimed to determine whether there is an association between influenza and new‐onset type 1 diabetes.Materials and methods: This population‐based retrospective cohort study used data from the National Database of Health Insurance Claims and Specific Health Check‐ups of Japan. Influenza was defined based on drug prescriptions and the onset of type 1 diabetes was defined using specific medical codes indicating a diagnosis of type 1 diabetes. The incidence rate ratio of new‐onset type 1 diabetes within 180 days after an influenza diagnosis was calculated and it was compared with that at other times using Poisson regression and generalized estimating equations. Sensitivity analyses were performed to confirm the robustness of this finding.Results: The data of 10,400 patients with new‐onset type 1 diabetes were analyzed, including 2,196 (952 male 1,244 female) patients diagnosed with influenza between 1 September 2014 and 31 August 2017. Although only patients with type 1 diabetes were included, adjusted analysis showed that individuals had a 1.3‐fold (95% confidence interval: 1.15–1.46) higher risk of developing type 1 diabetes in the first 180 days after influenza diagnosis than that at other times.Conclusions: In this Japanese population‐based cohort, the risk of new‐onset type 1 diabetes may increase after the diagnosis of influenza. These results, which must be confirmed in other populations, suggest that influenza may be a causal factor for new‐onset type 1 diabetes. The molecular mechanisms underlying the potential etiological relationship between influenza and type 1 diabetes should be elucidated.

Background: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents.Methods: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman’s rank-correlation coefficient.Results: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change − 0.6 ± 0.7%,P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change − 2.3 ± 2.8 kg,P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6,P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman’sρ = − 0.17,P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman’sρ = − 0.19,P = 0.011).Conclusions: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registrationUMIN-CTR: UMIN000016304

This study clarified the age of death in patients with or without diabetes using the largest health insurance database in Japan. This population‐based retrospective cohort study was performed using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) data. The ages of death between people with and without diabetes were compared. A total of 142,277,986 patients (74,488,962 women and 67,789,024 men) over 6 years, including 4,647,016 females, and 6,507,817 males with diabetes, were included. 2,786,071 females and 2,975,876 males died over 6 years, including 652,699 females and 954,655 males with diabetes. The average age of death in patients with diabetes was 2.6 years less than that of patients without diabetes. This descriptive epidemiological study illustrated the difference in age at death of patients with and without diabetes.

Background: Immune checkpoint inhibitors (ICIs) are associated with various endocrine abnormalities. However, their underlying pathophysiology remains unclear. We investigated the effect of multiple endocrine abnormalities on the overall survival (OS) of patients treated with ICIs. Methods: In total, 12 978 patients who received ICIs between 2014 and 2022 were investigated using the DeSC Japanese administrative claims database. Endocrine abnormalities were defined by each hormone replacement therapy, including levothyroxine, hydrocortisone, and insulin, in which it is difficult to distinguish central or primary hormone defect. Also, only patients with hypothyroidism after thyroiditis were included. Type 1 diabetes was additionally defined by the name of the disease and strict self-injection fees. Regression analyses were performed to identify risk factors for endocrine abnormalities and the effect of endocrine abnormalities on OS, adjusting for confounders including the number and duration of ICI administrations. Results: Single and multiple endocrine abnormalities were observed in 12.0% and 1.4% of patients, respectively. The most common combination was hypothyroidism and adrenal insufficiency (1.3%). Kaplan–Meier analysis indicated better survival in patients with multiple and single endocrine abnormalities than in those without (P < .01). Multivariable analysis revealed lower mortality in patients with multiple and single endocrine abnormalities [adjusted hazard ratio (aHR) 0.39; 95% confidence interval (CI), 0.28-0.54, P < .01; aHR 0.65; 95% CI, 0.5-80.72, P < .01, respectively) than in those without. Mortality was significantly lower with multiple abnormalities than with single (aHR 0.56; 95% CI, 0.39-0.79, P < .01). Conclusion: The development of multiple endocrine abnormalities in patients treated with ICIs is associated with improved survival compared with that of patients with a single abnormality.

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32–1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75–8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91–7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.