Novel subgroups of obesity and their association with outcomes: a data-driven cluster analysis.

BACKGROUND: Obesity is associated with various complications and decreased life expectancy, and substantial heterogeneity in complications and outcomes has been observed. However, the subgroups of obesity have not yet been clearly defined. This study aimed to identify the subgroups of obesity especially those for target of interventions by cluster analysis. METHODS: In this study, an unsupervised, data-driven cluster analysis of 9,494 individuals with obesity (body mass index ≥ 35 kg/m2) was performed using the data of ICD-10, drug, and medical procedure from the healthcare claims database. The prevalence and clinical characteristics of the complications such as diabetes in each cluster were evaluated using the prescription records. Additionally, renal and life prognoses were compared among the clusters. RESULTS: We identified seven clusters characterised by different combinations of complications and several complications were observed exclusively in each cluster. Notably, the poorest prognosis was observed in individuals who rarely visited a hospital after being diagnosed with obesity, followed by those with cardiovascular complications and diabetes. CONCLUSIONS: In this study, we identified seven subgroups of individuals with obesity using population-based data-driven cluster analysis. We clearly demonstrated important target subgroups for intervention as well as a metabolically healthy obesity group.

Adrenal Crisis Associated With COVID-19 Vaccination in Patients With Adrenal Insufficiency.

Vaccination is generally recommended for patients with adrenal insufficiency receiving glucocorticoid replacement therapy because they are at risk of experiencing adrenal crisis during infections. Conventional vaccinations, such as those for influenza virus, have rarely been associated with adrenal crisis in patients with adrenal insufficiency; therefore, increasing the glucocorticoid dose during vaccination is not necessarily recommended. The COVID-19 mRNA vaccines exhibit a higher degree of adverse reactions, including fever and general fatigue, than those of conventional vaccines. Here, we present 3 cases of adrenal crisis associated with mRNA COVID-19 (BNT162b2) vaccination in patients with secondary adrenal insufficiency. Two patients presented with adrenal crisis after the second dose, whereas 1 presented with adrenal crisis after the first dose. Within 24 hours of vaccination, all patients presented with fatigue and appetite loss, and 2 patients were febrile. None of them increased their glucocorticoid dosage at the time of vaccination, leading to an adrenal crisis. To date, 9 cases of adrenal crisis, including ours, associated with COVID-19 vaccination have been reported. Considering the high degree of adverse reactions to COVID-19 vaccination, administration of prophylactic stress dose of glucocorticoids is strongly recommended, particularly in patients with symptomatic adverse reactions, to protect them from adrenal crisis.

Risk of Lactic Acidosis in Hospitalized Diabetic Patients Prescribed Biguanides in Japan: A Retrospective Total-Population Cohort Study.

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.

Adrenal insufficiency in immunochemotherapy for small-cell lung cancer with ectopic ACTH syndrome.

SUMMARY: Ectopic ACTH (adrenocorticotrophic hormone) syndrome (EAS) is rarely associated with small-cell lung cancer (SCLC). Although chemotherapy is initially effective for SCLC, complicated EAS scarcely improves. Recently, immune checkpoint inhibitors have been used to treat SCLC. Atezolizumab plus chemotherapy for SCLC improved progression-free survival compared to conventional chemotherapy. However, little has been reported on the efficacy of the combination therapy for SCLC with EAS. We report a 72-year-old male who presented with 4-week history of leg oedema, proximal myopathy, weight loss, and worsened symptoms of diabetes and hypertension. Laboratory findings revealed hypokalaemia, increased plasma ACTH, and serum cortisol levels. Cortisol levels were not suppressed by the high-dose dexamethasone test. Chest and abdominal CT revealed a right lower lobe tumour with multiple metastases on the hilar lymph nodes, liver, lumbar spine, and bilateral enlarged adrenal glands. The patient was diagnosed with stage 4B SCLC with EAS. Hypercortisolaemia was then treated with metyrapone and atezolizumab plus chemotherapy, which was started for SCLC. After 10 days, the tumour shrank noticeably, and the ACTH level drastically decreased concomitantly with low cortisol levels with symptoms of fever, appetite loss, and general fatigue. Hydrocortisone treatment was initiated, and the symptoms resolved immediately. We describe a case of SCLC with EAS treated with atezolizumab plus chemotherapy, presenting with adrenal insufficiency. Close observation is required for patients with adrenal insufficiency receiving atezolizumab plus chemotherapy because of its stronger effect. Furthermore, advances in cancer therapy and care for endocrine paraneoplastic syndrome needs to be adapted. LEARNING POINTS: The immune checkpoint inhibitor atezolizumab has recently been approved for the treatment of small-cell lung cancer (SCLC). Approximately 1-6% of tumour ectopically produce ACTH and cause ectopic ACTH syndrome (EAS) as an endocrine paraneoplastic syndrome. The use of combined chemotherapy and atezolizumab in the ectopic ACTH syndrome secondary to small-cell lung cancer may cause a precipitous fall in circulating ACTH/cortisol, resulting in symptomatic adrenal insufficiency The advances in cancer therapy and treatment for endocrine paraneoplastic syndrome need to be adapted.

Development of a self-efficacy questionnaire, 'Insulin Therapy Self-efficacy Scale (ITSS)', for insulin users in Japanese: The Self-Efficacy-Q study.

AIMS/INTRODUCTION: Although patient self-efficacy is known to affect adherence to therapy, no available tool measures self-efficacy of insulin therapy administration while addressing the entire therapeutic process and management. In light of this, we developed the 'Insulin Therapy Self-efficacy Scale (ITSS).' MATERIALS AND METHODS: Development of the ITSS involved three phases: (i) item generation and creation of a questionnaire draft; (ii) testing and correcting the items through interviews with patients; and (iii) a multicenter, single-arm study to validate the questionnaire. RESULTS: A factor analysis and Cronbach's α both confirmed good internal consistency in the patients' confidence regarding the following four factors: the insulin injection procedure, insulin titration, glycemic control and ability to cope with hypoglycemia. Reproducibility was confirmed using weighted κ statistics and intraclass correlations. Good concurrent validity was confirmed with two other questionnaires. The ITSS score was also found to correlate with several patient characteristics and clinical parameters, as well as with a better adherence to injected insulin therapy 6 months later, suggesting the predictive validity of this scale. CONCLUSIONS: The ITSS is a reliable and valid tool for assessing and quantifying patients' self-efficacy. The ITSS estimation of self-efficacy can predict a patient's glycemic control and future adherence to insulin therapy. These characteristics will ensure the usefulness of the ITSS in ensuring a successful therapeutic process for patients and physicians.

Correction to: Reproducibility and Validity of a Questionnaire Measuring Treatment Burden on Patients with Type 2 Diabetes: Diabetic Treatment Burden Questionnaire (DTBQ).

In the original publication, second author's name was incorrectly published as Hiroki Shin. The correct name should read as 'Koki Shin'.

Dapagliflozin improves treatment satisfaction in overweight patients with type 2 diabetes mellitus: a patient reported outcome study (PRO study).

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's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 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 registration UMIN-CTR: UMIN000016304.

Reproducibility and Validity of a Questionnaire Measuring Treatment Burden on Patients with Type 2 Diabetes: Diabetic Treatment Burden Questionnaire (DTBQ).

INTRODUCTION: To measure the burden of pharmacotherapy on patients with type 2 diabetes mellitus (T2DM), we developed the Diabetes Treatment Burden Questionnaire (DTBQ), a patient-administered questionnaire composed of 18 questions, and evaluated its reproducibility and validity. METHODS: We enrolled 240 patients with T2DM under pharmacotherapy over 20 years of age at seven institutes in Japan. Their physicians filled out report forms on patient backgrounds, and the patients answered both the DTBQ and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). For evaluation of reproducibility, 48 of the enrolled subjects completed a 2nd DTBQ at home after leaving the medical institutes. RESULTS: Statistical analyses were performed for two sets of subjects, the validity analysis set (N = 236) and the reproducibility analysis set (N = 47). Factor analysis found a simple structure in the DTBQ item scores using a three-factor model with varimax rotation; the three subscales were designated as "implementation burden", "flexibility burden", and "blood glucose control burden". All intraclass correlation coefficients for the subscale scores were 0.8 or higher, indicating high reproducibility. Negative correlations were observed between the DTSQ satisfaction score and the DTBQ subscale scores. Moreover, as the dosing frequency of diabetic medicines increased, the DTBQ total score (total burden score) also became higher. Likewise, expected associations were observed between patient backgrounds and DTSQ scores. CONCLUSION: The DTBQ has adequate reproducibility and validity as a measurement scale for treatment burden on T2DM patients. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) 000026382. FUNDING: Eli Lilly Japan.