Modification effect of receipt of diabetes care on the association between COVID-19 infection and HbA1c level during the first year of the coronavirus pandemic using a nationwide population-based database.

AIMS/INTRODUCTION: We assessed the modification effect of adherence to diabetes care on the association between HbA1c levels and the risk of coronavirus disease 2019 (COVID-19) among individuals with diabetes using a population-based database. MATERIAL AND METHODS: We retrospectively identified individuals with diabetes during routine health checkups performed in 2019 in Japan using a population-based claims database (JMDC, Tokyo, Japan). We assessed the risk of COVID-19 infection in 2020 in relation to HbA1c levels during routine checkups, stratified by the presence/absence of follow-up for diabetes care in 2019. Several sensitivity analyses were performed. RESULTS: We identified 65,956 individuals with an HbA1c ≥6.5% and fasting glucose ≥126 mg/dL in routine checkups, including 52,637 and 13,319 with and without at least one physician consultation for diabetes care in 2019, respectively. Although high HbA1c levels were associated with an increased risk of COVID-19 infection in a dose-dependent manner among individuals without diabetes care in 2019 (odds ratios, 1.53 and 2.17 in individuals with HbA1c of 7.0-7.9% and ≥8.0%, respectively) with a reference to HbA1c of 6.5-6.9%, individuals with diabetes care had no such trend in 2019 (odds ratios, 0.99 and 0.97 among individuals with HbA1c of 7.0-7.9% and ≥8.0%, respectively). Sensitivity analyses yielded consistent results when the variable definitions were changed and after multivariable adjustment with multiple imputation. CONCLUSIONS: This population-based study suggests that adherence to diabetes care may modify the association between HbA1c levels and the risk of COVID-19 infection.

Proteinuria screening and risk of bone fracture: a retrospective cohort study using a nationwide population-based database.

Background and hypothesis: Proteinuria is associated with an increased risk of kidney function deterioration, cardiovascular disease, or cancer. Previous reports suggesting an association between kidney dysfunction and bone fracture may be confounded by concomitant proteinuria and were inconsistent regarding the association between proteinuria and bone fracture. Therefore, we aimed to evaluate the association using a large administrative claims database in Japan. Methods: Using the DeSC database, we retrospectively identified individuals with laboratory data including urine dipstick test between August 2014 and February 2021. We evaluated the association between proteinuria and vertebral or hip fracture using multivariable Cox regression analyses adjusted for various background factors including kidney function. We also performed subgroup analyses stratified by sex and kidney function and sensitivity analyses with Fine & Gray models considering death as a competing risk. Results: We identified 603 766 individuals and observed 21 195 fractures. With reference to the negative proteinuria group, the hazard ratio for hip or vertebral fracture was 1.10 [95% confidence interval (CI), 1.05-1.14] and 1.16 (95%CI, 1.11-1.22) in the trace and positive proteinuria group, respectively, in the Cox regression analysis. The subgroup analyses showed similar trends. The Fine & Gray model showed a subdistribution hazard ratio of 1.09 (95%CI, 1.05-1.14) in the trace proteinuria group and 1.15 (95% CI, 1.10-1.20) in the positive proteinuria group. Conclusions: Proteinuria was associated with an increased risk of developing hip or vertebral fractures after adjustment for kidney function. Our results highlight the clinical importance of checking proteinuria for predicting bone fractures.

Modification Effects of Albuminuria on the Association Between Kidney Function and Development of Anemia in Diabetes.

CONTEXT: Previous studies failed to adjust for estimated glomerular filtration rate (eGFR) in evaluating the association between albuminuria and anemia development, and we aimed to investigate whether albuminuria independently affects anemia development. METHODS: We conducted a retrospective cohort study and retrospectively identified adults with diabetes from a Japanese nationwide clinical database (JMDC, Tokyo, Japan). To assess the modification effects of albuminuria on the association between eGFR and anemia development, we estimated prevalence of anemia, defined as hemoglobin < 13 g/dL in men and < 12 g/dL in women, using a modified Poisson regression and marginal standardization form of predictive margins, stratified by albuminuria severity after adjusting for eGFR. Hence, we revealed at which eGFR level this modification effect appeared and the extent to which this modification effect increased the prevalence of anemia. RESULTS: We identified 327 999 data points from 48 056 individuals [normoalbuminuria: 186 472 (56.9%), microalbuminuria: 107 170 (32.7%), and macroalbuminuria: 34 357 (10.5%)]. As eGFR declined, anemia prevalence increased. Albuminuria severity modified this association induced by decreased eGFR among individuals with eGFR <30 mL/min/1.73 m2 after adjusting for multivariable factors, including age, sex, comorbidities, and medication use. Compared with the normoalbuminuric group, the macroalbuminuric group had a 5% to 20% higher anemia prevalence among individuals with eGFR of <30 mL/min/1.73 m2. CONCLUSION: We revealed that the severity of albuminuria modified the association between eGFR and anemia development among individuals with eGFR <30 mL/min/1.73 m2, highlighting the modification effect of albuminuria on the association between kidney function and anemia development in diabetes.

Diagnostic ability using fatty liver and metabolic markers for metabolic-associated fatty liver disease stratified by metabolic/glycemic abnormalities.

AIMS/INTRODUCTION: Although several noninvasive predictive markers for fatty liver and metabolic markers have been used for fatty liver prediction, whether such markers can also predict metabolic-associated fatty liver disease (MAFLD) remains unclear. We aimed to examine the ability of existing fatty liver or metabolic markers to predict MAFLD. MATERIALS AND METHODS: Participants in a high-volume center in Tokyo were classified into groups with and without MAFLD, based on the presence of metabolic abnormalities and fatty liver diagnosed through abdominal ultrasonography, between 2008 and 2018. The diagnostic abilities of three fatty liver markers: fatty liver index (FLI), hepatic steatosis index (HSI), and lipid accumulation product (LAP), and three common metabolic markers: waist-to-height ratio (WHR), body mass index (BMI), and waist circumference (WC), for predicting MAFLD, were evaluated. Analyses stratified by MAFLD subtypes were performed. RESULTS: Of 92,374 individuals, 19,392 (36.1%) had MAFLD. The diagnostic performances for MAFLD prediction, measured as c-statistics, for FLI, HSI, LAP, WHR, BMI, and WC were 0.906, 0.892, 0.878, 0.844, 0.877, and 0.878, respectively. Optimal cutoff values for diagnosing MAFLD for FLI, HSI, LAP, WHR, BMI, and WC were 20.3, 32.7, 20.0, 0.49, 22.9, and 82.1, respectively. Analyses stratified by MAFLD subtypes, based on BMI and metabolic/glycemic abnormalities, suggested that FLI and HSI had acceptable (c-statistics >0.700) diagnostic abilities throughout all the analyses. CONCLUSIONS: All six markers were excellent predictors of MAFLD in diagnosing among the general population, with FLI and HSI particularly useful among all sub-populations.

Major complications after percutaneous biopsy of native or transplanted liver in pediatric patients: a nationwide inpatient database study in Japan.

AIM: Although major complication rates following percutaneous liver biopsy (PLB) have been reported to be higher in children than in adults, scarce data are available regarding pediatric patients stratified by native and transplanted liver. We aimed to assess the factors associated with major complications after percutaneous biopsy of native or transplanted liver using a nationwide inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified pediatric patients who underwent PLB between 2010 and 2018. We described major complication rates and analyzed factors associated with major complications following PLB, stratified by native and transplanted liver. RESULTS: We identified 3584 pediatric PLBs among 1732 patients from 239 hospitals throughout Japan during the study period, including 1310 in the native liver and 2274 in the transplanted liver. Major complications following PLB were observed in 0.5% (n = 18) of the total cases; PLB in the transplanted liver had major complications less frequently than those in the native liver (0.2% vs. 1.0%, p = 0.002). The occurrence of major complications was associated with younger age, liver cancers, unscheduled admission, anemia or coagulation disorders in cases with native liver, while it was associated with younger age alone in cases with transplanted liver. CONCLUSIONS: The present study, using a nationwide database, found that major complications occurred more frequently in pediatric cases with native liver and identified several factors associated with its major complications.

Effect of Branched-Chain Amino Acid Infusion on In-Hospital Mortality of Patients With Hepatic Encephalopathy and End-Stage Kidney Disease: A Retrospective Cohort Study Using a National Inpatient Database.

OBJECTIVES: Renal failure and hepatic cirrhosis are mutually aggravating factors. However, no specific therapeutic strategies for hepatic encephalopathy (HE) and end-stage kidney disease have been established. The coexistence, with an extremely poor prognosis, makes randomized controlled trials unfeasible. We evaluated whether an infusion of branched-chain amino acids was associated with mortality in patients hospitalized for HE and end-stage kidney disease. DESIGN AND METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with HE and end-stage kidney disease who received hemodialysis within 2 days of admission from July 2011 to March 2017. We divided the patients into those who received branched-chain amino acid infusion within 2 days of admission and those who did not. We conducted analyses using overlap weights based on propensity scores to compare in-hospital mortality between the groups. Sub-group analysis was conducted by stratifying patients by Child-Pugh class. RESULTS: We identified 553 eligible patients, including 503 patients who received branched-chain amino acid infusion and 50 who did not. The patients who received branched-chain amino acid infusion had lower mortality than those who did not (10.2% vs. 20.1%, relative risk 0.51, 95% confidence interval 0.27-0.95). Sub-group analysis showed that branched-chain amino acid infusion was associated with decreased in-hospital mortality in patients with Child-Pugh class C (16.2% vs. 39.0%, relative risk 0.41, 95% confidence interval 0.23-0.76). CONCLUSIONS: Branched-chain amino acid infusion may improve the prognosis of HE in patients with end-stage kidney disease, particularly those with lower liver function. Further research is necessary to provide a suitable treatment for HE in patients with end-stage kidney disease.

Clinical Characteristics and Incidences of Benign and Malignant Insulinoma Using a National Inpatient Database in Japan.

CONTEXT: Insulinoma is the most common pancreatic functional neuroendocrine neoplasm, yet little information on recent clinical practice in patients with insulinoma, especially malignant insulinoma, is available. OBJECTIVE: This work aims to clarify the characteristics and practice patterns in patients with insulinoma using a national inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with insulinoma admitted between 2010 and 2018. We compared background characteristics and therapeutic interventions between patients with benign and malignant insulinoma. We also estimated the incidence of insulinoma using the number of patients with newly diagnosed insulinoma in 2012. RESULTS: We identified 844 patients with benign insulinoma and 102 patients with malignant insulinoma. Patients with malignant insulinoma were younger (median, 55.5 vs 66.0 years, P < .001) and less likely to be female (55.9% vs 65.3%, P = .061) than patients with benign insulinoma. Analysis of therapeutic interventions revealed that patients with malignant insulinoma more frequently received medications (71.6% vs 49.6%, P < .001) but less frequently underwent pancreatic surgery (57.8% vs 72.0%, P = .003). Older patients were a smaller proportion of those undergoing surgery and a larger proportion of those managed with medications without surgery (P < .001). The incidence of insulinoma was estimated to be 3.27 (95% CI, 2.93-3.61) individuals per million Japanese adult population per year. CONCLUSION: The present study using a nationwide database had a larger sample size than previous studies and revealed definitive differences in patient characteristics and therapeutic patterns between benign and malignant insulinoma.

Potassium Concentration in Initial Fluid Therapy and In-Hospital Mortality of Patients with Diabetic Ketoacidosis.

CONTEXT: Guidelines worldwide recommend potassium replacement of 10 to 40 mmol/L in the initial fluid therapy for patients with diabetic ketoacidosis. However, evidence is lacking as to the association between infused potassium concentration and mortality. OBJECTIVE: We aimed to determine the association between infused potassium concentration and in-hospital mortality. METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients admitted for treatment of diabetic ketoacidosis from July 2010 to March 2018. Patients with kidney dysfunction or serum potassium abnormalities were excluded. We evaluated the association of the potassium concentration in the total infused solutions in the first 2 days of hospitalization with 28-day in-hospital mortality using multivariable regression analysis with a cubic spline model. We also assessed the association between potassium concentration and occurrence of hyperkalemia. RESULTS: We identified 14 216 patients with diabetic ketoacidosis and observed 261 deaths. The quartile cut-points for potassium concentration were 7.7, 11.4, and 16.1 mmol/L. Within the range of approximately 10 to 40 mmol/L, potassium concentration was not associated with occurrence of hyperkalemia or death. Lower potassium concentrations were associated with higher 28-day in-hospital mortality; the odds ratio for patients receiving 8 mmol/L was 1.69 (95% CI, 1.03 to 2.78; reference: 20 mmol/L), and the odds ratio increased monotonically as potassium concentration decreased further. CONCLUSION: Patients receiving potassium replacement at concentrations of 10 to 40 mmol/L had similar in-hospital mortality rates, whereas lower concentrations were associated with higher mortality.