Lifestyle factors associated with a rapid decline in the estimated glomerular filtration rate over two years in older adults with type 2 diabetes-Evidence from a large national database in Japan.

BACKGROUND: The present study investigated lifestyle risk factors from metabolic syndrome-related lifestyles for a rapid decline in the estimated glomerular filtration rate (eGFR) among adults aged 40-74 years with treated and untreated type 2 diabetes. METHODS AND RESULTS: This study analyzed data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing the period from fiscal year (FY) 2017 to FY2020. We established FY2018 as our baseline year. The subjects of this study were adults aged 40-74 in FY2018(baseline) who had type 2 diabetes and underwent specific health checkups in FY2020. We excluded adults with a medical record of kidney dialysis between FY2017 and FY2018, records of suspected type 1 diabetes between FY2017 and FY2020, or a baseline eGFR >85 mL/min/1.73 m2 or missing eGFR data as of FY2020. Eventually we analyzed 573,860 individuals. The outcome variable was a rapid decline in eGFR (≥30%) during the follow-up. Exposure lifestyle factors included skipping breakfast, late-night dinners, regular smoking, a high alcohol intake, non-refreshing sleep, and a lack of habitual exercise. Logistic regression models were stratified by age (40-59 and 60-74 years) and baseline eGFR levels (60-85, 30-59, and <30 mL/min/1.73 m2). Covariates included sex, a history of heart disease, a history of stroke, a history of renal failure, anemia, low-density lipoprotein, systolic blood pressure, hemoglobin A1C, body mass index, antidiabetic medications, antihypertension drugs, lipid-lowering drugs, the oral adsorbent Kremezin, non-steroidal anti-inflammatory drugs, and drugs for the treatment of renal anemia. A rapid decline in eGFR was detected in approximately 1.3% of participants (7,683 cases). In the baseline eGFR >30 subgroups (60-85 or 30-59 mL/min/1.73 m2), skipping breakfast and regular smoking were associated with a rapid decline in eGFR in both age groups, while a lack of habitual exercise and late-night dinners in the 60-74 age group and non-refreshing sleep in the 40-59 age group were identified as risk factors. Additionally, skipping breakfast was a risk factor for a rapid decline in eGFR in the 60-74 age group regardless of baseline eGFR levels. In the baseline eGFR <30 mL/min/1.73 m2 subgroup, skipping breakfast and non-refreshed sleep were risk factors for a rapid decline in eGFR. CONCLUSIONS: We found specific lifestyle risk factors were associated with a rapid eGFR decline among people with type 2 diabetes from a nationwide database in Japan. The associations varied by baseline eGFR level, age, and sex. Lifestyle modifications may effectively prevent the aggravation of diabetic kidney disease.

Effect of the Diabetic Nephropathy Aggravation Prevention Program on medical visit behavior in individuals under the municipal national health insurance.

AIMS/INTRODUCTION: We aimed to clarify the effectiveness of the Diabetic Nephropathy Aggravation Prevention Program in Japan by comparing the diabetes-related medical visit behavior of individuals under the municipal national health insurance according to insurers' effort levels. MATERIALS AND METHODS: We assessed changes in medical visit behavior according to insurers' effort levels, "Full Efforts," "Some Efforts" and "No Effort," using longitudinal data from the National Database of Health Insurance Claims and Specific Health Checkups before 2015 and after 2018 regarding the national health insurance programs in Japan. We analyzed the effect of the Diabetic Nephropathy Aggravation Prevention Program using a generalized linear mixed model for 208,388 participants with diabetes. RESULTS: The additive effect on medical visit behavior was significantly higher for insurers with "Full Efforts" than for those with "No Effort;" the coefficient (log odds ratio) was 0.159 (95% confidence interval 0.063-0.256). The additive effects on medical visit behavior sizes for the people with hemoglobin A1c ≥7.0%, positive urinary protein and systolic blood pressure ≥140 mmHg were 0.508, 0.402 and 0.232, respectively, which were larger than the overall effect size (0.159) for insurers with "Full Efforts." CONCLUSIONS: Our findings showed that insurer efforts had an additive effect on the increase in the number of medical visits, suggesting that this national program could reduce the number of end-stage renal failures or dialysis in Japan.

Current status of the rapid decline in renal function due to diabetes mellitus and its associated factors: analysis using the National Database of Health Checkups in Japan.

The increasing number of patients undergoing dialysis due to diabetes mellitus (DM) is causing serious economic problems, and its reduction is an urgent policy issue in developed countries, including Japan. We aimed to assess the association between the annual rapid decline in renal function and health checkup measures, including blood pressure, to identify health guidance targets for preventing diabetic nephropathy (DN) and diabetic kidney disease (DKD) among individuals in a medical checkup system ("Tokuteikenshin" program) in 2018. This longitudinal analysis included 3,673,829 individuals who participated in the "Tokuteikenshin" program in 2018, had hemoglobin A1c (HbA1c) levels ≥5.6%, were available for follow-up, and underwent estimated glomerular filtration rate (eGFR) evaluation. We estimated the incidence of the relative annual decrease in eGFR ≥10% per 1000 person-years and odds ratios to evaluate the rapid decline in renal function and determine health guidance goals and their role in preventing DN and DKD. Overall, 20.83% of patients with DM had a rapid decline in renal function within the observation period. A rapid decline in renal function was associated with high systolic blood pressure, poor or strict DM control, increased urinary protein excretion, and decreased blood hemoglobin levels. The incidence of rapid decline in renal function is higher in DM, and appropriate systolic blood pressure and glycemic control are important to prevent the progression to DN or DKD. Our findings will be useful for researchers, clinicians, and other public health care members in establishing effective health guidance and guidelines for CKD prevention.

PAXgene-fixed paraffin-embedded sample is applicable to laser capture microdissection with well-balanced RNA quality and tissue morphology.

Assessing how gene expression analysis by RNA sequencing (RNA-Seq) correlates to a unique morphology is increasingly necessary, and laser capture microdissection (LCM) is a critical research tool for discovering the genes responsible in a region of interest (ROI). Because RNA-Seq requires high-quality RNA, a sample preparation procedure that can preserve morphology and give the required quality of RNA is essential. A PAXgene®-fixed paraffin-embedded (XFPE) block can satisfy the need for high-quality RNA, but there are few reports on adapting the method for LCM, such as how small an ROI is analyzable by RNA-Seq. In this study, we confirmed the morphology and preservation of RNA in XFPE and then assessed the relationship between the size of pieces cut by LCM and their RNA quality. In XFPE, the morphology was similar to that in alcohol-based fixed samples, the quality of the RNA extracted from a whole sample was excellent, that is equivalent to that of a fresh frozen sample, and the quality was maintained over one year later. Three sizes of pieces-large (25,000 µm2), medium (5,000 µm2), and small (1,000 µm2)-were cut by LCM so that the total areas of the sections cut per size were the same. RNA quality was found to be best preserved when tissue was cut into pieces of over 5,000 µm2. In summary, XFPE exhibits good morphology and excellent preservation of RNA quality. Furthermore, it can be a good tool when used with LCM and RNA-Seq, giving well-balanced RNA quality and tissue morphology in the ROI.