Status of screening and preventive efforts against diabetic kidney disease between 2013 and 2018: analysis using an administrative database from Kyoto-city, Japan.

Background: Japan has the second highest prevalence of dialysis use in the world. Approximately 40% of patients who begin dialysis have diabetic kidney disease (DKD). Local governments and medical facilities are required to provide preventive measures against worsening diabetes mellitus (DM). However, the percentage of patients with DM who receive such screening or interventions for DKD is unclear. This study aimed to reveal to what extent screening for DKD and preventive measures against worsening DKD are performed in patients with DM, using an administrative database in a municipality. Methods: This was a cross-sectional study that used the Kyoto-city's administrative medical and long-term care database. Patients with a diagnosis of DM and receiving antidiabetic medication between 2013 and 2018 were defined as patients with DM and included. Patients with DKD were defined as those diagnosed with diabetic nephropathy or those with chronic kidney disease. We described the characteristics of patients with DM, diabetic complications, and extent of DKD screenings and preventive efforts against worsening of DM by fiscal year. Results: Across fiscal years, 25.8% to 27.5% of patient with DM had DKD. More than 3% of patients were on dialysis due DM in each fiscal year; approximately 15% started receiving dialysis that year. The percentage of patients who were regularly prescribed antidiabetic medication and received glycosylated hemoglobin testing ranged from 64.0% to 67.2% and from 30.6% to 36.5%, respectively. Urine microalbuminuria testing at least once a year occurred in 9.3% to 10.0%. The percentage of patients who received nutritional guidance ranged from 19.0% to 21.0%. Approximately 1% of patients received guidance for preventing DM from progressing to a disease that requires dialysis each fiscal year. Conclusion: This study from Japan, where a super-aging society has developed, using an administrative database in a municipality covering most of the elderly population clearly demonstrated an evidence-practice gap in efforts to prevent worsening of DKD. Strengthening cooperation between government and medical facilities and support for providing preventive measures against DKD are urgently needed.

Effectiveness of a healthcare retreat for male employees with cardiovascular risk factors.

Lifestyle modification is the primary treatment strategy for obesity, hypertension, dyslipidemia, and hyperglycemia. Recently, the Japanese government designed a healthcare retreat program for persons with cardiovascular risk factors. However, the structure and effectiveness of this program has not been fully discussed. Employees of a company group with obesity and one or more other cardiovascular risk factors were enrolled in the study. The participants in the three-day retreat program were compared with those receiving a brochure-based advice for their subsequent changes in the annual health check-up data using the propensity score matching method. Among the 415 eligible employees, 220 underwent the intensive program and 195 received a brochure-based advice. In the propensity score-matched subjects, reduction in body weight (2.7 kg vs. 0.99 kg, p < 0.01), waist circumference (3.5 cm vs. 1.5 cm, p < 0.01), and non-HDL cholesterol (8.8 mg/dl vs. 1.3 mg/dl, p = 0.05) were significantly greater in the intensive care group one year later. The superiority of the intensive program, however, was gradually attenuted for subsequent two years later. This healthcare retreat with counseling and training program would improve body weight and waist circumference for one to two subsequent years.

Risk of Future Diabetes in Japanese People with High-normal Fasting Plasma Glucose Levels: A 4-Year Follow-up Study.

Objective There is no definite consensus regarding the treatment and guidance for individuals with high-normal fasting plasma glucose levels (FPG;100-109 mg/dL). The present study aimed to determine the risk factors for future diabetes in Japanese people with high-normal FPG. Methods Retrospective cohort studies were conducted from 2008 to 2012, including 15,097 individuals who underwent medical examinations. First, the participants were divided into normal FPG (n=13,065) and high-normal FPG (n=2,032) groups to compare the diabetes incidence. Second, the high FPG group was divided into diabetes onset (n=133) and non-diabetes onset (n=1,899) groups to compare the baseline values. Third, to determine the risk factors for future diabetes in the high-normal FPG group, multivariate analyses were conducted. Results The cumulative incidence during the mean follow-up of 4 years was 94/13,065 (0.72%) and 133/2,032 (6.55%) in the normal FPG and high-normal FPG groups, respectively. Within the high-normal FPG group, the baseline body mass index, waist circumference, triglycerides, FPG, alanine aminotransferase (ALT), and gamma-glutamyl transferase were significantly higher and high-density lipoprotein cholesterol (HDL-C) was significantly lower in the diabetes onset group than in the non-diabetes onset group. Obesity, abdominal obesity, hypertriglyceridemia, low HDL-C, and high ALT were significant risk factors for diabetes according to a multivariate analysis. Conclusion The high-normal FPG group had a higher risk of diabetes than the normal FPG group, particularly when accompanied with obesity, abdominal obesity, hypertriglyceridemia, low HDL-C, and high ALT. Thus, this high risk group should receive appropriate guidance for lifestyle changes to avoid developing diabetes at an early stage.

Association between reduced ADAMTS13 and diabetic nephropathy.

INTRODUCTION: Deficiency of Von Willebrand factor (VWF)-cleaving protease (ADAMTS13) causes platelet thrombosis in the microcirculation. Intrarenal coagulation is thought to be associated with the development and progression of diabetic nephropathy. Our aim was to clarify the association between plasma ADAMTS13 antigen (ADAMTS13Ag) levels and diabetic nephropathy. MATERIAL AND METHODS: We measured the plasma levels of VWF antigen (VWFAg) and ADAMTS13Ag, and calculated the VWF/ADAMTS13 ratio in 86 type 2 diabetic patients and 26 healthy volunteers, to investigate the relationship between these levels and renal function. With regard to diabetic macroangiopathy, the relationship between these levels and carotid intima-media thickness (IMT) was also investigated. RESULTS AND CONCLUSIONS: A significant positive and negative correlation was noted between ADAMTS13Ag and the estimated glomerular filtration rate (eGFR), vWF/ADAMTS13 ratio and eGFR, respectively. The diabetic patients were divided into normoalbuminuria (n=50), microalbuminuria (n=8) and overt nephropathy (n=28) groups. Compared among these three groups and the 26 healthy volunteers, ADAMTS13Ag was significantly lower only in the overt nephropathy group. The mean carotid IMT was measured in 69 patients and was significantly negatively correlated with ADAMTS13Ag and positively correlated with VWF/ADAMTS13 ratio. When these 69 patients were divided into four groups according to eGFR and ADAMTS13 levels (ADAMTS13/eGFR; low/low: n=12; high/low: n=7; low/high: n=25; high/high: n=25), the mean carotid IMT was increased in patients with a low ADAMTS13Ag in the same eGFR group. The present study suggests that reduced ADAMTS13 might be associated with diabetic nephropathy.

The antimetastatic role of thrombomodulin expression in islet cell-derived tumors and its diagnostic value.

Islet cell tumors, endocrine neoplasm arising from pancreatic islets of Langerhans, are histologically difficult to diagnose as benign or malignant. Molecular markers are associated with the clinical characteristics that most of insulinoma are usually benign tumors, whereas other islet cell tumors are malignant but have not been identified. In this context, we newly found that an endothelial anticoagulant thrombomodulin was expressed in the normal islet beta cells and insulinoma, but not of other islet components or noninsulinoma islet cell tumors. Clinically, all of the subjects (n=15) of the insulinoma group showed no metastasis together with thrombomodulin expression in the lesions, whereas the other islet cell tumor groups showed a high incidence of metastasis (82%) and a low expression rate of thrombomodulin (6%). To examine the functional role of thrombomodulin, especially regarding the clinical characteristics of islet cell tumors, we tested the effect of exogenous thrombomodulin overexpression on cell adhesiveness and proliferation using MIN6 insulinoma cell line. In cell-based experiments, thrombomodulin overexpression reduced cell proliferation and enhanced Ca2+-independent cell aggregation, possibly through direct interaction with neural cell adhesion molecule. Taken together, these results are suggesting that thrombomodulin may act as antimetastatic molecule of insulinomas. In addition, thrombomodulin is a clinically useful molecular marker not only for identifying beta-cell-origin islet cell tumors (i.e., insulinomas) but also for predicting disease prognosis of islet cell tumors.