Journal of Diabetes Investigation最新文献

Aims/introduction: This study aimed to identify clinical predictors associated with sustained decline in estimated glomerular filtration rate (eGFR) among Japanese individuals diagnosed with diabetes mellitus.

Materials and methods: We conducted a retrospective analysis using J-DREAMS (Japan Diabetes compREhensive database project based on an Advanced Electronic Medical record System), a large-scale registry integrated with electronic medical records. The study population included adults (≥18 years) with diabetes who had at least one documented visit at a referral institution between December 1, 2015, and March 31, 2021, with concurrent measurements of serum creatinine and hemoglobin.

Results: A total of 12,416 and 11,157 patients were eligible for assessment of eGFR change at 1 and 2 years, respectively. Multivariable logistic regression identified several consistent risk factors for ≥30% eGFR reduction at both time points: low serum albumin, elevated triglycerides, anemia as defined by JSDT, diabetic retinopathy, CKD Stage G4 or higher, albuminuria category A3, and chronic heart failure. Additional predictors at 1 year included age under 65 and elevated HbA1c, while smoking, hypertension, and diabetic neuropathy were significant only at 2 years.

Conclusion: Beyond retinopathy and advanced kidney disease, anemia, hypoalbuminemia, and heart failure independently contributed to persistent eGFR decline, supporting the clinical relevance of cardio-renal anemia syndrome in diabetic populations.

Aims/introduction: We examined the differences in diabetes care between public assistance recipients (PARs), exempt from medical costs and guaranteed a minimum income, and the National Health Insurance (NHI) beneficiaries, covering non-employed and self-employed individuals with some cost sharing in Japan.

Materials and methods: This observational study used claims data from a Japanese municipality (April 2017-March 2022) to identify individuals aged 20-68 with type 2 diabetes on antidiabetic medications. We analyzed care processes annually and cross-sectionally, focusing on tests, medications, and medical costs, and followed health outcomes (hypoglycemia and hospitalization) monthly and longitudinally. Multivariable Poisson regression models estimate the risk ratios for binary care processes, and a gamma regression model analyzes medical costs as continuous variables. Health outcome incidence rate ratios were assessed using multivariable Poisson regression, with the observation period as an offset.

Results: We included cross-sectional data from 11,385, 11,566, and 9,943 people (2018-2020) and longitudinal data from 18,655 individuals. In the analysis considering the whole periods, PARs were more likely to receive annual eye examinations (adjusted risk ratio 1.15, 95% confidence interval [CI] 1.08-1.22), use sodium-glucose cotransporter-2 inhibitors (1.22, 1.13-1.31), and use glucagon-like peptide-1 receptor agonists (1.63, 1.41-1.90). The total (1.16, 1.09-1.23) and outpatient medical costs (1.31, 1.24-1.38) were higher, whereas the inpatient costs (0.85, 0.77-0.94) were lower for PARs. Hypoglycemia incidence was also higher (adjusted incidence rate ratio 2.21, 95% CI 1.38-3.54).

Conclusions: Public assistance might improve the diabetes care process, but not fully health outcomes. These findings suggest additional supports for PARs and further research for NHI beneficiaries in poverty.

Aims/introduction: Diabetic polyneuropathy (DPN) is common in patients with diabetes. Its symptoms include pain, numbness, and impaired neurosensory function. ONO-2910 promotes Schwann cell differentiation and is being developed for DPN.

Materials and methods: This Phase IIa randomized controlled trial evaluated the effectiveness and safety of ONO-2910 in Japanese patients with type 2 diabetes and DPN. Patients were randomized to ONO-2910 (300 mg/day) or placebo, once daily, for 12 weeks. The primary endpoints were the changes in the sum scores for numbness and tingling (modified Toronto Clinical Neuropathy Scores [mTCNS]) and safety.

Results: The ONO-2910 and placebo groups comprised 76 (safety: 77 patients) and 77 patients, respectively. The mean (standard deviation) age and time since DPN diagnosis were 62.6 (8.48) and 4.89 (5.662) years, respectively. The least-squares mean (LSM) change in mTCNS sum scores for numbness and tingling at 12 weeks was -1.0 in both groups (LSM difference: 0.0; 95% confidence interval -0.4 to 0.4). The LSM changes in the mTCNS total scores were -2.6 (0.64) and -2.3 (0.67) in the ONO-2910 and placebo groups, respectively. There were no marked changes in nerve function and nerve conduction velocities in the ONO-2910 and placebo groups. Treatment-emergent adverse events (TEAEs) occurred in 37 (48.1%) and 39 (50.6%) patients in the ONO-2910 and placebo groups, respectively. TEAEs in ≥2 patients in the ONO-2910 group were nasopharyngitis (5 patients), diarrhea (3 patients), nausea (2 patients), and eczema (2 patients).

Conclusions: ONO-2910 was generally well-tolerated in Japanese patients with DPN. There were no obvious improvements in DPN symptoms or neurosensory function among patients who received ONO-2910 versus placebo.

Clinical trial registry: Japan Primary Registries Network jRCT2061210008.

Diabetic kidney disease (DKD) is one of the most common causes of chronic kidney disease that leads to end-stage kidney disease, and its progression is closely linked to metabolic stress within renal tubular cells. Under long-term hyperglycemia, cells shift their glucose metabolism from normal oxidative phosphorylation toward glycolysis. This change is driven in part by the conversion of pyruvate kinase M2 (PKM2) from its active tetramer form to the less active dimer form. The PKM2 dimer slows pyruvate production and promotes lactate accumulation, leading to redox imbalance and activation of stress pathways such as HIF-1α, STAT3, and NF-κB. These signaling events enhance cellular senescence and inflammation, which further aggravate tubular injury and fibrosis. Growing evidence suggests that stabilizing PKM2 in its tetrameric state or blocking its nuclear translocation can restore metabolic balance and reduce renal damage. Targeting PKM2 dimer-dependent metabolic reprogramming may therefore represent a promising therapeutic approach to slow or reverse the progression of DKD.

Introduction: Hyperglycemia or diabetes mellitus (DM) is a well-known risk factor for pancreatic cancer, but it is uncertain whether well-controlled glycemic status can affect the pancreatic cancer incidence rate.

Methods: This study used 2,993,519 individuals who underwent four consecutive national annual health screenings between 2009 and 2013. The study participants were divided into three groups: nondiabetes mellitus (non-DM), new-onset DM, and known DM. Each group was further subcategorized based on the fasting blood glucose (FBG) levels and use of antidiabetic medication: well-controlled (<100 mg/dL), moderately controlled (100-125), or poorly controlled (>126).

Results: During a median follow-up of 6.3 years, the incidence rate of pancreatic cancer in the non-DM group significantly increased in the moderately controlled group compared with that in the well-controlled group, regardless of whether the FBG level was recently or initially elevated. However, no dose-response relationship was observed between glucose control status and pancreatic cancer incidence, although the incidence of pancreatic cancer in the new DM and known DM groups was generally higher than that in the non-DM group.

Conclusion: The pancreatic cancer incidence rate in the non-DM group significantly increased in the poorly controlled group. These findings suggest that in populations without DM, maintaining optimal glucose control may be associated with a lower risk of developing pancreatic cancer.

Aims: Clinical inertia, the failure to intensify treatment despite unmet glycemic goals, is a key factor in poor glycemic management for type 2 diabetes. No studies have defined clinical inertia based on HbA1c trends. In this study, we aimed to assess treatment intensification according to HbA1c trends.

Materials and methods: We analyzed data from the Japan Diabetes Comprehensive Database Project based on an Advanced Electronic Medical Record System (J-DREAMS) between 2016 and 2023. Eligible patients with type 2 diabetes had (1) unchanged prescriptions for the past 90 days; (2) two consecutive consultations within 90 days; and (3) HbA1c levels ≥7%, or ≥7.5%, for patients aged ≥65 years at both consultations. Treatment intensification was defined as an addition or increased dose or switch in antidiabetic medications, inclusive of insulin, at the second consultation. Moreover, factors associated with treatment intensification were assessed.

Results: Of the 5,683 patients, 1,130 (19.9%) received intensified treatment at the second consultation. Intensification occurred more frequently with higher HbA1c levels or worsening HbA1c trends. However, treatments were not intensified in approximately 50% of the patients, with HbA1c levels >8% or a worsening of >1%. Predictive factors included the HbA1c levels at the second consultation, changes in the HbA1c levels between the first and second consultations, the number of oral hypoglycemic medications, and the use of sulfonylureas or glinides.

Conclusions: Physicians should consider HbA1c trends to guide treatment intensification when HbA1c levels exceed target thresholds. Clinical inertia remains an important issue in diabetes management.

Background: This study investigates the impact of glycemic variability on sudomotor dysfunction in type 2 diabetes mellitus.

Methods: A total of 206 type 2 diabetes mellitus patients and 34 healthy controls were included. Sweat function (SF) was assessed using electrochemical conductance of hands (HESC) and feet (FESC). Type 2 diabetes mellitus patients underwent continuous glucose monitoring (CGM), and blood glucose variability was analyzed using various metrics. Type 2 diabetes mellitus patients were classified into normal, abnormal, reversible, and persistent abnormal SF groups.

Results: In healthy controls, SF showed no circadian rhythm. Type 2 diabetes mellitus patients with abnormal SF had longer diabetes duration, higher glucose variability, and greater SF impairment (P < 0.05). The reversible group exhibited the largest SF fluctuations (~26 μS) and a significant correlation between glucose variability and SF (P < 0.05). Blood glucose levels of 5-10 mmol/L were associated with improved SF in this group.

Conclusions: The findings suggest that greater glucose variability correlates with more severe peripheral nerve damage, and controlling blood glucose within 5-10 mmol/L may improve SF, offering insights for personalized treatment strategies in diabetic peripheral neuropathy (DPN) prevention.

Introduction: Transition from the MiniMed™ 770G hybrid closed loop (HCL) to the MiniMed™ 780G advanced hybrid closed loop (AHCL) insulin pump system has been demonstrated to improve glycemic control in people with type 1 diabetes (T1D). However, evidence regarding changes in treatment satisfaction following insulin pump upgrades remains limited to date.

Methods: People with T1D who underwent sequential insulin pump transitions from the MiniMed™ 640G with predictive low glucose management (PLGM) to the 770G HCL and subsequently from the 770G HCL to the 780G AHCL were retrospectively analyzed. Changes in treatment satisfaction were assessed using the Diabetes Treatment Satisfaction Questionnaire status (DTSQs) and change (DTSQc), together with clinical and continuous glucose monitoring metrics.

Results: DTSQs scores remained unchanged after transition from the 640G PLGM to the 770G HCL and from the 770G HCL to the 780G AHCL. In contrast, DTSQc scores significantly increased after transition from the 770G HCL to the 780G AHCL (13; range: 12-16; P < 0.0001) and were significantly higher than those observed after transition from the 640G PLGM to the 770G HCL. Following the transition to the 780G AHCL, HbA1c significantly decreased and TIR^70-180 significantly increased. Notably, DTSQc scores after transition to the 780G AHCL were negatively correlated with HbA1c levels after the transition.

Conclusions: In people with T1D, transition from the 770G HCL to the 780G AHCL significantly improved treatment satisfaction, with greater benefits than those observed during the transition from the 640G PLGM to the 770G HCL.