ABSTRACTAims/IntroductionThis study evaluated the risk factors for insulin therapy before 24 gestational weeks (early insulin therapy) in pregnant women with gestational diabetes diagnosed before 24 gestational weeks (E‐GDM).Materials and MethodsThis study included 530 singleton mothers with E‐GDM who underwent a 75 g oral glucose tolerance test (OGTT) in the first trimester at Keio University Hospital between January 2013 and December 2021. E‐GDM can be classified according to its management into only diet therapy until delivery (Diet E‐GDM), insulin therapy started before 24 gestational weeks (EarlyIns E‐GDM), and insulin therapy started after 24 gestational weeks (LateIns E‐GDM). We analyzed the risk factors for EarlyIns E‐GDM.ResultsPatients with EarlyIns E‐GDM had a significantly higher maternal age at delivery, pre‐pregnancy BMI, first trimester hemoglobin A1c, 1 h plasma glucose levels (1 h‐PG), and 2 h‐PG, as well as a more pronounced initial increase and subsequent decrease, compared with those in the Diet E‐GDM group. However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E‐GDM than in those with Diet E‐GDM. The number of abnormal values in the OGTT showed the largest area under the receiver operating characteristic curve (AUC) for predicting EarlyIns E‐GDM (0.83, 95% confidence interval [CI]: 0.79–0.86), followed by the 1 h‐PG value (AUC: 0.81, 95% CI: 0.77–0.85). The initial increase showed the third largest AUC (0.78, 95% CI: 0.74–0.82).ConclusionsAlthough further research is needed, our data suggest the importance of early insulin therapy in cases of E‐GDM with multiple abnormal OGTT values, especially with high 1 h‐PG levels and initial increase.

Nocturia impairs the quality of life in patients with type 2 diabetes mellitus. Although sodium glucose co-transporter 2 inhibitors (SGLT2i) such as tofogliflozin increase urine volume, their impact on nocturia, in conjunction with dietary salt restriction, is less clear. This multicenter, open-label, randomized, parallel-group trial included 80 subjects with type 2 diabetes and nocturia. The patients were divided into two groups: one receiving tofogliflozin, the shortest half-life, without salt restriction, and the other receiving both tofogliflozin and dietary salt restriction. The primary endpoint was nocturia frequency at 12 weeks. The secondary outcomes included changes in daytime urination frequency, urine volume, and home blood pressure. At 12 weeks, there were no significant differences in nocturia changes between both groups. Nocturia frequency did not change in the tofogliflozin without salt restriction group from 1.5 ± 0.8 to 1.3 ± 1.1 times per night (P = 0.297), and significantly decreased from 1.6 ± 1.0 to 1.3 ± 0.7 times per night in the tofogliflozin and dietary salt restriction group (P = 0.049). There was a trend toward increased urine volume and frequency during the daytime in the group with salt restriction, indicating a time-shift effect of the short half-life tofogliflozin and salt restriction on urinary time. The frequency of nocturia after tofogliflozin did not increase. Tofogliflozin reduced nocturia when combined with salt restriction. Furthermore, daytime urine volume and frequency showed an increasing trend, suggesting a shift in urine production to daytime hours due to the short half-life of tofogliflozin. Dietary modifications can enhance the therapeutic benefits of tofogliflozin in managing nocturia in people with type 2 diabetes.

This study aimed to evaluate the problems in screening for gestational diabetes mellitus (GDM) by casual blood glucose (CBG) measurements at 24-28 gestational weeks. Overall, 763 pregnant women who underwent the 50-g glucose challenge test (GCT) at 24-28 gestational weeks were enrolled. The preload blood glucose (0-h BG) level of 50-g GCT was considered as CBG. A total of 240 women with BG levels at 1-h after loading (1-h BG) on 50-g GCT ≥140 mg/dL underwent the 75-g oral glucose tolerance test, and 98 (40.8%) were diagnosed with GDM. Of the 99 women with GDM, 71 (71.7%) had 0-h BG on 50-g GCT <100 mg/dL. This study, where pregnant women underwent both CBG and 50-g GCT simultaneously, showed that when CBG at 24-28 gestational weeks ≥100 mg/dL alone was used for screening GDM, many pregnant women with GDM were overlooked.

The 2023 Delphi consensus recommended the use of new term, metabolic dysfunction-associated steatotic liver disease (MASLD), aiming conceptual shift from the conventional non-alcoholic fatty liver disease (NAFLD). The association between NAFLD and type 2 diabetes mellitus (T2DM) development is well known. This study aimed to examine the correlation between MASLD and T2DM development, comparing their utility as predictors. This retrospective cohort study obtained data from a medical health checkup program conducted at Asahi University Hospital, Japan, between 2004 and 2021. Logistic regression analysis was used to assess the association between MASLD and incident T2DM over 5 years. To compare the predictive utility of NAFLD and MASLD, receiver operating characteristic curves were drawn, followed by area under the curve (AUC) comparisons. In total, 15,039 participants (59.6% males; median [interquartile range {IQR}] age, 44 [38, 50] years) were included. Out of 2,682 participants meeting the criteria for MASLD, 234 individuals (8.7%) developed T2DM. Multivariate analysis revealed a significantly elevated risk of T2DM in MASLD compared with the reference healthy group (without steatotic liver disease or cardiometabolic risk), presenting an OR of 127.00 (95% CI 40.40-399.00, P < 0.001). The concordance rate of diagnosis between NAFLD and MASLD was 98.7%. The AUC values were 0.799 for NAFLD and 0.807 for MASLD, respectively. Comparative analysis of the AUC showed a statistical difference between NAFLD and MASLD (P < 0.001). MASLD was shown to be a significant risk factor for incident T2DM, exhibiting a potentially higher predictive capacity than conventional NAFLD.

To investigated the association between serum asprosin and metabolic characteristics in type 2 diabetes mellitus patients with different durations. A total of 436 patients with type 2 diabetes mellitus were enrolled in this study from the community health service center in southeastern Shanxi Province. All the patients were divided into two groups according to their diabetes duration: diabetes duration ≤5 years group (n = 132) and diabetes duration ≥10 years group (n = 304). Fasting blood samples were gathered and serum asprosin was tested. Pearson/Spearman correlation analysis was carried out. Asprosin was comparable between the two groups. Asprosin was positively correlated with systolic blood pressure (SBP), triglycerides, creatinine, serum uric acid and low-density lipoprotein cholesterol in the diabetes duration ≤5 years group (P < 0.05). In the diabetes duration ≥10 years group, asprosin was independently correlated with SBP, diastolic blood pressure, body mass index, total cholesterol, triglycerides, low-density lipoprotein cholesterol, creatinine, serum uric acid, fasting plasma glucose and glycosylated hemoglobin (P < 0.05). Asprosin was associated with alanine aminotransferase and estimated glomerular filtration rate (P < 0.05). Multiple linear regression analysis found that SBP and diastolic blood pressure is an independent factor related to serum asprosin in the group with diabetes duration ≤5 years (P < 0.05). Fasting plasma glucose, SBP, total cholesterol and serum uric acid is an independent factor related to serum asprosin in the group with diabetes duration ≥10 years (P < 0.05). Serum asprosin was significantly increased in the group with diabetes duration ≥10 years, and glycosylated hemoglobin, blood pressure and estimated glomerular filtration rate were independent risk factors in long-duration type 2 diabetes mellitus.

The association between serum angiopoietin-like 4 (ANGPTL4) levels and the severity of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus remains unclear. A total of 1,115 type 2 diabetes mellitus patients were analyzed in this cross-sectional study. DKD index included DKD stages defined by estimated glomerular filtration rate, the albuminuria grades and DKD risk management grades. Serum levels of ANGPTL4 and other biomarkers were detected. Multivariable-adjusted linear and logistic analyses were used to study the association between ANGPTL4 and DKD. The protein levels of ANGPTL4 were assessed in the kidney. Renal tubular cells were stimulated with glucose to study ANGPTL4 expression. Compared with the participants in the third or fourth quantile of ANGPTL4, those in the first or second quantile of ANGPTL4 were younger, with lower glycated hemoglobin, triglycerides and urinary albumin creatinine ratio (all P < 0.05). There was a negative nonlinear relationship between ANGPTL4 and estimated glomerular filtration rate in type 2 diabetes mellitus patients. One standard deviation increased serum ANGPTL4 levels, the odds ratio of having DKD was 1.40 (95% confidence interval 1.08-1.80). The mediation analysis showed that triglycerides did not mediate the association between ANGPTL4 and DKD. Furthermore, ANGPTL4 could be the strongest among multiple panels of biomarkers in its association of DKD. Compared with mice at 8 weeks-of-age, db/db mice at 18 weeks-of-age had increased ANGPTL4 expression in glomeruli and tubular segments. In vitro, glucose could stimulate ANGPTL4 expression in tubular cells in a dose-dependent manner. ANGPTL4 could be a potential marker and therapeutic target for DKD treatment.

We aimed to explore the associations between income/employment status and diabetes care processes, health behaviors and health outcomes. This cross-sectional study used health insurance claims data between April 2021 and March 2022, and a questionnaire survey between December 2022 and January 2023 in Tsukuba City. The study analyzed the participants with diabetes (other than type 1) from those selected by stratified random sampling. We evaluated diabetes care processes, health behaviors and health outcomes by calculating weighted proportions among the groups. We also assessed the associations between income/employment status and these variables using multivariable modified Poisson regression models. Of the 264 identified participants, 161 (64.2%) were men and 168 (72.8%) were aged ≥65 years old. Compared with the low-income groups, the high-income group had a higher proportion of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists use (adjusted risk ratio [aRR] 1.70, 95% confidence interval (CI) 1.07-2.72), a higher proportion of attendance to annual health checkups for ≥2 years (aRR 1.68, 95% CI 1.07-2.64) and a lower proportion of all-cause hospitalization (aRR 0.15, 95% CI 0.04-0.48); additionally, the middle-income group had a lower proportion of high total outpatient medical expenses (aRR 0.57, 95% CI 0.35-0.92). Compared to the no work time group, the full-time work group had a lower proportion of exercise habits (aRR 0.59, 95% CI 0.35-0.99) and a higher proportion of good self-reported health (aRR 2.08, 95% CI 1.22-3.55). Several variables were associated with income/employment status. Policy intervention should focus on high-risk groups identified by considering these associations.

To assess whether the sodium-glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes. We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis. Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19-23) versus 22 (IQR 20-25; P < 0.0001) in all patients, 21 (IQR 19-23) versus 24 (IQR 22-26; P < 0.0001) in the henagliflozin group and 21 (IQR 19-22) versus 21 (IQR 19-23; P > 0.05) in the non-sodium-glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224-6.056, P < 0.0001). Additionally, plasma phosphorylated tau181 levels significantly decreased at 6-month follow up in all patients (OR 11.5, 95% CI 9.9-13.7 vs OR 10.1, 95% CI 7.8-12.9, P < 0.0001) and in the henagliflozin group (OR 11.5, 95% CI 10.3-13.0 vs OR 9.2, 95% CI 7.1-10.7, P < 0.0001), but not in the non-sodium-glucose cotransporter 2 inhibitor group. Henagliflozin treatment was independently associated with decreased phosphorylated tau181 levels (OR 3.670, 95% CI 1.598-4.213, P < 0.0001). Henagliflozin treatment was independently associated with improvements in Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels, indicating significant beneficial effects on cognitive impairment in patients with type 2 diabetes.

Coefficient of variation (CV) is an indicator for glucose variability in continuous glucose monitoring (CGM), and the target threshold of %CV in type 1 diabetes is proposed to be ≤36%. This study aimed to evaluate the clinical significance of CV in children and adolescents with type 1 diabetes. Participants included 66 children with type 1 diabetes. A total of 48 participants were treated with multiple daily injections of insulin, and 18 with continues subcutaneous insulin infusion, using intermittently scanned CGM. The frequencies of the CGM metrics and glycosylated hemoglobin values were examined, and the significance of a threshold %CV of 36% was evaluated. The mean frequencies in time in range (TIR), time below range, %CV and the mean glycosylated hemoglobin value were 59.3 ± 16.1, 4.0 ± 3.5, 39.3 ± 6.2 and 7.3 ± 0.8%, respectively. The frequencies of participants who achieved a TIR >70% and a %CV of ≤36% were 24.1 and 27.3%, respectively. A total of 18 participants with a %CV of ≤36% had significantly higher TIR, lower time below range and lower glycosylated hemoglobin than the 48 with a %CV of >36% (72.6 ± 12.6 vs 52.4 ± 13.6, 2.4 ± 1.9 vs 4.6 ± 3.6, 6.9 ± 0.8 vs 7.4 ± 0.7%, respectively). Children and adolescents with type 1 diabetes using intermittently scanned CGM had difficulties in achieving the recommended targets of TIR and CV. However, the target %CV of ≤36% seems to be an appropriate indicator for assessing glycemic control and risk of hypoglycemia in pediatric patients with type 1 diabetes with any treatment.

The study aim was to investigate sulfonylurea prescription patterns in elderly patients (age ≥65 years) with type 2 diabetes mellitus in Japan. Sulfonylurea use among older adults has been insufficiently examined, despite the associated risks of hypoglycemia. This retrospective cross-sectional survey entailed analysis of Japanese pharmacy data, extracted from the Musubi database, for patients (age 20-100 years) prescribed sulfonylureas between November 2022 and October 2023. Dose distribution, adherence to the Diabetes Treatment Guidelines for the Elderly 2023 and coprescription of other diabetes medications were investigated. Of the total 91,229 patients, 80.1% were prescribed glimepiride, 16.3% gliclazide and 3.6% glibenclamide. In patients aged ≥65 years, exceeding the recommended dose (>1 mg/day for glimepiride, >40 mg/day for gliclazide) was numerically higher for glimepiride (25.0%) than for gliclazide (7.8%). The most common prescribing patterns were quadruple therapy with a sulfonylurea, a dipeptidyl peptidase-4 inhibitor, an sodium-glucose transporter 2 inhibitor and a biguanide in patients aged 65 to <75 years, and dual therapy with a sulfonylurea and a dipeptidyl peptidase-4 inhibitor in patients aged ≥75 years. Unfortunately, glinide was coprescribed for 338 (0.5%) of elderly patients. Insulin was coprescribed for 3,682 (5.6%) of elderly patients. Analysis of real-world sulfonylurea prescription data found guideline non-adherence, namely, excessive prescription of glimepiride, use of glibenclamide in elderly patients, and common coprescription with dipeptidyl peptidase-4 inhibitors. These findings might provide an opportunity to reconsider the treatment of patients with type 2 diabetes mellitus who are over-prescribed sulfonylureas to reduce residual risks, such as hypoglycemia.