Diabetology International最新文献

Aims/introduction: Diabetic cardiomyopathy (DCM) is characterized predominantly by diastolic dysfunction. The multiple mechanisms underlying DCM include altered energy substrate utilization. Recent studies indicate that PPARα plays an important role in the pathogenesis of lipotoxic cardiomyopathy. Pemafibrate is known to be a selective PPARα modulator (SPPARMα). We thus investigated the effects of pemafibrate on cardiac diastolic function in patients with type 2 diabetes.

Materials and methods: Seventeen patients with type 2 diabetes (T2D) and hypertriglyceridemia were screened and treated with pemafibrate at a dose of 0.2 mg/day for 8-16 weeks. Fourteen patients were eligible for analysis. Echocardiography was used for assessment of diastolic function. Early diastolic filling velocity (E), late atrial filling velocity (A) and the E/A ratio were included in this study. Peak early diastolic annular velocities (e') were also assessed using color tissue Doppler images. The primary endpoints were changes in the ratio of E to A (E/A), e', and the ratio of E to e' (E/e') from baseline.

Results: Pemafibrate significantly increased average e' (7.24 ± 0.58 vs 7.94 ± 0.67, p = 0.019) and a significant reduction in E/e' (9.01 ± 0.94 vs 8.20 ± 0.91, p = 0.041). The increase in e' was significantly related to increases in fasting blood glucose (r = 0.607, p = 0.021) and non-esterified fatty acid (r = 0.592, p = 0.026).

Conclusion: Pemafibrate improved diastolic function in patients with T2D and hypertriglyceridemia, suggesting that PPARα activation by pemafibrate prevents the development of DCM at an early stage.

The significance of diagnosing gestational diabetes mellitus (GDM) in early pregnancy is controversial. We used the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria to investigate whether clinical background and neonatal outcomes differ depending on when GDM is diagnosed in early or late pregnancy. This was a single-center, observational study conducted between November 2012 and March 2020 at St. Marianna University Hospital (Kawasaki, Japan). We compared the background and perinatal outcomes of patients with GDM depending on the time of diagnosis (at < 24 gestational weeks or ≥ 24 weeks). Insulin sensitivity index, homeostasis model assessment of insulin resistance, and β-cell function were calculated from a 75-g oral glucose tolerance test. Stratified analysis was performed by pre-pregnancy BMI in patients with early GDM. As a result, in the 507 patients, 89.9% gave birth at our hospital. The pre-pregnancy BMI was significantly higher in patients with early GDM than in those with late GDM (the median [interquartile range], 22.7 [20.3, 26.3] and 21.5 [19.3, 23.8] kg/m², respectively; p = 0.001). Perinatal outcomes were not different between the two groups. However, in the subgroup analysis of patients with early GDM, the prevalence of large-for-gestational-age infants was significantly higher in the group with overweight (15.4% vs 2.1%, respectively; p = 0.008). In conclusion, patients with GDM using the IADPSG criteria in early pregnancy may be treated, especially in patients with pre-pregnancy overweight.

[This corrects the article DOI: 10.1007/s13340-022-00605-x.].

Background: Previous meta-analyses have assessed the relationship between carbohydrate intake and type 2 diabetes (T2D) risk; however, they included few studies of Asian populations who have a higher carbohydrate intake and lower insulin secretory capacity than non-Asians. Since the publication of the previous meta-analyses, three further studies of Asian populations have been conducted. Based on this background, the present study aimed to perform an updated systematically examine observational studies concerning the link between dietary carbohydrate intake and T2D risk.

Methods: We conducted a systematic search for cohort studies that investigated the target association. For each analyzed study, parameter-adjusted risk ratios were used to compare the lowest and highest carbohydrate-intake groups in terms of their risk of incident T2D. The risk ratios were calculated using a random-effects model.

Results: Ten publications were analyzed. Overall, carbohydrate intake was found not to be associated with increased risk ratios of incident T2D (risk ratio [RR] = 1.07; 95% confidence interval [95% CI] = 0.94, 1.21; P < 0.01, I² = 61.9%). However, studies of Asian populations reported that high carbohydrate intake is significantly associated with this risk (RR = 1.29; 95% CI 1.15, 1.45; P = 0.59, I² = 0.0%).

Conclusions: This updated meta-analysis showed that, overall, carbohydrate intake is not associated with the risk of T2D; nevertheless, a significant association exists among Asian populations. To confirm the association between dietary carbohydrate intake and T2D risk observed in this study, further evidence from long-term observational studies of Asian populations is required.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00642-0.

Objective: Prediabetes with a glycated hemoglobin (HbA1c) level of 5.7 - 6.4% is associated with a poor prognosis of coronavirus disease 2019 (COVID-19), but whether the degree of glycemic control is associated with COVID-19 severity is unknown. The aim of this study was to evaluate the association between the degree of glycemic control and COVID-19 severity in patients with prediabetes.

Materials and methods: We reviewed 254 patients with COVID-19 admitted to our hospital between April 2020 and September 2021. Based on their HbA1c level, patients were classified into low (HbA1c level < 5.7%), moderate (HbA1c level, 5.7 - 5.9%), and high risk of diabetes (HbA1c level, 6.0 - 6.4%). The association between risk of diabetes and the worst COVID-19 symptom in terms of severity during admission was evaluated using binary logistic regression analysis.

Results: Seventy-one and 88 patients had moderate and high risks of diabetes, respectively. Sixty-three and seven patients presented severe (requiring non-invasive oxygen therapy) or critical (intensive care unit admission or artificial respiratory management) COVID-19. The multivariate logistic regression analysis showed that a high risk of diabetes was correlated with severe COVID-19 (P = 0.01) after adjusting for baseline characteristics, whereas a moderate risk of diabetes was not (P = 0.17).

Conclusion: Prediabetes with a high risk of diabetes is associated with the worst COVID-19 symptom in terms of severity during admission. Our findings could aid in more efficient allocation of healthcare resources to a narrower population of prediabetic patients.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00643-z.

Recently in Japan, the term "tonyobyo sei jinzobyo", the Japanese translation of "diabetic kidney disease", has been increasingly used in place of the term "tonyobyo sei jinsho", the Japanese translation of "diabetic nephropathy". Many international diabetes and nephrology guidelines have defined diabetic kidney disease as a condition caused by diabetes, typically presenting with albuminuria, similar to or identical to current and historical definitions for diabetic nephropathy. However, recent guidelines from the Japanese Society of Nephrology propose a broader disease concept for the term diabetic kidney disease, including patients without albuminuria. A rationale for proposing a broader disease concept for diabetic kidney disease may have come from changes in the kidney phenotype of patients with diabetes observed in recent years. Epidemiological studies have shown that an increasing proportion of patients with diabetes have reduced kidney function, while the prevalence of those with albuminuria appears to have decreased. However, these studies also suggested that the more advanced age of patients presenting with diabetes and increased use of renin-angiotensin system blockers may have contributed to this change in disease phenotype. We believe the principal rationale for the nomenclature change from diabetic nephropathy to diabetic kidney disease was to create a more easily understood, lay-language term for English speakers, rather than to create a term to encompass a broader population of diabetes with chronic kidney disease (CKD). Further discussion and international consensus are needed for the definition of diabetic kidney disease, to avoid ambiguity or possible confusion.

Objective: The Scatchard plot of anti-insulin antibodies is curvilinear, indicating heterogeneity in binding sites. However, the relationship between bound insulin (B) and free insulin (F) in patients with anti-insulin antibodies has not yet been elucidated. This study aimed to determine this relationship.

Methods: We studied two insulin-treated patients with diabetes who had high titers of anti-insulin antibodies. The B and F levels were measured using daily blood samples. Assuming that the law of mass action is applicable to the reactions between insulin and anti-insulin antibody forms, we plotted the bound-to-free ratio (B/F) vs. B using patient data. We also performed an equilibrium binding assay in vitro.

Results: Some of the B/F vs. B plots of the daily variation showed an approximately linear relationship, while the Scatchard plots of in vitro data became curvilinear.

Conclusion: Our study suggests that the one-site (high-affinity site) of anti-insulin antibodies accounts, for the most part, for insulin pharmacokinetics within physiological insulin concentrations.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00641-1.

Introduction: The CAPTURE study estimated the global prevalence of established cardiovascular disease (CVD) and characterized the usage of glucose-lowering agents (GLAs) in adults with type 2 diabetes (T2D) across 13 countries. The purpose of this secondary analysis of data from the Japanese sites within CAPTURE (NCT03786406, NCT03811288) was to provide data about medication usage stratified by CVD status among Japanese participants with T2D.

Materials and methods: Data on GLA usage (including those with proven cardiovascular [CV] benefits) in Japanese participants with T2D managed in clinics or hospitals were collected and stratified by CVD subgroups.

Results: There were 800 Japanese participants in the CAPTURE study (n = 502 [no CVD group], n = 298 [CVD group], n = 268 [atherosclerotic CVD subgroup]). Oral antidiabetic agents and insulin were used by 88.5% and 23.4%, respectively, of participants overall. Among participants with established CVD, dipeptidyl peptidase-4 inhibitors (65.1%) were most frequently used, followed by biguanides (50.7%) and insulins (26.2%). The pattern was similar among participants with atherosclerotic CVD. A lower proportion of participants in the CVD group used glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) with proven CV benefits versus the no CVD group (GLP-1 RAs: 7.0% vs. 8.6%; SGLT-2is: 13.4% vs. 19.1%).

Conclusion: This analysis of the CAPTURE study provided a comprehensive overview of prescription patterns for the treatment of T2D in Japan. Use of GLAs with proven CV benefit was low, even in participants with established CVD, which was comparable to the findings from the global cohort.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00638-w.

Objective: Currently, the most frequently prescribed once weekly glucagon-like peptide-1 receptor agonists (GLP-1RA) in Japan are dulaglutide (DG) and semaglutide (SG). However, little is known about the differences between these two compounds in clinical practice in Japan. This study compared the efficacy and safety of DG and SG using professional CGM in 12 patients attending our outpatient with poorly controlled type 2 diabetes mellitus (T2DM) while using GLP-1RA.

Methods: The study subjects were 12 T2DM patients with HbA1c ≥ 7.0% on treatment with 0.75 mg/week DG for at least 24 weeks. All patients wore the professional CGM twice, once while receiving DG and once when the SG dose was increased to 0.5 mg/week.

Results: Time in range was significantly better with SG than with DG, which was the main outcome measure. Regarding the secondary outcome measures, standard deviation of glucose, average sensor glucose, time above range, maximum sensor glucose, interquartile range, SD of glucose during the nocturnal period (0000-0559), and average nocturnal sensor glucose (0000-0559) were significantly better with SG than DG. In contrast, SG had no effect on the time below range and minimum sensor glucose compared to DG.

Conclusions: Switching from 0.75 mg DG to 0.5 mg SG in patients with T2DM improved glycemic variability, mean glycemic index, and daily variability without increasing the hypoglycemic index. The results suggest that switching to SG may be a useful option in patients experiencing inadequate glycemic control with DG.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00640-2.

Aim: The incidence of cardiovascular and renal events was investigated in patients with type 2 diabetes who were classified according to anemia and the components of dialysis-independent chronic kidney disease (CKD) in a prospective observational study.

Methods: A population of 778 Japanese patients with type 2 diabetes was prospectively analyzed for 4 years. The outcomes were the incidence of cardiovascular events and renal events.

Results: In all subjects, the incidence of cardiovascular and renal events was found to be 5% and 11%, respectively. Even after adjusting for a reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m²), the incidence of cardiovascular events was significantly higher (hazard ratio [HR]: 5.73) in patients with anemia and albuminuria than in those without anemia and albuminuria. The incidence of renal events was significantly higher in patients with no anemia and albuminuria (HR: 2.93) and further in those with anemia and albuminuria (HR: 7.56) than in those without anemia and albuminuria even after adjusting for a reduced eGFR.

Conclusion: Anemia combined with albuminuria is a risk factor for vascular events in patients with type 2 diabetes, regardless of the eGFR.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00637-x.