Diabetology International最新文献

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.

[This corrects the article DOI: 10.1007/s13340-022-00601-1.].

Phase angle, obtained using bioelectrical impedance analysis, non-invasively reflects the whole-body cellular condition and nutritional status and may be helpful as a prognostic factor. Patients with diabetes had a smaller phase angle than healthy subjects. However, the clinical significance of phase angle has not yet been elucidated. Therefore, the purpose of this study was to clarify the relationship between phase angle and HbA1c in patients with diabetes and the clinical relevance of phase angle. A retrospective, multicenter, cross-sectional study was conducted with Japanese patients with diabetes. Body composition was determined with bioelectrical impedance analysis, and this was used to obtain phase angle. Phase angle was assessed in relation to clinical parameters, body composition parameters, and HbA1c levels. A total of 655 patients were enrolled (400 men and 255 women, aged 57.1 ± 14.8 years, body mass index 25.6 ± 5.2 kg/m², HbA1c 8.1 ± 1.9%). Even in patients with diabetes, the phase angle was higher in men than in women and did not differ between the types of diabetes. Multiple regression analysis, performed with phase angle as the objective variable, and age, sex, diabetes type, HbA1c, albumin level, and body mass index as explanatory variables, revealed that phase angle was negatively affected by HbA1c (B = - 0.043, 95% Confidence interval: - 0.07 to - 0.02, p < 0.001). HbA1c, age, sex, albumin level, and body mass index were independent determinants of phase angle in participants with diabetes.

A 34-year-old man with poorly controlled type 2 diabetes was admitted to our hospital because of fever, headache, vomiting, and impaired consciousness. His hemoglobin A1c level was as high as 11.0%. Abdominal computed tomography revealed a bacterial liver abscess, while head magnetic resonance imaging simultaneously showed a high-signal lesion on diffusion-weighted imaging and a low-signal lesion on the apparent diffusion coefficient map of the splenium of the corpus callosum. No significant findings were detected in the cerebrospinal fluid. The latter findings led to a diagnosis of mild encephalitis/encephalopathy with reversible splenial lesions. His impaired consciousness resolved on Day 5 after treatment with ceftriaxone and metronidazole infusion and intensive insulin therapy; magnetic resonance imaging on Day 20 showed that the lesion in the splenium of the corpus callosum had disappeared. We propose that when a person with poorly controlled diabetes develops a bacterial infection and presents with impaired consciousness and headache, clinicians should consider the complications of mild encephalitis/encephalopathy with reversible splenial lesion.

Background: Small-dense (sd)LDL-cholesterol (C) is a potent risk factor for atherosclerotic cardiovascular disease (ASCVD) beyond LDL-C, and 35 mg/dL has been proposed as a cut-off value for high-sdLDL-C. sdLDL-C levels are strongly regulated by triglycerides (TG) and LDL-C levels. LDL-C has detailed targets for the prevention of ASCVD, while TG is only defined as abnormal at  ≥ 150 mg/dL. We investigated the effect of hypertriglyceridemia on the prevalence of high-sdLDL-C in patients with type 2 diabetes and explored the optimal TG levels that would suppress high-sdLDL-C.

Methods: Fasting plasma was obtained from 1569 patients with type 2 diabetes who were enrolled in the regional cohort study. sdLDL-C concentrations were measured by the homogeneous assay established by us. High-sdLDL-C was defined as ≤ 35 mg/dL according to the Hisayama Study. Hypertriglyceridemia was defined as ≥ 150 mg/dL.

Results: All lipid parameters except HDL-C were higher in the high-sdLDL-C group than in the normal-sdLDL-C group. The receiver operating characteristic (ROC) curves revealed that high sdLDL-C was identified sensitively by TG and LDL-C, with cut-off values of 115 mg/dL for TG and 110 mg/dL for LDL-C. The presence of hypertriglyceridemia increased the prevalence of high-sdLDL-C sixfold more than the normotriglyceridemic counterpart, regardless of statin use. This substantial influence of hypertriglyceridemia was found even within the control target of LDL-C levels (70-120 mg/dL) for diabetic subjects.

Conclusions: The TG cut-off for high-sdLDL-C was well below 150 mg/dL in a diabetic population. Amelioration of hypertriglyceridemia is needed even when LDL-C targets for diabetes are achieved.

Hypertriglyceridemia has been recognized as a common complication of diabetes ketoacidosis (DKA), whereas severe hypertriglyceridemia, also known as diabetic lipemia, rarely occurs and is associated with an increasing risk of acute pancreatitis. We report the case of a 4-year-old girl with new-onset DKA associated with remarkable hypertriglyceridemia. Her serum triglyceride (TG) level was as high as 2490 mg/dL on admission and 11,072 mg/dL on day two during treatment with hydration and intravenous insulin infusion, whereas the critical situation was successfully stabilized by standard treatment for DKA without the occurrence of pancreatitis. We reviewed 27 cases of diabetic lipemia with or without pancreatitis that were described in the relevant literature to identify risk factors for the occurrence of pancreatitis in children with DKA. As a result, the severity of hypertriglyceridemia or ketoacidosis, age at onset, type of diabetes, and presence of systemic hypotension, were not associated with the development of pancreatitis; however, the occurrence of pancreatitis in girls over 10 years old tended to be higher than that in boys. The serum TG levels and DKA successfully normalized in most of the cases with insulin infusion therapy with hydration, without other specific treatments (e.g., heparin therapy and plasmapheresis). We conclude that the occurrence of acute pancreatitis in diabetic lipemia could be avoided with appropriate hydration and insulin therapy, without specific treatment for hypertriglyceridemia.

[This corrects the article DOI: 10.1007/s13340-023-00623-3.].