The change in Fibrosis-4 index in Japanese patients with type 2 diabetes treated by a fixed-ratio combination therapy of insulin degludec and liraglutide: A retrospective observational study.

AIM: The efficacy of titratable fixed-ratio combination therapy by a combination preparation of insulin degludec and liraglutide (IDegLira) in Japanese patients with type 2 diabetes, focusing particularly on the change in Fibrosis-4 index (FIB-4), a noninvasive method for the evaluation of liver fibrosis, was investigated. METHODS: As the full analysis set, 113 patients were treated with IDegLira. The patients were categorized into two groups according to the absence (GLP-1RA-naïve group, n = 72) or presence (GLP-1RA-treated group, n = 41) of glucagon-like peptide-1 receptor agonist (GLP-1RA) use before starting IDegLira. The clinical parameters were retrospectively determined over 6 months. RESULTS: The glycated hemoglobin value was significantly reduced in both groups. The bodyweight significantly decreased from 67.4 ± 11.0 kg at baseline to 66.4 ± 11.6 kg at 6 months in the GLP-1RA-naïve group, although it slightly increased in the GLP-1RA-treated group. FIB-4 significantly decreased from 1.60 ± 0.84 at baseline to 1.49 ± 0.74 at 6 months in the GLP-1RA-naïve group. Although FIB-4 significantly increased in the GLP-1RA-treated group, it remained within the low-risk level for liver fibrosis. CONCLUSION: Fixed-ratio combination therapy using IDegLira for the treatment of type 2 diabetes is useful for glycemic control and weight management. In particular, IDegLira may be more effective for lowering FIB-4 than adding unused oral antidiabetic agents or increasing the dose of insulin in GLP-1RA-naïve patients.

The prognosis of subjects showing a reduced estimated glomerular filtration rate without albuminuria in Japanese patients with type 2 diabetes: a cohort study for diabetic kidney disease.

BACKGROUND: To determine the renal and cardiovascular prognosis and all-cause mortality of Japanese patients with type 2 diabetes showing a reduced estimated glomerular filtration rate (eGFR) without albuminuria. METHODS: A population of 675 patients with type 2 diabetes was prospectively observed for 4 years to determine the renal and cardiovascular outcomes and mortality. The subjects were divided into the four groups: those with a preserved eGFR and no albuminuria (n = 306), a preserved eGFR and albuminuria (n = 151), a reduced eGFR and no albuminuria (n = 96), and a reduced eGFR and albuminuria (n = 122). The Cox proportional hazard model and Fine and Gray method were used to assess between-group differences in the risk of mortality and cardiovascular events. RESULTS: In the group with a reduced eGFR, the eGFR value did not significantly change in the subjects without albuminuria (0 ± 8 mL/min/1.73 m2), whereas it decreased continuously in those with albuminuria (-6 ± 12 mL/min/1.73 m2). The incidence of cardiovascular events was significantly (P = 0.03) higher in the subjects with albuminuria (17%) than those without albuminuria (7%) in the group with a reduced eGFR. Cardiovascular events were significantly (P < 0.01) more frequent in the group with a reduced eGFR than in those with a preserved eGFR in both subjects with and without albuminuria. CONCLUSIONS: The risk of end-stage kidney disease in non-albuminuric subjects with a reduced eGFR is considered to be low. We should focus on cardiovascular prognosis, because these patients are still at high risk of cardiovascular events, even though the prognosis is better in comparison to albuminuric patients.

Association between chronic kidney disease and the cognitive function in subjects without overt dementia
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AIM: The association between cognitive function and clinical parameters of chronic kidney disease (CKD) was investigated in Japanese patients without overt dementia in a cross-sectional study. MATERIALS AND METHODS: A population of 497 patients whose cognitive function had been examined using the mini-mental state examination (MMSE) were screened for this study. After the exclusion of 306 subjects who showed overt dementia, the association between the MMSE score and clinical characteristics was investigated in 191 subjects (male: 55%, age: 69 ± 12 years). RESULTS: The mean MMSE score of the study subjects was 26.7 ± 2.0. The MMSE score was negatively correlated with the patients' age and positively with the estimated glomerular filtration rate. It was significantly associated with age and proteinuria based on a multivariate analysis. The scores of "temporal orientation", "attention and calculation", and "remote memory" subitems of MMSE were significantly lower in the subjects ≥ 70 years of age than in those < 70 years of age. The scores of "temporal orientation" (4.3 ± 0.8 vs. 4.7 ± 0.6), "attention and calculation" (2.9 ± 1.6 vs. 3.9 ± 1.5), and "stage command" (2.7 ± 0.5 vs. 2.9 ± 0.3) were significantly lower in the subjects with proteinuria than in those without. CONCLUSION: Cognitive function was disturbed even in CKD patients without overt dementia. Intervention in patients with risk factors is deemed important for preventing future reductions in cognitive and renal functions in CKD patients without dementia.
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Case of Desbuquois dysplasia type 1: potentially lethal skeletal dysplasia.

We report a boy with Desbuquois dysplasia type 1. He had the typical skeletal changes: a "Swedish key" appearance of the proximal femora; advanced carpal ossification and other distinctive features of the hand, including an extra-ossification center at the base of the proximal phalanx of the index and middle fingers; dislocation of the metacarpophalangeal joint of the index finger; and bifid distal phalanx of the thumb. In addition, he presented with very severe prenatal growth failure, respiratory distress as a neonate, subsequent failure to thrive and susceptibility to airway infection, and sudden death in early childhood. Molecular analysis identified homozygous 1 bp deletion in the Calcium-Activated Nucleotidase 1 gene (CANT1). To our knowledge, this is the first report of Desbuquois dysplasia type 1 in Japan. Our experience suggests potential lethality in the disorder.

Relationship Between the Effect of Roxadustat and Comorbid Diabetes in Non-dialyzed Chronic Kidney Disease Patients: A Retrospective Observational Study.

Introduction The dose of roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, required to treat anemia, the hemoglobin level and the rate of hemoglobin target achievement were retrospectively investigated in non-dialyzed chronic kidney disease (CKD) patients with and without type 2 diabetes. Methods As the full analysis set, 25 subjects (10 with diabetes and 15 without diabetes) were observed over six months among 44 non-dialyzed CKD patients who received roxadustat. The target hemoglobin level was set at 110-130 g/L. Results The comorbidities of diabetes and body weight at baseline were significantly associated with each dose of roxadustat at six months and the change in each dose of roxadustat from the initiation of roxadustat treatment. There was no significant difference in the amount of increase in the hemoglobin level (14±11 g/L vs. 15±8 g/L) and the rate of hemoglobin target achievement (70% vs. 67%) between patients with and without diabetes. Each dose of roxadustat gradually decreased in patients without diabetes, whereas it increased in those with diabetes. Each dose of roxadustat was significantly higher in patients with diabetes than in those without diabetes at 3 (60±21 mg vs. 42±14 mg) and 6 (61±22 mg vs. 41±14 mg) months after the initiation of roxadustat treatment. Conclusion Roxadustat is useful for the treatment of anemia in both CKD patients with and without diabetes. However, the dose required to achieve the target hemoglobin level may be higher in patients with diabetes than in those without diabetes.

Changes in the estimated glomerular filtration rate and predictors of the renal prognosis in Japanese patients with type 2 diabetes: A retrospective study during the 12 months after the initiation of tofogliflozin.

BACKGROUND: The changes in the estimated glomerular filtration rate (eGFR) and predictors of the renal prognosis were retrospectively assessed over the 12 months after the initiation of tofogliflozin, which has the shortest half-life among sodium-glucose cotransporter 2 (SGLT2) inhibitors, in Japanese patients with type 2 diabetes and renal impairment. METHODS: In total, 158 patients treated with tofogliflozin between 2019 and 2021 were studied as the safety analysis set. One hundred and thirty subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into two groups based on the eGFR: normal- (eGFR ≥60 mL/min/1.73 m2, n = 87) and low- (eGFR <60 mL/min/1.73 m2, n = 43) eGFR groups. RESULTS: The body weight, blood pressure, urinary protein excretion, and serum uric acid concentration decreased from baseline in both eGFR groups while the hemoglobin level increased. The eGFR did not significantly differ over time, except for the initial dip (-4.3±9.6 mL/min/1.73 m2 in the normal-eGFR group and -1.5±5.3 mL/min/1.73 m2 in the low-eGFR group). The change in the eGFR at 12 months after the initiation of tofogliflozin was -1.9±9.0 mL/min/1.73 m2 and 0.2±6.0 mL/min/1.73 m2 in the normal- and low-eGFR group, respectively. In the normal-eGFR group, the change in the eGFR showed a significant negative correlation with the HbA1c and eGFR at baseline, according to a multiple regression analysis. In the low-eGFR group, the change in the eGFR showed a significant negative correlation with urate-lowering agent use. The frequencies of adverse events specific for SGLT2 inhibitors were not significantly different between the normal- and low-eGFR groups. CONCLUSIONS: Tofogliflozin may preserve renal function in the medium term in patients with type 2 diabetes and kidney impairment without an increase in specific adverse events.

Anemia combined with albuminuria increases the risk of cardiovascular and renal events, regardless of a reduced glomerular filtration rate, in patients with type 2 diabetes: a prospective observational study.

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.

Failure to paint the left quarter of a watercolor and no error in a line drawing: a case report of an art teacher with unilateral spatial neglect.

A 54-year-old art teacher, experienced a right putaminal hemorrhage, and thereafter suffered severe left hemiplegia and unilateral spatial neglect, and was transferred to the rehabilitation department of the University Hospital 1 month after the onset. Although the unilateral spatial neglect was improving, the patient was unable to paint the left quarter of a watercolor, but there was no error in line drawing. The occurrence of errors only in a watercolor suggests that the neural process for painting a watercolor is different from that of line drawing.

Efficacy of dulaglutide after switching from incretin-related drugs in patients with type 2 diabetes and inadequate glycemic control.

AIMS: The efficacy of dulaglutide was assessed according to the pretreatments administered before the initiation of dulaglutide in patients with type 2 diabetes. METHODS: In total, 89 patients treated using dulaglutide (0.75 mg, once a weekly) were investigated. The subjects were divided into the three groups based on the form in which therapy was started: additional therapy (n = 35), switched from dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 32) and switched from daily glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 30). The changes in medication adherence were determined in the daily GLP-1 RAs group using questionnaire surveys. RESULTS: The HbA1c values significantly decreased after the initiation of dulaglutide in all groups (additional therapy group, - 1.4 ± 1.6%; DPP-4 inhibitors group, - 1.2 ± 1.3%; and daily GLP-1 RAs group, - 0.5 ± 0.7%). Forty-six percent of the subjects in the daily GLP-1 RAs group reported that the incidence of forgetting injections of GLP-1 RA was decreased. The reduction of HbA1c was significantly greater in the subjects who reported a decrease in the incidence of forgetting injections (0.9 ± 0.9%) in comparison to those in which there was no change (0.1 ± 0.4%). CONCLUSIONS: Dulaglutide is considered effective in patients with type 2 diabetes and inadequate glycemic control, regardless of whether their pretreatment includes daily GLP-1 RA treatment.

Constipation Is a Frequent Problem Associated with Vascular Complications in Patients with Type 2 Diabetes: A Cross-sectional Study.

Objective Diabetes is recognized as an underlying disease of constipation. However, the prevalence of constipation varies according to the diagnostic criteria applied. We investigated the prevalence of constipation based on the new guideline for constipation in Japanese patients with type 2 diabetes and examined the relationship with the clinical background, including diabetic vascular complications. Methods Questionnaire surveys including items concerning the diagnosis and treatment status of constipation were administered to 410 patients with type 2 diabetes. Results Although 29% of the patients considered that they had experienced constipation (self-judged), only 14% had consulted a physician about constipation. The prevalence of chronic constipation based on the guideline was 26%. After including laxative users, constipation was finally found in 36%. Despite the use of laxatives (n=81), 51% of the patients were still diagnosed with chronic constipation. Patients with constipation (chronic constipation or laxative use) were significantly older and had a longer duration of diabetes than those without constipation. The body mass index (BMI) of patients with constipation (24.9±3.8 kg/m2) was significantly lower than that of those without constipation (26.3±4.6 kg/m2). Diabetic neuropathy (49% vs. 32%) and coronary heart disease (CHD) (27% vs. 13%) were significantly more frequent in the patients with constipation than in those without constipation. A multivariate logistic regression analysis revealed that gender, BMI, diabetic neuropathy, insulin use, and CHD were significantly associated with constipation. Conclusion An accurate diagnosis of constipation is desirable in patients with type 2 diabetes because constipation is independently associated with CHD.

Determinants of surgical repair of patent ductus arteriosus in low-birth-weight infants.

PURPOSE: To identify risk factors related to the failure of indomethacin therapy and the need for surgical repair in patent ductus arteriosus (PDA) in extremely low-birth-weight (<1000 g) infants (ELBWI). METHODS: Study subjects were 36 ELBWI with PDA born at a single tertiary perinatal center. They were classified into those who required surgery due to failure of indomethacin treatment (surgical group, n = 21) and those with effective indomethacin treatment (non-surgical group, n = 15). The odds ratios (ORs) and 95% confidence intervals (95% CIs) for the relationship between selected risk factors and surgical treatment of PDA were calculated. RESULTS: Gestational age of <28 weeks and diameter of PDA of 2 mm or more were independent and significant determinants of the need for surgical repair of PDA (adjusted ORs [95% CIs] = 9.91 [1.16-84.48] and 24.80 [2.72-225.74], respectively). The need for surgical repair of PDA did not correlate with sex, birth weight, 1-min Apgar score, left atrium diameter/aortic diameter (LA/Ao), left ventricular internal dimension at end-diastole, prophylaxes with indomethacin, and total dosage of indomethacin. CONCLUSIONS: Gestational age at birth of <28 weeks and diameter of PDA of 2 mm or more are determinants of failure of indomethacin treatment for PDA and the need for surgical repair.

Different renoprotective effects of luseogliflozin depend on the renal function at the baseline in patients with type 2 diabetes: A retrospective study during 12 months before and after initiation.

AIMS: The safety and efficacy, particularly, the factors associated with the renal prognosis, were assessed over 12 months after the initiation of luseogliflozin therapy in Japanese patients with type 2 diabetes and renal impairment. METHODS: In total, 238 patients treated with luseogliflozin (2.5 mg, once daily) were studied as the safety analysis set. Two hundred and two subjects whose medication was continued over 12 months were investigated as the full analysis set. The subjects were divided into 3 groups based on the estimated glomerular filtration rate (eGFR): high eGFR (n = 49), normal eGFR (n = 116) and low eGFR (n = 37) groups. RESULTS: The body weight, systolic blood pressure, HbA1c and urinary protein excretion gradually decreased from baseline in all eGFR groups. While the eGFR was significantly reduced from baseline in the high and normal eGFR groups, the eGFR did not significantly differ over time in the low eGFR group. There was no marked difference in the frequency of adverse events that were specific for SGLT2 inhibitors among the 3 groups in the safety analysis set. CONCLUSIONS: Luseogliflozin can preserve the renal function in the medium term in patients with type 2 diabetes and renal impairment without an increase in specific adverse events.

Early Improvement of Non-islet Cell Tumor Hypoglycemia by Chemotherapy Using Lenvatinib in a Case with Type 2 Diabetes and Hepatocellular Carcinoma Producing Big IGF-II.

A 77-year-old man was treated with a DPP-4 inhibitor for type 2 diabetes. Hypoglycemia occurred frequently, and an examination revealed a tumor with a maximum diameter of 140 mm in both lobes of the liver. Western immunoblotting detected a high-molecular-weight form of insulin-like growth factor-II, and non-islet cell tumor hypoglycemia was diagnosed. Although prednisolone 40 mg was started, hypoglycemia continued to occur frequently. Surgical tumor removal was not indicated, so lenvatinib was initiated. Hypoglycemia improved quickly, and the tumor shrank until it had partially disappeared. His condition continued to improve, and he was discharged.

Comparison of the changes in the factors associated with the renal prognosis of non-elderly and elderly subjects treated with empagliflozin- a retrospective observation study in Japanese patients with type 2 diabetes.

PURPOSE: The factors associated with the renal prognosis over six months after the initiation of empagliflozin were compared between the non-elderly and elderly Japanese patients with type 2 diabetes. PATIENTS AND METHODS: In total, 132 patients treated with empagliflozin (10 mg, once daily) were studied as the safety analysis set. One hundred ten subjects whose medications were not changed during the observation period were investigated as the full analysis set to assess the effectiveness. The subjects were divided into two groups: non-elderly subjects (n=72) of<65 years of age and elderly subjects (n=38) of≥65 years of age. RESULTS: Although the body weight and HbA1c, AST, ALT and γ-GTP levels were significantly reduced in both the non-elderly and elderly subjects, blood pressure, eGFR and urinary protein excretion were only significantly decreased in the non-elderly subjects. The hemoglobin, hematocrit and serum HDL-cholesterol levels were significantly elevated in both groups. The change in eGFR showed a significant positive association with the change in blood pressure. The change in urinary protein excretion tended to be correlated with the change in blood pressure. CONCLUSION: Although renoprotective effects might be limited, empagliflozin can safely and effectively improve metabolic parameters, even in elderly subjects.

Changes in medication adherence and unused drugs after switching from daily dipeptidyl peptidase-4 inhibitors to once-weekly trelagliptin in patients with type 2 diabetes.

AIMS: The changes in patients' satisfaction with the treatment, medication adherence and unused drugs before and after switching from daily DPP-4 inhibitors to once-weekly trelagliptin administration were prospectively investigated in patients with type 2 diabetes. METHODS: After excluding 46 patients who declined to switch from daily DPP-4 inhibitors, 79 subjects were included in the present study. The clinical parameters and results of questionnaire surveys regarding satisfaction with treatment as well as impressions of the amount of medicine/number of doses, medication adherence, and unused drug were examined at the baseline and 3 months after switching from daily DPP-4 inhibitors to trelagliptin in 75 patients with type 2 diabetes. RESULTS: Although the value of HbA1c did not change (7.0% ±â€¯0.5% to 7.0% ±â€¯0.6%), the scores representing satisfaction with the treatment (25.2 ±â€¯6.4 to 26.4 ±â€¯6.0), impression of the amount of medicine (-0.3 ±â€¯1.0 to 0.3 ±â€¯1.0) and number of doses (0.3 ±â€¯1.0 to 0.8 ±â€¯0.6), and medication adherence (0.8 ±â€¯0.4 to 0.9 ±â€¯0.3) as assessed by the questionnaire surveys were significantly improved after switching from DPP-4 inhibitors. The self-reported amount of unused drugs was significantly reduced after switching. CONCLUSIONS: Switching from daily DPP-4 inhibitors to once-weekly trelagliptin improved the satisfaction with the treatment, impression of the prescribed medicine and medication adherence in the type 2 diabetic patients who expresses a desire to reduce their prescription medicines. In such patients, improvements in the glycemic control and long-term prognosis might be expected through the reduction of unused drugs.

Brain metabolism of children with profound deafness: a visual language activation study by 18F-fluorodeoxyglucose positron emission tomography.

CONCLUSION: The use of fluorodeoxyglucose positron emission tomography (FDG-PET) with a visual language task provided objective information on the development and plasticity of cortical language networks. This approach could help individuals involved in the habilitation and education of prelingually deafened children to decide upon the appropriate mode of communication. OBJECTIVES: To investigate the cortical processing of the visual component of language and the effect of deafness upon this activity. SUBJECTS AND METHODS: Six prelingually deafened children participated in this study. The subjects were numbered 1-6 in the order of their spoken communication skills. In the time period between an intravenous injection of 370 MBq 18F-FDG and PET scanning of the brain, each subject was instructed to watch a video of the face of a speaking person. The cortical radioactivity of each deaf child was compared with that of a group of normal- hearing adults using a t test in a basic SPM2 model. RESULTS: The widest bilaterally activated cortical area was detected in subject 1, who was the worst user of spoken language. By contrast, there was no significant difference between subject 6, who was the best user of spoken language with a hearing aid, and the normal hearing group.

A comparison of the clinical courses of type 2 diabetic patients whose basal insulin preparation was replaced from insulin glargine 100 units/mL to insulin glargine biosimilar or 300 units/mL: a propensity score-matched observation study.

Objective: We compared the clinical course of type 2 diabetic patients whose basal insulin preparations were replaced from insulin glargine (IGlar) 100 units/mL (U100) to IGlar biosimilar or IGlar 300 units/mL (U300). Methods: After propensity score matching, 34 patients whose basal insulin preparation was switched from IGlar U100 to IGlar biosimilar and 102 switched to IGlar U300 were observed for 6 months. Results: The HbA1c level and body weight did not change significantly after the replacement in the IGlar biosimilar or IGlar U300 groups. In the IGlar biosimilar group, the frequency of subjects who experienced hypoglycemia after the replacement (12%) was not different from before (12%). However, the frequency was significantly lower after the replacement (2%) than before (13%) in the IGlar U300 group. The change in the HbA1c level after the replacement showed a significant association with the HbA1c level at the baseline but not with the kind of IGlar. Hypoglycemia was frequently observed in subjects who had experienced hypoglycemia before the replacement. Conclusions: IGlar biosimilar and IGlar U300 induced similar HbA1c and body weight changes among type 2 diabetic patients. IGlar biosimilar is a suitable option for patients with a low risk for hypoglycemia.

Biliary atresia associated with jejunal atresia and a review of the literature in Japan.

An unusual case of biliary atresia with jejunal atresia is herein described. Only 12 cases demonstrating biliary atresia associated with a jejunal atresia have been previously reported in Japan. The pathogenesis of biliary atresia is thought to be secondary to the influence of jejunal atresia.

Gypsum-bonded investment and dental precision casting (III) Composition of investment for the quick casting technique.

A simultaneous differential thermal analysis and thermogravimetry method previously established was used to estimate the composition of gypsum-bonded investment marketed for the quick casting technique. Three commercial investments of this type were heated to 700 degrees C at 10 degrees C/min and the hemihydrate content was estimated by the mass decrease reached at 300 degrees C after subtracting the mass decrease at 100 degrees C as moisture content. The hemihydrate contents were between 25% and 30%, which appears to be the range also chosen for the conventional gypsum-bonded investment of cristobalite type over 70 years by the industry. However, the new type of investment contained both cristobalite and quartz. The small sample size is a disadvantage of the present method but this can be overcome by more frequent use of the method by investigators.