Search

Managing complications in Type 1 diabetes (T1D) remains challenging. HLA genes, particularly DR and DQ, are linked to T1D susceptibility. We studied 48 Japanese T1D inpatients and revealed associations between DRB1*04:05-DQB1*04:01 and DRB1*09:01-DQB1*03:03 haplotypes and complications, offering a new perspective for future research., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective study. In the study, 6,338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using the t-test, χ 2 -test and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Of the total participants, 5,451 patients (mean age 61.4 years, duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased the risk for DSPN: age (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42-1.73), duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39) and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased the risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also showed the risk factors of DSPN., (© 2024 The Japan Diabetes Society. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/introduction: This study examined the association between the severity of diabetic polyneuropathy (DPN) based on the Baba classification, and sarcopenia and its related factors., Materials and Methods: The participants were 261 patients with type 2 diabetes mellitus. DPN was classified as stages 0-4 according to the Baba classification. Sarcopenia was diagnosed based on measurements of the skeletal mass index, grip strength and walking speed, using the Asia Working Group for Sarcopenia 2019 diagnostic criteria., Results: The median age of the participants was 67 years, the proportion of men was 58.6%, the median estimated duration of diabetes was 10 years and the median values for glycated hemoglobin were 10.3%. With regard to DPN, the prevalence of Baba classification stages 0-2 was 90.8% (n = 237), and that of stage 3 or 4 was 9.2% (n = 24). The prevalence of sarcopenia was 19.9%. A trend toward an increase in the frequency of slow walking speed was seen as the stage of DPN progressed. The frequencies of sarcopenia and slow walking speed were higher in the group with the Baba classification stages 3 and 4 than in the group with stages 0-2. On multiple logistic regression analyses, however, DPN was not significantly related to sarcopenia and walking speed., Conclusions: Although severe DPN might be related to sarcopenia, the frequency of severe DPN is low in the clinical setting, indicating that its contribution to sarcopenia is modest., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/introduction: To examine the three-dimensional morphology and vascular endothelial growth factor (VEGF) expression of skin microvasculature in patients with type 2 diabetes in relation to neuropathy, retinopathy and nephropathy., Materials and Methods: The present study enrolled 17 individuals with type 2 diabetes and 16 without. Skin sections were double-immunostained for type IV collagen and VEGF-A or protein gene product 9.5. Projected images from confocal microscopy served to quantify the occupancy rate of subepidermal type IV collagen-immunoreactive microvascular basement membrane area (OR-T4MBM), subepidermal VEGF-A-immunoreactive area and the VEGF/T4MBM ratio, as well as the protein gene product 9.5-immunoreactive intraepidermal nerve fiber density. Reduced intraepidermal nerve fiber density was applied for the diagnosis of neuropathy, fundic ophthalmoscopy and fluorescein angiography for retinopathy, and microalbuminuria or persistent proteinuria for nephropathy., Results: A total of 12 patients with diabetes had neuropathy, 10 had retinopathy and eight had nephropathy. Regardless of the presence or absence of neuropathy, retinopathy or nephropathy, OR-T4MBM was significantly increased in patients with diabetes compared with individuals without diabetes. In contrast, VEGF/T4MBM ratio was significantly decreased in those with neuropathy and retinopathy, as well as in those with and without nephropathy, whereas a trend toward a decreased VEGF/T4MBM ratio was seen in patients without retinopathy, as compared with individuals without diabetes., Conclusions: The present study is the first report to show that cutaneous microangiopathy, as indicated by subepidermal microvascular proliferation and impaired VEGF expression, appears to occur before the development of overt clinical neuropathy, retinopathy or nephropathy in patients with type 2 diabetes., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/introduction: Although nerve conduction study (NCS) using a standard electromyography system (EMGS) is considered to be the gold standard in evaluating diabetic polyneuropathy, this examination requires expensive equipment and well-trained technicians. We aimed to validate a point-of-care device, NC-stat/DPNCheck™, that has been developed for widespread use of NCS in diabetic polyneuropathy., Materials and Methods: Diabetes patients underwent two kinds of NCS: DPNCheck™ and electromyography system. Inter-/intrarater reliability of DPNCheck™ were also determined by the intraclass correlation coefficient., Results: A total of 57 patients were evaluated. The parameters of NCS between the two methods correlated well (r = 0.7734 for the sural nerve conduction velocity, r = 0.6155 for the amplitude of sural nerve action potential). The intraclass correlation coefficients were excellent (intrarater: the velocity 0.767, the amplitude 0.811; interrater: the velocity 0.974, the amplitude 0.834)., Conclusions: The point-of-care device has excellent reproducibility and good agreement with standard electromyography system. The device might be useful to evaluate diabetic polyneuropathy., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: It is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy. The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring (CGM)., Methods: This was a multicenter, prospective, open-label clinical trial. A total of 102 patients with type 2 diabetes were consecutively recruited for this study. GV was assessed by measuring the standard deviation (SD), glucose coefficient of variation (CV), and the mean amplitude of glycemic excursions (MAGE) during CGM. The BRS was analyzed from electrocardiogram and blood pressure recordings using the sequence method on the first day of hospitalization., Results: A total of 94 patients (mean diabetes duration 9.7 ± 9.6 years, mean HbA1c 61.0 ± 16.8 mmol/mol [7.7 ± 1.5%]) were analyzed. In the univariate analysis, CGM-SD (r = - 0.375, p = 0.000), CGM-CV (r = - 0.386, p = 0.000), and MAGE (r = - 0.395, p = 0.000) were inversely related to BRS. In addition to GV, the level of BRS correlated with the coefficient of variation in the R-R intervals (CVR-R) (r = 0.520, p = 0.000), heart rate (HR) (r = - 0.310, p = 0.002), cardio-ankle vascular index (CAVI) (r = - 0.326, p = 0.001), age (r = - 0.519, p = 0.000), and estimated glomerular filtration rate (eGFR) (r = 0.276, p = 0.007). Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS. These findings remained after adjusting the BRS for age, sex, hypertension, dyslipidemia, HR, eGFR, CAVI, and CGM-mean glucose. Additionally, BRS was divided according to quartiles of the duration of diabetes (Q1-4). BRS decreased after a 2-year duration of diabetes independently of age and sex., Conclusions: GV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients. Measurement of BRS may have the potential to predict CV events in consideration of GV. Trial registration UMIN Clinical Trials Registry UMIN000025964, 28/02/2017.

Background: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM), and baroreflex sensitivity (BRS) reportedly can predict cardiovascular prognosis in type 2 DM patients. The hypothesis that cardiovascular events are associated with gender differences in BRS was tested in the present study., Methods and Results: From 1998, we have evaluated BRS by phenylephrine methods in 185 consecutive type 2 DM patients. The long-term prognostic value of BRS was compared between 91 female (5812 years) and 94 male patients (5811 years). There was no significant difference in age or severity and duration of DM between the 2 groups. When compared to male, the BRS value in female patients was significantly lower (9.266.0 vs. 5.975.0 ms/mmHg, P < 0.0001). During a mean of 62.7 months of follow-up, 16 female patients developed cardiovascular events (17.6%) including stroke, acute myocardial infarction, angina pectoris requiring percutaneous coronary intervention or coronary artery bypass grafting and congestive heart failure requiring admission, while only 4 male patients developed events (4.3%, P < 0.005). In females, the Kaplan-Meier curves revealed that those with depressed BRS (< 6 ms/mmHg) had a higher incidence of cardiovascular events than those with preserved BRS (P < 0.05), but this relationship was not observed in male patients., Conclusions: Although the reason why females had a more depressed BRS remains unclear, our findings demonstrated that a depressed BRS value can accurately predict cardiovascular events, especially in female patients with type 2 DM.

Objective: The aim of this study was to determine the association between serum albumin and the severity of microvascular complications and presence of coronary artery disease in type 2 diabetic patients., Patients and Methods: The presence of diabetic complications was assessed in a total of 130 Japanese patients with type 2 diabetes mellitus. Retinopathy was classified as absent, simple or proliferative diabetic retinopathy. Neuropathy was considered to be present when the patient showed absence of Achilles tendon reflex, and also evaluated by measuring the median motor nerve conduction velocity (MNCV) in the nerve conduction study., Results: In relation to retinopathy, there were 83 patients with no retinopathy (absent), 26 with simple retinopathy and 21 with proliferative retinopathy. There was a significant difference in the serum albumin level between the "absent" group and the other two groups. In relation to nephropathy, there were 68 patients with no evidence of nephropathy, 49 with microalbuminuria and 13 with proteinuria. The results of logistic regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to proliferative retinopathy and proteinuria. In relation to neuropathy, serum albumin was found to be significantly related to the absence of Achilles tendon reflex, MNCV, and MFWL. The results of multiple regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to MNCV and MFWL., Conclusions: Serum albumin was significantly associated with the severity of retinopathy and neuropathy.

The aim of this study was to evaluate the relationship between the diagnosis of metabolic syndrome (MetS) or its components and the prevalence of microvascular and macrovascular complications in 130 Japanese type 2 diabetic patients. Out of the 130 patients, 58.5% satisfied the criteria of the MetS as defined by the IDF guideline. The results of logistic regression analysis with adjustment for three variables (age, gender and duration of diabetes) revealed that the presence of MetS as defined by the IDF guideline was not independently related to the presence of proliferative retinopathy, proteinuria, neuropathy, or macrovascular disease in the diabetic patients. The waist circumference per se was not associated with diabetic neuropathy, retinopathy, nephropathy, or macrovascular diseases. These results suggest that neither the presence of MetS, as defined by the IDF guideline, nor the waist circumference was associated with the presence of either microvascular or macrovascular complications in Japanese type 2 diabetic patients.

Peroxisome proliferator-activated receptor gamma (PPARgamma) controls adipocyte differentiation and regulates lipid and glucose homeostasis. Therefore, the PPARgamma gene may affect insulin sensitivity and resistance. We analyzed the relationship between C/T exon 6 polymorphism of the PPARgamma gene and various clinical parameters in type 2 diabetic patients. There were no significant differences in the frequencies of genotype and allele between diabetic patients with and without nephropathy. Diabetic patients were divided into two groups: patients bearing at least one T allele (CT/TT), and patients with no T allele (CC). Levels of serum triglyceride and body mass index (BMI) were significantly higher in the CT/TT genotype group than in the CC genotype group. Since obesity affects insulin resistance, the diabetic patients were also divided into two groups: those with a BMI of <23, and those with a BMI of >23. In patients with a BMI of <23, there was no significant change in the levels of glycosylated hemoglobin A1c (HbA1c) between the CC and CT/TT genotype groups. However, in patients with a BMI of >23, HbA1c levels were significantly higher in the CT/TT genotype group than in the CC genotype group. It appears that the CT/TT genotype with PPARgamma gene polymorphism may contribute to higher BMI and higher serum triglyceride and HbA1c levels in Japanese type 2 diabetic patients., ((c) 2004 Wiley-Liss, Inc.)

The relationship between diabetic complications and age, sex, duration, mode of therapy, body weight, control of blood glucose, blood pressure, and serum triglyceride and cholesterol was analyzed in a population with non-insulin-dependent diabetes in Japan. The prevalences of complications in the subjects varied from 6.5% for cerebrovascular strokes to 85.1% for sclerotic changes in retinal vessels; 35.8% of the patients had diabetic retinopathy and 19.8% had proteinuria. Univariate and multivariate analyses revealed that control of diabetes (blood glucose, mode of therapy, and duration) was closely correlated with retinopathy and proteinuria. However, blood glucose did not correlate with coronary insufficiency or cerebrovascular strokes. These macrovascular complications were related to aging and blood pressure. The data suggested that not only good glycemic control but also sufficient antihypertensive therapy was necessary for treating diabetic patients. The coefficient of determination of the risk factors was calculated for each diabetic complication. Except for sclerotic changes in retinal vessels, the coefficients were too small to fully explain the development of diabetic complications, especially for macrovascular diseases. The current data suggest that susceptibility of the individual patients to the diabetic complications is an important determinant.