Thirty-Year Trends in the Prevalence and Severity of Diabetic Retinopathy at the First Visit in Patients with Untreated Type 2 Diabetes Mellitus.

PURPOSE: Although the rate of diabetic retinopathy (DR)-related blindness has decreased in developed countries in recent years, the reasons for this decrease have remained unclear. The prevalence/severity trends of DR at the first visit in patients with untreated type 2 diabetes mellitus (T2DM) patients seen between the1986s and 2018s were assessed. METHODS: A total of 1979 Japanese T2DM patients diagnosed between 1986 and 2018 were divided into four groups by the decade of their first visit: the 1986 years (1986-1987), the 1996 years (1996-1997), the 2006 years (2006-2008), the 2016 years (2016-2018). The DR prevalence/severity trends were assessed. RESULTS: A significant decrease in the rate of prevalence of DR from the 1986s to 2016s was observed among previously untreated T2DM patients visiting our hospital for the first time (1986s: 25.5%; 1996s: 26.2%; 2006s: 22.2%; and 2016s: 15.6%). The prevalence was significantly higher in females (30.2%) than in males (21.3%). Although the severity trend of DR did not differ significantly among the four measurement years, the rate of simple DR was the highest in the 2016s. CONCLUSION: We found, for the first time, a significant decrease in the rate of prevalence of DR from the 1986s to 2016s in patients with untreated T2DM visiting our hospital for the first time. A decrease in the rate of DR prevalence could explain, at least in part, the observed reduction in the rate of blindness in patients with T2DM.

Decreased AdipoR1 signaling and its implications for obesity-induced male infertility.

Obesity is among the risk factors for male infertility. Although several mechanisms underlying obesity-induced male subfertility have been reported, the entire mechanism of obesity-induced male infertility still remains unclear. Here, we show that sperm count, sperm motility and sperm fertilizing ability were decreased in male mice fed a high-fat diet and that the expression of the AdipoR1 gene and protein was decreased, and the expression of pro-apoptotic genes and protein increased, in the testis from mice fed a high-fat diet. Moreover, we demonstrate that testes weight, sperm count, sperm motility and sperm fertilizing ability were significantly decreased in AdipoR1 knockout mice compared to those in wild-type mice; furthermore, the phosphorylation of AMPK was decreased, and the expression of pro-apoptotic genes and proteins, caspase-6 activity and pathologically apoptotic seminiferous tubules were increased, in the testis from AdipoR1 knockout mice. Furthermore, study findings show that orally administrated AdipoRon decreased caspase-6 activity and apoptotic seminiferous tubules in the testis, thus ameliorating sperm motility in male mice fed a high-fat diet. This was the first study to demonstrate that decreased AdipoR1/AMPK signaling led to increased caspase-6 activity/increased apoptosis in the testis thus likely accounting for male infertility.

Association of glucagon-like peptide-1 receptor agonist treatment with gastric residue in an esophagogastroduodenoscopy.

AIMS/INTRODUCTION: Previous studies have reported that the glucagon-like peptide-1 receptor agonist (GLP-1RA) delays gastric emptying, and gastric emptying was assessed by the 13 C breath test or paracetamol absorption technique. However, neither of them is clinically familiar in real-world clinical practice. The purpose of the present study was to investigate the association between GLP-1RA treatment and gastric residue in an esophagogastroduodenoscopy. MATERIALS AND METHODS: This study was a matched pair case-control study. The study population consisted of 1,128 individuals with diabetes who had esophagogastroduodenoscopy at our clinic between July 2020 and June 2022. To account for differences in characteristics, such as age, sex, insulin treatment and glycated hemoglobin, we carried out a one-to-one nearest neighbor propensity score matching analysis between diabetes patients with and without GLP-1RA treatment. After matching, we compared the presence of gastric residue in an esophagogastroduodenoscopy by the McNemar test between patients with and without GLP-1RA treatment. RESULTS: After the propensity score matching, we selected 205 pairs. In the propensity score-matched comparison, the proportion of gastric residue was statistically significantly higher in the GLP-1RA treatment group (0.49% vs 5.4%, P = 0.004). The details of GLP-1RA prescribed for the 11 patients with gastric residue were liraglutide once daily 1.8 mg (n = 2), dulaglutide once weekly 0.75 mg (n = 5), semaglutide once weekly 0.5 mg (n = 2) and semaglutide once weekly 1.0 mg (n = 2). CONCLUSION: GLP-1RA treatment is associated with gastric residue in an esophagogastroduodenoscopy in patients with diabetes.

Association of self-stigma with glycated hemoglobin: A single-center, cross-sectional study of adults with type 1 diabetes in Japan.

AIMS/INTRODUCTION: There has been an increase in research on diabetes-related stigma and its association with glycated hemoglobin (HbA1c) over the past years. However, little is known about the association of self-stigma with HbA1c in persons with type 1 diabetes. This study aims to examine the association between self-stigma and HbA1c in Japanese people with type 1 diabetes. MATERIALS AND METHODS: This cross-sectional study was conducted at a clinic in Tokyo. Questionnaires using nine items from the Japanese version of the Self-Stigma Scale was distributed to outpatients with type 1 diabetes, aged ≥18 years. We excluded outpatients with serious mental disorder, those who required urgent medical treatment or received hemodialysis. Adjusted linear regression analyses tested the association between the score of the 9-item Self-Stigma Scale and HbA1c. RESULTS: Questionnaires were distributed to 166 eligible participants. A total of 109 participants were included in the final analysis after excluding participants with incomplete answers and laboratory data. After adjusting for age, sex, employment status, body mass index, duration of diabetes and insulin secretion, there was a significant positive association between self-stigma and HbA1c (ß = 0.05, 95% confidence interval 0.01 to 0.08). CONCLUSIONS: This cross-sectional study showed a significant association between self-stigma and HbA1c in persons with type 1 diabetes. Addressing self-stigma might be as equally essential as measuring HbA1c in evaluating glycemic outcome among individuals with type 1 diabetes.

Clinical features and sulfonylurea usage among outpatients with diabetes aged ≥90 years in an urban diabetes clinic in Tokyo.

AIMS/INTRODUCTION: Aging of society is accelerating in many countries. The purpose of this study was to describe the clinical features and sulfonylurea usage among diabetes outpatients aged ≥90 years (nonagenarians). MATERIALS AND METHODS: This study was a retrospective observational study. The study population consisted of 69 nonagenarian diabetes outpatients and 857 diabetes outpatients aged <90 years. Patients were classified into four groups: group 1, <65 years; group 2, 65-74 years; group 3, 75-89 years; and group 4, ≥90 years. The presence of hypoglycemic episodes was defined as having self-reported symptoms, or self-monitored or clinically measured blood glucose level <70 mg/dL. RESULTS: The median glycated hemoglobin (HbA1c) in group 1 and group 4 was 7.0% and 7.2%, respectively (P = 0.506). The proportion of sulfonylurea treatment in group 4 was 45.5%, which is significantly higher compared with the other three groups (20.0-27.8%, P < 0.001). In group 4, there was no difference between patients with or without sulfonylurea in age, sex, body mass index, HbA1c and number of antihyperglycemic agents. Five out of 25 nonagenarian sulfonylurea-treated patients had hypoglycemic episodes within the last 2 years, their HbA1c were all 7.0 ≤ HbA1c < 8.0, and sulfonylurea or insulin was tapered in all cases after confirming hypoglycemia. Tapering dosage was attempted in all 25 sulfonylurea-treated nonagenarian patients, but 15 needed to continue sulfonylurea for glycemic control, and 10 continued sulfonylurea with unknown reasons from their medical records. CONCLUSIONS: Although tapering the dosage of sulfonylurea was attempted in nonagenarian patients, sulfonylurea was widely continued for glycemic control. Reverse clinical inertia may exist in some sulfonylurea-treated nonagenarian patients.

Substitution of telemedicine for clinic visit during the COVID-19 pandemic of 2020: Comparison of telemedicine and clinic visit.

AIMS/INTRODUCTION: The purpose of this retrospective observational cohort study was to compare outpatient diabetes care and glycated hemoglobin (HbA1c) level during the coronavirus disease 2019 pandemic in 2020 with 2019, and to compare the glucose-lowering effect of telemedicine and clinic visits during the state of emergency in Japan declared from 7 April to 25 May (inter-period) 2020. MATERIALS AND METHODS: A total of 13 weeks before and after the inter-period were designated as the pre-period and post-period, respectively. The number of study participants who had clinic visits during the pre-period and the post-period were 3,333 in 2020 and 3,608 in 2019. Propensity score matching was carried out to compare the effect of telemedicine and clinic visits on diabetes control in 2020 among diabetes patients with insufficient glucose control (HbA1c ≥7%). The primary outcome was post-period HbA1c. RESULTS: The major difference between 2020 and 2019 was the use of telemedicine in 2020. After adjustment for age, sex, diabetes type, pre-period HbA1c and pre-period body mass index, glycemic control evaluated by HbA1c was significantly worse in the post-period of 2020 than 2019. In the propensity score-matched 618 pairs, the clinic visit group had significantly better post-period HbA1c than the telemedicine group (7.5% vs 7.4%, P = 0.023). CONCLUSIONS: Glycemic control was slightly, but significantly, worse in 2020 than 2019. Although telemedicine significantly improved glycemic control during the coronavirus disease 2019 pandemic in 2020, clinic visits improved HbA1c significantly more. The substitution of telemedicine for clinic visits appears to be a viable option under emergency conditions, but clinic visits might be a better option when possible.

Diabetes management by either telemedicine or clinic visit improved glycemic control during the coronavirus disease 2019 pandemic state of emergency in Japan.

The purpose of this retrospective cohort study at a Tokyo diabetes clinic was to evaluate the effect of telemedicine and clinic visit on glycated hemoglobin (HbA1c) during the coronavirus disease 2019 state of emergency. The effect of telemedicine and clinic visit during the emergency period on the post-emergency measured HbA1c was evaluated by multiple regression models and logistic regression models adjusted for age, sex, type of diabetes, pre-emergency HbA1c and body mass index, and body mass index change during the emergency period. Among 2,727 patients who visited the clinic before and after the emergency period, the interval between clinic visits during the emergency period was significantly associated with HbA1c improvement. Telemedicine and clinic visit were independently associated with HbA1c improvement when pre-emergency HbA1c was ≥7%. In conclusion, clinic visit and telemedicine during the coronavirus disease 2019 emergency period were both independently effective in HbA1c improvement in Japanese diabetes patients who had insufficient HbA1c control.

Association of insulin treatment with gastric residue during an esophagogastroduodenoscopy.

The purpose of this study was to investigate the association of glycemic control and diabetes treatment to gastric residue observed during an esophagogastroduodenoscopy. Among 6,592 individuals who had esophagogastroduodenoscopy at our clinic between 2003 and 2019, we retrospectively and longitudinally identified those who had gastric residue during an esophagogastroduodenoscopy. Other data collected were age, sex, diagnosis of diabetes, glycated hemoglobin and diabetes medication. Cox proportional hazards models were used to assess the association of these data with the occurrence of gastric residue. To the best of our knowledge, this is the first retrospective cohort study finding that undergoing insulin treatment is a risk factor for gastric residue independent of age, sex and diabetes or glycated hemoglobin.

AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice.

Adiponectin receptors, AdipoR1 and AdipoR2 exert anti-diabetic effects. Although muscle-specific disruption of AdipoR1 has been shown to result in decreased insulin sensitivity and decreased exercise endurance, it remains to be determined whether upregulation of AdipoR1 could reverse them in obese diabetic mice. Here, we show that muscle-specific expression of human AdipoR1 increased expression levels of genes involved in mitochondrial biogenesis and oxidative stress-detoxification to almost the same extents as treadmill exercise, and concomitantly increased insulin sensitivity and exercise endurance in obese diabetic mice. Moreover, we created AdipoR-humanized mice which express human AdipoR1 in muscle of AdipoR1·R2 double-knockout mice. Most importantly, the small-molecule AdipoR agonist AdipoRon could exert its beneficial effects in muscle via human AdipoR, and increased insulin sensitivity and exercise endurance in AdipoR-humanized mice. This study suggests that expression of human AdipoR1 in skeletal muscle could be exercise-mimetics, and that AdipoRon could exert its beneficial effects via human AdipoR1.