Natural history of asymptomatic cervical internal carotid artery stenosis in diabetes mellitus patients.

INTRODUCTION: Diabetes mellitus (DM) is known to be a cause of cervical internal carotid artery stenosis (ICS). In this study, we investigated the natural history of asymptomatic ICS in DM patients without surgical intervention. METHODS: We conducted a retrospective study of 148 DM patients with asymptomatic ICS treated medically at the Kansai Electric Power Hospital from April 2013 to March 2023, inclusive. We examined the incidence of ischemic stroke with ICS and evaluated the patients' clinical characteristics and imaging findings. RESULTS: Ischemic stroke with ICS occurred in 7 patients (4.7 %), and only smoking history was significantly correlated with the incidence of ischemic stroke (p = 0.04). DISCUSSION: The incidence rate of ischemic stroke with ICS in this study (4.7%) was comparable to the previous report. The result that, the correlated factors of the incidence of ischemic stroke in DM patients with ICS was only smoking history, seemed acceptable. However, prospective studies with a larger number of cases may be needed in the future to determine the correlated factors more eligibly.

Effect of Roxadustat on Thyroid Function in Patients With Renal Anemia.

CONTEXT: Roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, a recently developed class of drugs for treatment of anemia in chronic kidney disease (CKD), is reported to have a structure unlike that of other HIF-PH inhibitors but similar to that of triiodothyronine and bind to the thyroid hormone receptor in vitro. However, reports on the effects of roxadustat on thyroid function are limited and not detailed, and it remains unknown whether other HIF-PH inhibitors also affect thyroid function. OBJECTIVE: To compare the effect of roxadustat with daprodustat, another HIF-PH inhibitor, on thyroid function in patients with renal anemia in CKD. METHODS: This retrospective observational study included a total of 26 patients with anemia in CKD who were treated with roxadustat or daprodustat; thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured before and after treatment with the drugs. RESULTS: After initiation of roxadustat, TSH showed a significant decrease (2.4732 [1.7858-4.9016] µIU/mL before treatment and 0.659 [0.112-2.005] µIU/mL after treatment, P < .05); FT4 showed a significant decrease (0.93 [0.84-1.05] ng/dL before treatment and 0.70 [0.53-0.85] ng/dL after treatment, P < .01). After daprodustat initiation, neither TSH nor FT4 showed a significant change (TSH: 3.044 [1.853-4.171] µIU/mL before treatment and 2.893 [1.866-4.894] µIU/mL after treatment, P = .635; FT4 was 0.93 [0.81-1.00] ng/dL before treatment and 0.97 [0.87-1.05] ng/dL after treatment, P = .328). CONCLUSION: Roxadustat decreases TSH and FT4 levels while daprodustat does not.

Stigma evaluation for diabetes and other chronic non-communicable disease patients: Development, validation and clinical use of stigma scale - The Kanden Institute Stigma Scale.

AIMS/INTRODUCTION: The aim of this study was to develop a scale to evaluate disease stigma in patients with lifestyle-related chronic non-communicable diseases (LCNCDs), which we named the Kanden Institute Stigma Scale (KISS), and to consider its possible clinical application for patients with diabetes. MATERIALS AND METHODS: An initial 90 questions were drafted and categorized into six subscales according to the manifestations of stigma. The final version of the KISS was developed as a 24-item questionnaire comprising four items for each subscale. RESULTS: A total of 539 outpatients including 452 patients with diabetes and 87 patients without diabetes were recruited. Construct validity was confirmed by assessing the correlation with previously established measures. Confirmatory factor analysis showed the KISS to have good model fitness (adjusted goodness-of-fit index = 0.856). Test-retest reproducibility analysis showed that the intraclass coefficient of the first and a second KISS was 0.843 (P < 0.001), indicating excellent reproducibility. The KISS showed higher scores for patients with diabetes than for patients without diabetes (12.23 ± 0.49 vs 5.76 ± 0.73, P < 0.05). The KISS score was significantly higher in type 1 and type 2 diabetes patients taking insulin therapy than in type 2 diabetes patients not taking insulin (P < 0.05). CONCLUSION: The KISS is a validated and reliable questionnaire for assessment of stigma among patients with diabetes as well as other lifestyle-related chronic non-communicable diseases, and might contribute to identifying and rectifying diabetes stigma, as well promoting awareness among health care professionals of this very consequential health problem.

Effects of physician's diabetes self-management education using Japan Association of Diabetes Education and Care Diabetes Education Card System Program and a self-monitoring of blood glucose readings analyzer in individuals with type 2 diabetes: An exploratory, open-labeled, prospective randomized clinical trial.

AIMS/INTRODUCTION: This 6-month, single-center, prospective, open-labeled, randomized trial was designed to investigate whether physicians' diabetes self-management education using an education tool developed by the Japan Association of Diabetes Education and Care and a self-monitoring of blood glucose (SMBG) analyzer improves glycemic control in individuals with type 2 diabetes receiving insulin and SMBG. MATERIALS AND METHODS: Participants were randomized into intervention (I) and control (C) groups. Both groups received physicians' diabetes self-management education at each hospital visit, whereas the Japan Association of Diabetes Education and Care education tool and the SMBG readings analyzer was used in group I, but not group C. All participants filled out a diabetes treatment-related quality of life form and an original questionnaire on SMBG use with five questions (Q1-Q5) before and after the study period. RESULTS: A total of 76 individuals were recruited and randomized. Glycated hemoglobin (HbA1c) was significantly improved during the study period in group I, whereas no significant change was observed in group C. The change in HbA1c was greater in group I, although it did not reach statistical significance. The diabetes treatment-related quality of life total score was not changed in either group. Interestingly, the score of Q1 ("How important is SMBG to you?") in the SMBG questionnaire was unchanged in group I, whereas it was significantly decreased in group C. HbA1c change was independently associated with changes in insulin dose and SMBG Q1 score. CONCLUSION: Greater HbA1c-lowering by physicians' diabetes self-management education using the Japan Association of Diabetes Education and Care education tool and SMBG analyzer in individuals with type 2 diabetes receiving insulin and SMBG was suggested, but not confirmed.

Lifestyle changes as a result of COVID-19 containment measures: Bodyweight and glycemic control in patients with diabetes in the Japanese declaration of a state of emergency.

To clarify the association between lifestyle changes as a result of coronavirus disease 2019 containment measures and changes in metabolic and glycemic status in patients with diabetes, a cross-sectional, single-center, observation study was carried out. A self-reported questionnaire was provided to ascertain the frequency of various lifestyle activities before and after the coronavirus disease 2019 containment measures in Japan. Among 463 patients, change in glycated hemoglobin was significantly associated with change in bodyweight. After stratification by age 65 years, binary logistic regression analysis showed that increased frequency of snack eating increased bodyweight (odds ratio 1.709, P = 0.007) and glycated hemoglobin (odds ratio 1.420, P = 0.025) in the younger group, whereas in the older patients, reduced walking activities resulted in weight gain (odds ratio 0.726, P = 0.010). In conclusion, changes in eating behavior and physical activity increased bodyweight and reduced glycemic control among diabetes patients, but by different processes depending on age under the coronavirus disease 2019 containment measures in Japan.

A novel splice-site mutation of the HNF1B gene in a family with maturity onset diabetes of the young type 5 (MODY5).

SUMMARY: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes mellitus characterised by early onset and dominant inheritance. Delayed diagnosis or misdiagnosis as type 1 or type 2 diabetes mellitus is common. Definitive genetic diagnosis is essential for appropriate treatment of patients with MODY. The hepatocyte nuclear factor 1-beta (HNF1B) gene is responsible for MODY type 5 (MODY5), which has distinctive clinical features including renal disease. MODY5 should always be considered by clinicians in patients with early onset diabetes and renal anomalies. We report a case of a 30-year-old Japanese male with early-onset diabetes mellitus, renal anomalies and family history of diabetes that was suggestive of MODY5. Renal histology showed no evidence of diabetic nephropathy. Genetic testing revealed a novel heterozygous splice-site mutation of the HNF1B gene in the family members. It was strongly suggested that the mutation could underlie our patient's MODY5. LEARNING POINTS: Genetic diagnosis of MODY is relevant for appropriate treatment. Dominantly inherited early-onset diabetes mellitus with renal cysts suggests MODY5. Scanning the non-coding regions is important for not missing a mutation in HNF1B.

Enhanced glucagon-like peptide-1 secretion in a patient with glucagonoma: implications for glucagon-like peptide-1 secretion from pancreatic α cells in vivo.

We examined GLP-1 secretion from the pancreas of a patient with glucagonoma and pancreatic resection by measuring GLP-1 after meal ingestion or selective arterial calcium injection, and immunohistochemical analysis. Our findings support the notion that GLP-1 is secreted from pancreatic α cells in humans.

Retrospective analysis of safety and efficacy of insulin-to-liraglutide switch in Japanese type 2 diabetes: A caution against inappropriate use in patients with reduced ß-cell function.

AIMS/INTRODUCTION: The safety and efficacy of insulin-to-liraglutide switch in type 2 diabetes has not been studied adequately. Here, we retrospectively characterize clinical parameters that might predict insulin-to-liraglutide treatment switch without termination due to hyperglycemia, and examine the effects of switching the therapies on glycated hemoglobin (HbA1c) and bodyweight in Japanese type 2 diabetes. MATERIALS AND METHODS: Japanese type 2 diabetes patients who underwent the switch of therapy were evaluated for their clinical data including ß-cell function-related indices, such as increment of serum C-peptide during glucagon stimulation test (GST-ΔCPR). HbA1c and bodyweight were analyzed in patients continuing with liraglutide after switching from insulin for 12 weeks. RESULTS: Of 147 patients, 28 failed in the switch due to hyperglycemia, nine failed because of other reasons and 110 continued with liraglutide for the 12-week period. Patients failing in the switch due to hyperglycemia showed longer duration and higher daily insulin dose, as well as lower GST-ΔCPR. Receiver-operating characteristic analysis showed that GST-ΔCPR of 1.34 ng/mL is a cut-off point for insulin-to-liraglutide switch without termination due to hyperglycemia. In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co-administration, body mass index, duration and total daily insulin dose. The switch also significantly reduced the percentage of body fat and visceral fat areas. CONCLUSIONS: Insulin-to-liraglutide switch can improve glycemic control and reduce bodyweight in Japanese type 2 diabetes patients. However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST-ΔCPR.

Drug-induced generalized skin eruption in a diabetes mellitus patient receiving a dipeptidyl peptidase-4 inhibitor plus metformin.

A generalized skin eruption with strong itching was induced by sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in a patient almost 6 months after initiation of the drug. Physical examination revealed a spread of skin rash from chest to back, and abdomen and thigh. Discontinuation of the drug eliminated the skin rash immediately. The emergence of new rash ended, and the rash itself withered after 1 week. The spread of the rash gradually shrank and the skin lesions subsided, leaving pigmentation 1 month later. Two months after cessation of sitagliptin, the skin eruption had subsided and oral steroid medication was stopped, but some small eczematous eruptions continued to appear intermittently. Although a drug-induced lymphocyte stimulation test was negative for sitagliptin, nonspecific radioimmunosorbent test for immunoglobulin E was increased to 532 IU/mL, with a percentage of eosinophil of 7.4%. Sitagliptin has a phenyl ring, carbonyl group, and an absorption spectrum showing three absorption peaks (199.9, 265.0, 400.1 nm), and its photosensitive mechanism could have been responsible for the itchy edematous plaque. In the present case, the initial generalized skin eruption may have been induced by an allergic reaction to sitagliptin. Close attention should be paid to patients receiving this drug with a history of urticaria, and to the development of photosensitivity.

Comparison of incretin immunoassays with or without plasma extraction: Incretin secretion in Japanese patients with type 2 diabetes.

UNLABELLED: Aims/Introduction: The effectiveness of incretin-based therapies in Asian type 2 diabetes requires investigation of the secretion and metabolism of glucose-dependent insulinotropic polypepide (GIP) and glucagon-like peptide 1 (GLP-1). Plasma extractions have been suggested to reduce variability in intact GLP-1 levels among individuals by removing interference that affects immunoassays, although no direct demonstration of this method has been reported. We have evaluated the effects of ethanol and solid-phase extractions on incretin immunoassays. We determined incretin levels during meal tolerance tests in Japanese patients with type 2 diabetes and characterized predictors for incretin secretion. MATERIALS AND METHODS: Japanese patients with type 2 diabetes (23 anti-diabetic drug-naïve and 18 treated with sulfonylurea [SU] alone) were subjected to meal tolerance tests, and incretin levels were determined by immunoassays with or without extraction. RESULTS: Intact GLP-1 levels determined by an intact GLP-1 immunoassay with ethanol and solid-phase extractions were lower than those determined without extraction. Intact GLP-1 levels determined by the extractions were highly correlated with each other, much more so than the levels with and without extraction. Total GLP-1 was unaffected by extractions, showing that extractions remove interference only in the case of intact GLP-1. Incretin secretion after meal ingestion was similar between drug-naïve and SU-treated patients. Fasting and postprandial GLP-1 levels were correlated positively with fasting free fatty acids and negatively with dipeptidyl peptidase-4 activity. CONCLUSIONS: Ethanol and solid-phase extractions remove interference for intact GLP-1 immunoassay. SU showed little effect on incretin secretion. GLP-1 and GIP secretion were predicted by different factors. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00141.x, 2012).

Predicting efficacy of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Association of glycated hemoglobin reduction with serum eicosapentaenoic acid and docosahexaenoic acid levels.

This study was initiated to identify clinical and dietary parameters that predict efficacy of dipeptidyl peptidase-4 inhibitors. A total of 72 untreated Japanese patients with type 2 diabetes who received DPP-4 inhibitors (sitagliptin, alogliptin or vildagliptin) for 4 months were examined for changes of glycated hemoglobin (HbA1c) and body mass index (BMI), and self-administered 3-day food records, as well as serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DPP-4 inhibitors significantly reduced HbA1c (before initiation of DPP-4 inhibitors 7.2 ± 0.7%, 4 months after initiation of DPP-4 inhibitors 6.7 ± 0.6% [paired t-test, P < 0.01 vs before]). Multiple regression analysis showed that changes of HbA1c were significantly correlated with baseline HbA1c, as well as estimated intake of fish. Furthermore, changes of HbA1c were significantly correlated with serum levels of EPA (r = -0.624, P < 0.01) and DHA (r = -0.577, P < 0.01). HbA1c reduction by DPP-4 inhibitors is significantly correlated with estimated intake of fish and serum levels of EPA and DHA. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00214.x, 2012).

[The history of incretin hormones].

'Incretin' hormones has lately attracted considerable attention as new strategy improving insulin secretion of type 2 diabetes mellitus. Spending many years for study of incretin hormones, GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1), we can use incretin mimetics as new drugs for type 2 diabetes clinically today in Japan. In this section, we describe the concept and the history of incretin hormones.

The role of family nutritional support in Japanese patients with type 2 diabetes mellitus.

OBJECTIVE: We investigated the role of family support in glycemic control by nutritional self-care behavior of Japanese patients with type 2 diabetes. METHODS: One hundred twelve Japanese out-patients with type 2 diabetes were recruited for the study at Kansai Electric Power Hospital. Interviews were conducted and HbA1c and triglyceride levels were measured. RESULTS: HbA1c levels were significantly related to family nutritional support. Patients under 60 years old with family nutritional support showed significantly lower HbA1c than patients without family support (p<0.05). Female patients with family support showed significantly lower HbA1c than those without family support (p<0.05). In addition, male patients with family support showed significantly lower triglyceride levels than those without family support (p<0.05). In male patients, those who were supported by cooking or buying light meals showed significantly lower HbA1c than those who were supported by advice or encouragement (p<0.05). The frequency of support (every day, 2-3 days, 1 week) showed similar outcomes in glycemic control. Patients who appreciate the support and follow the advice showed lower HbA1c (6.88 +/- 0.22%) than (7.43 +/- 0.23%) patients who appreciate the advice but sometimes feel emotional barriers. CONCLUSION: Family nutritional support is useful in improving metabolic outcome of diabetic patients. Self-care practice in disease management should be carefully adjusted to the family setting of type 2 diabetic patients. Emotional barriers to family support may affect the metabolic consequences, especially in the Japanese elderly.

Little enhancement of meal-induced glucagon-like peptide 1 secretion in Japanese: Comparison of type 2 diabetes patients and healthy controls.

Although glucose-dependent insulinotropic polypeptide (GIP) levels have been characterized previously, GLP-1 levels in Asians remain unclear. Here, we investigate total and intact levels of GLP-1, as well as GIP during oral glucose and meal tolerance tests (OGTT and MTT) in Japanese patients with or without type 2 diabetes (T2DM). Seventeen Japanese healthy controls and 18 age-matched and untreated patients with T2DM of short duration participated in the present study. Fasting levels of total GPL-1 were similar between the two groups (approximately 15 pM), and intact GLP-1 levels were considerably low in both groups (less than 1 pM). In both groups, total GLP-1 reached a peak 30 min after glucose ingestion (30-40 pM), whereas intact GLP-1 levels remained low with no significant peak. In MTT, total and intact GLP-1 showed no obvious peak. The current data indicate that intact GLP-1 levels are considerably low in the Japanese and that meal-induced enhancement of GLP-1 secretion is negligible in the Japanese. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00010.x, 2010).