IL-33 Reduces Saturated Fatty Acid Accumulation in Mouse Atherosclerotic Foci.

The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.

Association of Elevated Serum Branched-chain Amino Acid Levels With Longitudinal Skeletal Muscle Loss.

Context: Branched-chain amino acids (BCAA) are substrates for protein synthesis. Although their intake may contribute to an increase in skeletal muscle mass, elevated serum BCAA levels have been reported to be associated with insulin resistance, potentially resulting in decreased skeletal muscle mass. Objective: This study aimed to explore the association between elevated serum BCAA levels and longitudinal skeletal muscle loss. Design and Setting: A cohort analysis was conducted, in which serum amino acids were analyzed in healthy individuals who underwent a medical health checkup at Kameoka Municipal Hospital (HOZUGAWA study), Japan. Patients: Seventy-one participants (37 men and 34 women) underwent follow-up checkups after the baseline visit. The follow-up duration was 1.2 ± .4 years. Main Outcome Measures: The relationship between fasting baseline serum BCAA levels and lifestyle factors, body composition, blood test results, dietary history, and changes in skeletal muscle mass was evaluated. Results: In both men and women, serum BCAA levels were positively correlated with body weight, body mass index, skeletal muscle mass index (SMI), and serum triglycerides but inversely correlated with serum high-density lipoprotein cholesterol. In men, fasting serum BCAA levels were inversely associated with the rate of change in SMI (adjusted ß = -.529, P = .006), and elevated BCAA levels were independently associated with a longitudinal decrease in skeletal muscle mass (odds ratio: 1.740; 95% confidence interval: 1.023-2.960 per 50 nmol/mL serum BCAAs increase). Conclusion: Increased circulating BCAAs could be an indicator of skeletal muscle loss in men.

Predictive power of isolated high home systolic blood pressure for cardiovascular outcomes in individuals with type 2 diabetes mellitus: KAMOGAWA-HBP study.

AIMS/INTRODUCTION: Isolated high home systolic blood pressure (IHHSBP) is a risk for cardiovascular disease (CVD). However, no study has shown an association between IHHSBP and CVD in diabetes. We examined the association between IHHSBP and CVD in type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study included 1082 individuals with type 2 diabetes, aged 20 to 90 years, without a history of macrovascular complications. Home blood pressure (HBP) was measured three times every morning and evening for 14 days. Cox proportional hazards models were used to examine the relationship between IHHSBP and CVD incidence. RESULTS: With the normal HBP group as the reference, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for CVD was 1.58 (1.02-2.43) in the IHHSBP group. Correcting for antihypertensive medication use did not change HR. Based on sex, the adjusted HR (95% CI) for CVD was 1.25 (0.74-2.13) in males and 2.28 (1.01-5.15) in females. CONCLUSIONS: In individuals with type 2 diabetes, those with IHHSBP had a higher HR for cardiovascular disease than those with normal HBP. But, Isolated high home diastolic blood pressure and high HBP were not. The association between IHHSBP and CVD was stronger in females than in males.

Impact of continued high blood pressure on the progression of diabetic nephropathy after 10 years: KAMOGAWA-HBP study.

Albuminuria is a prognostic marker of worsening renal outcomes in people with hypertension and type 2 diabetes. High home systolic blood pressure is associated with the development of diabetic nephropathy. We assessed the impact of chronic high home blood pressure on diabetic nephropathy progression 10 years after study entry. The participants measured their blood pressure three times in the morning for 14 days at study entry and 10 years after study entry. A retrospective cohort of 165 people with type 2 diabetes at a single hospital was classified into four groups (good control maintenance, improvement, deterioration, and continuous high blood pressure groups) according to a morning home systolic blood pressure ≥125 mmHg at study entry and 10 years after study entry. Logistic regression analysis was performed to determine the association between home blood pressure control and the progression of diabetic nephropathy. After 10 years of entry, the status of nephropathy improved for 5.5% of the participants, remained unchanged for 72.1%, and progressed for 22.4%. The odds ratio of the continuous high blood pressure group versus that of the good control maintenance group for the progression of diabetic nephropathy was 10.41 (95% CI, 1.26-86.15). After adjusting for the introduction of renin-angiotensin-aldosterone system inhibitors during the follow-up period, there was no significant difference in the odds ratio of worsening nephropathy between these groups. The deterioration and improvement groups did not have significant diabetic nephropathy progression compared to the good control maintenance group. Chronic high home blood pressure was associated with the progression of diabetic nephropathy, and RAAS inhibitors could attenuate the negative effect. We demonstrated that chronic home blood pressure was associated with the progression of diabetic nephropathy.

The effect of COVID-19 pandemic on the lifestyle and glycemic control in patients with type 1 diabetes: a retrospective cohort study.

Background: To investigate the acute effects of coronavirus disease (COVID-19) on lifestyle and metabolic parameters in patients with type 1 diabetes (T1D). Methods: This retrospective cohort study included 34 patients who were admitted to our hospital from April 16 to May 1, 2020. Data on stress levels, sleep duration, exercise, total diet, snacks, and prepared food intake were obtained from the questionnaires. Changes in the values of hemoglobin A1c (HbA1c) and body weight from 3 months before the administration of the questionnaire to the time the study questionnaire was administered (pandemic year), and those from 15 months before to 12 months before the administration of the questionnaire (pre-pandemic year) were evaluated. Results: Increased stress levels and decreased exercise volumes were observed in approximately 60% and 50% of participants during the COVID-19 pandemic, respectively. Decreased sleep duration was associated with changes in the body weight for 3 months during pandemic year (r = - 0.40, p = 0.043). Furthermore, compared with changes in HbA1c for 3 months during pre-pandemic year, changes in HbA1c during the pandemic year were worse (0.12% [0.33] % during pandemic year vs. - 0.09 [0.39] % during pre-pandemic year, p = 0.027). Conclusions: Many patients experienced stress and exercised less due to the COVID-19 pandemic. Glycemic control in patients with T1D was worse than that in the previous year. Since the pandemic is currently ongoing, more attention should be paid to stress and lifestyle factor management in patients with T1D. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00507-4.

Effects of probiotic Bifidobacterium bifidum G9-1 on the gastrointestinal symptoms of patients with type 2 diabetes mellitus treated with metformin: An open-label, single-arm, exploratory research trial.

AIMS/INTRODUCTION: Metformin is associated with the risk of gastrointestinal complications, and probiotic Bifidobacterium bifidum G9-1 (BBG9-1) can improve the symptoms of diarrhea. This study aimed to clarify the effects of probiotic BBG9-1 on the gastrointestinal symptoms of type 2 diabetes mellitus patients using metformin. MATERIALS AND METHODS: In this open-label single-arm exploratory study, 40 patients (mean age 64.0 ± 9.4 years) were given probiotic BBG9-1 for 10 weeks. Changes in the gastrointestinal symptom rating scale total score, which was the primary end-point, gastrointestinal symptom rating scale subscale scores, glycated hemoglobin levels and gut microbiota after the administration of probiotic BBG9-1 were evaluated by the Student's t-test. RESULTS: The gastrointestinal symptom rating scale total score significantly improved (from 2.02 ± 0.51 to 1.59 ± 0.43, change, -0.43 ± 0.49, P < 0.001). Furthermore, all gastrointestinal symptom rating scale subscale scores, including diarrhea (from 2.32 ± 1.14 to 1.89 ± 0.99, change, -0.42 ± 0.95, P = 0.007) and constipation (from 3.00 ± 1.16 to 2.20 ± 1.07, change, -0.80 ± 1.19, P < 0.001), scores also significantly improved. However, the glycated hemoglobin levels did not change (from 7.0 ± 0.7 to 7.0 ± 0.6%, change, 0.0 ± 0.4, P = 0.91). The relative abundance of the genus Sutterella decreased by the use of probiotic BBG9-1 (from 0.011 ± 0.009 to 0.008 ± 0.006, change, -0.003 ± 0.006, P = 0.002). CONCLUSIONS: Type 2 diabetes mellitus patients treated with metformin showed significant improvement in all gastrointestinal symptom rating scores after using probiotic BBG9-1 without changing the glucose control. This study showed the potential usefulness of probiotic BBG9-1 for improving gastrointestinal symptoms, including constipation and diarrhea, in type 2 diabetes mellitus patients treated with metformin.

Development of application to automatically calculate mean amplitude of glycaemic excursions using intermittently scanned continuous glucose monitoring data.

AIM: We aimed to develop an application to calculate mean amplitude of glycaemic excursions (MAGE) automatically and to evaluate its accuracy. MATERIALS AND METHODS: We named the application intermittently scanned continuous glucose monitoring (isCGM) calculator KAMOGAWA (Kyoto Auto MAGE Of Glucose cAlcutator With isCGM Application). The isCGM data from 20 patients, 10 with and 10 without diabetes, were used to compare manually calculated MAGE values with those calculated using KAMOGAWA. The rate of agreement for the MAGE values was calculated. RESULTS: Comparing the MAGE values calculated manually with those calculated using KAMOGAWA, the total mean rate of agreement was 81.6%. Nonmatching values were checked and it was found that the inconsistencies were all attributable to errors in manual calculations. After correcting errors in the manual calculation, the MAGE values matched to one decimal place for all data in the manual and KAMOGAWA calculations. CONCLUSIONS: KAMOGAWA can help diabetologists use MAGE in clinical practice, which could contribute to improving glycaemic control in patients who use isCGM.

Effect of COVID-19 Pandemic on the Change in Skeletal Muscle Mass in Older Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Background: The aim of this study was to investigate the effect of the coronavirus disease (COVID-19) pandemic restrictions on the change in muscle mass in older patients with type 2 diabetes (T2D), who were not infected with COVID-19. Methods: In this retrospective cohort study, data were obtained from outpatients who underwent bioelectrical impedance analysis at least twice before April 2020 and at least once thereafter. Skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg) divided by height squared (m2). Change in SMI (kg/m2/year) was calculated as (follow-up SMI-baseline SMI/follow-up period). The differences between the changes in SMI before and after the start of the COVID-19 pandemic were evaluated using paired t test. Results: This study recruited 56 patients, with a mean (SD) age of 75.2 (7.1) years. SMI changed from 6.7 (0.9) to 6.8 (0.9) kg/m2 before the COVID-19 pandemic, whereas SMI changed from 6.8 (0.9) to 6.6 (0.9) kg/m2 after the start of the COVID-19 pandemic. SMI decreased after the start of the COVID-19 pandemic compared with before the pandemic (-0.117 (0.240) vs. 0.005 (0.289) kg/m2/year, p = 0.049). This decrease was observed in men (-0.159 (0.257) vs. 0.031 (0.325) kg/m2/year, p = 0.038), patients with poor glycemic control (-0.170 (0.264) vs. 0.031 (0.285) kg/m2/year, p = 0.042), and those with a long diabetes duration (-0.153 (0.229) vs. 0.082 (0.291) kg/m2, p = 0.049). Conclusions: The COVID-19 pandemic restrictions caused muscle mass loss in older patents with T2D. Actions, including recommendation of exercise and adequate diet intake, are needed to prevent loss of muscle mass.

Effect of coronavirus disease 2019 pandemic on the lifestyle and glycemic control in patients with type 2 diabetes: a cross-section and retrospective cohort study.

To investigate the acute effects of the coronavirus disease 2019 (COVID-19) on the lifestyle and metabolic parameters in patients with type 2 diabetes mellites. This cross-sectional and retrospective cohort study induced 203 patients who completed a questionnaire regarding stress levels and lifestyles. Data regarding stress levels, sleep time, exercise, and total diet, snack, and prepared food intake were obtained from the questionnaires. The changes in the body weight or HbA1c levels were determined by comparing the values at the time the questionnaire was administered to those noted 3 months ago. Increased levels of stress and decreased exercise levels were reported in approximately 40% and >50%. During the COVID-19 pandemic. There was a negative correlation between stress and exercise (r = -0.285, p < 0.001) and a positive correlation between stress and prepared food intake (r = 0.193, p = 0.009). Decreased exercise levels (r = -0.33, p < 0.001) and increased snack consumption (r = 0.24, p = 0.002) were associated with increased body weight. Furthermore, increased total diet intake (r = 0.16, p = 0.031) was associated with increased HbA1c levels. These relationships remained significant for patients aged <65 years and patients who did not engage in regular exercise. Many patients experienced stress and lifestyle changes due to the COVID-19 pandemic, and these changes were associated with increased body weight and HbA1c levels.

Effect of probiotics, Bifidobacterium bifidum G9-1, on gastrointestinal symptoms in patients with type 2 diabetes mellitus: study protocol for open-label, single-arm, exploratory research trial (Big STAR study).

Metformin is associated with risks of gastrointestinal complications in patients with type 2 diabetes. In contrast, probiotic Bifidobacterium bifidum G9-1 (BBG9-1) could improve the symptoms of diarrhea caused by metformin in animal models. Thus, the primary outcome of this study will be the effect of the probiotic BBG9-1 on gastrointestinal symptoms, including diarrhea, in patients with type 2 diabetes who use metformin. This open-label, single-arm, and exploratory study will examine 40 patients with type 2 diabetes who use metformin and have symptoms of constipation or diarrhea. After the baseline examination (objective 1), patients will be administered probiotic BBG9-1 for 10 ± 2 weeks. Then, examinations will be performed (objective 2). The primary outcome will be changes in the symptoms of constipation or diarrhea from objective 1 to objective 2. Secondary outcomes will include changes in gut microbiota, and correlations between changes in fecal properties and biomarkers, including HbA1c level and body mass index. This is the first study to investigate the effect of probiotic BBG9-1 on the change in the symptom of constipation or diarrhea in patients with type 2 diabetes who use metformin.