Protocol of a Prospective Observational Study on Lifestyle and Quality of Life in Adults with Type 1 Diabetes in Japan.

INTRODUCTION: Recent studies have shown that the quality of life (QOL) of people living with type 1 diabetes (T1D) is poor and must be improved. However, the living situation and QOL of adults living with T1D in Japan have not been fully clarified. This study will examine their lifestyle, QOL, and clinical situation, as well as the relationships between them. METHODS: This is a prospective, 5-year follow-up observational study. Between December 2019 and September 2021, we enrolled adults in Japan who were living with T1D and receiving insulin therapy, and are acquiring longitudinal clinical data and the responses to seven questionnaires regarding lifestyle and QOL. The primary study outcomes are (1) the relationship between Problem Areas in Diabetes (PAID) scores and various factors including demographic data, clinical characteristics, medical history, lifestyle habits, treatment history, biochemical data, and the scores of questionnaires; and (2) the relationship between Beck Depression Inventory (BDI)-II scores and various factors aforementioned. The secondary outcomes are the relationships between various factors aforementioned and each of the following: (1) blood glucose control, (2) blood lipid control, (3) dietary patterns, (4) fear of hypoglycemia, (5) sleep patterns, and (6) physical activity. PLANNED OUTCOME: We registered 352 participants. The median age was 49 (41-63) years, and the median duration of T1D was 13 (8-20) years. All the results will be available in 2026. We expect to clarify the factors associated with decreased QOL, and that this knowledge will contribute to improving QOL in adults in Japan who are living with T1D and receiving insulin therapy. TRIAL REGISTRATION: Clinical Trials.gov identifier, UMIN000044088.

A 7 day inpatient diabetes education program improves quality of life and glycemic control 12 months after discharge.

AIMS: For long-term management of diabetes, patients with type 2 diabetes mellitus require a high level of treatment adherence, which is associated with treatment satisfaction and their quality of life (QOL). To achieve it, patient education about diabetes self-management is essential. We routinely conduct a 7 day inpatient diabetes education program and administer the diabetes treatment-related (DTR)-QOL questionnaire to all participants, both before admission and at discharge. Here, we investigated whether our program improves QOL and post-discharge glycemic control. MATERIALS AND METHODS: This retrospective study utilized data from patients with type 2 diabetes mellitus who participated in our program between July 2017 and March 2020 and who had been treated in our outpatient department for more than 1 year. We evaluated the relationship between at admission and at discharge diabetes treatment-related quality of life scores and glycemic control after discharge. RESULTS: Data from 140 patients were analyzed in this study, which showed a significant improvement in the total, 'Anxiety and dissatisfaction with treatment', and 'Satisfaction-with-treatment' scores. A significant improvement was evident in HbA1c at 12 months after discharge. Multiple regression analysis showed that HbA1c after 12 months was independently associated with gender, duration of diabetes, and HbA1c at admission. CONCLUSIONS: Our program effectively improves quality of life and post-discharge glycemic control in patients with type 2 diabetes mellitus. It is particularly effective in patients of the male gender, with a shorter duration of diabetes mellitus and higher HbA1c at admission.

Energy loss is related to CT fractional flow reserve progression in type 2 diabetes mellitus patients.

Background: We aimed to investigate the diagnostic value of energy loss (EL) and baseline CT fractional flow reserve (CT-FFR) computed using computational fluid dynamics to predict functional progression of coronary stenosis in patients with type 2 diabetes mellitus. Methods: This single-center prospective study included 61 patients with type 2 diabetes mellitus (mean age, 61 years ±9 [SD]; 43 men) showing 20-70 % stenosis who underwent serial coronary CT performed at 2-year interval between October 2015 and March 2020. A mesh-free simulation was performed to calculate the CT-FFR and EL. Functional progression was defined as ≥ 0.05 decrease in CT-FFR on the second coronary CT. Models using baseline CT-FFR and EL were compared by analyzing the receiver operating characteristic (ROC) curve. Results: Of the 94 vessels evaluated, 25 vessels (27 %) showed functional progression. EL at distal stenosis (ELdis) of vessels with functional progression was higher than that of vessels without functional progression (27.6 W/m3 [interquartile range (IQR): 15.0, 53.0] vs. 5.7 W/m3 [IQR: 2.3, 10.1], p < 0.001). Multivariable analysis showed that ELdis (per unit Ln(EL); odds ratio, 11.8; 95 % CI: 4.0-34.9; p < 0.001) remained as a predictor of functional progression after adjustment for diameter stenosis and baseline CT-FFR. The area under the ROC curve using ELdis (0.89; 95 % CI: 0.82-0.96) was higher than that using baseline CT-FFR (0.71; 95 % CI: 0.59-0.83; p < 0.001). Conclusion: When ELdis and baseline CT-FFR were considered, ELdis was a better predictor of functional progression of coronary stenosis.

Genetic ablation of p62/SQSTM1 demonstrates little effect on pancreatic ß-cell function under autophagy deficiency.

Autophagy is known to play an essential role in intracellular quality control through the degradation of damaged organelles and components. We previously demonstrated that ß-cell-specific autophagy deficient mice, which lack Atg7, exhibited impaired glucose tolerance, accompanied by the accumulation of sequestosome 1/p62 (hereafter referred to as p62). Whereas p62 has been reported to play essential roles in regulating cellular homeostasis in the liver and adipose tissue, we previously showed that ß-cell-specific p62 deficiency does not cause any apparent impairment in glucose metabolism. In the present study, we investigated the roles of p62 in ß cells under autophagy-deficient conditions, by simultaneously inactivating both Atg7 and p62 in a ß-cell specific manner. Whereas p62 accumulation was substantially reduced in the islets of Atg7 and p62 double-deficient mice, glucose tolerance and insulin secretion were comparable to Atg7 single-deficient mice. Taken together, these findings suggest that the p62 accumulation appears to have little effect on ß-cell function under conditions of autophagy inhibition.

Identification of Risk Factors for Coronary Artery Disease in Asymptomatic Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Patients with diabetes mellitus (DM) are a high-risk group for coronary artery disease (CAD). In the present study, we investigated predictive factors to identify patients at high risk of CAD among asymptomatic patients with type 2 DM based on coronary computed tomographic angiography (CCTA) findings. METHODS: A single-center prospective study was performed on 452 consecutive patients with type 2 DM who were provided with a weekly hospital-based diabetes education program between 3 October 2015, and 31 March 2020. A total of 161 consecutive asymptomatic patients (male/female: 111/50, age: 57.3 ± 9.3 years) with type 2 DM without any known CAD underwent CCTA. Based on conventional coronary risk factors and non-invasive examination, i.e., measurement of intima-media thickness, subcutaneous and visceral fat area, a stress electrocardiogram test, and the Agatston score, patients with obstructive CAD, CT-verified high-risk plaques (CT-HRP), and optimal revascularization within 90 days were evaluated. RESULTS: Current smoking (OR, 4.069; 95% C.I., 1.578-10.493, p = 0.0037) and the Agatston score ≥100 (OR, 18.034; 95% C.I., 6.337-51.324, p = 0.0001) were independent predictive factors for obstructive CAD, while current smoking (OR, 5.013; 95% C.I., 1.683-14.931, p = 0.0038) was an independent predictive factor for CT-HRP. Furthermore, insulin treatment (OR, 5.677; 95% C.I., 1.223-26.349, p = 0.0266) was the only predictive factor that correlated with optimal revascularization within 90 days. CONCLUSIONS: In asymptomatic patients with type 2 DM, current smoking, an Agatston score ≥100, and insulin treatment were independent predictive factors of patients being at high-risk for CAD. However, non-invasive examinations except for Agatston score were not independent predictors of patients being at high risk of CAD.

Left atrial dysfunction and stiffness in pediatric and adult patients with Type 1 diabetes mellitus assessed with speckle tracking echocardiography.

BACKGROUND: Subclinical diastolic dysfunction in patients with Type 1 diabetes mellitus (T1DM) caused by myocardial injury due to diabetic cardiomyopathy leads to a high risk of death and heart failure. This myocardial injury extends not only to the left ventricle (LV) but also to the left atrium (LA). However, LA function in children and young adults with T1DM has not been extensively studied. OBJECTIVE: Therefore, the aim of this study was to assess LA dysfunction in pediatric and adult patients with T1DM using LA strain analysis with echocardiography. SUBJECTS: Fifty-three patients (median age: 23 [range: 5-41] years) with T1DM. METHODS: We divided the patients into three age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-41 years); 53 age- and sex-matched controls were divided into three corresponding groups (C1, C2, and C3). LA and LV functions were evaluated using echocardiography. RESULTS: LA reservoir strain was lower in the D2 and D3 groups than in the C2 and C3 groups (P = 0.001, P = 0.004, respectively). LA conduit strain was lower in the D2 group than in the C2 group (P = 0.002). LA stiffness was significantly greater in the D3 group than in the C3 group (P < 0.001). CONCLUSIONS: In patients with T1DM, LA phasic function decreased in adolescents and young adults, and LA stiffness increased in adult patients aged >30 years. LA phasic function and LA stiffness can be potentially used as early markers for diastolic dysfunction.

Effect of real-life insulin pump with predictive low-glucose management use for 3 months: Analysis of the patients treated in a Japanese center.

AIMS/INTRODUCTION: In Japan, an insulin pump with predictive low-glucose management (PLGM) was launched in 2018. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. The aim of this study was to analyze the safety and efficacy of PLGM in patients treated in a Japanese center. MATERIALS AND METHODS: We carried out a retrospective observational analysis of 16 patients with type 1 diabetes mellitus and one patient after pancreatectomy. They switched from the MiniMed 620G device to the 640G device with PLGM. The primary outcome was the change in the percentage of time in hypoglycemia. The secondary outcome was the change in HbA1c (%) over a period of 3 months. We also explored the presence of "post-suspend hyperglycemia" with the 640G device. RESULTS: After changing to the 640G device, the percentage of time in hypoglycemia (glucose <50 mg/dL) significantly decreased from 0.39% (0-1.51%) to 0% (0-0.44%; P = 0.0407). The percentage of time in hyperglycemia (glucose >180 mg/dL) significantly increased from 25.53% (15.78-44.14%) to 32.9% (24.71-45.49%; P = 0.0373). HbA1c significantly increased from 7.6 ± 1.0% to 7.8 ± 1.1% (P = 0.0161). From 1.5 to 4.5 h after the resumption of insulin delivery, the percentage of time in hyperglycemia was 32.23% (24.2-53.75%), but it was significantly lower, 2.78% (0-21.6%), when patients manually restarted the pump within 30 min compared with automatic resumption 31.2% (20-61.66%; P = 0.0063). CONCLUSIONS: Predictive low-glucose management is an effective tool for reducing hypoglycemia, but possibly elicits "post-suspend hyperglycemia." This information is useful for achieving better blood glucose control in the patients treated with PLGM.

In-Depth Insight Into the Mechanisms of Cardiac Dysfunction in Patients With Type 1 Diabetes Mellitus Using Layer-Specific Strain Analysis.

BACKGROUND: Although the subclinical left ventricular (LV) dysfunction caused by diabetes mellitus (DM) results in a high risk of death and heart failure, the details of cardiac dysfunction across a wide age range remain unclear. The aim of this study was to assess LV dysfunction in patients with type 1 DM (T1DM) using layer-specific strain analysis by echocardiography.Methods and Results:The 52 patients (median age: 23 [range: 5-40] years) with T1DM were divided into 3 age groups (D1: 5-14 years, D2: 15-24 years, D3: 25-40 years); 78 age- and sex-similar controls were divided into 3 corresponding groups (C1, C2, and C3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of the 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Strains did not decrease in D1. Epicardial and midmyocardial CS at the basal level and LS in all layers were decreased in D2 compared with C2. CS at the basal level and LS in all layers were lower in D3 than in C3. The strains correlated with the duration of T1DM and LV wall thickness. CONCLUSIONS: In patients with T1DM, longitudinal deformation in all layers and epicardial and midmyocardial circumferential deformation at the basal level decreased from the late teens, which correlated with the duration of the disease and LV hypertrophy.

Postprandial Plasma Glucagon Kinetics in Type 2 Diabetes Mellitus: Comparison of Immunoassay and Mass Spectrometry.

CONTEXT: Accurate glucagon level measurements are necessary for investigation of mechanisms for postprandial hyperglycemia in type 2 diabetes. OBJECTIVE: To evaluate the accuracy of postprandial glucagon level measurements using a sandwich ELISA vs a recently established liquid chromatography-high resolution mass spectrometry (LC-HRMS) method in type 2 diabetes mellitus. DESIGN AND PARTICIPANTS: Twenty patients with type 2 diabetes treated with insulin underwent a meal test before and after administration of the dipeptidyl peptidase-4 inhibitor anagliptin for 4 weeks. Blood samples were taken serially after the meal, and glucagon levels were measured using both ELISA and LC-HRMS. We compared the change from baseline to 4 weeks (Δ0-4W) using the area under the curve for plasma glucagon during the meal test [area under the curve (AUC)0-3h] measured using ELISA and LC-HRMS. RESULTS: ELISA-based glucagon AUC0-3h was higher than LC-HRMS-based AUC0-3h at baseline and 4 weeks. However, differences in Δ0-4W-AUC0-3h measured using ELISA and LC-HRMS were not statistically significant. Additionally, Δ0-4W-AUC0-3h measured using ELISA and LC-HRMS were strongly correlated (r = 0.87, P < 0.001). CONCLUSIONS: Plasma glucagon levels during a meal test in patients with type 2 diabetes measured using ELISA were consistently higher than those measured using LC-HRMS. However, given that the changes in glucagon levels measured using ELISA before and after dipeptidyl peptidase-4 inhibitor therapy were similar to those based on LC-HRMS, this ELISA seems to be useful for evaluating the effect of the drug interventions on postprandial glucagon levels.

NEUROD1-deficient diabetes (MODY6): Identification of the first cases in Japanese and the clinical features.

AIMS: Only a few families with neuronal differentiation 1 (NEUROD1)-deficient diabetes, currently designated as maturity-onset diabetes of the young 6 (MODY6), have been reported, but mostly in Caucasian, and no mutation has been identified by family-based screening in Japanese. Accordingly, the phenotypic details of the disease remain to be elucidated. METHODS: We examined a total of 275 subjects having diabetes suspected to be MODY who were negative for mutations in MODY1-5 referred from 155 medical institutions throughout Japan. So as not to miss low penetrant cases, we examined non-obese Japanese patients with early-onset diabetes regardless of the presence of family history by direct sequencing of all exons and flanking regions of NEUROD1 . Large genomic rearrangements also were examined. RESULTS: Four patients with 3 frameshift mutations and 1 missense mutation, all of which were heterozygous and 3 of which were novel, were identified. Diabetic ketosis was found occasionally in these patients even under conditions of chronic hyperglycemia, for unknown reasons. Although the capacity of early-phase insulin secretion was low in these patients, the insulin secretory capacity was relatively preserved compared to that in hepatocyte nuclear factor (HNF)1A- and HNF1B-MODY. One of the patients and 2 of their diabetic mothers were found to have some mental or neuronal abnormality. CONCLUSIONS: This is the first report of NEUROD1 mutations in Japanese, who have a genetic background of intrinsically lower capacity of insulin secretion. NEUROD1-deficient diabetes appears to be low penetrant, and may occur in concert with other genetic factors.

One year follow-up after a randomized controlled trial of a 130 g/day low-carbohydrate diet in patients with type 2 diabetes mellitus and poor glycemic control.

BACKGROUND & AIMS: Recently, we conducted a prospective randomized controlled trial (RCT) showing that a 6-month 130g/day low-carbohydrate diet (LCD) reduced HbA1c and BMI more than a calorie restricted diet (CRD). [1] To assess whether the benefits of the LCD persisted after the intensive intervention, we compared HbA1c and BMI between the LCD and CRD groups at 1 year after the end of the 6-month RCT. METHODS: Following the end of the 6-month RCT, patients were allowed to manage their own diets with periodic outpatient visits. One year later, we analyzed clinical and nutrition data. RESULTS: Of the 66 participants in the original study, 27 in the CRD group and 22 in the LCD group completed this trial. One year after the end of the original RCT, the carbohydrate intake was comparable between the groups (215 [189-243]/day in the CRD group and 214 (176-262) g/day in the LCD group). Compared with the baseline data, HbA1c and BMI were decreased in both groups (CRD: HbA1c -0.4 [-0.9 to 0.3] % and BMI -0.63 [-1.20 to 0.18] kg/m2; LCD: HbA1c -0.35 [-1.0 to 0.35] % and BMI -0.77 [-1.15 to -0.12] kg/m2). There were no significant differences in HbA1c and BMI between the groups. CONCLUSIONS: One year after the diet therapy intervention, the beneficial effect of the LCD on reduction of HbA1c and BMI did not persist in comparison with CRD. However, combining the data of both groups, significant improvements in HbA1c and BMI from baseline were observed. Although the superiority of the LCD disappeared 1 year after the intensive intervention, these data suggest that well-constructed nutrition therapy programs, both CRD and LCD, were equally effective in improving HbA1c for at least 1 year. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) ID000010663.

Safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin and low-dose metformin.

BACKGROUND: This study investigated the safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin (100 mg/day) and low-dose metformin (500 or 750 mg/day). RESEARCH DESIGN AND METHODS: Fifty patients were randomly allocated to the control group (maintaining the initial low-dose of metformin) and the dose increase group (up-titrating of metformin to 1,500-2,250 mg/day) for 24 weeks. The primary outcome was change in HbA1c from baseline to 24 weeks. RESULTS: Among the 25 patients allocated to the dose increase group, four patients were not able to complete the study protocol because of gastrointestinal symptoms. HbA1c in the dose increase group was significantly but modestly lower than in the control group (change in HbA1c: 0.22 ± 0.57 vs. -0.15 ± 0.58%, group comparison, P < 0.05). The dose increase group did not gain weight during the study period, and no hypoglycemic events were reported in both groups. The rate of gastrointestinal symptoms in the dose increase group was profoundly higher than in the control group (32 vs. 0%, P < 0.01). CONCLUSIONS: In Japanese patients with type 2 diabetes treated with vildagliptin and low-dose metformin, metformin up-titration significantly but modestly improved glycemic control without hypoglycemia and weight gain.

Probiotic reduces bacterial translocation in type 2 diabetes mellitus: A randomised controlled study.

Gut bacterial translocation to the blood may play an important role in the development of insulin resistance in type 2 diabetes. Here, we performed an interventional randomised control study to investigate whether probiotics could reduce bacterial translocation and cause changes in the gut microbiota. Seventy Japanese patients with type 2 diabetes were randomised to two groups: the probiotic group drank Lactobacillus casei strain Shirota-fermented milk, while the control group ingested no probiotics. The trial was conducted for 16 weeks. At baseline, 8 and 16 weeks, the gut microbiota composition in feces and blood, fecal organic acids, and other biochemical parameters were measured. At the end of the study, the fecal counts of the Clostridium coccoides group and Clostridium leptum subgroup in the probiotic group were significantly higher than in the control group. As expected, the fecal counts of total Lactobacillus were significantly higher in the probiotic group. Intriguingly, the total count of blood bacteria was significantly lower in the probiotic group. However, fecal organic acids were comparable between the two groups. Our results showed that probiotic administration reduced bacterial translocation and altered the gut microbiota in Japanese patients with type 2 diabetes mellitus.

Efficacy and Safety of Vildagliptin as an Add-On Therapy in Inadequately Controlled Type 2 Diabetes Patients Treated With Basal Insulin.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of vildagliptin as an add-on therapy for patients with type 2 diabetes mellitus inadequately controlled with basal insulin. METHODS: Twenty-four patients treated with basal insulin and oral anti-diabetes drugs were randomly allocated into two groups: the control group (did not receive any add-on drugs) and vildagliptin group (received vildagliptin 100 mg/day for 6 months). The primary outcome was changes in hemoglobin A1c (HbA1c) from baseline to end of study. RESULTS: Treatment with vildagliptin significantly reduced HbA1c from 8.1±0.7% at baseline to 7.1±0.7% (P < 0.01), while there was no significant change of HbA1c in the control group. Vildagliptin group showed significant reduction of HbA1c compared with control group (-1.0±0.3% vs. 0.2±0.8%, P < 0.01). In addition, vildagliptin group showed a significant increase in 1,5-anhydroglucitol compared with the control group (4.5 ± 3.4 vs. 0.5 ± 4.1 µg/mL, P < 0.05). Mild hypoglycemia was reported in one patient of the vildagliptin group and two patients of the control group. CONCLUSION: Vildagliptin improved glycemic control without increasing hypoglycemia in Japanese type 2 diabetes inadequately controlled with basal insulin treatment and other oral anti-diabetes drugs. This study was registered with UMIN (University Hospital Medical Information Network ID#000010849).

A randomized controlled trial of 130 g/day low-carbohydrate diet in type 2 diabetes with poor glycemic control.

BACKGROUND & AIMS: The usefulness of low-carbohydrate diet (LCD) for Japanese patients with type 2 diabetes mellitus (T2DM) has not been fully investigated. Therefore, we compared the effectiveness and safety of LCD with calorie restricted diet (CRD). METHODS: This prospective, randomized, open-label, comparative study included 66 T2DM patients with HbA1c >7.5% even after receiving repeated education programs on CRD. They were randomly allocated to either the 130g/day LCD group (n = 33) or CRD group (n = 33). Patients received personal nutrition education of CRD or LCD for 30 min at baseline, 1, 2, 4, and 6 months. Patients of the CRD group were advised to maintain the intake of calories and balance of macronutrients (28× ideal body weight calories per day). Patients of the LCD group were advised to maintain the intake of 130 g/day carbohydrate without other specific restrictions. Several parameters were assessed at baseline and 6 months after each intervention. The primary endpoint was a change in HbA1c level from baseline to the end of the study. RESULTS: At baseline, BMI and HbA1c were 26.5 (24.6-30.1) and 8.3 (8.0-9.3), and 26.7 (25.0-30.0) kg/m2 and 8.0 (7.6-8.9) %, in the CRD and LCD, respectively. At the end of the study, HbA1c decreased by -0.65 (-1.53 to -0.10) % in the LCD group, compared with 0.00 (-0.68 to 0.40) % in the CRD group (p < 0.01). Also, the decrease in BMI in the LCD group [-0.58 (-1.51 to -0.16) kg/m2] exceeded that observed in the CRD group (p = 0.03). CONCLUSIONS: Our study demonstrated that 6-month 130 g/day LCD reduced HbA1c and BMI in poorly controlled Japanese patients with T2DM. LCD is a potentially useful nutrition therapy for Japanese patients who cannot adhere to CRD. This trial was registered at http://www.umin.ac.jp/english/ (University Hospital Medical Information Network: study ID number 000010663).

Effect of treatment guidance using a retrospective continuous glucose monitoring system on glycaemic control in outpatients with type 2 diabetes mellitus: A randomized controlled trial.

OBJECTIVES: To assess the effect of treatment guidance based on data from a continuous glucose monitoring (CGM) device on glycaemic control, and patient satisfaction, in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with poorly-controlled T2DM treated with insulin were randomly assigned to the intervention or nonintervention group. Continuous blood-glucose levels were recorded for 4-5 days using a CGM device on three separate occasions during the 8-month study period. The intervention group received treatment guidance based on the CGM data; the nonintervention group received advice based on blood glucose and glycosylated haemoglobin (HbA1c) levels. RESULTS: A total of 34 patients were enrolled in the study. The mean ± SD baseline HbA1c was 8.2 ± 1.2% in the intervention group and 8.2 ± 0.9% in the nonintervention group. At the study end, there was no significant difference in the change from baseline of HbA1c between the two groups. There was also no significant difference in the change from baseline in the Diabetes Treatment Satisfaction Questionnaire score between the two groups. CONCLUSIONS: The present study did not demonstrate that treatment guidance using retrospective CGM data was effective for improving glycaemic control and therapeutic satisfaction in Japanese patients with T2DM.

Switching from Twice-Daily Basal Insulin Injections to Once-Daily Insulin Degludec Injection for Basal-Bolus Insulin Regimen in Japanese Patients with Type 1 Diabetes: A Pilot Study.

The aim of this study was to investigate the efficacy of insulin degludec used for basal-bolus insulin regimen after switching from twice-daily basal insulin in Japanese patients with type 1 diabetes mellitus. The subjects were 22 type 1 diabetes patients treated with basal-bolus insulin regimen with twice-daily basal insulin. Basal insulin was switched to once-daily injection of insulin degludec with 10% dose reduction. HbA1c and fasting plasma glucose (FPG) were measured before and 12 weeks after switching. The frequency of hypoglycemic episodes, standard deviation (SD) of blood glucose, and mean of daily difference (MODD) were evaluated by continuous glucose monitoring (CGM) before and 4 weeks after switching. HbA1c and FPG before and 12 weeks after switching were comparable (HbA1c 8.5 ± 1.4 versus 8.7 ± 1.6%, P = 0.28; FPG 203.2 ± 81.2 versus 206.5 ± 122.4 mg/dL, P = 0.91). The frequency of hypoglycemia during nighttime was not significantly different at 4 weeks after switching (14.4 ± 17.0 versus 11.1 ± 15.0%, P = 0.45). In addition, SD and MODD before and 4 weeks after switching were also comparable. In conclusion, glycemic control under once-daily insulin degludec injection was almost comparable to that under twice-daily basal insulin injections in Japanese type 1 diabetes patients. This study was registered with ID: UMIN000010474.

Comparison of sitagliptin with nateglinide on postprandial glucose and related hormones in drug-naïve Japanese patients with type 2 diabetes mellitus: A pilot study.

AIMS/INTRODUCTION: Dipeptidyl peptidase-4 inhibitors and glinides are effective in reducing postprandial hyperglycemia. However, little information is available on the comparative effects of the two drugs on the levels of postprandial glucose. The aim of the present study was to compare the effects of sitagliptin and nateglinide on meal tolerance tests in drug-naïve patients with type 2 diabetes mellitus. MATERIALS AND METHODS: The study participants were 19 patients with type 2 diabetes mellitus, which was inadequately controlled by diet and exercise. An open-label, prospective, cross-over trial was carried out to compare the effects of single-dose sitagliptin and nateglinide on the postprandial glucose level and its related hormones during meal tests. RESULTS: The change in area under the curve (AUC) of glucose from 0 to 180 min (AUC0-180 min) during the meal test by nateglinide was similar to that by sitagliptin. As expected, the change in active glucagon like peptide-1 was significantly higher after a single-dose of sitagliptin than nateglinide. Then, insulin secretion relative to glucose elevation (ISG) (ΔISG0-180 min: ΔAUC0-180 min insulin/AUC0-180 min glucose) was significantly enhanced by nateglinide compared with sitagliptin. Conversely, glucagon level (ΔAUC0-180 min glucagon) was increased by administration of nateglinide, whereas the glucagon level was reduced by administration of sitagliptin. CONCLUSIONS: The effects of sitagliptin on postprandial glucose levels were similar to those of nateglinide in drug-naïve type 2 diabetes patients. However, the induced changes in insulin, active glucagon-like peptide-1 and glucagon during meal loading suggest that reduction of postprandial hyperglycemia was achieved by the unique effect of each drug.

Gut dysbiosis and detection of "live gut bacteria" in blood of Japanese patients with type 2 diabetes.

OBJECTIVE: Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and "live gut bacteria" in the systemic circulation of Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using a sensitive reverse transcription-quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. RESULTS: The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive. CONCLUSIONS: This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream.

Comparison of effects of cilnidipine and azelnidipine on blood pressure, heart rate and albuminuria in type 2 diabetics with hypertension: A pilot study.

Previous studies reported that both cilnidipine and azelnidipine have a renoprotective effect compared with amlodipine. The aim of this study was to compare the effects of cilnidipine and azelnidipine on blood pressure, heart rate and albuminuria. An open-label prospective crossover trial was carried out. We recruited 19 type 2 diabetics treated with amlodipine (5 mg/day) at least for 12 weeks. At study entry, amlodipine was changed to cilnidipine (10 mg/day) or azelnidipine (16 mg/day) and each administered for 16 weeks. Then, the drugs were switched and the treatment was continued for another 16 weeks. Despite no differences in 24-h blood pressure and heart rate between cilnidipine and azelnidipine, treatment with cilnidipine resulted in a greater reduction in urinary albumin:creatinine ratio than azelnidipine. Our results suggested that cilnidipine is more efficient in reducing albuminuria than azelnidipine independent of its blood pressure lowering effect in type 2 diabetic patients with hypertension. This trial was registered with UMIN (no. 000007201).