Efficacy and safety of a telemedicine system in subjects with gestational diabetes mellitus (TELEGLAM): Study protocol for a randomized controlled trial.

Background: Strict glycemic control is important to prevent perinatal complications in patients with gestational diabetes mellitus (GDM). Patients often require insulin injection, and frequent hospital visits are necessary to adjust the dose of insulin, which is considered burdensome for pregnant patients. Telemedicine may reduce the burden of hospital visits, and previous studies have reported its safety in GDM patients. This study aimed to evaluate the efficacy of telemedicine in GDM patients, focusing on patient satisfaction and health economic indicators. Methods: This is a single-center, two-arm, randomized, open-label parallel-group study. Subjects will be selected from the patient population attending the Department of Endocrinology, Metabolism, and Nephrology, Keio University School of Medicine, Japan. Patients diagnosed with GDM by an oral glucose tolerance test (OGTT) by 29 weeks and 6 days of gestation who have undergone self-monitoring of blood glucose (SMBG) and insulin injection are eligible for inclusion. In the intervention group, telemedicine will be administered using the MeDaCa telemedicine system developed by the Medical Data Card, Inc., Tokyo, Japan. Subjects in the control group will be examined face-to-face every 2-3 weeks, as usual. We set health economic indicators and patient satisfaction as the primary endpoints, and will perform a cost-consequence analysis. Glycemic control indicators and perinatal outcomes will be evaluated as secondary endpoints. Conclusions: Eligible patients are currently being recruited. Recruitment will be completed when the expected number of patients are enrolled.

Possible Relationship between the Deteriorated Accuracy of Intermittent-Scanning Continuous Glucose Monitoring Device and the Contact Dermatitis: Post-hoc analysis of the ISCHIA Study.

OBJECTIVE: We previously reported the mean average relative difference (MARD) of the sensor glucose (SG) of the first-generation FreeStyle Libre with the original algorithm, an intermittent scanning continuous glucose monitoring (isCGM) device, was 15.6% in the Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study). In the present study, we aimed to further analyze its accuracy in detail by conducting a post-hoc analysis of the study. METHODS: The ISCHIA Study was a multicenter, randomized, cross-over trial to assess the efficacy of isCGM. The SG levels of isCGM and the measured capillary blood glucose (BG) levels of 91 participants were used for the analysis. RESULTS: Bland-Altman analysis showed bias of -13.0 mg/dl when the SG levels were compared to the BG levels, however no proportional bias was observed (r = 0.085). MARD of the participants without and with contact dermatitis were 15.0 ± 6.0% and 27.4 ± 21.4% (P = 0.001), respectively. CONCLUSION: There was negative bias in the SG levels of isCGM compared to the BG levels. There is a possibility that the complication of the contact dermatitis during isCGM use may be related with deteriorated accuracy of the SG levels.

Dietary protein intake and all-cause mortality: results from The Kawasaki Aging and Wellbeing Project.

BACKGROUND: Increased protein intake has been recommended to prevent sarcopenia/frailty, reports on the quantity and quality of protein intake needed and the associated prognosis, particularly in the aging population of Asia, are limited. In this study, we aimed to investigate the relationship between protein intake and mortality in Japanese individuals, aged 85 years and older. METHODS: The data were obtained from The Kawasaki Aging and Wellbeing Project, which is a prospective cohort study of older adults aged between 85 and 89 years with no physical disability at baseline. Of the 1,026 adults in the cohort, 833 were included in the analysis, after excluding those who had not completed a brief, self-administered diet history questionnaire or those who scored less than 24 on the Mini-Mental State Examination. The participants were grouped into quartiles based on protein intake: Q1 (protein < 14.7, %Energy), Q2 (14.7 ≤ protein < 16.7, %Energy), Q3 (16.7 ≤ protein < 19.1, %Energy), and Q4 (≥ 19.1, %Energy). Multivariate Cox proportional hazards models were utilized to evaluate the association between protein intake and all-cause mortality. Kaplan-Meier survival curves were employed to investigate the relationship between protein intake and all-cause mortality. RESULTS: The mean protein intake of our study population was 17.0% of total energy. Animal protein intake, particularly fish intake, increased significantly along with total protein intake. The study had an average observation period of 1,218 days and recorded 89 deaths. After adjusting for age, sex, skeletal muscle mass index, cardiovascular disease, cancer, education, and serum albumin levels, a lower risk of all-cause mortality was observed in the highest protein intake (Q4) group than in the lowest protein intake (Q1) group (hazard ratio: 0.44, 95% confidence interval: 0.22-0.90, p-value: 0.020). CONCLUSION: Protein intake is associated with a reduced risk of all-cause mortality in older adults (aged ≥ 85 years) who engage in independent activities of daily living. This association may impact all-cause mortality independent of muscle mass.

Impact of coronavirus disease 2019 in seasonal variation of hemoglobin A1c in adults with type 1 diabetes and the effect of the mode of treatment: a single-center retrospective study for 2019 and 2021 and analysis by the mode of treatment.

The study was aimed to investigate the seasonal variation of hemoglobin A1c (HbA1c) in adults with type 1 diabetes (T1D) and the impact of coronavirus disease 2019 (COVID-19) by comparing 2019 and 2021 data and differences in treatment modes. This was a single-center retrospective observational study including 52 adult patients with T1D who regularly visited hospital in 2019 and 2021. Twenty-five patients used multiple daily injections (MDI)/self-measurement of blood glucose (SMBG), 16 used MDI/intermittently scanned continuous glucose monitoring (isCGM), 9 used sensor-augmented pump (SAP), and 2 used continuous subcutaneous insulin infusion (CSII)/isCGM. The mean HbA1c level was calculated for each month. The correlation between monthly means of temperature and HbA1c was investigated. Similar analyses were performed for the MDI/SMBG, MDI/isCGM, and SAP + CSII/isCGM groups. HbA1c levels in 2019 decreased in summer and increased in winter and showed a significant negative correlation with temperature (r = -0.652, p = 0.022). However, HbA1c in 2021 showed no seasonal variation and no correlation with temperature (r = -0.134, p = 0.678) and tended to decline after the three emergency declarations. HbA1c in the MDI/SMBG group showed the same trend as the whole group in 2019 and 2021. However, the effect of seasonal variation in HbA1c was lower in the MDI/isCGM group and the lowest in the SAP + CSII/isCGM group in 2019. The impact of emergency declaration on HbA1c level was small for the MDI/isCGM group and smaller for the SAP + CSII/isCGM group in 2021. The COVID-19 pandemic has affected the seasonal variation of HbA1c levels in T1D; the variation differed according to the treatment mode.

Newly developed type 1 diabetes after coronavirus disease 2019 vaccination: A case report.

The vaccine for the coronavirus disease 2019 (COVID-19) has been reported to potentially cause or worsen diabetes. A 73-year-old Japanese woman received two doses of Moderna COVID-19 vaccine. Four weeks after the second vaccination, her glycemic control began to deteriorate, and 8 weeks after the second vaccination, the patient was diagnosed with new-onset type 1 diabetes that was strongly positive for autoantibodies and showed a disease-susceptible human leukocyte antigen haplotype, DRB1*04:05:01-DQB1*04:01:01. The glucagon stimulation test suggested an insulin-dependent state, and induction of intensive insulin therapy brought about fair glycemic control. The time period from the COVID-19 vaccination to the development of type 1 diabetes was relatively longer than to the onset or exacerbation of type 2 diabetes, as previously reported, suggesting the complicated immunological mechanisms for the destruction of ß-cells associated with the vaccination. In recipients with the disease-susceptible haplotypes, one should be cautious about autoimmune responses for several months after the vaccination.

Transient Dexamethasone Loading Induces Prolonged Hyperglycemia in Male Mice With Histone Acetylation in Dpp-4 Promoter.

Glucocorticoid causes hyperglycemia, which is common in patients with or without diabetes. Prolonged hyperglycemia can be experienced even after the discontinuation of glucocorticoid use. In the present study, we examined the time course of blood glucose level in hospital patients who received transient glucocorticoid treatment. In addition, the mechanism of prolonged hyperglycemia was investigated by using dexamethasone (Dexa)-treated mice and cultured cells. The blood glucose level in glucose tolerance tests, level of insulin and glucagon-like peptide 1 (GLP-1), and the activity of dipeptidyl peptidase 4 (DPP-4) were examined during and after Dexa loading in mice, with histone acetylation level of the promoter region. Mice showed prolonged hyperglycemia during and after transient Dexa loading accompanied by persistently lower blood GLP-1 level and higher activity of DPP-4. The expression level of Dpp-4 was increased in the mononuclear cells and the promoter region of Dpp-4 was hyperacetylated during and after the transient Dexa treatment. In vitro experiments also indicated development of histone hyperacetylation in the Dpp-4 promoter region during and after Dexa treatment. The upregulation of Dpp-4 in cultured cells was significantly inhibited by a histone acetyltransferase inhibitor. Moreover, the histone hyperacetylation induced by Dexa was reversible by treatment with a sirtuin histone deacetylase activator, nicotinamide mononucleotide. We identified persistent reduction in blood GLP-1 level with hyperglycemia during and after Dexa treatment in mice, associated with histone hyperacetylation of promoter region of Dpp-4. The results unveil a novel mechanism of glucocorticoid-induced hyperglycemia, and suggest therapeutic intervention through epigenetic modification of Dpp-4.

One-year estimated glomerular filtration rate decline as a risk factor of cardiovascular and renal end-points in high-risk Japanese patients.

AIMS/INTRODUCTION: As estimated glomerular filtration rate (eGFR) progression might correlate with cardiovascular prognosis, the correlation between 1-year decline in eGFR and cardiovascular incidences and renal outcome was investigated. MATERIALS AND METHODS: The 1-year percentage decline in eGFR at the first observation year was calculated in a cohort of the standard versus intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) trial participants. The primary end-point was the composite cardiovascular end-point including the renal end-point. The associations between the incidence of each end-point and clinical markers were analyzed using the Cox proportional hazards regression model. RESULTS: A total of 4,461 patients were analyzed. The mean observation period was 765.3 ± 363.1 days. The best cut-off value of 1-year eGFR decline was 0.099 in the first year for renal end-point prediction by receiver operating characteristic curve analysis. The area under the curve of the model including the 1-year eGFR decline of the first year was significantly larger than the model without it (0.943, 95% confidence interval 0.915-0.971 to 0.967, 95% confidence interval 0.950-0.983, P = 0.019). Primary end-point incidences and the renal end-point were much higher in rapid eGFR decliners compared with non-decliners (P < 0.0001). The cardiovascular end-point incidence, except for the renal end-point, was not different between the groups. According to Cox regression analysis, 1-year eGFR decline during the first year was a significant risk factor for the end-points, including the renal end-point, independent of albuminuria and eGFR at baseline. CONCLUSIONS: The 1-year eGFR decline rate provided useful information for cardiovascular end-point predictions, including the renal end-point, in addition to the conventional risk factors.

Efficacy and safety of once-weekly exenatide after switching from twice-daily exenatide in patients with type 2 diabetes.

AIMS/INTRODUCTION: To evaluate the efficacy and safety of once-weekly (q.w.) extended-release exenatide after switching from twice-daily (b.i.d.) exenatide in patients with type 2 diabetes. MATERIALS AND METHODS: This was an investigator-initiated, prospective, single-arm, multicenter study. Individuals with type 2 diabetes who had been treated with exenatide b.i.d. for at least 3 months were enrolled and switched to exenatide q.w. for 24 weeks. The primary end-point was change in HbA1c at week 24 to test the glucose-lowering effect of exenatide q.w. versus exenatide b.i.d. RESULTS: A total of 58 Japanese individuals with type 2 diabetes completed the study. Glycated hemoglobin was reduced by 0.2% at week 24 (7.2 ± 1.2% vs 7.0 ± 1.2% [56 ± 13 vs 53 ± 13 mmol/mol], 95% confidence interval -0.4 to -0.03%, P < 0.005 for non-inferiority, P = 0.01 for superiority). Fasting plasma glucose was reduced by 12 mg/dL at week 24 (154 ± 46 vs 142 ± 46 mg/dL, P = 0.02). ß-Cell function assessed by homeostasis model assessment of ß-cell function and C-peptide index was significantly improved at week 24. The incidence of self-reported hypoglycemia was reduced, and treatment satisfaction assessed by the Diabetes Treatment Satisfaction Questionnaire and Diabetes Medication Satisfaction Questionnaire was improved at week 24, with no change in body weight. There was no serious adverse event related to the study drug. CONCLUSIONS: Switching from exenatide b.i.d. to exenatide q.w. resulted in a reduction in glycated hemoglobin, fasting plasma glucose and the incidence of hypoglycemia, and improvement in ß-cell function and treatment satisfaction in patients with type 2 diabetes. These findings will be useful for selecting optimal treatment in individuals with type 2 diabetes.

Treatment preference for weekly versus daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: outcomes from the TRINITY trial.

Objective: To examine patient preference for treatment with the oral once-weekly dipeptidyl peptidase-4 inhibitor (DPP-4i), trelagliptin, and oral once-daily DPP-4i, alogliptin, administered for 8 weeks each in patients with type 2 diabetes mellitus prescribed a daily DPP-4i.Methods: In this randomized, open-label, two-way crossover study, patients received trelagliptin followed by alogliptin (T-A group) or alogliptin followed by trelagliptin (A-T group), for 8 weeks each (NCT03231709, JapicCTI-173662). Treatment preference was assessed using a standardized questionnaire in the overall population and by baseline characteristics. Other outcomes included patient satisfaction with diabetes treatment (assessed using the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), hemoglobin A1c (HbA1c) levels after 8 weeks of treatment with each agent, and safety.Results: Sixty patients from two clinical sites were randomized 1:1 to T-A and A-T groups (each n = 30); baseline characteristics were similar between groups. After 16 weeks of treatment, 51.7% of patients preferred treatment with alogliptin compared with 30.0% selecting trelagliptin (p = .014); preference for alogliptin was consistently greater than for trelagliptin in the secondary analyses by baseline characteristics. DTSQ score and HbA1c levels were similar between treatments after 8 weeks of therapy. Both treatments demonstrated favorable safety and tolerability profiles.Conclusions: Patients expressed a significantly greater treatment preference for once-daily alogliptin than once-weekly trelagliptin, although patient satisfaction and HbA1c levels were similar across treatments. The decision to administer a once-weekly or once-daily DPP-4i is likely to depend on patient preference, patient-physician discussions, and treatment practices of the prescribing physician.

Efficacy and safety of switching to insulin glargine 300 U/mL from 100 U/mL in Japanese patients with type 2 diabetes: A 12-month retrospective analysis.

AIMS: To evaluate the efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) from insulin glargine 100 U/mL (Gla-100) in Japanese patients with type 2 diabetes (T2DM). METHODS: This was a 12-month retrospective study comprising 109 patients. Primary endpoint was glycated hemoglobin (HbA1c) level at month 12. Secondary endpoints were hypoglycemia for the overall study period as well as body weight and insulin dose at month 12. RESULTS: Similar glycemic control was achieved with mean (standard deviation) HbA1c level of 7.7 (1.1)% (61 [12] mmol/mol) at baseline and 7.7 (1.3)% (61 [14] mmol/mol) at month 12. Fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events were observed (0.52 vs. 0.85 events per patient-year; rate ratio 0.61; 95% confidence interval 0.38-0.97; p = 0.037), but the percent of patients experiencing ≥1 hypoglycemic event did not differ. There was no difference in confirmed (≤3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia and nocturnal hypoglycemia. CONCLUSIONS: In Japanese patients with T2DM who switched to Gla-300 from Gla-100, similar glycemic control was achieved with fewer confirmed (<3.0 mmol/L [< 54 mg/dL]) or severe hypoglycemic events over a 12-month period, although the absolute benefit was marginal.

Difference of seasonal variation between glycated albumin and glycated haemoglobin.

Background Glycated albumin reflects 2-3-week glycaemic controls, and in addition to glycated haemoglobin, it has been used as a glycaemic control indicator. We presumed that glycated albumin also has seasonal variations and is related to temperature, similar to glycated haemoglobin. Methods The subjects were diabetic outpatients from April 2007 to March 2013. This resulted in the enrolment of 2246 subjects and the collection of a total of 53,968 measurements. Mean glycated haemoglobin, glycated albumin, and plasma glucose were calculated for each month over six years. The associations of the measures with each other and the average temperature for each month in Tokyo were assessed using Spearman rank correlation coefficients. Results Plasma glucose was highest in January and lowest in May. Glycated haemoglobin was highest in March and lowest in September. Glycated albumin was highest in May and lowest in December. Glycated albumin tended to have a disjunction with plasma glucose in winter. Glycated haemoglobin had seasonal variation, but glycated albumin did not. Plasma glucose and glycated haemoglobin showed significant negative correlations with temperature (rs = -0.359, P < 0.001, rs = -0.449, P < 0.001, respectively), but glycated albumin did not. However, glycated albumin was inter-correlated with plasma glucose (rs = 0.396, P < 0.001) and glycated haemoglobin (rs = 0.685, P < 0.001), and glycated haemoglobin was inter-correlated with plasma glucose (rs = 0.465, P < 0.001). Conclusion Glycated albumin and glycated haemoglobin showed different seasonal variations from each other over the six-year study period. Thus, further studies to identify factors that contribute to glycated albumin are needed.

Association of Maternal Factors with Perinatal Complications in Pregnancies Complicated with Diabetes: A Single-Center Retrospective Analysis.

OBJECTIVE: The aim of this study was to clarify the association of maternal factors with perinatal complications in pregnancies complicated with type 1 (T1D) or type 2 diabetes (T2D). METHODS: We conducted a retrospective chart review and enrolled 26 Japanese pregnant women with diabetes who received perinatal care at our hospital between 2008 and 2015. Perinatal complications were defined as one or more of the following: miscarriage, fetal death, fetal dysfunction, fetal structural anomaly, small-for-gestational age, large-for-gestational age (LGA), premature birth, neonatal hypoglycemia, pregnancy-induced hypertension (PIH), deterioration of maternal kidney function, and urgent Caesarean section (CS). The associations between perinatal complications and maternal factors were examined. RESULTS: Approximately 70% and 50% of women with T1D and T2D experienced perinatal complications, respectively. LGA, neonatal hypoglycemia, and urgent CS were major perinatal complications in women with T1D, while PIH and urgent CS were major complications in those with T2D. In women with T1D, pre-gestational HbA1c was significantly higher in women with perinatal complications than in those without. In women with T2D, pre-gestational body mass index was significantly higher in women with perinatal complications than in those without. CONCLUSIONS: These findings suggest that while pre-gestational glycemic control remains the most important issue in women with T1D, pre-gestational weight control in addition to glycemic control should be greater emphasized in women with T2D to reduce the risk of perinatal complications.

One-year eGFR decline rate is a good predictor of prognosis of renal failure in patients with type 2 diabetes.

It is difficult to distinguish the onset of renal function decline from the typical variation in estimated glomerular filtration rate (eGFR) measurements in clinical practice. In this study, we used data analysis incorporating smoothing techniques to identify significant trends despite large amounts of noise. We identified the starting points of meaningful eGFR decline based on eGFR trajectories. This was a retrospective observational study of 2533 type 2 diabetes patients. We calculated 1-year eGFR decline rates from the difference between each eGFR value and that of the previous year. We examined the prediction capacity of 1-year eGFR decline rate for renal prognosis. When we performed receiver operating characteristic analysis, the area under the curve of 1-year eGFR decline rate was 0.963 (95% confidence interval: 0.953-0.973). With a cut-off value of more than 7.5% eGFR decline during a 1-year period, the sensitivity was 98.8% and specificity was 82.3%. The predictive accuracy of 1-year eGFR decline rate for renal prognosis was high.

Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese.

Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese. Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally. Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r = -0.411, p < 0.0001), fasting glucose (r = -0.330, p < 0.0001), HbA1c (r = -0.231, p = 0.0146), and systolic blood pressure (r = -0.224, p = 0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r = -0.416, p < 0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects. Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.

A case of autoimmune polyendocrine syndrome type I with strong positive GAD antibody titer, followed up with glucose tolerance measured by oral glucose tolerance test.

A 26-year-old Japanese woman presented with adrenal insufficiency, and treatment was started with cortisone and fludrocortisone in 1975. A few years later, she presented with hypoparathyroidism and was diagnosed with autoimmune polyendocrine syndrome type I (APS I), and treatment with calcium and alfacalcidol was started. She was found to have subacute thyroiditis and relative adrenal failure in 2006. Her condition remained stable under treatment with cortisone, fludrocortisone, levothyroxine, calcium lactate, precipitated calcium carbonate and alfacalcidol. While antibodies against pancreatic glutamic acid decarboxylase (GAD) were strongly positive (7,690 U/ml), fasting glucose level was 4.9 mmol/L and HbA1c was 6.3% on admission. As GAD antibody showed a high-titer of >10,000 U/ml and fasting plasma glucose level showed a rising trend, we performed 75-g oral glucose tolerance test (OGTT) 6 years after discharge. Whereas OGTT in 2012 showed impaired glucose tolerance, glucose tolerance had reverted to normal in 2014. A patient with a high-titer GAD antibody does not always have progressive glucose intolerance. GAD antibody positivity is common in not only type 1 diabetes, but also APS I and stiff-person syndrome (SPS). There are differences in recognized epitopes among the three disorders. Epitopes for GAD65 antibody associated with type 1 diabetes are located in the middle region and the COOH-terminal of the GAD65 protein, whereas epitopes associated with SPS reside in the NH2-terminal in addition to the middle region and COOH-terminal. The present case suggests that these differences in epitopes may be related to various pathogenic mechanisms including glucose intolerance.

A Reduction of HbA1c after 3 Months Predicts 2-year Responsiveness to Sitagliptin Treatment.

OBJECTIVE: This retrospective study evaluated the long-term efficacy of sitagliptin and the factors contributing to its glucose-lowering effect. METHODS: Six hundred and sixteen dipeptidyl peptidase-4 inhibitor-naïve outpatients with type 2 diabetes who began sitagliptin treatment between December 1, 2009 and December 31, 2011 were included in this study. The inclusion criteria were that the patient had regularly visited our hospital for a period of ≥700 days from the initiation of sitagliptin treatment and the measurement of hemoglobin A1c (HbA1c) had been performed at 0, 3, 6, 12, 18, and 24 months after the initiation of treatment. From the population of 616 patients, 447 and 169 had received sitagliptin for ≥700 and <700 days, respectively. The primary endpoint was ΔHbA1c at 24 months. The factors associated with the hypoglycemic effect of sitagliptin were also investigated. RESULTS: Sitagliptin treatment significantly decreased the level of HbA1c, and the hypoglycemic effect was sustained for at least 2 years. The baseline HbA1c level, duration of diabetes, Δbody weight value, and ΔHbA1c value at 3 months were independently associated with the hypoglycemic effect of sitagliptin. CONCLUSION: Sitagliptin has a long-term hypoglycemic effect in type 2 diabetes patients. A patient's ΔHbA1c at 3 months may be a predictor of their ΔHbA1c at 24 months.

Effects of Liraglutide Monotherapy on Beta Cell Function and Pancreatic Enzymes Compared with Metformin in Japanese Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of the KIND-LM Randomized Trial.

BACKGROUND AND OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming one of the major therapeutic options for the treatment of type 2 diabetes mellitus (T2DM). This study was conducted as an exploratory analysis to clarify the effects of liraglutide, a GLP-1RA, on beta cell function, fat distribution and pancreas volume compared with metformin in Japanese overweight/obese patients with T2DM. METHODS: A subpopulation of the Keio study for Initial treatment of type 2 Diabetes with Liraglutide versus Metformin (KIND-LM) study participants (n = 20, 10 in oral metformin group and 10 in subcutaneous liraglutide group) who were enrolled at Keio University Hospital and underwent frequently sampled mixed meal tolerance test (MTT) and abdominal computed tomography (CT) at weeks 0 and 24 were included in this analysis. The patients were treated with either metformin or liraglutide throughout the 24-week study period. RESULTS: Changes in glycemic parameters such as glycated hemoglobulin (HbA1c), glycated albumin and 1,5-anhydroglucitol at week 24 were comparable between the groups. An oral minimal model based on MTT revealed that static-phase beta cell responsiveness (Φ s) and static-phase disposition index were significantly increased at week 24 in the liraglutide group but not in the metformin group. There was no significant change in fat distribution as well as body weight at week 24 in either group. Serum amylase and lipase levels modestly but significantly increased in the liraglutide group during the study; however, there was no incidence of pancreatitis and pancreas volume was not changed in the liraglutide group. CONCLUSION: Liraglutide monotherapy for 24 weeks improved beta cell responsiveness with no change in either body weight or fat distribution. Further investigation is needed to clarify the mechanism by which liraglutide increases serum pancreatic enzymes. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ); UMIN000004243.

Efficacy and safety of liraglutide monotherapy compared with metformin in Japanese overweight/obese patients with type 2 diabetes.

There is little information on direct comparison between metformin and glucagon-like peptide-1 (GLP-1) receptor agonists in the Asian population. This study examined the efficacy and safety of liraglutide monotherapy compared with metformin monotherapy in overweight/obese Japanese patients with type 2 diabetes (T2DM). The study was a 24-week, open-labeled, randomized controlled study. Overweight or obese patients with T2DM aged 20-75 years with suboptimal glycemic control were randomized to liraglutide or metformin monotherapy. The primary endpoint was change in HbA1c at week 24. Secondary endpoints included changes in daily glycemic profile, body weight, incidence of hypoglycemia and other adverse events. The study, which was originally planned to enroll 50 subjects in each group, was ended with insufficient recruitment. A total of 46 subjects completed the study, and analysis was conducted in this cohort. Reduction in HbA1c at week 24 was comparable between the metformin (n = 24) and liraglutide (n = 22) groups (-0.95 ± 0.80% vs. -0.80 ± 0.88%, p = 0.77), while the liraglutide group reached maximal reduction more rapidly than did the metformin group. There was no significant difference in weight gain or incidence of hypoglycemia between the groups. Diarrhea was more frequent in the metformin group, while constipation was more frequent in the liraglutide group. There was no significant difference in treatment satisfaction between the groups. In conclusion, liraglutide and metformin monotherapy showed similar reduction in HbA1c during 24 weeks, with no difference in weight gain or incidence of hypoglycemia in overweight or obese Japanese patients with T2DM.

C-peptide immunoreactivity index is associated with improvement of HbA1c: 2-Year follow-up of sitagliptin use in patients with type 2 diabetes.

AIMS: This retrospective study aimed to determine the hypoglycaemic effect of 2 years of sitagliptin administration in terms of changes in HbA1c and C-peptide immunoreactivity (CPR) index (plasma CPR [ng/mL]/glucose [mg/dL]×100). METHODS: The inclusion criteria for DPP-4 inhibitor-naive outpatients with type 2 diabetes (n=285) were: continuation of sitagliptin for ≥700 days from initial administration and measurement of HbA1c, serum CPR, and plasma glucose levels at 0, 3, 6, 12, 18, and 24 months after sitagliptin initiation. Logistic regression analyses determined the factors contributing to the response to sitagliptin, based on responder (ΔHbA1c ≤-0.4% [≤-4 mmol/mol]) and non-responder (ΔHbA1c >-0.4% [>-4 mmol/mol]) groups. RESULTS: The HbA1c level decreased and CPR index increased from baseline to 3, 6, 12, 18, and 24 months after the start of sitagliptin administration (HbA1c: 7.4 ± 0.8% [57 ± 9 mmol/mol], 7.3 ± 0.9% [57 ± 9 mmol/mol], 7.4 ± 0.9% [58 ± 10 mmol/mol], 7.1 ± 0.8% [55 ± 9 mmol/mol], and 7.3 ± 0.9% [57 ± 10 mmol/mol], respectively, all P<0.001 vs. baseline [8.0 ± 1.0%, 64 ± 11 mmol/mol] and CPR index: 1.69 ± 0.96, 1.71 ± 1.10, 1.62 ± 0.96, 1.64 ± 0.92, and 1.66 ± 0.96, respectively, all P<0.05 vs. baseline [1.47 ± 0.81]). Higher baseline HbA1c level, shorter diabetes duration, and greater CPR index increase after sitagliptin administration were associated with the response to sitagliptin. CONCLUSIONS: Our results suggest that sitagliptin improves glycaemic control via an improved intrinsic insulin response.