Clinical background of Japanese patients with type 1 diabetes mellitus who have received insulin therapy for 50 years or longer.

AIMS: We clarified the clinical background of Japanese patients with type 1 diabetes mellitus (T1DM) who have received insulin therapy for 50 years or longer. METHODS: Of 1,412 patients diagnosed with T1DM at an age younger than 30 years old between 1962 and 2000, 29 had a 50-year or longer history of diabetes. We investigated the mean values of HbA1c and systolic blood pressure (SBP) during follow-up, as well as diabetic retinopathy, diabetic nephropathy, and macroangiopathy. RESULTS: The mean age of the subjects at the time of diagnosis was 10 years and that at the completion of this survey was 66 years. The mean follow-up period was 43 years. The mean HbA1c value and SBP during the follow-up period were 8.2% and 130 mmHg, respectively. Seventeen percent of patients did not have diabetic retinopathy, 59% had proliferative retinopathy, and 66% had undergone photocoagulation. Fifty-four percent of patients did not have microalbuminuria and 11% had end-stage renal disease. Macroangiopathy was observed in 46%, cardiovascular disease (CVD) in 25%, and ischemic stroke in 18%. CONCLUSIONS: It became possible for patients with T1DM to live more than 50 years in Japan.

Body Weight Reduction of 5% Improved Blood Pressure and Lipid Profiles in Obese Men and Blood Glucose in Obese Women: A Four-Year Follow-up Observational Study.

Background: Body weight reduction (BWR) of at least 3% in obese Japanese individuals through lifestyle interventions has improved the risk factors for cardiovascular disease (CVD). We aimed to assess the relation between body weight change (BWC) and CVD risk change and to identify lifestyle improvement related to BWR in obese Japanese individuals. Methods: Subjects were 2579 health checkup examinees without medicated diabetes, hypertension or dyslipidemia, and a body mass index ≥25 kg/m2 who completed lifestyle questionnaires in 2008 and 2012. The 4-year changes in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipids, and blood pressure (BP) levels were compared across the five groups based on the 4-year BWC, and presented as <-5%, -5% to -3%, -3% to -1%, -1% to 1%, and ≥1%. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for lifestyle improvement related to BWR. Results: Comparing the groups to the reference group (BWC ranging from -1% to +1%), we observed that FPG and HbA1c levels were lower in women in the <-5% group; BP levels were also lower in the <-5% group; triglyceride levels had improved in the <-3% group, and low-density lipoprotein cholesterol levels in the <-5% group; high-density lipoprotein cholesterol levels had improved in men in the <-5% group. In men, the adjusted OR (95% CI) for BWR related to lifestyle improvement pertaining to "over 30 min exercise" was 2.6 (2.0-3.6). In women, the adjusted ORs for BWR related to "walking or physical activity," "drinking alcohol," and "drinking more than a glass of sake" were 1.7 (1.1-2.7), 1.9 (1.1-3.5), and 1.8 (1.1-3.0), respectively. Conclusions: A 5% BWR improved FPG and HbA1c levels in obese women, and BP and lipid levels in obese men. Improvements in exercise and alcohol consumption habits were associated with BWR in this population.

Analysis of the effect of seasonal administration on the efficacy of sitagliptin: Subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study.

AIMS/INTRODUCTION: Hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus fluctuate throughout the year. However, there are few studies that have evaluated the therapeutic effect of hypoglycemic agents while considering such fluctuations. In a multicenter study (Januvia Multicenter Prospective Trial in Type 2 Diabetes Study), pretreatment patients with type 2 diabetes mellitus were divided into seven groups and given sitagliptin for 1 year. The aim of the present study was to evaluate the differences in the therapeutic effect, and the efficacy of sitagliptin in patients with type 2 diabetes mellitus based on the month the administration of the drug began as a subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes Study. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus were divided into four groups according to the month of initiation of sitagliptin. Changes in HbA1c in each group were compared at 3 and 12 months after administration of sitagliptin. As a negative correlation has been reported between baseline HbA1c and the degree of change after administration of sitagliptin, an analysis using the residual error from the approximate line was carried out. RESULTS: In the analysis of the degree of change in HbA1c, patients in the group in which administration of sitagliptin was started between August and October had the lowest degree of improvement at 3 months after starting sitagliptin. However, there was no significant intergroup difference in improvement at 12 months after the start of sitagliptin. The same result was also obtained in residual analysis. CONCLUSIONS: The present study suggested that the season of administration of sitagliptin influenced the subsequent hypoglycemic effect even after analysis excluding the influence of HbA1c value at the start of treatment. This study provides possibility, showing that seasonal fluctuations have an effect on the efficacy of antidiabetic drugs.

Erratum to: Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus and comparison of hypoglycemic action of concomitant medications: a subanalysis of the JAMP study.

[This corrects the article DOI: 10.1007/s13340-017-0330-2.].

Renal Function During an Open-Label Prospective Observational Trial of Sitagliptin in Patients With Diabetes: A Sub-Analysis of the JAMP Study.

BACKGROUND: The aim of the study was to determine the effects of sitagliptin on renal function in a diabetic population including patients with normal renal function. METHODS: We analyzed the association between 12-month, 50 mg/day sitagliptin and renal function in outpatients with type 2 diabetes mellitus and poor blood glucose control in a subset of patients in the larger Januvia Multicenter Prospective Trial in Type 2 Diabetes observational study. Stratified analyses of changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were performed. Factors associated with changes in eGFR at 3 months were examined by multivariate regression analysis. RESULTS: Of the 779 patients enrolled, 585 were followed up for 12 months. eGFR decreased significantly from baseline at 3 and 12 months in patients with a baseline eGFR of ≥ 90 mL/min/1.73 m2 and in those with a baseline eGFR of ≥ 60 to < 90 mL/min/1.73 m2. Conversely, eGFR tended to increase at 3 and 12 months in patients with a baseline eGFR of ≥ 45 to < 60 mL/min/1.73 m2 and in those with a baseline eGFR of ≥ 30 to < 45 mL/min/1.73 m2. UACR decreased significantly (-21.6 (-46.8, 7.8)) at 3 months in patients with a baseline UACR of ≥ 30 mg/g Cre. Multivariate regression analysis of factors associated with changes in eGFR at 3 months revealed that higher baseline eGFR and greater decline in UACR were associated with more conspicuous decreases in eGFR. CONCLUSIONS: In this group of diabetic patients receiving sitagliptin, eGFR declined in patients with high baseline eGFR, but not in those with a low baseline eGFR.

Efficacy and safety of sitagliptin in elderly patients with type 2 diabetes mellitus and comparison of hypoglycemic action of concomitant medications: a subanalysis of the JAMP study.

PURPOSE: To determine the efficacy and safety of sitagliptin when used with some therapeutic drugs to treat elderly patients. METHODS: Sitagliptin (50 mg/day) was added to the pre-existing therapy for type 2 diabetes. Changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline, and exploratory analysis was performed. These analyses were conducted as subanalyses of the JAMP study, which was an open-label observational study. RESULTS: For patients who were ≥65 years of age, the change in HbA1c level from baseline ranged from -0.50 to -0.87% at 3 months after starting treatment. There was no significant difference in the change in HbA1c level between the patients treated with different concomitant drugs. No significant difference in HbA1c variations at 3 and 12 months from baseline was noted among the three age groups (≥75, 65-74, and <65 years). Multiple regression analysis was performed, and it revealed that patients with higher HbA1c levels at baseline were likely to show decreased HbA1c levels, while those with higher triglyceride (TG) levels were unlikely to show decreased HbA1c levels. CONCLUSION: Sitagliptin has the potential to both improve glycemic control and prevent hypoglycemia, and can be considered a potent alternative drug.

Factors involved in decreasing the therapeutic effect of sitagliptin: a subanalysis of the JAMP study.

OBJECTIVE: As a subanalysis of the Januvia Multicenter Prospective Trial in Type 2 Diabetes (JAMP study), we examined factors that decreased blood glucose control effect of sitagliptin after 3 months and patients requiring an addition or increase of diabetes treatment. METHODS: We selected patients in whom glycated hemoglobin (HbA1c) levels decreased by month 3 after initiation of sitagliptin treatment and conducted two analyses: (1) in patients who did not change drugs until month 12, we compared changes in HbA1c levels between concomitant drugs and examined factors that decreased blood glucose control effect of sitagliptin; (2) compared changes in HbA1c levels and backgrounds between patients who did and did not require an addition to or increased dose of the antidiabetic agent. RESULTS: Four hundred and ninety-eight patients were chosen. In 369 patients without drug change until month 12, changes in HbA1c levels during months 3-12 were not significantly different among concomitant drugs; factors causing rebound HbA1c were smoking and weight gain. Patient characteristics were compared between those who did and did not require an additional drug or a dose increase (n = 114) (n = 384). Drug changes were associated with longer disease duration, younger age, higher rate of smoking, and higher degree of insulin resistance but not with concomitantly administered drugs. CONCLUSION: Smoking and weight gain were factors that decreased the effect of sitagliptin on reducing blood glucose levels. Differences in concomitant drugs did not affect sitagliptin's effects on glycemic control. A dose increase or the addition of the antidiabetic drug was not associated with concomitant drugs.

Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study.

BACKGROUND: To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs. METHODS: Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis. RESULTS: HbA1c levels were significantly decreased after 1 month of treatment compared to baseline, with a mean change in HbA1c level from baseline of -0.73% (range, -0.80 to -0.67) in the entire study population at 3 months. Patients who received a medium dose of glimepiride showed the least improvement in HbA1c levels. The percentage of patients who achieved an HbA1c level of <7.0% significantly increased after 1 month of treatment, reaching 53.1% at 3 months. The percentage of patients who achieved a fasting blood glucose level of <130 mg/dL significantly increased after 1 month of treatment, reaching 50.9% at 3 months. CONCLUSIONS: Sitagliptin improved the HbA1c level and rate of achieving the target control levels in patients with type 2 diabetes mellitus who were previously untreated with, or poorly responsive to, existing antidiabetic drugs. Thus, sitagliptin is expected to be useful in this patient group. However, the additional administration of sitagliptin in patients treated with medium-dose glimepiride only slightly improved blood glucose control when corrected for baseline HbA1c level.

Follow-up survey of all participants at the first and second juvenile diabetes summer camp in Japan in 1963 and 1964.

This report documents the status of all 10 participants in the first (1963) and second (1964) summer camp in Japan as of 31 December 2008. The eight living participants continue to function as adults in society without hemodialysis.

Time-course changes in clinical features of early-onset Japanese type 1 and type 2 diabetes: TWMU hospital-based study.

Using a database of patients with type 1 (n=1675) and type 2 (n=2259) diabetes diagnosed before the age of 30 years at the Diabetes Center, Tokyo Women's Medical University (TWMU), in which such Japanese patients have been registered at the time of first visit since the 1960s, we performed a hospital-based study over the last 40 years to clarify time-course changes in clinical features of type 1 and type 2 diabetes diagnosed before the age of 30 years. Type 2 diabetes had a male dominancy, while there has been a female dominancy in patients with type 1 diabetes as in previous reports of Japanese childhood-onset type 1 diabetes. Such dominances had been continued over the last 40 years. The number of patients with type 2 diabetes and with a past history of obesity increased with time. The age at which type 2 diabetes was diagnosed was suggested to have been getting lower with time, whereas that of type 1 diabetes has been higher with time. There was no marked difference in family history of diabetes in the first-degree relatives of patients with type 2 diabetes, regardless of the presence or absence of a past history of obesity. More female patients with type 2 diabetes diagnosed before the age of 15 years had mothers with type 2 diabetes compared to corresponding male patients.

Impact on mortality and incidence of end-stage renal disease of education and treatment at a diabetes center among patients with type 1 diabetes: comparison of two subgroups in the Japanese DERI cohort.

The aim of this study was to compare mortality and incidence of end-stage renal disease (ESRD) in patients with type 1 (insulin-dependent) diabetes who had attended a diabetes center with those who had not. The cohort consisted of a total of 1430 patients diagnosed with Type 1 diabetes at 18 years or younger, and between 1965 and 1979. This population-based cohort in Japan was subdivided into two groups: patients who had visited a large diabetes center in Tokyo (n=162) and those who had not (n=1212). Mortality and incidence of ESRD were compared between the two subgroups as of January 1, 1990. Crude mortality was 1.95 per 1000 person-years (95% CI: 0.49-5.06) for those who had visited the center and 6.05 (4.86-7.41) for those who had not. A multivariate Cox proportional hazard model showed that the patients who had visited the center were three times less likely to die (hazard ratio: 0.31, 95% CI: 0.10-0.98) than those who had not. Crude incidence of ESRD was 1.32 (0.22-4.09) and 5.86 (4.65-7.26) for those who had visited the center and for those who had not, respectively. After adjusting for covariates, the patients who had visited the center were five times less likely to develop ESRD (hazard ratio: 0.19, 0.05-0.78) than those who had not. Education and treatment of type 1 diabetes with an integrated management system under specialists and a multidisciplinary team appears to be associated with a better prognosis.