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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.

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

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. 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. 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. 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.

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 m 2 and in those with a baseline eGFR of ≥ 60 to < 90 mL/min/1.73 m 2 . Conversely, eGFR tended to increase at 3 and 12 months in patients with a baseline eGFR of ≥ 45 to < 60 mL/min/1.73 m 2 and in those with a baseline eGFR of ≥ 30 to < 45 mL/min/1.73 m 2 . 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. J Clin Med Res. 2018;10(1):32-40 doi: https://doi.org/10.14740/jocmr3225w

To determine the efficacy and safety of sitagliptin when used with some therapeutic drugs to treat elderly patients. 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. 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

To compare the efficacy of spironolactone and trichlormethiazide, as add‐on therapy to renin–angiotensin system (RAS) blockade, for reduction of albuminuria in diabetic patients with chronic kidney disease (CKD), we conducted this randomized, open‐labeled, parallel‐group, active‐controlled, per‐protocol‐design study. Type 2 diabetic patients receiving an angiotensin‐converting enzyme inhibitor or angiotensin II receptor blocker, with persistent albuminuria (≥100 mg/g creatinine) were randomly assigned to either spironolactone (25 mg/day) or trichlormethiazide (2 mg/day). The primary outcome was the change in albuminuria at 24 weeks of treatment. In patients who completed 24 weeks of treatment with spironolactone (n = 18) and trichlormethiazide (n = 15), albuminuria decreased significantly by −57.6 ± 21.3% (SD) (P

The A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene (mt.3243A>G) is associated with both diabetes mellitus and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Recently, this mutation was found in three diabetic subjects with progressive kidney disease, suggesting that it may be a contributing factor in the development of kidney disease in patients with diabetes. The aim of this study was to evaluate the contribution of this mutation to the development of end stage renal disease (ESRD) in patients with diabetes. The study group consisted of 135 patients with diabetes and ESRD. The control group consisted of 92 non-diabetic subjects with ESRD who were receiving hemodialysis. The mt.3243A>G mutation was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found the mt.3243A>G mutation in eight patients (8/135; 5.9%), all of whom were initially diagnosed with type II diabetes. Five of the eight patients were subsequently also diagnosed with MELAS. We did not find the mutation in any of the 92 nondiabetic subjects with ESRD. The prevalence of this mutation was 6.5-fold higher in patients with diabetes and ESRD than in those with diabetes alone (8/135 vs 5/550, respectively; chi2 = 13.704; P = 0.0002). The mt.3243A>G mutation may be a contributing genetic factor in the development of ESRD in Japanese patients with diabetes.

Glutamic acid decarboxylase (GAD) is an autoantigen of the islet cell antibodies (ICAs) present in type I diabetes. GAD autoantibodies are also found in patients with stiffman syndrome and in certain ICA-positive individuals who rarely develop diabetes on long-term follow-up. This latter subset of ICA has been termed restricted or beta-cell-specific ICA because the antibodies react with only the beta-cells of the islet. By immunoprecipitation of recombinant GAD65 and GAD67 protein and protein fragments, 83% of sera from individuals with new-onset diabetes or prediabetes (n = 30) had GAD65 autoantibodies, but only 26% had GAD67 autoantibodies. In contrast, all restricted ICA sera (n = 6) had both GAD65 and GAD67 autoantibodies. In both types of sera, the binding of GAD67 autoantibodies could be blocked by preincubation of the serum with GAD65 and GAD67, but the binding of GAD65 autoantibodies could not be blocked by preincubation with GAD67. The titer of GAD65 autoantibodies was much higher in the restricted ICA sera (titer > 1:1,000) than in the sera from individuals with new-onset diabetes or prediabetes (titer < 1:100) and was reflected by the greater amount of GAD65 protein immunoprecipitated by restricted ICA sera (2.61 ± 1.39 U) compared with sera from individuals with new-onset diabetes (0.51 ± 0.34 U). The restricted ICA sera immunoprecipitated equimolar amounts of GAD65 protein fragments, suggesting a non-conformational or linear epitope; epitope mapping localized the major epitope region to amino acids 361–442 and a second minor epitope region to amino acids 1–195. For the monoclonal antibody GAD6, the GAD65 epitope region localized to amino acids 529–585. In contrast, the sera from individuals with new-onset diabetes or prediabetes immunoprecipitated equal amounts of full-length GAD65 protein and a GAD65 fragment containing amino acids 188–585, but did not immunoprecipitate smaller GAD65 protein fragments, which suggests an epitope(s) dependent on protein conformation. These results suggest that subsets of GAD autoantibodies exist and indicate a heterogeneity in the immune response to GAD.

The objectives of this study were to determine the association between angiotensin converting enzyme (ACE) gene polymorphism and left ventricular (LV) geometry, and to clarify independent effects of ACE genotype on mortality after commencing dialysis in diabetic patients with end-stage renal disease (ESRD). A total of 106 diabetic patients, 71 men and 35 women, 11 type 1 and 95 type 2 diabetic, 57±12 ( mean ± standard deviation ( S.D. ) ) years of age, who started dialysis were studied. Patients with cardiac diseases and those treated with ACE inhibitors were excluded because of potential effects on LV performance. Echocardiographic examination was performed within ±2 months of the start of dialysis. Relation between ACE genotype and LV mass index (LVMI) or relative wall thickness (RWT) at onset of dialysis, and impact of ACE genotype on survival after commencing dialysis were evaluated. There were no significant differences in LVMI or RWT in the three ACE genotype groups at onset of dialysis. However, mortality of patients with the ACE–DD genotype was significantly higher than patients with the DI and II genotypes (hazard ratio, 2.318; P=0.043), based on a survival analysis with a mean follow-up duration of 60 months. The higher mortality in patients with the DD genotype was confirmed to be independent of LV hypertrophy and increases in RWT. In diabetic patients with ESRD, ACE genotype has no association with LV mass or RWT at the start of dialysis, but does have an independent impact on patient survival thereafter.