OBJECTIVEUrinary liver-type fatty acid–binding protein (L-FABP) is a promising indicator of tubular but not glomerular damage. The aim of this study was to evaluate the clinical usefulness of urinary L-FABP as a prognostic biomarker in impaired diabetic nephropathy in type 2 diabetes.RESEARCH DESIGN AND METHODSThis investigation involved a cross-sectional and longitudinal analysis of the relationship between urinary L-FABP levels and progressive nephropathy. Urinary L-FABP was measured with enzyme-linked immunosorbent assay. In the cross-sectional analysis, the association of urinary L-FABP, with the severity of diabetic nephropathy, was investigated in 140 patients with type 2 diabetes and in 412 healthy control subjects. Of the patients in the former study, 104 have been followed for 4 years. The progression of diabetic nephropathy was defined as progressive albuminuria, end-stage renal disease, or induction of hemodialysis.RESULTSUrinary L-FABP levels were progressively increased in subjects with normo-, micro-, or macroalbuminuria and further increased in patients with end-stage renal disease. In the longitudinal analysis, high urinary L-FABP levels were associated with the increase in albuminuria, progression to end-stage renal disease, or induction of hemodialysis. This was particularly demonstrated in the subgroup of patients without renal dysfunction (n = 59), where high urinary L-FABP levels were associated with the progression of diabetic nephropathy.CONCLUSIONSUrinary L-FABP accurately reflected the severity of diabetic nephropathy in type 2 diabetes, and its level was high in the patients with normoalbuminuria. Moreover, higher urinary L-FABP was a risk factor for progression of diabetic nephropathy.

Abstract. in order to evaluate the relationship between clinical markers of glycemia and glucose excursion, we performed 48-hour continuous glucose monitoring (Cgm) in 43 diabetic patients. For the clinical markers, hba1c, glycoalbumin (ga), and 1,5-anhydroglucitol (1,5-ag) were measured, and for the parameters of glucose excursion from Cgm, average glucose (ag), standard deviation of glucose (SD), the area under the curve for glucose levels >180 mg/dL (auC>180), and the difference between the maximum and minimum glucose levels during 48 hours (ΔG48hr) were analyzed. all patients were treated without any changes of the dosages of oral anti-diabetic agents or insulin for at least the previous 6 months with coefficient of variation (CV) of HbA1c less than 4 %. in results, while hba1c did not show any single correlation with ag, SD, auC>180, or ΔG48hr, both GA and 1,5-AG were significantly related to all these parameters. Furthermore, GA significantly correlated to all CGM parameters, and SD significantly correlated to GA in multiple regression analyses. These results suggest that ga may be a different marker from hba1c for diabetic complications, because ga, but not hba1c, may reflect not only short-term average glucose but also fluctuation of glucose.Key words: glycoalbumin, glycated hemoglobin, 1,5-anhydroglucitol, Continuous glucose monitoringThe sTAble frAcTion of glycated hemoglobin (hba 1c ) is routinely measured in the majority of patients with diabetes around the world, since hba 1c reflects the mean glucose level over the preceding 3 months [1]. hba 1c is not only used to determine whether a patient's metabolic control has been maintained within the target range, but also to estimate the risk of chronic diabetic complications in each patient. Previous the large-scale prospective studies of diabetic patients have used hba 1c as a marker of glycemic control to evaluate the association of consistent hyperglycemia with the development or progression of chronic diabetic complications [2,3]. however, recent studies have indicated that postprandial hyperglycemia or fluctuations of the glucose level may be an independent risk factor for macrovascular complications in diabetic patients, which cannot be evaluated by measuring hba 1c alone [4]. Since hba 1c is a marker of the average level of glycemia, it does not reflect acute glucose fluctuations and is poorly correlated with glucose excursions [5]. Therefore, in order to assess the risk of diabetic complications, especially macrovascular complications, it may be necessary to evaluate not only the mean level of glycemic control, but also the extent of glucose excursions such as glucose fluctuations or postprandial elevation of glucose.To assess daily blood glucose excursions, portable devices for self-monitoring of blood glucose (Smbg) are now widely used by insulin-treated diabetic patients. although such devices are helpful, the number of measuring times is limited. Recently, a continuous subcutaneous glucose monitoring (Cgm) device was developed to evaluate the...

BackgroundIpragliflozin is a sodium-glucose co-transporter 2 inhibitor that can improve glycemic control and reduce body weight and blood pressure in patients with type 2 diabetes mellitus (T2DM). We evaluated the efficacy and safety of ipragliflozin in the real-world clinical setting, with a focus on the changes of body composition up to 3 months of treatment.MethodsThis was a prospective multicenter interventional trial. We investigated changes of the blood pressure, body composition, blood glucose, hemoglobin A1c (HbA1c), ketone bodies, lipids, and insulin after treatment with ipragliflozin (50 - 100 mg/day) for 12 weeks in Japanese patients with T2DM who showed poor glycemic control despite receiving diet and exercise therapy with or without oral antidiabetic drugs for more than 12 weeks.ResultsTwo hundred and fifty-seven subjects were included in the efficacy analysis up to 12 weeks of treatment and 301 subjects were included in the safety analysis. From baseline to 12 weeks, HbA1c showed a change of -0.68% (95% confidence interval (CI): -0.83, -0.53) and fasting blood glucose showed a change of -23.9 mg/dL (95% CI: -30.5, -17.2), with both parameters displaying a significant reduction (P < 0.001). The difference of body weight from baseline was -1.82 kg (95% CI: -2.14, -1.50), and it also showed significant reduction (P < 0.001). Analysis of body composition revealed that body fat changed by -1.46 kg (95% CI: -1.79, -1.14, P < 0.001) and body water changed by -0.37 kg (95% CI: -0.60, -0.14, P < 0.01). Laboratory tests demonstrated improvement of liver function and the lipid profile. Adverse events (AEs) occurred in 22.6% of the subjects, with frequent events being vulvovaginal candidiasis in 2.7% and cystitis in 2.0%. Serious AEs occurred in three subjects.ConclusionsIn patients with T2DM, ipragliflozin improved glycemic control after 1 month of treatment and caused weight loss by reducing body fat more than body water.

BackgroundSitagliptin is a DPP-4 inhibitor that became available for use in Japan three years ago. This study was conducted to identify the pleiotropic effects of sitagliptin other than blood glucose lowering in Japanese type 2 diabetes mellitus patients.MethodsA retrospective, observational study of 940 type 2 diabetes mellitus patients was conducted. The primary outcome measures were HbA1c, blood pressure, and lipid profiles measured at 0, 4, and 12 weeks of sitagliptin therapy.ResultsAfter 12 weeks of sitagliptin treatment, compared with baseline, HbA1c decreased 0.64% ± 0.86%; systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly; and serum creatinine (Cr) and uric acid (UA) levels were mildly but significantly elevated. A correlation analysis of the changes in systolic blood pressure, diastolic blood pressure, creatinine, and uric acid (ΔSBP, ΔDBP, ΔCr, ΔUA) from baseline to 12 weeks showed significant negative correlations between ΔSBP and ΔCr, ΔSBP and ΔUA, and ΔDBP and ΔCr. Total cholesterol and postprandial triglycerides were significantly decreased at both 4 and 12 weeks. Alkaline phosphatase (ALP) decreased significantly, and there was a significant positive correlation between changes in ALP and HbA1c.ConclusionsSitagliptin seems to be effective not only in lowering blood glucose but also in lowering blood pressure, lipid, and ALP levels. Sitagliptin appears to contribute to a Na-diuretic action due to GLP-1.

BackgroundThere have only been a few reports about use of dipeptidyl peptidase 4 (DPP-4) inhibitors in elderly patients with type 2 diabetes mellitus (T2DM), suggesting that the safety of these agents has not been sufficiently demonstrated. We performed a comparative review of the efficacy and safety of sitagliptin for Japanese patients with T2DM managed in the real-world clinical setting.MethodsAn age-stratified analysis was performed of 831 patients who were treated with sitagliptin for 2 years. Parameters assessed included the hemoglobin A1c (HbA1c), body weight, serum creatinine, and adverse events. HbA1c and the incidence of hypoglycemia were also evaluated in patients treated with sitagliptin and a sulfonylurea (SU), who were divided into three age groups (<65 years, 65–74 years, and ≥75 years).ResultsComparison of glycemic control parameters, laboratory values, and adverse events revealed significant improvement of HbA1c, casual postprandial plasma glucose, and fasting plasma glucose in each age group with no change in body weight. Serum creatinine increased significantly in all age groups. Hypoglycemia only occurred in patients who received combined treatment with an SU and sitagliptin, and there was no age-related difference in its incidence.ConclusionsHbA1c was improved by 2 years of sitagliptin therapy in all three age groups, and age did not seem to influence the incidence of hypoglycemic events. These results confirm the efficacy and safety of sitagliptin in patients ≥ 75 years old, suggesting that it is also useful for treating elderly patients with T2DM.