Search

We validated the effect of linagliptin, an oral dipeptidyl peptidase-4 inhibitor, on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). A total of 50 patients with NAFLD and T2DM treated with metformin were randomized (1:1) to metformin plus add-on linagliptin (linagliptin group) or to an increased dose of metformin (metformin group) for 52 weeks. The primary endpoint was change in hepatic steatosis from baseline to week 52 as quantified by unenhanced computed tomography imaging. Secondary endpoints included changes in the levels of anthropometric, biochemical and adipokinetic markers. The linagliptin group showed no statistically significant reduction in hepatic steatosis as compared to the metformin group (P = 0.97), although changes in hepatic steatosis were significantly correlated with decreased liver enzymes in both groups. Body weight was significantly reduced in the metformin group but not in the linagliptin group (P = 0.002). Serum leptin levels were significantly increased in the linagliptin group compared to the metformin group (P = 0.003), and were correlated with the changes body weight in whole samples. Adverse events were not different between the two groups (P = 0.78). Add-on linagliptin demonstrated a safe profile but was not superior to increased metformin in reducing hepatic steatosis.

Aim: Low-density lipoprotein cholesterol (LDL-C) is routinely estimated using the Friedewald equation [LDL-C(F)]. A novel method for LDL-C [LDL-C(M)] estimation recently proposed by Martin et al. was reported to be more accurate than the Friedewald formula in subjects in the United States. The validity of LDL-C(M) in different races and patients with diabetes mellitus (DM) has not been elucidated. The purpose of this study was to validate the LDL-C(M) estimates in Japanese population with type 2 DM by comparing with LDL-C(F) and directly measured LDL-C [LDL-C(D)]. Methods: Both LDL-C(M) and LDL-C(F) levels were compared against LDL-C(D) measured by selective solubilization method in 1,828 Japanese patients with type 2 DM. Results: On linear regression analysis, LDL-C(M) showed a stronger correlation than that shown by LDL-C(F) (R = 0.979 vs. R = 0.953, respectively) with LDL-C(D). We further analyzed the effect of serum triglyceride (TG) concentrations on the accuracy of LDL-C(F) and LDL-C(M). Although LDL-C levels showed a positive correlation with TG levels, the LDL-C(F) levels tended to show a greater divergence from LDL-C(D) levels than that shown by LDL-C(M) with changes in TG levels. Conclusion: We for the first time demonstrated a more useful measurement of LDL-C levels estimated by Martin's method than that estimated by the Friedewald equation in Japanese patients with DM.

Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors are reported to have BP-lowering effect in addition to blood glucose-lowering effect, however, its mechanism is still unknown. This study aimed to investigate the mechanism of blood pressure (BP) lowering effects of SGLT2 inhibitors using 24-h urinary collection in obese type 2 diabetes patients. Methods Twenty patients with type 2 diabetes (age 48.2 ± 10.7 years, BMI 33.0 ± 4.9 kg/m2) were enrolled. Urine volume, 24-h urinary glucose and sodium excretion, and BP at baseline and 2 weeks and 6 months after administration were measured. Body weight, glycosylated hemoglobin, and BP were evaluated before and 1, 3, and 6 months after SGLT2 inhibitor administration. We evaluated the changes in urine volume and urinary excretion of glucose and sodium as well as correlations among urine volume and urinary sodium glucose excretion at 2 weeks and 6 months after administration of the SGLT2 inhibitors. Furthermore, we investigated the correlations between changes in BP and urinary excretion of sodium and glucose at the same time. Results Two weeks after administration, systolic BP (SBP) significantly decreased (128.5 ± 11.0 to 123.2 ± 9.8 mmHg, P = 0.0314), but diastolic BP (DBP) did not (74.4 ± 10.4 to 73.4 ± 8.5 mmHg, P = 0.5821). The decreased SBP significantly correlated with increased urinary glucose excretion (R = −0.62, P = 0.0073), but not increased urinary sodium excretion. At 6 months, SBP (118.6 ± 11.0 mmHg, P = 0.0041) and DBP (68.4 mmHg, P = 0.0363) significantly decreased. The decreased SBP significantly correlated with increased urinary sodium excretion (R = −0.60, P = 0.0014), but not increased urinary glucose excretion. Conclusions SGLT2 inhibitors significantly decreased SBP after 1 month and DBP after 6 months in obese patients with type 2 diabetes. The main mechanism of the BP-lowering effect may be plasma volume reduction by osmotic diuresis at 2 weeks and by natriuresis at 6 months after SGLT2 inhibitor administration.

Background: The purpose of this study was to analyze the effect of valsartan on abnormal adipocyte metabolism and prothrombotic state in hypertensive patients with metabolic syndrome (MetS). Methods and Results: We conducted a multicenter, prospective, randomized, parallel-group controlled trial in 150 hypertensive patients with MetS. They were randomly assigned to receive either 80-160mg valsartan per day (valsartan group, n=79) or other conventional treatment without a renin-angiotensin system (RAS) inhibitor (non-RAS inhibitor group, n=71). After 1 year, there were no significant differences between the 2 groups in the changes in systolic and diastolic blood pressures (valsartan: 153±15/86±15 to 138±16/77±12mmHg; non-RAS inhibitor: 150±14/82±15 to 137±15/76±10mmHg). There was a significant difference in the change in the levels of plasminogen activator inhibitor-1 (PAI-1) between the 2 groups after 1 year (valsartan: 3.7±3.2ng/ml; non-RAS inhibitor: 5.8±3.3ng/ml, P=0.04). There was no significant difference between groups in the change in the concentration of adiponectin after 1 year (valsartan: 0.3±0.4μg/ml; non-RAS inhibitor: 0.9±0.4μg/ml, P=0.22). The animal study showed aortic PAI-1 protein expression was reduced in double knockout mice of angiotensin II type 1a receptor and apolipoprotein E (apoE) compared with the apoE knockout mice. Conclusions: Valsartan reduced plasma PAI-1 levels compared to non-RAS inhibitor in hypertensive patients with MetS, which suggests it may be useful for improving fibrinolytic function. (Circ J 2012; 76: 843-851)

Our objective was to test if tight glycemic control versus loose glycemic control in gestational diabetic patients and a gestational age of32 weeks influence fetal growth, fetal distress, and neonatal complication. We performed a retrospective study with 250 gestational diabetes mellitus in Japanese women. Two groups were categorized according to the timing at which good maternal glycemic control was attained at32 weeks and kept so until delivery (group 1) and32 weeks or never until delivery (group 2). In these two groups, neonatal growth (large-for-gestational age: LGA; appropriate- : AGA; and small- : SGA), neonatal complications (hypoglycemia, jaundice, polycythemia, and cumulative incidence), and incidence of fetal distress were compared. The chi2 test, unpaired t test, one-way analysis of variance (ANOVA) and multiple logistic regression analyses were used for statistical analyses. Maternal age, height, prepregnancy body mass index (BMI), gestational age at delivery were not different between the groups. In group 2 (32 weeks), LGA, macrosomia (4 kg), neonatal hypoglycemia was significantly increased compared with those in group 1. Incidence of SGA, fetal distress, and neonatal jaundice were not different between the groups. Multiple logistic regression analysis for LGA showed significant relation to timing of maternal glycemic control. We concluded that good glycemic control should be attained at32 weeks and maintained until delivery to reduce LGA infants and neonatal hypoglycemia in gestational diabetes mellitus. This management did not appear to decrease SGA infants or fetal distress.

Our purpose was to investigate the relationship between the birth weights and 24-h urinary C-peptide in infants of diabetic mothers.Sixty pregnancies with gestational diabetes mellitus (DM) were enrolled. Neonatal urine was collected for the first and second 24 h for measuring C-peptide. Birth weights were classified into 3 categories according to the Japanese standard curves; heavy-for-date (HFD), appropriate-for-date (AFD), and light-for-date (LFD). Unpaired t-test was used for comparison of 24-h urinary C-peptide in the 3 birth weight categories, with P-value0.05. There were 7 HFD, 47 AFD, and 6 LFD infants. Birth weight averaged 3.9+/-0.7, 3.0+/-0.4, and 2.3+/-0.3 kg, respectively.Insulin concentrations of the umbilical artery were significantly higher in HFD than in AFD, and significantly higher in AFD than in LFD (49.5+/-45.1, 16.8+/-15.2, and 6.3+/-6.1 microU/ml). During the first 24 h, urinary C-peptide was significantly higher in HFD than in AFD (2.73+/-1.52 vs. 0.76+/-0.81 microg/day), and significantly higher in AFD than in LFD (0.27+/-0.27). On the second day, there was no longer statistical significance.Measurement of 24-h urinary C-peptide revealed that, among infants of diabetic mothers, HFD infants continue to secrete more insulin than AFD and LFD infants for the first 24 h.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level by increasing urinary glucose excretion, and are used for the treatment of diabetes mellitus (DM). However, they are expected to have various effects in addition to blood glucose-lowering effect. The purpose of this study

INTRODUCTION: Self-monitoring of blood glucose (SMBG) helps patients with diabetes mellitus maintain glycemic control. However, few reports exist on whether ambient temperature can influence SMBG values. AIM: To investigate the effect of ambient temperature on the association between SMBG and plasma glucose (PG) values. METHODS: The study was conducted between 2003 and 2010 in diabetic patients (n=2777, male/female = 1216/1561, mean age = 60.5 ±13.6 years) for whom the measurements of SMBG and PG were performed simultaneously (66 197 samples were measured). SMBG and PG were both measured by enzyme methods. Correlation coefficients were determined between SMBG and PG values, and the differences between their values were compared based on the temperature. RESULTS: SMBG and PG were closely correlated at each temperature. The PG–SMBG difference was smallest at an ambient temperature of 20°C, around which SMBG differed from PG with temperature; namely, the SMBG value decreased as the ambient temperature increased, while the SMBG value increased as the ambient temperature decreased. DISCUSSION: The present data indicate that the ambient temperature can minimally but significantly influence SMBG values. Further studies about the relevance of these findings on patient self-care are warranted. KEYWORDS: Blood glucose self-monitoring; diabetes mellitus; patient education; self care; skin temperature; temperature

The purpose of this study was to analyze the effect of valsartan on abnormal adipocyte metabolism and prothrombotic state in hypertensive patients with metabolic syndrome (MetS).We conducted a multicenter, prospective, randomized, parallel-group controlled trial in 150 hypertensive patients with MetS. They were randomly assigned to receive either 80-160 mg valsartan per day (valsartan group, n=79) or other conventional treatment without a renin-angiotensin system (RAS) inhibitor (non-RAS inhibitor group, n=71). After 1 year, there were no significant differences between the 2 groups in the changes in systolic and diastolic blood pressures (valsartan: 153±15/86±15 to 138±16/77±12 mmHg; non-RAS inhibitor: 150±14/82±15 to 137±15/76±10 mmHg). There was a significant difference in the change in the levels of plasminogen activator inhibitor-1 (PAI-1) between the 2 groups after 1 year (valsartan: 3.7±3.2 ng/ml; non-RAS inhibitor: 5.8±3.3 ng/ml, P=0.04). There was no significant difference between groups in the change in the concentration of adiponectin after 1 year (valsartan: 0.3±0.4 µg/ml; non-RAS inhibitor: 0.9±0.4 µg/ml, P=0.22). The animal study showed aortic PAI-1 protein expression was reduced in double knockout mice of angiotensin II type 1a receptor and apolipoprotein E (apoE) compared with the apoE knockout mice.Valsartan reduced plasma PAI-1 levels compared to non-RAS inhibitor in hypertensive patients with MetS, which suggests it may be useful for improving fibrinolytic function.