Dapagliflozin Monotherapy in Type 2 Diabetic Patients With Inadequate Glycemic Control by Diet and Exercise: A randomized, double-blind, placebo-controlled, phase 3 trial

OBJECTIVE - Dapagliflozin, a highly selective inhibitor of the renal sodium-glucose co-transporter-2, increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner. We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - This was a 24-week parallel-group, double-blind, placebo-controlled phase 3 trial. Patients with A1C 7.0-10% (n = 485) were randomly assigned to one of seven arms to receive once-daily placebo or 2.5, 5, or 10 mg dapagliflozin once daily in the morning (main cohort) or evening (exploratory cohort). Patients with A1C 10.1-12% (high-A1C exploratory cohort, it n=73) were randomly assigned 1:1 to receive blinded treatment with a morning close of 5 or 10 mg/day dapagliflozin. The primary end point was change from baseline in A1C in the main cohort, statistically tested using an ANCOVA. RESULTS - In the main cohort, mean A1C changes from baseline at week 24 were -0.23% with placebo and -0.58, -0.77 (P = 0.0005 vs. placebo), and -0.89% (P < 0.0001, vs. placebo) with 2.5, 5, and 10 mg dapagliflozin, respectively. Signs, symptoms, and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms. There were no major episodes of hypoglycemia. Data from exploratory cohorts were consistent with these results. CONCLUSIONS - Dapagliflozin lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes. The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes

Blood Viscosity and Hematocrit as Risk Factors for Type 2 Diabetes Mellitus: The Atherosclerosis Risk in Communities (ARIC) Study

Several lines of evidence support the notion that elevated blood viscosity may predispose to insulin resistance and type 2 diabetes mellitus by limiting delivery of glucose, insulin, and oxygen to metabolically active tissues. To test this hypothesis, the authors analyzed longitudinal data on 12,881 initially nondiabetic adults, aged 45–64 years, who were participants in the Atherosclerosis Risk in Communities (ARIC) Study (1987–1998). Whole blood viscosity was estimated by using a validated formula based on hematocrit and total plasma proteins at baseline. At baseline, estimated blood viscosity was independently associated with several features of the metabolic syndrome. In models adjusted simultaneously for known predictors of diabetes, estimated whole blood viscosity and hematocrit predicted incident type 2 diabetes mellitus in a graded fashion (Ptrend (linear) < 0.001): Compared with their counterparts in the lowest quartiles, adults in the highest quartile of blood viscosity (hazard ratio = 1.68, 95% confidence interval: 1.53, 1.84) and hematocrit (hazard ratio = 1.63, 95% confidence interval: 1.49, 1.79) were over 60% more likely to develop diabetes. Therefore, elevated blood viscosity and hematocrit deserve attention as emerging risk factors for insulin resistance and type 2 diabetes mellitus

Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease

Background. It is unclear whether the presence of kidney disease modifies the associations of uric acid with cardiovascular events and death

Blood Viscosity in Subjects With Normoglycemia and Prediabetes

OBJECTIVE Blood viscosity (BV) is higher in diabetic patients and might represent a risk factor for the development of insulin resistance and type 2 diabetes. However, data in subjects with normal glucose or prediabetes are missing. In the current study, we evaluated the relationship between BV and blood glucose in subjects with normal glucose or prediabetes. RESEARCH DESIGN AND METHODS Enrolled subjects were divided into three groups according to blood glucose: group A ( n = 74), blood glucose <90 mg/dL; group B ( n = 96), blood glucose ranging from 90 to 99 mg/dL; and group C ( n = 94), blood glucose ranging from 100 to 125 mg/dL. BV was measured at 37°C with a cone-plate viscometer at shear rates ranging from 225 to 22.5 s−1. RESULTS Blood pressure, blood lipids, fibrinogen, and plasma viscosity were similar in the three groups. BMI and waist circumference were significantly increased in group C. Hematocrit ( P < 0.05) and BV ( P between 0.01 and 0.001) were significantly higher in groups B and C compared with group A. Blood glucose was significantly and inversely correlated with HDL cholesterol and directly with BMI, waist, hematocrit ( r = 0.134), and BV (from 225 s−1 to 22.5 s−1; r ranging from 0.162 to 0.131). BV at shear rate 225 s−1 was independently associated with blood glucose. CONCLUSIONS The current study shows a direct relationship between BV and blood glucose in nondiabetic subjects. It also suggests that, even within glucose values considered completely normal, individuals with higher blood glucose levels have increased BV comparable with that observed in subjects with prediabetes