Type 2 diabetes mellitus and hypertension overlap in the population. In many subjects, development of diabetes mellitus is characterized by a relatively rapid increase in plasma glucose values. Whether a similar phenomenon occurs during the development of hypertension is not known. We analyzed the pattern of blood pressure (BP) changes during the development of hypertension in patients with or without diabetes mellitus using data from the MCDS (Mexico City Diabetes Study; a population-based study of diabetes mellitus in Hispanic whites) and in the FOS (Framingham Offspring Study, a community-based study in non-Hispanic whites) during a 7-year follow-up. Diabetes mellitus at baseline was a significant predictor of incident hypertension (in FOS, odds ratio, 3.14; 95% confidence interval, 2.17–4.54) independently of sex, age, body mass index, and familial diabetes mellitus. Conversely, hypertension at baseline was an independent predictor of incident diabetes mellitus (in FOS, odds ratio, 3.33; 95% CI, 2.50–4.44). In >60% of the converters, progression from normotension to hypertension was characterized by a steep increase in BP values, averaging 20 mm Hg for systolic BP within 3.5 years (in MCDS). In comparison with the nonconverters group, hypertension and diabetes mellitus converters shared a metabolic syndrome phenotype (hyperinsulinemia, higher body mass index, waist girth, BP, heart rate and pulse pressure, and dyslipidemia). Overall, results were similar in the 2 ethnic groups. We conclude that (1) development of hypertension and diabetes mellitus track each other over time, (2) transition from normotension to hypertension is characterized by a sharp increase in BP values, and (3) insulin resistance is one common feature of both prediabetes and prehypertension and an antecedent of progression to 2 respective disease states.

Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential amino acids widely studied for their crucial role in the regulation of protein synthesis mainly through the activation of the mTOR signaling pathway and their emerging recognition as players in the regulation of various physiological and metabolic processes, such as glucose homeostasis. BCAA supplementation is primarily used as a beneficial nutritional intervention in chronic liver and kidney disease as well as in muscle wasting disorders. However, downregulated/upregulated plasma BCAAs and their defective catabolism in various tissues, mainly due to altered enzymatic activity of the first two enzymes in their catabolic pathway, BCAA aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), have been investigated in many nutritional and disease states. The current review focused on the underlying mechanisms of altered BCAA catabolism and its contribution to the pathogenesis of a numerous pathological conditions such as diabetes, heart failure and cancer. In addition, we summarize findings that indicate that the recovery of the dysregulated BCAA catabolism may be associated with an improved outcome and the prevention of serious disease complications.

Context Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate. Objective To evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes. Design Prospective cohort study. Setting Outpatient diabetes clinic of a tertiary academic center. Patients Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled. Intervention Fifty patients were treated with dapagliflozin for 3 months. To exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia, 30 patients treated with insulin degludec were used for comparison. Main Outcome Measure Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy. Results In multivariate analysis urine metabolome was significantly altered by dapagliflozin (R²X = 0.819, R²Y = 0.627, Q²Y = 0.362, and coefficient of variation analysis of variance, P < 0.001) but not insulin. After dapagliflozin, the urine concentrations of ketone bodies, lactate, branched chain amino acids (P < 0.001), betaine, myo-inositol (P < 0001), and N-methylhydantoin (P < 0.005) were significantly increased. Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased (P < 0001, P <0.0001, and P <0.0005, respectively) whereas anserine decreased (P < 0005). Conclusions Dapagliflozin significantly affects urine metabolome in patients with type 2 diabetes in a glucose lowering-independent way. Most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.