Increased urinary excretion of hedgehog interacting protein (uHhip) in early diabetic kidney disease.

Glomerular endothelial cell (GEC) dysfunction occurs in diabetic kidney disease (DKD) and generally precedes albuminuria. We recently reported that hedgehog interacting protein (Hhip), highly expressed in GECs, contributes to DKD development in diabetic mice. Here, we hypothesized that urinary Hhip (uHhip) could identify early DKD; we tested uHhip in mice and humans with diabetes (DM).

Modulation of CYP450 Activities in Patients With Type 2 Diabetes.

We conducted a comprehensive in vivo study evaluating the influence of type 2 diabetes (T2D) on major cytochrome P450 (CYP450) activities. These activities were assessed in 38 T2D and 35 non-T2D subjects after a single oral administration of a cocktail of probe drugs: 100 mg caffeine (CYP1A2), 100 mg bupropion (CYP2B6), 250 mg tolbutamide (CYP2C9), 20 mg omeprazole (CYP2C19), 30 mg dextromethorphan (CYP2D6), 2 mg midazolam (CYP3As), and 250 mg chlorzoxazone (alone; CYP2E1). Mean metabolic activity for CYP2C19, CYP2B6, and CYP3A was decreased in subjects with T2D by about 46%, 45%, and 38% (P < 0.

Use of 4β-Hydroxycholesterol Plasma Concentrations as an Endogenous Biomarker of CYP3A Activity: Clinical Validation in Individuals With Type 2 Diabetes.

The relevance of endogenous 4β-hydroxycholesterol (4β-OHC) plasma concentrations or of the 4β-OHC/total cholesterol concentration ratio (4β-OHC ratio) as surrogate markers of cytochrome P450 3A (CYP3A) activity was evaluated in individuals with (n = 38) or without (n = 35) type 2 diabetes (T2D). Midazolam was used as a comparator to validate exploratory measures of phenotypic CYP3A activity. Metabolic ratios of orally administered midazolam in nondiabetic and diabetic populations correlated significantly with 4β-OHC (r  = 0.

Hedgehog Interacting Protein Promotes Fibrosis and Apoptosis in Glomerular Endothelial Cells in Murine Diabetes.

We investigated whether renal hedgehog interacting protein (Hhip) expression contributes to the progression of diabetic nephropathy (DN) and studied its related mechanism(s) in vivo and in vitro. Here, we show that Hhip expression is highly elevated in glomerular endothelial cells of adult type 1 diabetic (T1D) Akita and T2D db/db mouse kidneys as compared to non-diabetic control littermates. Hyperglycemia enhances reactive oxygen species (ROS) generation via NADPH oxidase 4 (Nox4) activation and stimulates renal Hhip gene expression, and that elevated renal Hhip gene expression subsequently activates the TGFβ1- Smad2/3 cascade and promotes endothelial to mesenchymal transition associated with endothelial cell fibrosis/apoptosis in vivo and in vitro.

Evaluating the impact of type 2 diabetes mellitus on CYP450 metabolic activities: protocol for a case-control pharmacokinetic study.

Introduction: Diabetes affects more than 9% of the adult population worldwide. Patients with type 2 diabetes mellitus (T2DM) show variable responses to some drugs which may be due, in part, to variability in the functional activity of drug-metabolising enzymes including cytochromes P450 (CYP450s). CYP450 is a superfamily of enzymes responsible for xenobiotic metabolism.

Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

Background: The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced.

Methods: The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China.

Effects of Changing the Amount and Source of Dietary Carbohydrates on Symptoms and Dietary Satisfaction Over a 1-Year Period in Subjects with Type 2 Diabetes: Canadian Trial of Carbohydrates in Diabetes (CCD).

Objectives: To determine the long-term effects of changing the amount or source of dietary carbohydrate on quality of life (QOL), symptoms and dietary satisfaction in people with type 2 diabetes.

Methods: Subjects with diabetes treated by diet alone (n=162) were randomly assigned to high-carbohydrate/high-glycemic-index (HGI) diets; high-carbohydrate/low-glycemic-index (LGI) diets; or lower-carbohydrate/high-monounsaturated-fat (LC) diets for 1 year. We measured QOL at baseline and at study's end, and we measured symptoms and dietary satisfaction quarterly.

Longitudinal testing of the Information-Motivation-Behavioral Skills model of self-care among adults with type 2 diabetes.

Objective: The study's aim was to test prospective associations between information, motivation, and behavioral skills (IMB model) and self-care behaviors (diet, exercise, and blood glucose testing) among patients with type 2 diabetes.

Methods: 295 participants were surveyed one (T1), six (T2), and 12 (T3) months after a diabetes course. Cross-lagged panel analyses were performed to test unidirectional and bidirectional relationships between IMB model variables and self-care behaviors.

Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial.

Aims/hypothesis: The aim of this study was to assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared with the single-hormone (insulin alone) artificial pancreas during two types of exercise.

Methods: An open-label randomised crossover study comparing both systems in 17 adults with type 1 diabetes (age, 37.2 ± 13.

Comparison of Two Continuous Glucose Monitoring Systems, Dexcom G4 Platinum and Medtronic Paradigm Veo Enlite System, at Rest and During Exercise.

Background: Despite technological advances, the accuracy of continuous glucose monitoring (CGM) systems may not always be satisfactory with rapidly changing glucose levels, as is notable during exercise. We compare the performance of two current and widely used CGM systems, Dexcom G4 Platinum (Dexcom) and Medtronic Paradigm Veo Enlite system (Enlite), during both rest and exercise in adults with type 1 diabetes (T1D).

Research Design And Methods: Paired sensor and plasma glucose (PG) values (total of 431 data pairs for Dexcom and 425 for Enlite) were collected from 17 adults (37.

Socioeconomic status and glycemic control in adult patients with type 2 diabetes: a mediation analysis.

Objective: The purpose of this study is to examine the contribution of health behaviors (self-management and coping), quality of care, and individual characteristics (depressive symptoms, self-efficacy, illness representations) as mediators in the relationship between socioeconomic status (SES) and glycemic control.

Methods: A sample of 295 adult patients with type 2 diabetes was recruited at the end of a diabetes education course. Glycemic control was evaluated through glycosylated hemoglobin (HbA1c).

Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial.

Objective: This study determined the effects of insulin versus liraglutide therapy on liver fat in patients with type 2 diabetes inadequately controlled with oral agents therapy, including metformin.

Research Design And Methods: Thirty-five patients with type 2 diabetes inadequately controlled on metformin monotherapy or in combination with other oral antidiabetic medications were randomized to receive insulin glargine or liraglutide therapy for 12 weeks. The liver proton density fat fraction (PDFF) was measured by MRS.

Oxytocin treatment prevents the cardiomyopathy observed in obese diabetic male db/db mice.

Oxytocin (OT) is involved in the regulation of energy metabolism and in the activation of cardioprotective mechanisms. We evaluated whether chronic treatment with OT could prevent the metabolic and cardiac abnormalities associated with diabetes and obesity using the db/db mice model. Four-week-old male db/db mice and their lean nondiabetic littermates (db/+) serving as controls were treated with OT (125 ng/kg · h) or saline vehicle for a period of 12 weeks.

All-trans retinoic acid stimulates gene expression of the cardioprotective natriuretic peptide system and prevents fibrosis and apoptosis in cardiomyocytes of obese ob/ob mice.

In hypertensive rodents, retinoic acid (RA) prevents adverse cardiac remodelling and improves myocardial infarction outcome, but its role in obesity-related changes of cardiac tissue are unclear. We hypothesized that all-trans RA (ATRA) treatment will improve the cardioprotective oxytocin-natriuretic peptides (OT-NP) system, preventing apoptosis and collagen accumulation in hearts of ob/ob mice, a mouse model of obesity and insulin resistance. Female 9-week-old B6.

Rationale for and design of the Acarbose Cardiovascular Evaluation (ACE) trial.

Patients with cardiovascular disease and impaired glucose tolerance are at increased risk of cardiovascular events and type 2 diabetes mellitus (T2DM). Lifestyle modification or pharmacological intervention can delay progression to T2DM, but there is no clear evidence that they reduce cardiovascular risk in this population. Acarbose, an α-glucosidase inhibitor that lowers postprandial blood glucose, has been shown to reduce T2DM risk by 25%, and possibly cardiovascular risk in impaired glucose tolerance subjects without cardiovascular disease.

Estimating the population prevalence of diagnosed and undiagnosed diabetes.

Objective: Health administrative data are frequently used for diabetes surveillance, but validation studies are limited, and undiagnosed diabetes has not been considered in previous studies. We compared the test properties of an administrative definition with self-reported diabetes and estimated prevalence of undiagnosed diabetes by measuring glucose levels in mailed-in capillary blood samples.

Research Design And Methods: A stratified random sample of 6,247 individuals (Quebec province) was surveyed by telephone and asked to mail in fasting blood samples on filter paper to a central laboratory.

Efficacy and safety of taspoglutide versus sitagliptin for type 2 diabetes mellitus (T-emerge 4 trial).

Introduction: The efficacy and safety of taspoglutide, a long-acting human glucagon-like peptide-1 analog, were compared with sitagliptin or placebo, as adjunct to metformin, in patients with inadequately controlled type 2 diabetes.

Methods: In this randomized, double-blind, double-dummy, parallel-group trial, patients were randomized to taspoglutide 10 mg once weekly (QW), 20 mg QW, 100 mg sitagliptin once daily (QD), or placebo for 24 weeks, followed by 28-week short-term and 104-week long-term extension periods. The primary endpoint was change in glycosylated hemoglobin (HbA(1c)) after 24 weeks.

Conversion of IGT to type 2 diabetes mellitus is associated with incident cases of hypertension: a post-hoc analysis of the STOP-NIDDM trial.

Background: Type 2 diabetes mellitus and hypertension are closely associated and contribute together to microvascular and macrovascular end-organ damage. Prevalence of hypertension is increased even in the prediabetic state. However, there is little information available about the relationship between incidence of hypertension and a deterioration of glucose tolerance from impaired glucose tolerance (IGT) to diabetes.

The effects of exercise training on γ-butyrobetaine hydroxylase and novel organic cation transporter-2 gene expression in the rat.

The concentration of carnitine in plasma is generally increased with exercise training, suggesting that either carnitine biosynthesis is stimulated or renal reabsorption of carnitine is enhanced, or both. Carnitine, an essential cofactor in the oxidation of fatty acids, is released into the plasma following hydroxylation by γ-butyrobetaine hydroxylase (BBH), the final enzyme in the biosynthetic pathway found primarily in the liver. The organic cation transporter (OCTN2), the carnitine transporter found in kidney, is important in the distribution of carnitine by facilitating its renal reabsorption from urine.

Development and validation of a risk-score model for subjects with impaired glucose tolerance for the assessment of the risk of type 2 diabetes mellitus-The STOP-NIDDM risk-score.

Aims: To develop a risk-score model, based on available clinical data to assess absolute risk of type 2 diabetes among people with impaired glucose tolerance (IGT).

Methods: Data from the study to prevent non-insulin dependent diabetes mellitus (STOP-NIDDM) investigating acarbose treatment in individuals with IGT were used to develop multivariable Cox proportional hazards model for the time to onset of diabetes. The final model equation was externally validated using data from the Finnish Cardiovascular Risk Factor (FINRISK) population.