Alberta Diabetes Institute

Edmonton, Canada

Alberta Diabetes Institute

Edmonton, Canada
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Brocks D.R.,University of Alberta | Ben-Eltriki M.,University of Alberta | Gabr R.Q.,University of Alberta | Padwal R.S.,University of Alberta | Padwal R.S.,Alberta Diabetes Institute
Expert Opinion on Drug Metabolism and Toxicology | Year: 2012

Introduction: Being overweight is widespread in most societies and represents a major health threat. Gastric bypass surgery offers a highly effective mode of treatment for the morbidly obese patients. The procedures cause an alteration in normal gastrointestinal anatomy and physiology, with consequences not only on nutrient absorption, but also possibly on orally administered drugs. Bypass of the acidic environment of the stomach, partial impairment of bile salts-drug interactions and reduced absorptive surface, all create the potential for reduced absorption of drugs. Areas covered: This article provides an overview of the effects of obesity and the most prevalent type of gastric bypass (Roux-en-Y) on pharmacokinetics. Articles for review were searched using Pubmed. Expert opinion: The absorption of those drugs with known bioavailability issues generally seem to be most affected by bypass surgery. It is important to consider the effect of obesity on pharmacokinetics independent of the bypass procedure, because it leads to a dramatic drop in body mass over a relatively short period of time. This may be associated with reversals in the influence of obesity on drug disposition to characteristics more in line with leaner patients. Drugs will differ in their pharmacokinetic response to surgery, limiting any general conclusions regarding the impact of the surgery on drug disposition. © 2012 Informa UK, Ltd.

Kushner J.A.,Baylor College of Medicine | MacDonald P.E.,University of Alberta | MacDonald P.E.,Alberta Diabetes Institute | Atkinson M.A.,University of Florida
Cell Stem Cell | Year: 2014

Two groups recently reported the in vitro differentiation of human embryonic stem cells into insulin-secreting cells, achieving an elusive goal for regenerative medicine. Herein we provide a perspective regarding these developments, compare phenotypes of the insulin-containing cells to human β cells, and discuss implications for type 1 diabetes research and clinical care. ©2014 Elsevier Inc.

Padwal R.S.,University of Alberta | Padwal R.S.,Alberta Diabetes Institute | Bienek A.,Public Health Agency of Canada | McAlister F.A.,University of Alberta | Campbell N.R.C.,Libin Cardiovascular Institute
Canadian Journal of Cardiology | Year: 2016

Background: High blood pressure (BP) is the leading cause of death and disability in the world. The objective of this analysis was to perform a detailed update of the epidemiology of hypertension in Canada. Methods: Five population-based data sources were analyzed. We used the Canadian Health Measures Survey to determine the latest directly measured prevalence, awareness, and control estimates (2012-2013); the National Population Health Survey, and Canadian Community Health Survey to assess crude and age-standardized self-reported prevalence (1994-2013); the Canadian Chronic Disease Surveillance System to assess administrative data-ascertained prevalence and mortality trends (1998-2010); and Intercontinental Medical Statistics Health data to examine antihypertensive drug-prescribing trends and costs (2007-2014). Results: In 2012-2013, the prevalence of hypertension (defined as drug treatment for high BP or BP ≥ 140/90 mm Hg) in Canadian adults was 22.6%, and the proportion of disease controlled was 68.1%. In Canadians with diabetes, the prevalence (defined as drug treatment or BP ≥ 130/80 mm Hg) was 67.1%, and 60.1% of cases were controlled. Self-reported hypertension prevalence has increased by approximately 2-fold over nearly 2 decades. Age-standardized mortality rates are falling in hypertensive Canadians (from 9.4 to 7.9 deaths per 1000 individuals), but to a lesser extent than in nonhypertensive individuals. Total antihypertensive drug prescription volume has increased steadily since 2007 amid falling drug costs. Conclusions: Hypertension prevalence in Canada continues to rise. Increased use of antihypertensive drugs and improvements in control are apparent. Coordinated efforts to further improve the treatment and control of hypertension in Canada are needed. © 2016 Canadian Cardiovascular Society.

Van Der Veen J.N.,Alberta Diabetes Institute | Van Der Veen J.N.,University of Alberta | Lingrell S.,Alberta Diabetes Institute | Lingrell S.,University of Alberta | And 6 more authors.
Diabetes | Year: 2014

Phosphatidylethanolamine (PE) N-methyltransferase (PEMT) catalyzes the synthesis of phosphatidylcholine (PC) in the liver. Mice lacking PEMT are protected against diet-induced obesity and insulin resistance. We investigated the role of PEMT in hepatic carbohydrate metabolism in chow-fed mice. A pyruvate tolerance test revealed that PEMT deficiency greatly attenuated gluco-neogenesis. The reduction in glucose production was specific for pyruvate; glucose production from glycerol was unaffected. Mitochondrial PC levels were lower and PE levels were higher in livers from Pemt-/- compared with Pemt+/+ mice, resulting in a 33% reduction of the PC-to-PE ratio. Mitochondria from Pemt-/- mice were also smaller and more elongated. Activities of cytochrome c oxidase and succinate reductase were increased in mitochondria of Pemt-/- mice. Accordingly, ATP levels in hep-atocytes from Pemt-/- mice were double that in Pemt+/+ hepatocytes. We observed a strong correlation between mitochondrial PC-to-PE ratio and cellular ATP levels in hep-atoma cells that expressed various amounts of PEMT. Moreover, mitochondrial respiration was increased in cells lacking PEMT. In the absence of PEMT, changes in mito-chondrial phospholipids caused a shift of pyruvate toward decarboxylation and energy production away from the car-boxylation pathway that leads to glucose production. © 2014 by the American Diabetes Association.

Padwal R.S.,University of Alberta | Padwal R.S.,Alberta Diabetes Institute | Chang H.-J.,University of Alberta | Klarenbach S.,University of Alberta | And 4 more authors.
International Journal for Equity in Health | Year: 2012

Background: Bariatric surgery is the most effective current treatment for severe obesity. Capacity to perform surgery within Canadas public health system is limited and potential candidates face protracted wait times. A better understanding of the gaps between demand for surgery and the capacity to provide it is required. The purpose of this study was to quantify and characterize the bariatric surgery-eligible population in Canada in comparison to surgery-ineligible subjects and surgical recipients. Methods. Data from adult (age>20) respondents of the 2007-09 nationally representative Canadian Health Measures Survey (CHMS) were analyzed to estimate the prevalence and characteristics of the surgery-eligible and ineligible populations. Federally mandated administrative healthcare data (2007-08) were used to characterize surgical recipients. Results: In 2007-09, an estimated 1.5 million obese Canadian adults met eligibility criteria for bariatric surgery. 19.2 million were surgery-ineligible (3.4 million obese and 15.8 million non-obese). Surgery-eligible Canadians had a mean BMI of 40.1kg/m2 (95% CI 39.3 to 40.9kg/m2) and, compared to the surgery-ineligible obese population, were more likely to be female (62 vs. 44%), 40-59years old (55 vs. 48%), less educated (43 vs. 35%), in the lowest socioeconomic tertile (41 vs. 34%), and inactive (73 vs. 59%). Self-rated mental health and quality of life were lower and comorbidity was higher in surgery-eligible respondents compared with the ineligible populations. The annual proportion of Canadians eligible for surgery that actually underwent a publicly funded bariatric surgery between 2007-09 was 0.1%. Surgical recipients (n=847) had a mean age of 43.6years (SD 11.1) and 82% were female. With the exception of type 2 diabetes, obesity-related comorbidity prevalence was much lower in surgical recipients compared to those eligible for surgery. Conclusions: The proportion of bariatric surgery-eligible Canadians that undergo publicly funded bariatric surgery is very low. There are notable differences in sociodemographic profiles and prevalence of comorbidities between surgery-eligible subjects and surgical recipients. © 2012 Padwal et al.; licensee BioMed Central Ltd.

Padwal R.,University of Alberta | Padwal R.,Alberta Diabetes Institute | Padwal R.,University of British Columbia | Lin M.,University of Alberta | And 4 more authors.
Hypertension | Year: 2014

Olmesartan has been linked with increased risk of cardiovascular mortality and sprue-like enteropathy. We compared outcomes between olmesartan and other angiotensin receptor blockers in a large clinical registry of patients with diabetes mellitus. A retrospective cohort analysis using nationwide US-integrated insurance and laboratory claims was performed in 45 185 incident diabetic angiotensin receptor blocker users, including 10 370 (23%) olmesartan users. Hazard ratios were computed using time-dependant Cox models adjusted for sociodemographic characteristics, comorbidities, laboratory data, drug use, healthcare utilization, and the propensity to receive olmesartan. Blood pressure data were unavailable. Subjects were followed up for 116 721 patient-years. The primary end point was all-cause hospitalization or all-cause mortality and occurred in 10 915 (24%) patients. Average age was 54.3±9.6 years, 52% were men, 17% had cardiovascular disease, and 10% chronic kidney disease. Compared with other angiotensin receptor blockers, the adjusted hazard for olmesartan was 0.99 (95% confidence interval, 0.94-1.05) for all-cause hospitalization and mortality; 0.90 (0.62-1.30) for all-cause mortality; 0.99 (0.94-1.05) for all-cause hospital admission; 0.88 (0.78-1.00) for cardiovascular disease-related admission, and 1.09 (0.98-1.20) for gastrointestinal disease-related hospitalization in the overall cohort. Olmesartan use was associated with an adjusted hazard for the primary outcome of 1.11 (0.99-1.24) in subjects with history of cardiovascular disease and 1.21 (1.04-1.41) in subjects with chronic kidney disease. In conclusion, there is no robust signal for harm with olmesartan use. Risk may be increased in kidney disease; thus, given the widespread availability of alternate agents, olmesartan should be used with caution in this subgroup pending further study. © 2014 American Heart Association, Inc.

Cawsey S.,University of Alberta | Padwal R.,University of Alberta | Padwal R.,Alberta Diabetes Institute | Sharma A.M.,University of Alberta | And 3 more authors.
Osteoporosis International | Year: 2014

Summary: Among women with obesity, those with the lowest bone density have the highest fracture risk. The types of fractures include any fracture, fragility-type fractures (vertebra, hip, upper arm, forearm, and lower leg), hand and foot fractures, osteoporotic, and other fracture types.Introduction: Recent reports have contradicted the traditional view that obesity is protective against fracture. In this study, we have evaluated the relationship between fracture history and bone mineral density (BMD) in subjects with obesity.Methods: Fracture risk was assessed in 400 obese women in relation to body mass index (BMI), BMD, and clinical and laboratory variables.Results: Subjects (mean age, 43.8 years; SD, 11.1 years) had a mean BMI of 46.0 kg/m2 (SD, 7.4 kg/m2). There were a total of 178 self-reported fractures in 87 individuals (21.8 % of subjects); fragility-type fractures (hip, vertebra, proximal humerus, distal forearm, and ankle/lower leg) were present in 58 (14.5 %). There were higher proportions of women in the lowest femoral neck BMD quintile who had any fracture history (41.3 vs. 17.2 %, p < 0.0001), any fragility-type fractures (26.7 vs. 11.7 %, p = 0.0009), hand and foot fractures (16.0 vs. 5.5 %, p = 0.002), other fracture types (5.3 vs. 1.2 %, p = 0.02), and osteoporotic fractures (8.0 vs. 1.2 %, p < 0.0001) compared to the remaining population. The odds ratio for any fracture was 0.63 (95 % CI, 0.49–0.89; p = 0.0003) per SD increase in BMD and was 4.3 (95 % CI, 1.9–9.4; p = 0.003) in the lowest BMD quintile compared to the highest quintile. No clinical or biochemical predictors of fracture risk were identified apart from BMD.Conclusions: Women with obesity who have the lowest BMD values, despite these being almost normal, have an elevated risk of fracture compared to those with higher BMD. © 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.

Warkentin L.M.,University of Alberta | Warkentin L.M.,Alberta Diabetes Institute | Das D.,University of Alberta | Majumdar S.R.,University of Alberta | And 5 more authors.
Obesity Reviews | Year: 2014

The aim of this study was to examine the effect of weight loss on health-related quality of life (HRQL) in randomized controlled intervention trials (RCTs). MEDLINE, HealthStar and PsycINFO were searched. RCTs of any weight loss intervention and 20 HRQL instruments were examined. Contingency tables were constructed to examine the association between statistically significant weight loss and statistically significant HRQL improvement within five HRQL categories. In addition, Short Form-36 (SF-36) outcomes were pooled using random-effects models. Fifty-three trials were included. Seventeen studies reported statistically significant weight loss and HRQL improvement. No statistically significant associations between weight loss and HRQL improvement were found in any contingency table. Because of suboptimal endpoint reporting, quantitative data pooling could only be performed using 25% of SF-36 trials in any one model. Significant improvements in physical health were found: mean difference 2.83 points, 95% CI 0.55-5.1, for the physical component score, and mean difference 6.81 points, 95% CI 2.99-10.63, for the physical functioning domain score. Conversely, no significant improvements in mental health were found. No significant association was found between weight loss and overall HRQL improvement. Weight loss may be associated with modest improvements in physical, but not mental, health. © 2013 International Association for the Study of Obesity.

Padwal R.S.,University of Alberta | Padwal R.S.,Alberta Diabetes Institute | Ben-Eltriki M.,University of Alberta | Wang X.,University of Alberta | And 5 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2012

Objectives: Azithromycin is used widely for community-acquired infections. The timely administration of azithromycin in adequate doses minimizes treatment failure. Gastric bypass, a procedure that circumvents the upper gut, may compromise azithromycin plasma levels. We hypothesized that azithromycin concentrations would be reduced following gastric bypass. Methods: A single-dose pharmacokinetic study in 14 female post-gastric bypass patients and 14 sex- and body mass index (BMI)-matched controls (mean age 44 years and BMI 36.4 kg/m. 2) was performed. Subjects were administered two 250 mg azithromycin tablets at time 0 and plasma azithromycin levels were sampled at 0.5, 1, 1.5, 2, 3, 5, 7 and 24 h. The AUC of the plasma azithromycin concentrations from time 0 to 24 h (AUC. 0-24) was the primary outcome. Results: Azithromycin concentrations were lower in gastric bypass patients compared with controls throughout the entire duration of sampling. Compared with controls, the AUC0-24 was reduced in gastric bypass subjects by 32% [1.41 (SD 0.51) versus 2.07 (0.75) mg h/L; P = 0.008], and dose-normalized AUC0-24 was reduced by 33% [0.27 (0.12) versus 0.40 (0.13) kg h/L; P = 0.009]. Peak azithromycin concentrations were 0.260 (0.115) in bypass subjects versus 0.363 (0.200) mg/L in controls (P = 0.08), and were reached at 2.14 (0.99) h in gastric bypass subjects and 2.36 (1.17) h in controls (P = 0.75). Conclusions: Azithromycin AUC was reduced by one-third in gastric bypass subjects compared with controls. The potential for early treatment failure exists, and dose modification and/or closer clinical monitoring of gastric bypass patients receiving azithromycin should be considered. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Rueda-Clausen C.F.,Alberta Diabetes Institute | Padwal R.S.,Alberta Diabetes Institute | Sharma A.M.,Alberta Diabetes Institute
Nature Reviews Endocrinology | Year: 2013

Obesity, which results from an imbalance between calorie intake and expenditure, now affects over 500 million individuals worldwide. Lifestyle and behavioural interventions aimed at reducing calorie intake and/or increasing energy expenditure have limited long-term effectiveness due to complex and persistent hormonal, metabolic and neurochemical adaptations that defend against weight loss and promote weight regain. Surgical treatments for obesity, although highly effective, are unavailable or unsuitable for the majority of individuals with excess adiposity. Accordingly, few effective treatment options are available to most individuals with obesity. In the past, the use of antiobesity drugs, seemingly the logical choice to fill this therapeutic gap, has been limited because of a lack of efficacy, poor long-term adherence rates and serious adverse effects. In 2012, the FDA approved two new medications - lorcaserin and phentermine-topiramate controlled release - and is currently reviewing the resubmission of naltrexone sustained release-bupropion sustained release. This Review presents the available data on the efficacy and safety of these three medications and discusses future perspectives and challenges related to pharmacological weight management. © 2013 Macmillan Publishers Limited. All rights reserved.

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