A comparison of the assessment and management of cardiometabolic risk in patients with and without type 2 diabetes mellitus in Canadian primary care.

AIM: To investigate the cardiometabolic risk (CMR) assessment and management patterns for individuals with and without type 2 diabetes mellitus (T2DM) in Canadian primary care practices. METHODS: Between April 2011 and March 2012, physicians from 9 primary care teams and 88 traditional non-team practices completed a practice assessment on the management of 2461 patients >40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least one of the following risk factor-T2DM, dyslipidaemia or hypertension. RESULTS: There were 1304 individuals with T2DM and 1157 without. Pharmacotherapy to manage hyperglycaemia, dyslipidaemia and hypertension was widely prescribed. Fifty-eight percent of individuals with T2DM had a glycated haemoglobin (HbA1c) ≤7.0%. Amongst individuals with dyslipidaemia, median low-density lipoprotein cholesterol (LDL-C) was 1.8 mmol/l for those with T2DM and 2.8 mmol/l for those without. Amongst individuals with hypertension, 30% of those with T2DM achieved the <130/80 mmHg target, whereas 60% of those without met the <140/90 mmHg target. The composite glycaemic, LDL-C and blood pressure (BP) target outcome was achieved by 12% of individuals with T2DM. Only 17% of individuals with T2DM and 11% without were advised to increase their physical activity. Dietary modifications were recommended to 32 and 10% of those with and without T2DM, respectively. CONCLUSIONS: Patients at elevated CMR were suboptimally managed in the primary care practices surveyed. There was low attainment of recommended therapeutic glycaemic, lipid and BP targets. Advice on healthy lifestyle changes was infrequently dispensed, representing a missed opportunity to educate patients on the long-term benefits of lifestyle modification.

Perivascular adipose tissue-derived relaxing factors: release by peptide agonists via proteinase-activated receptor-2 (PAR2) and non-PAR2 mechanisms.

BACKGROUND AND PURPOSE: We hypothesized that proteinase-activated receptor-2 (PAR2)-mediated vasorelaxation in murine aorta tissue can be due in part to the release of adipocyte-derived relaxing factors (ADRFs). EXPERIMENTAL APPROACH: Aortic rings from obese TallyHo and C57Bl6 intact or PAR2-null mice either without or with perivascular adipose tissue (PVAT) were contracted with phenylephrine and relaxation responses to PAR2-selective activating peptides (PAR2-APs: SLIGRL-NH(2) and 2-furoyl-LIGRLO-NH(2) ), trypsin and to PAR2-inactive peptides (LRGILS-NH(2) , 2-furoyl-OLRGIL-NH(2) and LSIGRL-NH(2) ) were measured. Relaxation was monitored in the absence or presence of inhibitors that either alone or in combination were previously shown to inhibit ADRF-mediated responses: L-NAME (NOS), indomethacin (COX), ODQ (guanylate cyclase), catalase (H(2) O(2) ) and the K(+) channel-targeted reagents, apamin, charybdotoxin, 4-aminopyridine and glibenclamide. KEY RESULTS: Endothelium-intact PVAT-free preparations did not respond to PAR2-inactive peptides (LRGILS-NH(2) , LSIGRL-NH(2) , 2-furoyl-OLRGIL-NH(2) ), whereas active PAR2-APs (SLIGRL-NH(2) ; 2-furoyl-LIGRLO-NH(2) ) caused an L-NAME-inhibited relaxation. However, in PVAT-containing preparations treated with L-NAME/ODQ/indomethacin together, both PAR2-APs and trypsin caused relaxant responses in PAR2-intact, but not PAR2-null-derived tissues. The PAR2-induced PVAT-dependent relaxation (SLIGRL-NH(2) ) persisted in the presence of apamin plus charybdotoxin, 4-aminopyridine and glibenclamide, but was blocked by catalase, implicating a role for H(2) O(2) . Surprisingly, the PAR2-inactive peptides, LRGILS-NH(2) and 2-furoyl-OLRGIL-NH(2) (but not LSIGRL-NH(2) ), caused relaxation in PVAT-containing preparations from both PAR2-null and PAR2-intact (C57Bl, TallyHo) mice. The LRGILS-NH(2) -induced relaxation was distinct from the PAR2 response, being blocked by 4-aminopyridine, but not catalase. CONCLUSIONS: Distinct ADRFs that may modulate vascular tone in pathophysiological settings can be released from murine PVAT by both PAR2-dependent and PAR2-independent mechanisms.

Canadian Physicians' Use of Antiobesity Drugs and Their Referral Patterns to Weight Management Programs or Providers: The SOCCER Study.

Antiobesity pharmacotherapy and programs/providers that possess weight management expertise are not commonly used by physicians. The underlying reasons for this are not known. We performed a cross-sectional study in 33 Canadian medical practices (36 physicians) examining 1788 overweight/obese adult patients. The frequency of pharmacotherapy use and referral for further diet, exercise, behavioral management and/or bariatric surgery was documented. If drug treatment or referral was not made, reasons were documented by choosing amongst preselected categories. Logistic regression models were used to identify predictors of antiobesity drug use. No single antiobesity management strategy was recommended by physicians in more than 50% of patients. Referral was most common for exercise (49% of cases) followed by dietary advice (46%), and only 5% of eligible patients were referred for bariatric surgery. Significant predictors of initiating/continuing pharmacotherapy were male sex (OR 0.70; 95% CI 0.52-0.94), increasing BMI (1.02; 95% CI 1.01-1.03), and private drug coverage (1.78; 95% CI 1.39-2.29). "Not considered" and "patient refusal" were the main reasons for not initiating further weight management. We conclude that both physician and patient factors act as barriers to the use of weight management strategies and both need to be addressed to increase uptake of these interventions.

Dietary cholesterol and other nutritional considerations in people with diabetes.

BACKGROUND: Nutrition therapy is an integral component of lifestyle intervention and self-management of people with diabetes. The goals of nutrition therapy are to optimise or maintain quality of life, physiological and mental health, and to prevent and treat acute and long-term complications of diabetes, the associated comorbid conditions and concomitant disorders. Monitoring dietary cholesterol consumption and salt intake are important nutritional aspects to lower the risk for and treatment of cardiovascular disease and hypertension. AIMS: To evaluate the role of nutritional therapy and notably the effect of egg consumption on cardiovascular disease (CVD) risk in people with diabetes. METHODOLOGY: Literature review of nutritional therapy and clinical studies on egg consumption and CVD risk for people with diabetes were conducted and appraised. RESULTS: The Harvard Egg Study on two large prospective US cohorts found that eating one or more eggs a day had no adverse effects on lipid profile or cardiovascular disease risk in men or women. Similar findings were observed in the NHANES-I and Physicians' Health Study. The only exception was people with diabetes, where CVD was increased with eating more than one egg per day. CONCLUSIONS: Consumption of one or more eggs per day is associated with an elevated risk of coronary heart disease in people with diabetes. The mechanism for this association remains unknown but should be explored in randomised clinical trials.

Long-term pharmacotherapy for obesity and overweight.

BACKGROUND: Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established. OBJECTIVES: To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed. SELECTION CRITERIA: Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss. MAIN RESULTS: Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate. REVIEWERS' CONCLUSIONS: Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.

Long-term pharmacotherapy for obesity and overweight.

BACKGROUND: Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established. OBJECTIVES: To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed. SELECTION CRITERIA: Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss. MAIN RESULTS: Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate. REVIEWER'S CONCLUSIONS: Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.

Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Safe and effective strategies to curb rising obesity prevalence rates are urgently needed and medications may play a more prominent role in future therapeutic regimens. OBJECTIVE: To review systematically the long-term efficacy and safety of approved antiobesity medications. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Drug manufacturers and two obesity experts were contacted. No language restrictions were imposed. STUDY SELECTION: Double-blind, randomized controlled studies of approved antiobesity medications with follow-up periods of 1 y or greater were eligible for inclusion. DATA EXTRACTION: Two reviewers independently assessed all potentially relevant studies for inclusion and methodological quality using standardized abstraction forms. RESULTS: A total of 11orlistat (n=6021) and three sibutramine (n=929) studies met inclusion criteria. Attrition rates averaged 33% in orlistat studies and 48% in sibutramine studies. A random effects model was used for meta-analysis. Compared to placebo, orlistat-treated patients displayed a 2.7 kg (95% CI: 2.3-3.1 kg) or 2.9% (95% CI: 2.3-3.4%) greater reduction in weight and patients on sibutramine displayed a 4.3 kg (95% CI: 3.6-4.9 kg) or 4.6% (95% CI: 3.8-5.4%) greater weight reduction after 1 y of follow-up. The number of patients achieving 10% or greater weight loss was 12% (95% CI: 8-16%) higher with orlistat and 15% (95% CI: 4-27%) higher with sibutramine compared to placebo. Orlistat caused gastrointestinal side effects and sibutramine increased blood pressure and pulse rate. CONCLUSION: There is a relative paucity of long-term studies of antiobesity agents. In weight loss trials of 1-y duration, orlistat and sibutramine appear modestly effective in promoting weight loss. Longer, more methodologically rigorous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.

Acarbose in the treatment of elderly patients with type 2 diabetes.

AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.