Optimal diabetes management during medical weight loss for cardiovascular risk reduction

Obesity has long been recognized as a significant risk factor for type 2 diabetes. Both obesity and type 2 diabetes are associated with an increase in cardiovascular risk. As cardiovascular disease continues to be the number one killer in the USA and western adult populations, the rise in prevalence of obesity and type 2 diabetes is alarming. This is especially disturbing in the tripling of overweight children and adolescents, accompanied by the increase in prevalence of pediatric type 2 diabetes. Optimal strategies for long-term diabetes management aim at effectively controlling, reducing and ultimately preventing obesity. This review explores the clinical recommendations in place, new clinical investigations, diet therapy, medical nutrition therapy, meal replacements, behavior therapy, exercise therapy, pharmacotherapy and surgical therapy as strategies to achieve weight-loss success in diabetic patients and ultimately reduce cardiovascular disease.     

Clinical trial evidence for cardiovascular risk reduction in type 2 diabetes.

Major clinical trials have shown that excellent glycemic control, sustained over time, can prevent or delay the microvascular complications of diabetes, including retinopathy, nephropathy, and neuropathy. No prospective trial has clearly shown that glycemic intervention can prevent the macrovascular complications of diabetes, such as myocardial infarction, cerebrovascular accident, and amputation. However, a number of landmark clinical trials have shown the efficacy of control of blood pressure and lipids and use of antiplatelet agents (mainly aspirin) in protecting the macrovasculature of individuals with diabetes. In this article, glycemic, blood pressure, lipid, and antiplatelet trials relevant to the treatment of people with type 2 diabetes are reviewed.     

Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes

OBJECTIVE

Overweight and obese individuals are encouraged to lose 5–10% of their body weight to improve cardiovascular disease (CVD) risk, but data supporting this recommendation are limited, particularly for individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We conducted an observational analysis of participants in the Look AHEAD (Action For Health in Diabetes) study (n = 5,145, 40.5% male, 37% from ethnic/racial minorities) and examined the association between the magnitude of weight loss and changes in CVD risk factors at 1 year and the odds of meeting predefined criteria for clinically significant improvements in risk factors in individuals with type 2 diabetes.

RESULTS

The magnitude of weight loss at 1 year was strongly (P < 0.0001) associated with improvements in glycemia, blood pressure, tryiglycerides, and HDL cholesterol but not with LDL cholesterol (P = 0.79). Compared with weight-stable participants, those who lost 5 to <10% ([means ± SD] 7.25 ± 2.1 kg) of their body weight had increased odds of achieving a 0.5% point reduction in HbA_1c (odds ratio 3.52 [95% CI 2.81–4.40]), a 5-mmHg decrease in diastolic blood pressure (1.48 [1.20–1.82]), a 5-mmHg decrease in systolic blood pressure (1.56 [1.27–1.91]), a 5 mg/dL increase in HDL cholesterol (1.69 [1.37–2.07]), and a 40 mg/dL decrease in triglycerides (2.20 [1.71–2.83]). The odds of clinically significant improvements in most risk factors were even greater in those who lost 10–15% of their body weight.

CONCLUSIONS

Modest weight losses of 5 to <10% were associated with significant improvements in CVD risk factors at 1 year, but larger weight losses had greater benefits.Overweight and obese individuals are frequently encouraged to lose 5–10% of their weight and are told that weight losses of that magnitude will help improve their cardiovascular disease (CVD) risk factors. For example, the Centers for Disease Control and Prevention website (www.cdc.gov/healthyweight/losing_weight/index.html) states, “The good news is that no matter what your weight loss goal is, even a modest weight loss, such as 5 to 10% of your total body weight, is likely to produce health benefits, such as improvements in blood pressure, blood cholesterol, and blood sugars.” The benefits of modest weight loss also are noted by the Surgeon General (www.surgeongeneral.gov/), the Institutes of Medicine (1), and the National Institutes of Health (e.g., www.nhlbi.nih.gov/ and www2.niddk.nih.gov/), with citations to a variety of reviews of the literature (2–4) and meta-analyses (5). For example, the statement from the Centers for Disease Control and Prevention website cites a review by Blackburn (6) for the benefits of 5% weight loss and the National Heart, Lung, and Blood Institute Clinical Guidelines (7) as the reference for the benefit of a 10% weight loss. However, the studies included in these reviews often had limited sample sizes, focused on nondiabetic individuals, and typically presented only average weight loss and the average reduction in risk factors, which did not allow a careful analysis of the association between specific magnitudes of weight loss and consequent improvements in CVD risk factors.Look AHEAD (Action for Health in Diabetes) provides a unique opportunity to carefully assess the effects of modest weight loss on CVD risk factors in individuals with type 2 diabetes, a population at high risk for CVD. Look AHEAD is a multicenter, randomized clinical trial examining the long-term effects of lifestyle interventions on cardiovascular morbidity and mortality in 5,145 overweight or obese participants with type 2 diabetes who were randomly assigned to intensive lifestyle intervention (ILI) or to usual care, referred to as diabetes support and education (DSE) (8,9). Differences between ILI and DSE at 1 year have been reported previously (9). In this article, we examine the associations between the magnitude of weight loss and the degree of improvement in glycemic control, blood pressure, and lipid levels at 1 year in the full cohort. We also determine the average risk factor change and the odds of meeting predefined criteria for clinically significant improvement in risk factors that are associated with specific categories of weight change. These analyses provide important data to address the recommendations regarding modest weight loss.     

Effect of weight loss with lifestyle intervention on risk of diabetes

OBJECTIVE: Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants. RESEARCH DESIGN AND METHODS: For this study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up. RESULTS: A total of 1,079 participants were aged 25-84 years (mean 50.6 years, BMI 33.9 kg/m(2)). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.51]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence. CONCLUSIONS: Interventions to reduce diabetes risk should primarily target weight reduction.     

Weight management issues and strategies for people with high cardiovascular risk undertaking an Australian weight loss program: A focus group study

Obesity is particularly hazardous for people with multiple cardiovascular risk factors and existing cardiovascular disease, although few studies investigate experiences and perceptions of weight loss in this population. This study provides an understanding of participants' knowledge, attitudes, and experiences of managing multiple risk factors and/or existing cardiovascular disease of participants who were undertaking a weight loss program. Thirty‐five participants were recruited from the first 50 completing a multicomponent group‐based weight loss intervention designed to follow cardiovascular disease and diabetes disease management programs. Four focus group interviews were conducted using a semistructured interview schedule. Data were analyzed using an inductive approach, and themes developed. Participants found the process of weight loss to be complex, dynamic, and challenging, as the conflicting needs of existing health conditions, social support, ambivalence, and time limitations required careful balance. In response, participants determinedly developed and tested strategies based on simplified principles, establishing routines for new health habits and portion control, and going back to basics in food selection. Therefore, weight loss programs for this population need to be specifically tailored to support patients' efforts and strategies.     

Glycaemic control is essential for effective cardiovascular risk reduction across the type 2 diabetes continuum

The growing prevalence of diabetes, an established risk factor for cardiovascular disease, threatens to significantly increase the global burden of cardiovascular morbidity and mortality. The risk of cardiovascular mortality is substantially higher in individuals with early glucose intolerance than in those with normal glucose levels and the pathological changes in vascular function begin many years before the diagnosis of overt type 2 diabetes. Postprandial hyperglycaemia is particularly deleterious to vascular function, and impaired glucose tolerance (IGT) - but not impaired fasting glucose - and may be an independent risk factor for cardiovascular disease throughout the glucose intolerance continuum. Evidence that molecular mechanisms induced by postprandial hyperglycaemia contribute to vascular damage has further highlighted the importance of targeting this component of the metabolic syndrome. Indeed, clinical trials have failed to convincingly show that interventions targeting fasting hyperglycaemia significantly reduce diabetes-associated cardiovascular risk. It may be necessary to refocus therapy to target postprandial hyperglycaemia to effectively reduce cardiovascular risk in the diabetic population. There is now direct evidence that pharmacological intervention, in the form of acarbose, to reduce postprandial hyperglycaemia, can significantly decrease the risk of cardiovascular events in individuals with IGT or type 2 diabetes.     

Glycaemic control is essential for effective cardiovascular risk reduction across the type 2 diabetes continuum

The growing prevalence of diabetes, an established risk factor for cardiovascular disease, threatens to significantly increase the global burden of cardiovascular morbidity and mortality. The risk of cardiovascular mortality is substantially higher in individuals with early glucose intolerance than in those with normal glucose levels and the pathological changes in vascular function begin many years before the diagnosis of overt type 2 diabetes. Postprandial hyperglycaemia is particularly deleterious to vascular function, and impaired glucose tolerance (IGT) – but not impaired fasting glucose – and may be an independent risk factor for cardiovascular disease throughout the glucose intolerance continuum. Evidence that molecular mechanisms induced by postprandial hyperglycaemia contribute to vascular damage has further highlighted the importance of targeting this component of the metabolic syndrome. Indeed, clinical trials have failed to convincingly show that interventions targeting fasting hyperglycaemia significantly reduce diabetes‐associated cardiovascular risk. It may be necessary to refocus therapy to target postprandial hyperglycaemia to effectively reduce cardiovascular risk in the diabetic population. There is now direct evidence that pharmacological intervention, in the form of acarbose, to reduce postprandial hyperglycaemia, can significantly decrease the risk of cardiovascular events in individuals with IGT or type 2 diabetes.     

Diabetes management in older people: a focus on cardiovascular risk reduction

Cardiovascular disease remains the most common cause of death in persons with diabetes regardless of age. Increasing age combined with diabetes exert a synergistic effect on the vascular system increasing the atherosclerosis burden in older people with diabetes. Due to their high baseline risk, they stand to benefit most from interventions to reduce cardiovascular risk. Older people with diabetes are functionally heterogeneous and their management is challenging. Fit and independent individuals are likely to benefit from tight targets while a relaxed approach putting quality of life at the heart of management plans is more appropriate in the frail and dependent individuals with limited life expectancy.     

肥胖者或超重者血脂联素和心血管危险因素在减体重后的变化

目的：通过运动训练和饮食控制减体重，观察肥胖或超重者的血脂联素及心血管危险因素的变化特点。方法：对198名肥胖或超重者采取6周封闭管理形式集中减肥，严格控制饮食，进行运动训练。在减重前后对减体重较多的44名受试者采用酶联免疫法进行空腹血脂联素及胰岛素测定，同时测定全部受试者血脂、血糖及与肥胖有关的身体测量指标。结果：通过6周受试者体重下降后，血清脂联素明显升高，多元线性回归分析显示．减重前后BMI及HDL—C的差值成为影响减重前后血脂联素水平的差值的主要因素。受试者的腰围、臀围、腰臀围比、体脂含量及百分比、静息血压、总胆固醇、甘油三酯、低密度脂蛋白、胰岛素及胰岛素抵抗指数明显下降（P〈0．001）。结论：通过运动训练结合饮食控制的方法减轻体重，可有效提高肥胖或超重者血脂联素水平，减少心血管系统疾病的危险因素。     

Requirements for controlled clinical trials of preoperative cardiovascular risk reduction

Although controlled clinical trials have had a major impact in many areas of cardiovascular disease management, they have had little influence on preoperative cardiac risk reduction. Over the past 2 years, we have conducted the Reduction of Cardiac Operative Risk (RCOR) Trial, a pilot study designed to determine enrollment and event rates for a definitive trial evaluating a strategy to reduce cardiac risk associated with noncardiac surgery. This experience indicates that a successful, definitive trial will require recognition of the multiple questions to be answered, accurate identification of the study population, a large sample size, cooperation between internists, surgeons, and anesthesiologists, and strategies to minimize cost. The high costs and difficulties of such a trial are likely to be outweighed by the enormous benefit of identifying the proper strategy for the use of the expensive testing methods that are currently employed.     

Deficiencies of cardiovascular risk prediction models for type 1 diabetes

OBJECTIVE: Cardiovascular risk prediction models are available for the general population (Framingham) and for type 2 diabetes (U.K. Prospective Diabetes Study [UKPDS] Risk Engine) but may not be appropriate in type 1 diabetes, as risk factors including younger age at diabetes onset and presence of diabetes complications are not considered. Therefore, our objective was to examine the accuracy of Framingham and UKPDS models for predicting coronary heart disease (CHD) in a type 1 diabetic cohort. RESEARCH DESIGN AND METHODS: Ten-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a prospective cohort study of 658 subjects with childhood-onset type 1 diabetes diagnosed between 1950 and 1980 first seen in 1986-1988, were analyzed. EDC study data were used to calculate the 10-year probability of CHD (fatal CHD, nonfatal myocardial infarction, or Q-waves) applying to the Framingham and UKPDS equations. RESULTS: Mean age at CHD onset was 39 years. When fatal/nonfatal myocardial infarction and CHD death were modeled, both the UKPDS and Framingham models showed significant lack of calibration (P < 0.0001) but moderate discrimination (0.76 UKPDS, 0.77 Framingham men, and 0.88 Framingham women). Both the UKPDS and Framingham models underestimated probability of events in highest risk deciles. CONCLUSIONS: Currently available CHD models poorly predict events in type 1 diabetes. Future research should focus on determining the risk factors accounting for the lack of fit and developing prediction models specific to this high-risk group.     

Clinical experience with rosuvastatin in the management of hyperlipidemia and the reduction of cardiovascular risk

On the basis of large randomized clinical trials, pharmacological antagonists of HMG-CoA reductase (statins) have become increasingly used in clinical practice for the prevention of cardiovascular disease. Rosuvastatin was developed as a potent statin, which appeared to raise levels of HDL-cholesterol, in addition to marked reductions in levels of LDL-cholesterol. These effects on lipids are associated with a beneficial impact of rosuvastatin on progression of various stages of atherosclerosis and cardiovascular outcomes in clinical trials. The clinical experience of rosuvastatin will be reviewed in this article.     

Clinical experience with rosuvastatin in the management of hyperlipidemia and the reduction of cardiovascular risk

On the basis of large randomized clinical trials, pharmacological antagonists of HMG-CoA reductase (statins) have become increasingly used in clinical practice for the prevention of cardiovascular disease. Rosuvastatin was developed as a potent statin, which appeared to raise levels of HDL-cholesterol, in addition to marked reductions in levels of LDL-cholesterol. These effects on lipids are associated with a beneficial impact of rosuvastatin on progression of various stages of atherosclerosis and cardiovascular outcomes in clinical trials. The clinical experience of rosuvastatin will be reviewed in this article.