Updates on insulin resistance

Abstract

World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease

Hollywood, CA, USA, 1–3 November 2012

The World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease is a unique multidisciplinary program held on 1–3 November 2012 in Hollywood, CA, USA. It was well attended by a large contingent of endocrinologists, cardiologists, internists, diabetologists, obstetricians/gynecologists, pediatricians, dieticians, registered nurses and other healthcare professionals interested in insulin resistance. In recent years, the Congress has advanced awareness of the contribution of multiple endocrine and paracrine systems to obesity, diabetes and cardiovascular disease.

The World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease has become a multidisciplinary clinical environment that evaluates these multiple metabolic systems. The congress primarily focuses on innovative approaches in metabolic syndrome (MetS) patients to manage risk factors and concomitant disease, and the treatments that include both lifestyle modifications and medications. The Congress concluded with a special symposium, ‘Diabetes and the Heart’. Lectures in this closing session of the meeting focused on liver fat and cardiovascular disease (CVD), cardiovasvular (CV) thrombosis in diabetes, and incretins and their CV implications. This session also featured a lecture focusing on CVD screening in diabetes patients with coronary calcium scanning and noninvasive computed tomographic angiography.

Arun Sanyal, from Virginia Commonwealth University Health System (VA, USA), gave a talk discussing the links between fatty liver and CVD, entitled ‘NASH and the Cardiovascular Connection’. Patients with fatty liver had a 6.7-times higher probability to have CVD independent of features of the MetS. He presented data showed that cholesterol synthesis is increased in this disease, as a potential mechanism for the increased probability. He also presented studies supporting increased free cholesterol, lower HDL and increased inflammation. He noted more outcome studies are needed, but the associations known about nonalcoholic fatty liver disease and CVD are consistent.

Screening for heart disease

One of the more recent advances in the realm of diabetes and CVD is related to screening for heart disease among asymptomatic persons. Matthew Budoff, from Los Angeles Biomedical Research Institute (CA, USA) reminded the audience that although guidelines suggest that diabetes is a coronary heart disease (CHD) risk equivalent, and should qualify as ‘secondary prevention’, most studies have not supported this observation. Large epidemiologic trials have consistently demonstrated that not all persons with diabetes achieve a 20% 10-year CVD risk. One such large cohort is the MESA study, a population-based longitudinal observational study of 6814 men and women with no known CVD at entry. Many with diabetes in the MESA cohort did not reach the expected 2% annual CHD rate [1]. Malik et al. demonstrated that unless coronary artery calcium (CAC) was significant, CHD or CVD event rates in MetS and diabetes mellitus (DM) were as low as in those without these conditions [1]. This demonstrates that diabetes is not a universal CHD risk equivalent, but rather is dependent on the presence of atherosclerosis (calcified plaque in this study) to predict increased risk. In fact, in the 38% of those with diabetes who did not have CAC, the annual CHD event rate was <1%. These data support the concept that CAC screening strongly stratifies CHD and CVD event risk in individuals with MetS and diabetes. This further demonstrates that they have a wide range of risk based on the extent of CAC present. This finding is similar to a large meta-analysis [2], demonstrating that many individuals with diabetes are not at CHD-risk equivalent status and suggesting that treatment should be based on individualized CHD risk assessment. Calcium scoring consistently demonstrates that those with no detectable coronary calcium (score of 0) are at a very low risk, and those with elevated scores (typically >100) are at a seven- to ten-fold increased risk of CV events over the next 3–5 years. These consistent findings, across multiple studies, corroborate the recommendations of the 2010 guidelines, by the American Heart Association and the American College of Cardiology, and favor the use of CAC in assessment of CVD risk in asymptomatic adults, including those with diabetes aged >40 years. These have recommended screening with CAC testing in asymptomatic persons [3]. Those with the highest levels of CAC are at highest risk, which has been shown to help motivate such individuals (and their physicians) to be more adherent to or to intensify treatment recommendations. Similar outcome prediction was seen using CAC testing whether the person had MetS alone, DM alone or MetS and DM. The MESA study also looked at carotid intimal–media thickness, and found that CAC was a more powerful predictor of both CHD and CVD events in these groups as compared with carotid intimal–media thickness. These results are consistent with others who have shown, in large cohorts of persons with and without diabetes, CAC to improve prediction of total mortality over Framingham Risk Score [4]. The lecture also discussed the potential uses of computed tomographic angiography to evaluate soft plaque and early detection of heart disease, especially important in those with early onset atherosclerosis, such as persons with MetS and DM.

Peter Grant, from the University of Leeds School of Medicine in the UK, then gave an overview of ‘Cardiovascular Thrombosis in Diabetes’. Diabetes and CVD are conditions underpinned by an inflammatory atherothrombotic insulin resistance syndrome related to obesity. Plasminogen activator inhibitor-1 (PAI-1) is elevated in Type 2 DM (T2DM), and first degree relatives of persons with DM; this marker is associated with microalbuminuria. PAI-1 increased in relation to insulin resistance and obesity. It is predominantly produced by adipose tissue; it has been shown that weight loss leads to a fall in PAI-1, and this biomarker is elevated in venous thrombosis and acute myocardial infarction.

Obesity-related insulin resistance underpins this relationship, which is augmented by the development of hyperglycemia and increased glycation. Proatherogenic changes occur in endothelial cells, platelets and macrophages. Alterations occur in thrombosis, inflammation and nitric oxide production.

The closing talk was given by Richard P Shannon, the Chair, Department of Medicine at the University of Pennsylvania Perelman School of Medicine (PA, USA), on ‘The Effect of Anti-Hyperglycemia medications on CVD and CHF Focus on Incretins’.

CV safety has emerged as a critical factor in the development of new mechanism-of-action agents to treat diabetes. Classes of agents that have emerged during this period are those that modulate the incretin pathway, including native GLP-1 (7–36) amide, GLP-1 mimetics and DPP4 inhibitors. To establish the safety of a new T2DM therapy, pharmaceutical companies need to demonstrate that therapy will not result in an unacceptable increase in CV risk.

Currently, GLP-1 infusion studies have demonstrated improvement in regional and global left ventricular function in patients with acute myocardial infarction and congestive heart failure. Incretins have been shown to be effective agents in treatment of T2DM. Early CV outcomes in T2DM have also been favorable with several post-approval studies underway. Incretins may have a second indication as metabolic adjuvants in the treatment of heart failure. It remains uncertain as to which class is most effective in CV disease and comparative studies would be helpful.

More information about the society and upcoming congress meetings can be viewed online [101]. The next planned congress will be held on 7–9 November 2013 in Los Angeles, CA, USA.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.