Notes from the world congress on insulin resistance, diabetes, and cardiovascular disease

Abstract

The 16th annual World Congress on Insulin Resistance, Diabetes, and Cardiovascular disease (WCIRDC) was held in Los Angeles, California, on November 29-December 1, 2018. It is fascinating that this topic has remained so important to our understanding and of the development of cardiometabolic conditions and to new therapeutic approaches. The Congress addressed a wide spectrum of conditions related to insulin resistance and new understandings of obesity: fat cells, diabetes, circadian related pathology, cardiovascular (CV), renal, and hepatic disease. This year the Congress honored and celebrated the science and life of its co-founder, Professor Gerald Reaven from Stanford University, who recently passed away. Ronald Krauss, Oakland, CA reviewed new concepts of the relationship between diet and cardiovascular disease and dyslipidemia. He pointed out that population-based dietary studies are flawed by inaccuracies of recall, as well as by the challenge of incomplete ascertainment of confounders and covariates. Furthermore, simplistic attribution of changes in outcome to variations in one nutrient must take into account corresponding increases and decreases in others. Nevertheless, many studies now strongly suggest that dietary saturated fats (SFA) are not causally related to CVD. However, SFA from meat is associated with higher and from dairy with lower CVD risk, suggesting additional mediators such as trimethylamine N-oxide, a byproduct of the microbiome in response to red meat. High intake of simple carbohydrates (CHO) appeared to be most strongly associated with mortality, most strongly shown in the PURE study, in which 135 335 persons from 18 countries were compared. In this study, both SFA and unsaturated fat intake were associated with lower mortality. Furthermore, higher dietary CHO were associated with lower LDL and HDL cholesterol and apolipoproteins B and A1, with the apoB/apoA1 ratio appearing to be a somewhat better predictor, decreasing with higher dietary SFA. A number of other studies suggest this ratio to be an important CVD risk marker, one which is associated with higher levels of small, dense LDL particles, which reflect lower insulin sensitivity. Insulin resistance is associated with higher levels of inflammatory mediators such as C-reactive protein (CRP). Brendan Everett, Boston, MA discussed the role of inflammation in CVD, initially remarked upon with the “common soil hypothesis” that there is a linkage of both diabetes and CVD to an underlying condition, with inflammation, as well as insulin resistance, likely as the underlying explanatory mediator. The strong relationships between interleukin-6 and diabetes, and between CRP and both CVD and vascular death, suggests inflammation as a therapeutic target. This hypothesis was given further support in a large trial of rosuvastatin treatment of persons with elevated CRP, showing that along with reduction in LDL cholesterol was a nearly as great reduction in CRP, and with decrease in risk of a variety of CVD endpoints, including mortality, appearing to be linked to the lipid and CRP changes. A CVD outcome trial of administration of canakinumab, a human monoclonal antibody targeting interleukin-1β, to 10 061 patients with previous myocardial infarction and CRP ≥2 mg/L, showed reduction both in CRP and in CVD endpoints. Everett suggested, however, that “inflammation reduction is a catchall term that applies to a wide array of intricate biological processes,” so that anti-inflammatory treatments may or may not be disease-modifying, with a small study showing reduction in CVD with a low dose of colchicine, but a more recent trial of methotrexate not showing benefit. Whatever the contributory role of inflammation in the pathology of atherosclerosis, the outcome of the interventions studied to date suggest that treatment of established CVD with antiinflammatory agents may be “too late” to reverse the damage. Along these lines, Sanjay Kaul, Los Angeles, CA argued that the results of the canakinumab study decidedly did not constitute “extraordinary proof [of the] extraordinary claim” that such an approach might be beneficial, going into the complexities of interpreting such complex interventions. Timothy Garvey, Birmingham, AL discussed treatment of obesity as a crucial approach to stemming the diabetes epidemic, reviewing the large number of lifestyle and pharmacologic interventions, and the potential role of bariatric surgery, so that “we can do this,” but stressed the urgency of such approaches, with some 40% of the US population having either diabetes or prediabetes (and similar prevalences DOI: 10.1111/1753-0407.12888