Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years

Abstract

A high level of circulating triglycerides is a risk factor for type 2 diabetes, myocardial infarction, ischemic heart disease, and all-cause mortality (1-4). A recent Mendelian randomization study supports a causal effect of triglycerides on coronary heart disease risk (5). Regulation of blood levels of triglycerides involves a complex interplay implicating both the liver and pancreas. Some of the important players in this regard are body adiposity, insulin resistance, and glucose homeostasis (6). In addition, circulating triglyceride levels are heritable, as shown in a recent population-based study of twins (H 2 = 0.59; h 2 = 0.33) (7). Genetic association studies have identified more than 40 SNPs Abstract Blood concentrations of triglycerides are influenced by genetic factors as well as a number of environmental factors, including adiposity and glucose homeostasis. The aim was to investigate the association between a serum triglyceride weighted genetic risk score (wGRS) and changes in fasting serum triglyceride level over 5 years and to test whether the effect of the wGRS was modified by 5 year changes of adiposity, insulin resistance, and lifestyle factors. A total of 3,474 nondiabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5 year follow-up physical examinations and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex, and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years [per allele effect = 1.3% (1.0-1.6%); P = 1.0 × 10 17 ]. This triglyceride-increasing effect of the wGRS interacted with changes in insulin resistance (P interaction = 1.5 × 10 6). This interaction indicated that the effect of the wGRS was stronger in individuals who became more insulin resistant over 5 years. In conclusion, our findings suggest that increased genetic risk load is associated with a larger

Causal relationships between lipid and glycemic levels in an Indian population: A bidirectional Mendelian randomization approach

“…It was also observed in the Danish Inter99 cohort, which included 3,474 non-diabetic individuals, that over a period of 5 years a wGRS comprised of 39 genetic variants was associated with an increase in serum triglyceride levels and change in insulin resistance acted as an effect modifier. Although the results indicated that increased insulin resistance accentuated the effect of wGRS, no causality can be deduced from these findings [38].…”

An 8-week ketogenic diet improves exercise endurance and liver antioxidant capacity after weight loss in obese mice

“…Therefore, incorporating a ketogenic diet may unlock greater metabolic efficiency in the human body (29). High serum TC and TG are closely associated with many health problems including atherosclerosis, type 2 diabetes and coronary heart disease (44,45). Lei et al found that a high-fat diet for 11 weeks exhibited significantly higher TC and TG levels compared to non-obese mice on a normal diet (46).…”