Components of metabolic syndrome and 5‐year change in insulin clearance – the Insulin Resistance Atherosclerosis Study

Abstract

Aims Cross-sectional evidence indicates that abdominal adiposity, hypertension, dyslipidemia and glycemia are associated with reduced metabolic clearance of insulin (MCRI). Little is known about the progression of MCRI and whether components of metabolic syndrome are associated with the change in MCRI. In this study, we examined the association between components of metabolic syndrome and the 5-year change of MCRI. Methods and Materials At baseline and 5-year follow-up, we measured fasting plasma triglycerides (TG), high density lipoprotein (HDL)-cholesterol, blood pressure (BP), waist circumference (WC) and fasting blood glucose (FBG) in 784 non-diabetic participants in the Insulin Resistance Atherosclerosis Study. MCRI, insulin sensitivity (SI) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Results We observed a 29% decline of MCRI at follow-up. TG, systolic BP and WC at baseline were inversely associated with a decline of MCRI regression models adjusted for age, sex, ethnicity, smoking, alcohol consumption, energy expenditure, family history of diabetes, BMI, SI and AIR (β= −0.057 [95% CI −0.11, −0.0084] for TG, β= −0.0019 [95% CI −0.0035, −0.00023] for systolic BP, β= −0.0084 [95% CI −0.013, −0.0039] for WC; all p<0.05). Higher HDL-cholesterol at baseline was associated with an increase in MCRI (multivariable-adjusted β= 0.0029 [95% CI 0.0010, 0.0048], p=0.002). FBG at baseline was not associated with MCRI at follow-up (multivariable-adjusted β= 0.0014 [95% CI −0.0026, 0.0029]). Conclusions MCRI declined progressively over 5 years in a non-diabetic cohort. Components of metabolic syndrome at baseline were associated with a significant change in MCRI.

Insulin Clearance Is Associated with Hepatic Lipase Activity and Lipid and Adiposity Traits in Mexican Americans

“…This is consistent with prior studies linking decreased insulin clearance with an adverse metabolic profile and increased risk of diabetes [4, 12, 37–39]. …”

“…Other studies have shown a positive correlation between HDL-C and MCRI; however, the multivariate models in these studies did not include apoA-I [12, 37]. The physical relationship of apoA-I and HDL may explain why HDL-C level did not correlate with MCRI when analyzed jointly.…”

“…While large scale studies have investigated the relationship of anthropometric, cardiovascular, glucose homeostasis, and lipid trait domains with insulin clearance derived from the frequently sampled intravenous glucose tolerance test [12, 37, 39], until now no extensive study looking at multiple domains had been performed using euglycemic clamp-derived insulin clearance. The availability of multiple traits in the MACAD cohort allowed interrogation of several key domains, including commonly available traits (e.g., BMI) as well as more unique traits (e.g., total fat mass).…”

Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)

“…The inverse association between plasma BCAAs and insulin clearance could be linked through metabolic syndrome. Previous studies have shown that metabolic syndrome is associated with reduced insulin clearance (26,27) and, further, that the gene expression of BCAA catabolic enzymes is reduced in individuals with metabolic syndrome (28). Although the significant association between BCAAs and insulin clearance remained after additional adjustment for waist circumference, HDL cholesterol, systolic blood pressure, and plasma triglycerides, the magnitude of the association was attenuated, suggesting that these components of metabolic syndrome may, in part, link plasma BCAA to insulin clearance.…”

Differential Effects of Red Meat/Refined Grain Diet and Dairy/Chicken/Nuts/Whole Grain Diet on Glucose, Insulin and Triglyceride in a Randomized Crossover Study

“…Therefore, only half of the increase in insulin was attributable to increased glycemic load and the other half was due to insulin resistance. Several studies showed that decreased insulin sensitivity was associated with decreased insulin clearance [19,20,21], and reduced insulin clearance correlated with risk of incidence of T2DM [22]. The Insulin Resistance Atherosclerosis Study 5-year follow-up showed a negative correlation between plasma plasminogen activator inhibitor (PAI)-1 concentrations and insulin clearance [23].…”