Background: Metabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type-2 diabetes and coronary artery disease (CAD). The Lipoprotein Insulin Resistance (LP-IR) index, derived from measures of lipoprotein subclass particle concentration and size, is useful for assessing IR and identifying patients with increased diabetes/CAD risk.
Hypothesis: This study addressed the hypothesis that lifestyle modification programs differing in scope and intensity both improve IR through changes in lipoprotein profiles.
Methods: Patients with CAD or significant CAD risk factors participated in one of two clinical lifestyle interventions: 1) an intensive nonrandomized program with a strict vegetarian diet (n=90 subjects, 90 matched controls) or 2) a moderate randomized trial following a Mediterranean-style diet (n=89 participants, 58 controls). On-treatment and intention-to-treat analyses used regression modelling adjusted for CAD risk factors and lipid-lowering medication use to assess changes over one year in LP-IR, lipoprotein profiles, and CAD risk factors in intervention and control participants in both programs.
Results: Participants in the intensive lifestyle intervention had poorer baseline cardiovascular health than patients in the moderate program. In the on-treatment analysis, both lifestyle interventions led to weight loss [-8.9% (95% CI: -10.3, -7.4), intensive program; -2.8% (95% CI: -3.8, -1.9), moderate program; adjusted p<0.001] and a decrease in the LP-IR index [-13.3% (95% CI: -18.2, -8.3), intensive; -8.8% (95% CI: -12.9, -4.7), moderate; adjusted p<0.01] compared to respective controls over one year. Of the six lipoprotein parameters comprising LP-IR, only large very-low-density lipoprotein (VLDL) particle concentrations decreased significantly in patients compared to controls in both programs [-26.3% (95% CI: -43.0, -9.6), intensive; -14.2% (95% CI: -27.4, -1.0), moderate; p<0.05]. Intention-to-treat analysis confirmed and strengthened the primary results.
Discussion: In conclusion, moderate lifestyle modification following a Mediterranean diet is comparable to a stringent intervention with a vegetarian diet for improving IR defined by the LP-IR index. Significant reductions in large VLDL particles may drive improvement in IR irrespective of the magnitude of lifestyle changes.