Temporal and mediation relations of weight loss, and changes in insulin resistance and blood pressure in response to 2-year weight-loss diet interventions: the POUNDS Lost trial

Purpose Body weight and insulin resistance (IR) are closely correlated, and their temporal sequences in affecting blood pressure (BP) remain poorly defined. We examined the temporal sequences of weight loss and IR change, and their relations with BP in the Pounds Lost trial, a randomized weight-loss diet intervention study. Methods The present study included overweight/obese adults, who were randomized in a 2 x 2 factorial design to low-calorie diets containing 20 or 40% fat and 15 or 25% protein (diets with 65, 55, 45 and 35% carbohydrate). Weight, IR, systolic and diastolic BP levels were measured at baseline, 6 and 24 months. After excluding the subjects who took antihypertensive drugs, cross-lagged path and mediation analyses were performed among 540 participants. Results After adjusting for age, race, sex, and diet groups, the cross-lagged path coefficient from baseline weight to 24-month IR (beta(1) = 0.135, P = 0.04) was significantly greater than the path coefficient (beta(2) = 0.022, P > 0.05) from baseline IR to 24-month weight (P < 0.05 for the difference in beta s), indicating that weight-loss preceded change of IR. The mediation effects of 24-month IR on the 24-month systolic BP and diastolic BP were estimated at 20.94% (P = 0.004) and 17.03% (P = 0.034), respectively. Conclusions Our data indicate that weight loss precedes change of IR, which mediates a significant proportion of the effects of weight loss on changes of BP in response to the diet interventions.