Worldwide association between diet with high glycemic index and increased MACE and death

Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality

Literature - Jenkins DJA, Dehghan M, Mente A, et al. - N Engl J Med. 2021 Feb 24. doi: 10.1056/NEJMoa2007123.

Introduction and methods

There is a general agreement on the value of whole grain and high-fiber foods for the prevention of chronic disease [1-5]. Ample data support a diet with low glycemic index (a rating system to measure how much 50 g of carbohydrate from a type of food raises the blood glucose level) for the prevention and treatment of diabetes, while data in regard to the association between a diet with a low glycemic index and reduction in CV risk are more mixed [2,6,7]. In addition, most of this data have been collected in high-income Western populations, with limited information from non-Western low or middle income countries. This study assessed the association between glycemic index and CVD and all-cause death in a diverse population from multiple countries and geographic and economic regions with a very broad dietary pattern.

The study used the international Prospective Urban Rural Epidemiology (PURE) study and included participants (n=137,851; 35-70 years) from 4 high-income, 11 middle-income and 5 low-income countries on 5 continents [8-10]. Participants filled out country-specific food-frequency questionnaires that covered a total of 3200 food items, with a range of 98 to 220 items per questionnaire to determine dietary intake. An individual’s mean glycemic index was estimated by weighting the glycemic indexes of seven carbohydrate categories (dairy: 38, fruit: 69, fruit juice: 68, vegetables: 54, starchy food: 93, legumes: 42, and soft drinks: 87) based upon the daily net carbohydrate consumption of the seven categories . A participant’s glycemic load was calculated by multiplying the mean net carbohydrate intake by the glycemic index and then dividing by 100 [11]. The primary outcome was a composite of MACE (CV death, non-fatal MI, stroke, or HF) or all-cause death. Secondary outcomes were the individual components of MACE and non-CV related death. Participants were stratified according to the presence or absence of CVD at baseline and grouped into quintiles of glycemic index and glycemic load. Median of the lowest glycemic index quintile was 76 (IQR 74-78) and for the highest quintile median was 91 (IQR 90-91). Median of lowest glycemic load quintile was 136 (IQR 111-155) g/day and median of highest glycemic load quintile was 468 (IQR 418-548) g/day. Median follow-up was 9.5 years (range 3.2-11.9 years).

Main results

  • The mean glycemic index calculated by the seven-category food approach was 81 compared to 77 by the conventional method (r=0.69), and captured 92.5% of the net carbohydrate in the diets of participants.
  • Fully adjusted regression analysis demonstrated an increased risk for the primary endpoint MACE and all-cause death for participants in the highest quintile of glycemic index compared to those in the lowest quintile in the total population (HR 1.25, 95% CI: 1.15-1.37) and among those with CVD (HR 1.51, 95% CI: 1.25-1.82) and without preexisting CVD (HR 1.21, 95% CI: 1.11-1.34). A high glycemic index was similarly associated with increased risk of death from CV causes, MACE, and stroke.
  • An high glycemic index was also significantly associated with an increased risk of non-CV death and all-cause death in the total cohort (both Ptrend<0.001), and in participants with CVD (non-CV death Ptrend=0.02; all cause death Ptrend=0.005) and without preexisting CVD (both Ptrend<0.001).
  • In individuals with baseline CVD and in the total population, high glycemic load was associated with increased risk for MACE and all-cause death compared to those with a low glycemic load. This association was absent among participants without preexisting CVD.
  • In persons with a BMI ≥25, high glycemic index was stronger associated with MACE or all-cause death compared to those with a BMI <25 (HR 1.38, 1.22-1.55 vs. HR 1.14. 1.00-1.30). There was no difference between the association of glycemic index and the primary outcome for exercise status (light or heavy), smoking, or the use of BP medications or statins.
  • High glycemic load had the strongest association with the primary outcome in the total population of high-income countries (HR 1.93, 95% CI: 1.05-3.53, Ptrend=0.01).


This study showed that individuals on a diet with a high glycemic index had an increased risk of CVD and all-cause death compared to those who consumed a diet with a low glycemic index.


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Find this article online at New Eng J Med

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