DIETARY CHOLESTEROL LOWERS RISK OF TYPE 2 DIABETES IN THE FRAMINGHAM OFFSPRING STUDY
Authors: Mott Melanie M. , Singer Martha , Bradlee M. Loring , Moore Lynn L. 
Published: November 2023

Beginning in the 1960s, limiting dietary cholesterol (DC) was widely considered a strategy for protecting against cardiovascular disease (CVD) risk. Recently, the 2013 American College of Cardiology/American Heart Association Lifestyle Guidelines for the Reduction of Cardiovascular Disease concluded that the evidence was insufficient to support continued restriction of DC intake for prevention of CVD; the Dietary Guidelines Advisory Committee no longer considers DC to be a “nutrient of concern”. However, questions remain about whether DC is a risk factor for type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the effects of DC alone and in combination with selected markers of a healthy diet (e.g. fruits & vegetables, whole grains, fiber) on fasting glucose (FG) and risk of developing T2DM. Men and women without T2DM who were 35–64 years of age at the time of dietary assessment in the Framingham Offspring Study were included these analyses and followed for 20 years. Three‐day food records were collected at exams 3 and 5. Individuals were classified according to sex‐specific DC intake (low, moderate, and high intakes for men: <200, 200–<400, and ≥400 mg/day; for women: <150, 150–<350, and ≥350 mg/day). Longitudinal mixed models were used to estimate the adjusted mean fasting glucose (FG) at five follow‐up exams, 4 years apart. Cox proportional hazard's models were used to estimate the risk of developing T2DM; final models were adjusted for age, education, physical activity, cigarette smoking, alcohol intake, and baseline body mass index (BMI). At baseline, men consuming ≥400 mg of DC had lower mean FG than those consuming <200 mg (FG: 93.8 vs 96.6, p‐trend: 0.0006); results were similar in women. There was no evidence that higher DC intake had an adverse effect on FG throughout all years of follow‐up. Among both men and women, longitudinal mixed models showed that those consuming the highest (vs. lowest) amounts of DC had the lowest FG levels at baseline (p<0.0001) and lowest throughout the 20 years of follow‐up (p=0.0008). In addition, those subjects with high intakes of DC had a 22% lower risk of developing T2DM (HR: 0.78; 95% CI: 0.52–1.15) over time. To evaluate the combined effects of DC and other healthy diet patterns, we cross‐classified subjects according to their intake of both DC and the particular food serving as a marker of a healthy diet. The foods most strongly associated with a lower risk of T2DM and that modified the effects of DC were whole grains and fiber. Adults consuming ≥300 mg/day of DC and ≥0.5 servings/day of whole grains had a 38% lower risk of developing T2DM (95% CI: 0.41–0.93), while those consuming ≥300 mg/day of DC who had low whole intakes had only a 21% lower risk and those with lower DC intakes but higher intakes of whole grains had a 13% lower risk. These results suggest a positive synergistic effect between DC and whole grain consumption. Dietary fiber also modified the effects of DC on T2DM risk. Subjects consuming ≥300 mg/day of DC and ≥15 grams of dietary fiber had a 43% lower risk of T2DM (95% CI: 0.40–0.83) than those consuming less DC and less fiber. These results suggest that higher intakes of DC do not adversely affect fasting glucose levels or risk of T2DM and may even be beneficial when consumed in combination with a healthy diet.Support or Funding InformationNational Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. HHSN268201500001I) and a small grant from the American Egg Board ‐ Egg Nutrition Center.