Comparing the Effects of Consuming Egg-based Breakfast Meals, versus Higher Carbohydrate Breakfast Meals, on Cardiometabolic Risk Factors

Comparing the Effects of Consuming Egg-based Breakfast Meals, versus Higher Carbohydrate Breakfast Meals, on Cardiometabolic Risk Factors

By Mary R Dicklin, PhD and Kevin C Maki, PhD, CLS, FNLA

 

Recently, our group conducted a clinical trial that compared the effects of consuming egg-based breakfast meals with non-egg, higher carbohydrate breakfast meals on cardiometabolic risk factors in overweight or obese adults with prediabetes and/or metabolic syndrome.1  Thirty men and women with a mean age of 54.1 years and mean body mass index of 31.9 kg/m2 incorporated into their habitual diets either breakfast meals containing 2 eggs per day for 6 days per week, or energy-matched, non-egg higher-carbohydrate-based meals, for a 4-week period.  After a 4-week washout, subjects crossed over to the other diet condition for a second 4-week period.  The non-egg breakfast meals had, on average, 25 g higher mean sugar content than the egg breakfasts, and the egg breakfast meals had 19 g higher protein content.  Consumption of 12 eggs/week contributed ~315 mg/d of cholesterol to the diet.  Compared to baseline, dietary cholesterol intake was 128 mg/d lower during the non-egg condition and 232 mg/d higher during the egg condition.  Total daily energy intake from diet record analyses during the egg condition was significantly higher than that reported during the non-egg condition (2145 vs. 1996 kcal), but this difference was determined to be due to the intake of foods other than the study products, and there was no significant difference in weight change between the diet conditions.

The primary outcome variable, an insulin sensitivity index from a short intravenous glucose tolerance test, was not significantly altered by either diet condition, and there were no significant differences between or within diet conditions for most other carbohydrate metabolism indicators.  Homeostasis model insulin resistance increased by 24% from baseline during the non-egg condition and was not significantly altered (1.4% increase) during the egg condition, resulting in a significant difference in response between conditions (p = 0.028 between diet conditions).

Low-density lipoprotein cholesterol (LDL-C) declined less from baseline (-2.9%) during the egg vs. the non-egg condition (-6.0%; p = 0.023 between diet conditions), and systolic blood pressure was reduced by 2.7% during the egg condition but was unchanged during the non-egg condition (p = 0.018 between diet conditions).  There were no other significant differences noted in the cardiometabolic risk factor profile.

These results suggest that there was a neutral or modestly favorable effect of egg intake on insulin sensitivity associated with the replacement of higher carbohydrate, non-egg-based foods by egg-based foods at the breakfast meal.  Prior research from our group showed that partial replacement of carbohydrate with a combination of unsaturated fatty acids and egg protein increased insulin sensitivity by 24%.4  Another study by our group showed that 3 servings/day of sugar-sweetened products reduced insulin sensitivity by 18% (HOMA2-%S) compared to the baseline habitual diet, whereas 3 servings/day of dairy products produced no change.5

The Dietary Guidelines for Americans 2015-2020, unlike previous editions, removed the recommendation to limit dietary cholesterol to <300 mg/d, and did not set a limit on egg consumption in a healthy diet.6,7  The 2018 American Heart Association (AHA)/American College of Cardiology/Multi-society Guideline on the Management of Blood Cholesterol also made no specific recommendations on dietary cholesterol.8  Levels of LDL-C were reduced from baseline during both diet conditions in our study.  However, the decline was larger during the non-egg condition (6.0% vs. 2.9%).  With a difference in daily cholesterol intake of ~360 mg/d, the difference in median LDL-C between conditions was 7 mg, or approximately 1.9 mg/dL per 100 mg/d difference in dietary cholesterol.  This difference is approximately what would have been predicted based on linear meta-regression models developed by our group and others.9,10

A recent Science Advisory from the AHA recommended that healthy individuals can include up to one whole egg or equivalent per day as part of a healthy dietary pattern.11  The results from our study are consistent with this recommendation.  Eggs contain cholesterol, but are also a source of important nutrients including unsaturated fatty acids, high quality protein, vitamin D, carotenoids, and choline.12

 

References

  1. Maki KC, Palacios OM, Kramer MW, Trivedi R, Dicklin MR, Wilcox ML, Maki CE. Effects of substituting eggs for high-carbohydrate breakfast foods on the cardiometabolic risk factor profile in adults at risk for type 2 diabetes mellitus. Eur J Clin Nutr. 2020;E-pub ahead of print.
  2. Gadgil MD, Appel LJ, Yeung E, Anderson CA, Sacks FM, Miller ER, 3rd. The effects of carbohydrate, unsaturated fat, and protein intake on measures of insulin sensitivity: results from the OmniHeart trial. Diabetes Care. 2013;36:1132-1137.
  3. Chiu S, Williams PT, Dawson T, Bergman RN, Stefanovski D, Watkins SM, Krauss RM. Diets high in protein or saturated fat do not affect insulin sensitivity or plasma concentrations of lipids and lipoproteins in overweight and obese adults. J Nutr. 2014;144:1753-1759.
  4. Maki KC, Palacios OM, Lindner E, Nieman KM, Bell M, Sorce J. Replacement of refined starches and added sugars with egg protein and unsaturated fats increases insulin sensitivity and lowers triglycerides in overweight or obese adults with elevated triglycerides. J Nutr. 2017;147:1267-1274.
  5. Maki KC, Nieman KM, Schild AL, Kaden VN, Lawless AL, Kelley KM, Rains TM. Sugar-sweetened product consumption alters glucose homeostasis compared with dairy product consumption in men and women at risk of type 2 diabetes mellitus. J Nutr. 2015;145:459-466.
  6. Dietary Guidelines Advisory Committee. Scientific Report of the 2015 Dietary Guidelines Advisory Committee: Advisory Report of the Secretary of Health and Human Services and the Secretary of Agriculture. U.S. Department of Agriculture, Agricultural Research Service, Washington, DC. Available at: https://health.gov/sites/default/files/2019-09/Scientific-Report-of-the-2015-Dietary-Guidelines-Advisory-Committee.pdf.
  7. S. Department of Health and Human Services and U.S. Department of Agriculture. 2015 – 2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Available at http://health.gov/dietaryguidelines/2015/guidelines/.
  8. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC, Jr., Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASI guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-e1143.
  9. Clarke R, Frost C, Collins R, Appleby P, Peto R. Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ. 1997;314:112-117.
  10. Vincent MJ, Allen B, Palacios OM, Haber LT, Maki KC. Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol. Am J Clin Nutr. 2019;109:7-16.
  11. Carson JAS, Lichtenstein AH, Anderson CAM, Appel LJ, Kris-Etherton PM, Meyer KA, Petersen K, Polonsky T, Van Horn L; American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Peripheral Vascular Disease; and Stroke Council. Dietary cholesterol and cardiovascular risk: a science advisory from the American Heart Association. Circulation. 2020;141:e39-e53.
  12. US Department of Agriculture, Agricultural Research Service, Nutrient Data Laboratory. USDA National Nutrient Database for Standard Reference, Release 28. Version Current: September 2015, slightly revised May 2016.  Available at: https://www.ars.usda.gov/northeast-area/beltsville-md-bhnrc/beltsville-human-nutrition-research-center/methods-and-application-of-food-composition-laboratory/mafcl-site-pages/sr11-sr28/.

 

Photo by Morgane Perraud

Comparing the Effectiveness of Second-line Antidiabetic Medications on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

Comparing the Effectiveness of Second-line Antidiabetic Medications on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

By Mary R Dicklin, PhD and Kevin C Maki, PhD, CLS, FNLA

 

Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes (T2D).1  Metformin is widely recommended as first-line therapy, but metformin alone may be inadequate for achieving glycemic control, or may not be tolerated, in which case clinicians have several second-line antidiabetic medication (ADM) prescription options.2  The second-line ADMs include sulfonylureas (SFUs), thiazolidinediones (TZDs), insulin, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose-cotransporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors.3  Understanding how these ADMs differ in their effects on cardiovascular outcomes may assist clinicians in preventing comorbidities in patients with diabetes.

 

Results were recently published from a large, retrospective cohort study that examined major adverse cardiovascular events among insured adults with T2D who had recently started therapy with a second-line ADM after either taking metformin alone or not having received prior ADM.4  Nationwide U.S. administrative claims data were used from 2011-2015.  The primary outcome of the study was time to first cardiovascular event (defined as the composite of hospitalization for congestive heart failure, stroke, ischemic heart disease or peripheral artery disease) after starting a second-line ADM.  Patients were censored after either their first cardiovascular event, discontinuation of insurance coverage, transition of medical claims data coding from the International Classification of Diseases 9th revision to the 10th revision, or two years of follow up.

 

Among the 132,737 adults evaluated in this study, SFUs were used by 47.6%, DPP-4 inhibitors by 21.8%, basal insulin by 12.2%, GLP-1 receptor agonists by 8.6%, TZDs by 5.6% and SGLT-2 inhibitors by 4.3%.4  During the 169,384 person-years of follow-up there were 3480 incident cardiovascular events.  After adjusting for patient, prescriber and health plan characteristics, the risk of composite cardiovascular events according to second-line ADM was determined.  DPP-4 inhibitors were considered to have a neutral effect on cardiovascular outcomes, based on previous clinical trial evidence.5-7  Thus, DPP-4 inhibitor use was the referent (1.0) in the Cox proportional hazard regression analysis.4  The hazard ratios (95% confidence intervals) were:

  • DPP-4 inhibitors: 1.00 (reference)
  • GLP-1 receptor agonists: 0.78 (0.63-0.96)
  • SGLT-2 inhibitors: 0.81 (0.57-1.53)
  • TZDs: 0.92 (0.76-1.11)
  • SFUs: 1.36 (1.23-1.49)
  • Basal insulin: 2.03 (1.81-2.27)

 

Higher cardiovascular risk was associated with use of SFUs or basal insulin.  The risk associated with GLP-1 receptor agonist use was lower than with DPP-4 inhibitor use, but this finding was not statistically significant in all of the sensitivity analyses.  The risks associated with SGLT-2 inhibitors and TZDs were not significantly different from DPP-4 inhibitors.

 

Recent randomized clinical trials that have evaluated the cardiovascular risk associated with newer ADMs have also suggested reduced cardiovascular events.8,9  Unlike those randomized trials, in which most of the participants already had cardiovascular disease, just 5.5% of participants in this observational study had a history of prior cardiovascular events, although cardiovascular risk factors, such as dyslipidemia (61.6%) and hypertension (70.1%), were present in the majority of subjects.

 

In summary, these results suggest that, with regard to managing cardiovascular comorbidity in their patients with T2D, after metformin, clinicians may consider prescribing any of the newer ADMs (i.e., GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors) that were shown to be similarly associated with lower cardiovascular risk, instead of SFUs or basal insulin, which were associated with greater cardiovascular risk.

 

References:

  1. American Diabetes Association. 10. Cardiovascular disease and risk management: Standard of medical care in diabetes – 2019. Diabetes Care. 2019;42(Suppl 1):S102-S123.
  2. American Diabetes Association. 3. Prevention or delay of type 2 diabetes: Standards of medical care in diabetes – 2019. Diabetes Care. 2019;42(Suppl 1):S29-S33.
  3. Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Cardiol. 2017;120:S4-S16.
  4. O’Brien MJ, Karam SL, Wallia A, et al. Association of second-line antidiabetic medications with cardiovascular events among insured adults with type 2 diabetes. JAMA Network Open. 2018;1:e1816125.
  5. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-1326.
  6. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232-242.
  7. White WB, Kupfer S, Zannad F, et al. Cardiovascular mortality in patients with type 2 diabetes and recent acute coronary syndromes from the EXAMINE trial. Diabetes Care. 2016;39:1267-1273.
  8. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2018; Epub ahead of print.
  9. Sposito AC, Berwanger O, de Carvalho LSG, Saraiva JFK. GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data. Cardiovasc Diabetol. 2018;17:157.
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