Date of Award


Document Type

Open Access Dissertation


Epidemiology and Biostatistics


Norman J. Arnold School of Public Health

First Advisor

Anwar T. Merchant


Introduction: Much evidence shows that the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) style diet are associated with risk reduction of cardiometabolic disease as well as lower risk of all-cause, cardiovascular disease (CVD), and cancer mortality. A subgroup of obese individuals (metabolically healthy obese (MHO) phenotype) and normal weight individuals (metabolically obese normal weight (MONW) phenotype) have been identified to have different cardiometabolic risks compared with their counterparts in the same category of body mass index (BMI). Scarce evidence exists demonstrating a relationship between adherence to Mediterranean diet or DASH style diets with MHO and MONW phenotypes, or on the role of MHO and MONW phenotypes as important effect modifiers of the relationship between Mediterranean and DASH style diets with mortality risk. In addition, it is unclear how much the adjustment for adiposity modifies or attenuates the association of the Mediterranean diet and DASH style diet with cardiometabolic risk.

Methods: Data from adults aged 20-90 years were analyzed from participants of the National Health and Nutrition Examination Survey III, 1988–1994 with its mortality file linked until December 31, 2011. Mediterranean diet scores (MDS) and DASH index were calculated using food frequency questionnaires and the 24-hr dietary recall data. MHO and MONW individuals were identified using the criterion including high fasting glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein, and low high-density lipoprotein-cholesterol. For aim 1, multiple logistic regression analyses were conducted to generate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the associations of tertiles of MDS and DASH index with the presence of MHO and MONW phenotypes. For aim 2, multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of mortality across the tertiles of MDS and DASH index and 1-SD increment of MDS and DASH index. For aim 3, multiple linear regression analyses were applied using traditional and causal mediation analysis to estimate the regression coefficients between diet score, obesity parameters, and markers for insulin resistance and inflammation.

Results: For aim 1, higher MDS was associated with higher odds of MHO phenotype (tertile 3 vs 1; OR, 2.57 [95% CI, 1.04-6.35]; P trend = 0.04), whereas higher DASH index was associated with lower odds of MONW phenotype (tertile 3 vs 1; OR, 0.59 [95% CI, 0.38-0.93]; P trend = 0.03) only in the younger age group, after adjusting for potential confounders. For aim 2, in MHO individuals, the multivariable-adjusted HR of all-cause mortality in the highest tertile compared to the first tertile of MDS was 0.44 (95% CI, 0.26-0.75; P for trend <0.001). The corresponding HR was 0.23 (95% CI, 0.02-2.10; P for trend = 0.03) for cancer mortality. A 5-point increment in the adherence to MDS was associated with a 43% reduction in the risk of all-cause mortality (HR, 0.59; 95% CI, 0.37-0.94). However, no risk reduction of all-cause, CVD, and cancer mortality was found in MUO phenotype. In MONW individuals, 1-SD increment in the adherence to DASH style diet was significantly associated with 23% reduction in the risk of all-cause mortality (HR, 0.77 [95% CI, 0.66-0.90]), after adjustment for potential confounders. The corresponding HRs for CVD mortality were 0.70 (95% CI, 0.53-0.93). However, no association was observed in MHNW phenotype. For aim 3, waist circumference mediated the association of MDS with log insulin, log HOMA-IR, fasting glucose, post-load glucose, HbA1c, log hs-CRP, white blood cell, and fibrinogen, with proportion of mediation ranging from 14.4% to 42.3%. In addition, the mediated effects of waist circumference were greater than those of BMI consistently in all markers in both traditional and causal mediation analysis. However, no mediation effect by adiposity was observed in the association of DASH style diet with the markers for insulin resistance and inflammation.

Conclusions: Adherence to Mediterranean diet or DASH style diet was associated with MHO and MONW phenotypes only in the younger age group, suggesting that potential dietary intervention to prevent cardiometabolic disease may be different by age group. Adherence to a Mediterranean dietary pattern appears to improve longevity in the MHO phenotype within an obese population, whereas higher DASH index was associated with a lower risk of mortality in MONW adults. Waist circumference mediated the association of the Mediterranean diet with insulin resistance and inflammation to a greater extent than BMI, suggesting that lowering abdominal obesity may be one of the pathways through which the Mediterranean diet reduces insulin resistance and inflammation.

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