Tina Costacou

Contributions to Public Health

• The role of diet in disease causation has been extensively studied. Within the EPIC study, I was active in developing statistical methodology that overcomes complexities of dietary data analysis (e.g., multiple testing, high correlations). We focused on dietary pattern assessment and extended to both a priori and a posteriori approaches. Manuscripts published described the methodology used, the dietary patterns derived and their relationship to mortality.

  • Costacou T, Bamia C, Ferrari P, Trichopoulou A, Trichopoulos D. Tracing the Mediterranean diet through principal components and cluster analyses in the Greek population. Eur J Clin Nutr. 2003;57(11):1378-1385.
  • Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348(26):2599-2608.
• Although oxidative stress has been implicated in vascular disease pathophysiology, clinical trials largely failed to show protection with antioxidant supplementation. We hypothesized that antioxidants are beneficial only in subgroups inadequately able to respond to (oxidative/inflammatory) stress. Indeed, the plasma α-tocopherol (antioxidant) to urinary isoprostanes (oxidant) ratio –used as a measure of response to stress- and adiponectin trajectories were negatively related to CAD incidence. Importantly, Hp 2 allele was associated with elevated isoprostane and WBC levels.
  • Costacou T, et al. Oxidative stress and response in relation to coronary artery disease in type 1 diabetes. Diabetes Care 2013;36(11):3503-3509. PMCID: PMC3816903
  • Costacou T, et al. Does the concentration of oxidative and inflammatory biomarkers differ by Haptoglobin genotype in type 1 diabetes?  Antioxidants and Redox Signaling 2015;23(18):1439-1444. doi: 10.1089/ars.2015.6355. PMCID: PMC4692105.
• Hp 2-2 genotype is associated with diabetic heart and kidney complications. I have led this research in type 1 diabetes, showing a strong independent association between the Hp 2 allele and the incidence of CAD, declining kidney function, end-stage renal disease, and cardio-renal mortality, which likely relate to the lower antioxidative/anti-inflammatory capacity of the Hp 2 vs Hp 1 allele. Being a potent angiogenic factor, however, Hp 2 was associated with a lower stroke incidence.
  • Costacou T, et al. Haptoglobin genotype: a determinant of cardiovascular complication risk in type 1 diabetes. Diabetes 2008;57(6):1702-1706. PMCID: PMC2780877
  • Costacou T, et al. Haptoglobin genotype and renal function decline in type 1 diabetes. Diabetes 2009;58(12):2904-2909. PMCID: PMC2780877.
• In investigating mechanisms by which Hp 2-2 contributes to diabetic complications, we showed that the Hp 2-2-CAD association is, at least partly, related to HDL dysfunction, which vitamin E may ameliorate. We also provided data supporting the hypothesis that abnormal glomerular permeability in diabetes allows large molecules such as the Hp 2-2–hemoglobin complex to cross the glomerular barrier, potentially leading to increased iron accumulation in renal proximal tubules, oxidative stress, hypertrophy, and kidney dysfunction.
  • Costacou T, et al. Effect of vitamin E supplementation on HDL function by Haptoglobin genotype in type 1 diabetes: Results from the HapE randomized crossover pilot trial. Acta Diabetologica 2016;53(2):243-250. DOI: 10.1007/s00592-015-0770-8.
  • Costacou T, et al. Is Magnetic Resonance Imaging Detection of Kidney Iron Deposition Increased in Haptoglobin 2-2 Genotype Carriers with Type 1 Diabetes?  Antioxid Redox Signal. 2018;29(8):735-741. PMCID: PMC6067098.
• It is widely believed that type 1 diabetic kidney disease (DKD) is more prevalent in men. We showed that females are at higher DKD risk in more recently diagnosed cohorts, although sex differences are not observed with long duration. Another common belief is that a minority of type 1 diabetes patients develop advanced DKD. We showed that some degree of kidney disease in type 1 diabetes is virtually universal at long durations and not declining.
  • Costacou T, et al. Sex differences in the development of kidney disease in individuals with type 1 diabetes mellitus: a contemporary analysis. Am J Kidney Dis. 2011;58(4):565-573.
  • Costacou T, Orchard TJ. Cumulative Kidney Complication Risk by 50 Years of Type 1 Diabetes: The Effects of Sex, Age, and Calendar Year at Onset. Diabetes Care. 2018;41(3):426-433. PMC5829956.