[Skip to Content]
[Skip to Content Landing]
Editor's Correspondence
January 22, 2007

Coffee and Diabetes: Is Homocysteine the Missing Link?

Arch Intern Med. 2007;167(2):204. doi:10.1001/archinte.167.2.204-a

We read with great interest the article by Pereira et al1 showing an inverse association of coffee intake with risk of type 2 diabetes mellitus in a large prospective study of postmenopausal women. The protective effect of coffee against diabetes could not be attributed to caffeine because the inverse associations of coffee consumption with diabetes risk were stronger for decaffeinated coffee than for regular (caffeinated) coffee.1 The authors concluded that other components of coffee such as antioxidants could reduce the risk of diabetes, but the question remains of why regular coffee consumption might not decrease the risk of diabetes. In this setting, it would have been interesting to investigate the contribution of the homocysteine-raising effect of caffeine to the risk of diabetes.

Indeed, a dose-response association between coffee consumption and homocysteine level was reported in several studies. In a large population-based sample of Greek adults, a positive association was observed between homocysteine and coffee consumption (P = .04), even after adjusting for age, sex, physical activity, blood pressure, and total cholesterol levels, as well as fruits and vegetables consumed.2 It is now well established that caffeine is responsible, at least in part, for the homocysteine-raising effect of coffee.3

Furthermore, recent findings indicate that high homocysteine level is a risk factor for the development of diabetes.4,5 Notably, increased total homocysteine levels were reported in obese children with hyperinsulinemia compared with obese children with normal insulin levels (P = .002).4 In multivariant regression analysis, insulin resistance was an independent predictive factor for plasma homocysteine level (P = .01).4 Accordingly, hyperhomocysteinemia has been proposed as an additional component of metabolic syndrome.4 However, it remains unclear whether hyperhomocysteinemia precedes the onset of diabetes or results from it. Recently, during a 4-year follow-up of women with a history of gestational diabetes mellitus, Cho et al5 demonstrated that high homocysteine level in the early postpartum period was an independent risk factor for the development of diabetes.

Taken together, we hypothesize that the lack of protective effect of regular coffee consumption against diabetes might be due to caffeine-induced hyperhomocysteinemia.

Correspondence: Dr Peyrin-Biroulet, Department of Hepatogastroenterology, University Hospital of Nancy, Allée du Morvan, 54 511 Vandoeuvre-les-Nancy CEDEX, France (peyrin-biroulet@netcourrier.com).

Pereira  MAParker  EDFolsom  AR Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women.  Arch Intern Med 2006;1661311- 1316PubMedGoogle ScholarCrossref
Panagiotakos  DBPitsavos  CZeimbekis  AChrysohoou  CStefanadis  C The association between lifestyle-related factors and plasma homocysteine levels in healthy individuals from the “ATTICA” Study.  Int J Cardiol 2005;98471- 477PubMedGoogle ScholarCrossref
Jacques  PFBostom  AGWilson  PWRich  SRosenberg  IHSelhub  J Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.  Am J Clin Nutr 2001;73613- 621PubMedGoogle Scholar
Martos  RValle  MMorales  RCanete  RGavilan  MISanchez-Margalet  V Hyperhomocysteinemia correlates with insulin resistance and low-grade systemic inflammation in obese prepubertal children.  Metabolism 2006;5572- 77PubMedGoogle ScholarCrossref
Cho  NHLim  SJang  HCPark  HKMetzger  BE Elevated homocysteine as a risk factor for the development of diabetes in women with a previous history of gestational diabetes mellitus: a 4-year prospective study.  Diabetes Care 2005;282750- 2755PubMedGoogle ScholarCrossref