Original Article

Association of Type 2 Diabetes Mellitus and Seroprevalence for Cytomegalovirus

Authors: Bertram W. Roberts, MD, DRPH, Irina Cech, PHD

Abstract

Background: Infection is known to play a role in type 1 diabetes, but there is a paucity of information on its role in diabetes mellitus type 2. We examined the seroprevalence of selected viruses in a group of predominantly Hispanic patients with type 2 diabetes and control subjects without diabetes.


Methods: One hundred thirteen patients, 83 with type 2 diabetes and 30 control subjects, all undergoing hemodialysis at the same facility in San Antonio, Texas, were tested for antibodies against coxsackie B viruses, cytomegalovirus (CMV), and parvovirus. Sixty-six of these patients and 25 control subjects were tested bimonthly for 6 months.


Results: We observed a greater seroprevalence of anti-CMV IgG antibodies among patients with diabetes (97.6%), compared with control subjects (86.7%), and the difference was statistically significant [OR = 6.2, 95% CI: 1.1 to 36.0, P < 0.05]. Three draws on a subset of 91 patients produced still greater odds [OR = 12.4, 95% CI: 1.3 to 117, P < 0.05]. There were significantly more (P ≤ 0.001) vascular complications among patients with diabetes. There was a colinearity of trends between diabetes, seropositivity to CMV, and age.


Conclusions: Our findings indicated an up to 12 times greater odds of having type 2 diabetes for persons previously exposed to CMV. Since accelerated atherosclerosis is also associated with diabetes and CMV, past CMV infection may be a common factor that links atherosclerosis and diabetes. No other viruses tested in this study, either coxsackie B viruses or parvovirus, showed a significant association with type 2 diabetes.


Key Points


* Up to 12 times greater odds for having type 2 diabetes were observed for persons with elevated immunoglobulin G titers for cytomegalovirus, indicating previous exposure to this virus.


* Past exposure to cytomegalovirus may be a common factor that links atherosclerosis and diabetes.

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References

1. Vaaler S. Time for more effective secondary intervention. IDF Bull 1997;42:10–13.
 
2. Haffner SM. Lipoprotein (a) and diabetes. Diabetes Care 1993;16:835–840.
 
3. Brownlee M. Glycation and diabetic complications. Diabetes 1994;43:834–841.
 
4. Clark CM, Lee DA: Prevention and treatment of the complications of diabetes mellitus. N Engl J Med1995;332:1210–1217.
 
5. Westermark P, Johnson KH, O’Brien TD, Betsholtz C. Islet amyloid polypeptide-a novel controversy in diabetes research. Diabetologia 1992;35.
 
6. Dennis VW, Robinson K. Homocysteinemia and vascular disease in end-stage renal disease. Kidney Int 1996;50:S11–S17.
 
7. Robinson JC, Folsom AR, Nabulsi AA, et al. Can postmenopausal hormone replacement improve plasma lipids in women with diabetes? The arteriosclerosis risk in communities study investigators.Diabetes Care 1996;19:480–485.
 
8. Wilson PW, Hoeg JM, D’Agostino RB, et al. Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis. N Engl J Med 1996;337:516–522.
 
9. McCulloch DK, Robertson RP. Pathogenesis of type 2 diabetes mellitus. UpToDatewww.uptodate.com 2003.
 
10. Horikawa Y, Oda N, Cox NJ. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 2000;26:163.
 
11. Bierman E. Atherogenesis in diabetes. Arterioscler Thromb 1992;12:647–657.
 
12. Vercellotti GM. Overview of infection and cardiovascular diseases. J Allergy Clin Immunol2001;108:S117–S119.
 
13. Espinola-Klein C, Rupprecht HJ, Blankenburg S, et al. Impact of infectious burden on extent and long-term prognosis of atherosclerosis. Circulation 2002;105:15–21.
 
14. Szopa TM, Titchener PA, Portwood ND, et al. Diabetes mellitus due to viruses-some recent developments. Diabetologia 1993;36:687–695.
 
15. Frisk G, Friman G, Tuvemo T, et al. Coxsackie B virus IgM in children at onset of type 1 (insulin-dependent) diabetes mellitus: evidence for IgM induction by a recent or current infection. Diabetologia1992;35:249–253.
 
16. Foy CA, Quirke P, Williams DJ, et al. A search for candidate viruses in type 1 diabetic pancreas using the polymerase chain reaction. Diabetic Med 1994;11:564–569.
 
17. Pak CY, McArthur RG, Eun HM, et al. Association of cytomegalovirus infection with autoimmune type diabetes. Lancet 1988;2:1–4.
 
18. Gamble DR, Taylor KW, Cumming H. Coxsackie viruses and diabetes mellitus. Br Med J1973;4:260–262.
 
19. Huff JC, Hierholzer JC, Farris WA. An “outbreak” of juvenile diabetes mellitus: consideration of a viral etiology. Am J Epidemiol 1974;100:277–287.
 
20. Anderson OO, Christy M, Amung K, et al. Viruses and Diabetes, in: Diabetes, Proceedings of the Ninth Congress of the International Diabetes Federation, in: Ninth Congress of the International Diabetes Federation, New Delhi, India, 1977, pp 294–298.
 
21. Schmidt WAK, Brade L, Munterfering H, et al. Course of Coxsackie B antibodies during juvenile diabetes. Med Microbiol Immunol (Berl) 1978;164:291–298.
 
22. Yoon JW, Austin M, Onodera T, et al. Virus-induced diabetes mellitus isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 1979;300:1173.
 
23. Hazra DK, Singh R, Wahal PK, et al. Coxsackie antibodies in young Asian diabetics. Lancet1980;1:877.
 
24. Palmer JP, Cooney MK, Ward RH, et al. Reduced coxsackie antibody titres in type 1 (insulin-dependent) diabetic patients presenting during an outbreak of coxsackie B3 and B4 infection.Diabetology 1982;22:426–429.
 
25. Sakurami T, Nabeya N, Nagaoka K, et al. Antibodies to coxsackie B viruses and HLA in Japanese with juvenile-onset type 1 (insulin dependent) diabetes mellitus. Diabetology 1982;22:375–377.
 
26. King ML, Shaikh A, Bidwell D, et al. Coxsackie-B-virus-specific IgM responses in children with insulin-dependent (juvenile-onset; type 1) diabetes mellitus. Lancet 1983;1:1397–1399.
 
27. Mertens T, Gruneklee D, Hegges HJ. Neutralizing antibodies against coxsackie B viruses in patients with recent onset of type 1 diabetes. Eur J Pediatr 1983:140–293.
 
28. Prince MA, Vialettes B, Zevaco-Mattei C, et al. Clinical characteristics and etiological markers in insulin-dependent diabetes associated with an organ-specific autoimmune disease. Acta Diabetol Lat1983;20:221.
 
29. Bell EJ, Mcartney RA. A study of coxsackie B virus infections 1972–1983. J Hyg Camb1984;93:197.
 
30. Frisk G, Fohlman J, Kobbah M, et al. High frequency of coxsackie-B-virus-specific IgM in children developing type 1 diabetes during a period of high diabetes morbidity. J Med Virol 1985;17:219–227.
 
31. Frisk G, Nilsson E, Tuverno T, et al. The possible role of coxsackie A and echoviruses in the pathogenesis of type 1 diabetes mellitus studied by IgM analysis. J Infect 1992;24:13.
 
32. McCulloch DK. Pathogenesis of type 1 diabetes mellitus. UpToDate www.uptodate.com, 2003.
 
33. Foulis AK, McGill M, Farquharson MA, et al. A search for evidence of viral infection in pancreases of newly diagnosed patients with IDDM. Diabetologia 1997;40:53.
 
34. Barrett-Connor E. Is insulin-dependent diabetes mellitus caused by coxsackievirus B infection? A review of the epidemiologic evidence. Rev Infect Dis 1985;7:207.
 
35. Toniolo A, Federico G, Basolo F, et al. Diabetes Mellitus: Coxsackieviruses: A General Update. New York, Plenum Press, 1988.
 
36. Visseren FLJ, Bouter KP, Pon MJ, et al. Patients with diabetes mellitus and atherosclerosis, a role for cytomegalovirus? Diabetes Res Clin Pract 1997;36:49–55.
 
37. Lennette EH, Schmidt NJ (eds): Diagnostic Procedures for Viral, Rickettsial, and Chlamydial Infections. American Public Health Association, Washington, DC, 1979.
 
38. Hekker AC, Brand-Saathof B, Vis J, et al. Indirect immunofluorescence test for detection of IgM antibodies to cytomegalovirus. J Infect Dis 1979;140:596–600.
 
39. Brown CS, van Bussel MJA, Wassenaar ALM, et al. An immunofluorescence assay for the detection of parvovirus B19 IgG and IgM antibodies based on recombinant viral antigen. J Virol Methods1990;29:53–62.
 
40. Norusis MJ. SPSS Advanced Statistics User’s Guide. SPSS Inc., Chicago, 1989.
 
41. Dean AG, Dean JA, Coulombier D, et al. Epi Info Version 6. Atlanta, GA, Centers for Disease Control and Prevention, 1994.
 
42. Melnick JL, Adam E, Debakey ME. Cytomegalovirus and atherosclerosis. Eur Heart J 1993;14:30–38.
 
43. Bennett PH, Bogardus C, Tuomilehto J, et al. Epidemiology and natural history of NIDDM: non-obese and obese, in Alberti RA, DeFronzo H, Zimmet K, et al (eds): International Textbook of Diabetes Mellitus. John Wiley & Sons Ltd, Hoboken, 1992, pp 147–170.
 
44. Harris MI, Klein R, Welborn TA, et al. Onset of NIDDM occurs at least 4–7 yr before clinical diagnosis. Diabetes Care 1992;15:815–819.
 
45. Roberts B, Cech I. The Texas-Mexico border in 1993: important issues for the Clinton administration. San Antonio Med 1993;46:10–12.
 
46. Roberts B, Cech I, Alvarado NA. Diabetes educational programme in Texas: STOP reaches out.Diabetes Voice 1999;64:3–7.
 
47. Versallotti GM. Viruses and atherosclerosis: do they play a pathogenic role? J Invest Med1998;46:403–407.
 
48. Speir E, Modali R, Huang E, et al. Potential role of human cytomegalovirus and P53 interaction in coronary restenosis. Science 1994;265:391–394.
 
49. Melnick JL, Hu C, Burek J, et al. Cytomegalovirus DNA in arterial walls of patients with atherosclerosis. J Med Virol 1994;42:170–174.
 
50. Watt S, Aesch B, Lanotte P, et al. Viral and bacterial DNA in carotid atherosclerotic lesions. Eur J Clin Microbiol Infect Dis 2003;22:99–105.
 
51. Jackson RA. Mechanisms of age-related glucose intolerance. Diabetes Care 1990;13:9–19.
 
52. Gu K, Cowie CC, Harris MI. Mortality in adults with and without diabetes in a national cohort of the US population, 1971–1993. Diabetes Care 1998;21:1138–1145.
 
53. Bertoni AJ, Saydah S, Brancati FL. Diabetes and the risk of infection-related mortality in the US.Diabetes Care 2001, 24:1044–1049.
 
54. Saxena AK, Panhotra BR. The susceptibility of patients with type 2 diabetes to hepatitis C virus infection during long-term haemodialysis. Swiss Med Wkly 2003;133:611–618.
 
55. Kawakami K. Tuberculosis in compromised hosts. Kekkaku 2003;78:717–722.
 
56. Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26:510–513.
 
57. Murray A, Foley R, Chavers B, et al. Infectious Complications of Hemodialysis, Peritoneal Dialysis, Transplant, and Chronic Kidney Disease Patients. United States Renal Data System Coordinating Center, Minneapolis, 2003.
 
58. Gerberding JL. Diabetes: Disabling, Deadly, and on the Rise. Atlanta, GA, Centers for Diseases Control and Prevention, 2004.
 
59. Lohr JM, Oldstone MB. Detection of cytomegalovirus nucleic acid sequences in pancreas in type 2 diabetes. Lancet 1990;336:644–648.
 
60. Grenmark S, Tilburg T, Soderberg-Naucler C. Human cytomegalovirus inhibits cytokine-induced macrophage differentiation. J Virol 2004;78:10378–10389.
 
61. Mujais SJ, Ivanovicj P. Membranes for extra corporeal therapy, in Maher JF (ed): Replacement of Renal Functions by Dialysis. Kluwer Academic Publishers, Boston, 1989.
 
62. Grundy JE, Ehrnst A, Einsele H, et al. A three-center European external quality control of study of PCR for detection of cytomegalovirus. J Clin Microbiol 1996;34:1166–1170.