Congenital rubella and diabetes mellitus

Abstract

To the Editor: In his interesting Editorial on the association between congenital rubella (CR) and diabetes mellitus, Edwin Gale proposes that CR is the only viral infection that can claim, somewhat tenuously, to be a cause of type 1 diabetes [1]. But imbedded in his discussion is the suggestion that this association may have occurred by chance as there are relatively few well-documented reports of individuals with insulin-dependent, childhood-onset, antibody-positive disease in the literature. However, Gale appears to accept an association with type 2 disease. We believe, on the basis of clinical reports and on its pathogenesis, that CR leads to both type 1-like and type 2like diabetes; that the prevalence of diabetes in children and adolescents with CR is higher than the 1% suggested in the Editorial; and that about 20% of CR patients develop type 2-like disease as they age. Congenitally acquired rubella viral infection causes inhibition of intrauterine cellular growth [2]. Live-born infants remain actively infected [3] and are mostly of low birthweight [4, 5]. Some infants also have microvascular disease [6], and most have an altered cellular and humoral immune response to rubella virus [7]. Rubella virus has been isolated from the pancreas of infants at autopsy [3] and intimal proliferation has been documented in pancreatic blood vessels [8]. Between 3 and 12 months of age some infants develop a generalised rash and severe pneumonitis [9]. This condition, which can be fatal, is thought to be due to an immunological process, but may respond to steroids. The first cohort of CR patients to be carefully studied for diabetes was born in 1940–1942 and examined by us as adults [10]. This cohort was drawn partly from the patients first described by the Australian ophthalmologist Dr (later Sir) Norman Gregg [4]. Survival of infants born with CR at that time was far poorer than that of those born following the large worldwide outbreak of rubella in 1964–1965 because more effective neonatal intensive care and surgery increased the survival prospects of affected infants. So long-term survivors of the 1941 and earlier outbreaks have less extensive pathology than many who have survived since then. Our adult cohort has been followed up progressively to the age of 60 years [11]. By then, seven of 32 (22%) had type 2-like diabetes: two of the three requiring insulin had diabetic retinopathy and elevated levels of GAD antibodies and insulin autoantibodies (IAAs); one of the seven had elevated levels of GAD and IAAs. Seven individuals had clinical or biochemical evidence of thyroid disease, and eight of the 11 women in the cohort had experienced early menopause, three before the age of 38 years. We had previously recorded that some of this cohort were found to have pancreatic islet cell antibodies before they had reached the age of 30 years [12]. Diabetologia (2009) 52:369–370 DOI 10.1007/s00125-008-1227-1