HLA antigens and other risk factors in the development of retinopathy in type 1 diabetes.

Abstract

SUMMARY Factors possibly influencing the development of diabetic retinopathy were studied in 112 randomly selected type I diabetics having no or minimal retinopathy (group A) and in 82 type 1 diabetics with known severe diabetic retinopathy. The latter comprised those with severe background retinopathy (group B, n= 17) and those having proliferative retinopathy without (group C, n=38) and with (group D, n=27) diabetic nephropathy. Nonretinopaths (group A) were of similar sex ratio, body weight, and age at diagnosis of diabetes but had been diabetic longer (p<O0OO1) and were thus older (p<OO01) than retinopaths (groups B-D). The distribution of HLA antigens of the A, B, and C loci was similar in nonretinopaths and retinopaths with the exception that HLA B7 showed a reduced (p<O0O5) prevalence in the retinopaths (6% versus 17%) and was singularly underrepresented in group D, where no patients had this antigen. Mean postprandial plasma glucose and HbA, concentrations were higher (p<O0O1 and p<O0OO1) and cigarette smoking was more prevalent (p<OO1) in the retinopathy groups B-D than in group A. Systolic and diastolic blood pressures were similar in groups A-C, with higher (p<O0OO1) values only in group D. There was no association between insulin antibody binding in the serum or measurable plasma C-peptide immunoreactivity and retinopathy status. The risk of development of diabetic retinopathy in type I diabetes may be related to HLA-associated genetic factors and to cigarette smoking.

Association of Cigarette Smoking With Diabetic Retinopathy

“…This result was supported by many earlier studies (13)(14)(15)(16)(17)(18)(19)(20)(21)(22), but not by others (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In the younger-onset group, there was some suggestion of a relationship between smoking and the incidence of any retinopathy in both univariate and multivariate analyses, but it was weak.…”

“…Cigarette smoking, a characteristic with potential for modification, if proved to be a risk factor for retinopathy, would have great public health implications for the prevention of this complication. Some studies have found an association between cigarette smoking and diabetic retinopathy (3)(4)(5)(6)(7)(8)(9)(10)(11)(12), whereas others have not (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Many of these studies are hampered by their cross-sectional design or small sample sizes.…”

Immunological Responses to Exogenous Insulin

“…Specifically, no relation has been found between IAs and histological findings of nephropathy (331), muscle basement membrane thickness (332), clinical nephropathy (114, 333,334), clinical retinopathy (114, 273,[321][322][323][332][333][334][335][336], clinical autonomic neuropathy (337), clinical peripheral neuropathy (338), or complement activation in patients with diabetes (339).…”

Genetic Marker Associations With Proliferative Retinopathy in Persons Diagnosed With Diabetes Before 30 yr of age

“…The results of these studies have been inconsistent as some reported an association between B8 and proliferative retinopathy (4,5), others found an association with B15 (6)(7)(8)(9), and others reported no HLA-B antigen associations (10)(11)(12)(13)(14)(15)(16)(17). With the advent of DR typing, attention shifted to these antigens, partly because of their stronger associations with IDDM development.…”