Conclusions
There is no direct and conclusive evidence that genetic factors play a role in the pathogenesis of microangiopathy in diabetes. Associations between HLA antigens and complications, which would contribute conclusive evidence of a genetic contribution to the genesis of these complications, have been reported but not consistently confirmed. On the other hand, circumstantial evidence from studies of the natural history of the disease and its complications and from twin studies strongly suggest that genes do contribute to the susceptibility to small vessel disease. The most important genes providing this susceptibility are probably unrelated to HLA. Even if the total genetic contribution to susceptibility for microangiopathy turns out to be small in comparison with that provided by metabolic factors, their knowledge early in the course of the disease would serve the important role of identifying subjects in need of more intensive diabetic management to prevent vascular complications.
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References
Ross H, Rifkin H (1980) Metabolic control and vascular disease in diabetes mellitus. In: Podolsky S (ed) Clinical diabetes: modern management. Appleton-Century-Crofts, New York, pp 565–588
Barbosa J (1980) Nature and nurture: the genetics of diabetic microangiopathy. In: Podolsky S, Viswanathan M (eds) Secondary diabetes: the spectrum of diabetic syndromes. Raven Press, New York, pp 67–75
Kohner EM, McLeod D, Marshall J (1982) Diabetic eye disease. In: Keen H, Jarrett RJ (eds) Complications of diabetes, 2nd edn. Edward Arnold, London, pp 19–108
Cudworth AG, Bodansky HJ (1982) Genetic and metabolic factors in relation to the prevalence and severity of diabetic complications. In: Keen H, Jarrett RJ (eds) Complications of diabetes, 2nd edn. Edward Arnold, London, pp 1–12
Pyke D, Tattersall R (1973) Diabetic retinopathy in identical twins. Diabetes 22: 613–618
Johnston C, Pyke D, Cudworth A, Wolf E (1983) HLA-DR typing in identical twins with insulin-dependent diabetes: difference between concordant and discordant pairs. Br Med J 286: 253–255
Leslie R, Pyke D (1982) Diabetic retinopathy in identical twins. Diabetes 31: 19–21
West K (1978) Epidemiology of diabetes and its vascular lesions. Elsevier, New York, pp 402–436
Siperstein M, Unger R, Madison L (1968) Studies of muscle capillary basement membranes in normal subjects, diabetic and prediabetic patients. J Clin Invest 47: 1973–1999
Siperstein M, Feingold K, Bennett P (1978) Hyperglycaemia and diabetic microangiopathy. Diabetologia 15: 365–367
Siperstein M, Raskin P, Burns H (1973) Electron microscopic quantification of diabetic microangiopathy. Diabetes 22: 514–524
Camerini-Davalos R, Opperman W, Rebagliati H, Classer M, Bloodworth J (1979) Muscle capillary basement membrane width in genetic prediabetes. J Clin Endocrinol Metab 48: 251–259
Kilo C, Vogler N, Williamson J (1972) Muscle capillary basement membrane changes related to aging and to diabetes mellitus. Diabetes 21: 881–905.
Osterby R (1965) A quantitative estimate of the peripheral glomerular basement membrane in recent juvenile diabetes. Diabetologia 1: 97–100
Karam J, Rosenthal M, O'Donnell J, Tsalikian E, Lorenzi M, Gerich J, Siperstein M, Forsham P (1976) Discordance of diabetic microangiopathy in identical twins. Diabetes 25: 24–28
Barnett A, Spiliopoulos A, Pyke D, Stubbs W, Rowold E, Hoffman P, Faller A, Kilo C, Miller J, Williamson J (1983) Muscle capillary basement membrane in identical twins discordant for insulin-dependent diabetes. Diabetes 32: 557–560
Ganda O, Williamson J, Soeldner J, Gleason R, Kilo C, Kaldany A, Miller J, Garovoy M, Carpenter C (1983) Muscle capillary basement membrane width and its relationship to diabetes mellitus in monozygotic twins. Diabetes 32: 549–556
Barbosa J, Chavers B, Steffes M, Szalapski E, Cohen R, Michael A, Hoogwerf B, Mauer M (1980) Muscle extracellular membrane immunofluorescence and HLA as possible markers of prediabetes. Lancet 1: 330–333
Mauer S, Miller K, Goetz F, Barbosa J, Simmons R, Najarian J, Michael A (1976) Immunopathology of renal extracellular membranes in kidneys transplanted into patients with diabetes mellitus. Diabetes 25: 709–712
Cohn R, Mauer S, Barbosa J, Michael A (1978) Immunofluorescence studies of skeletal muscle extracellular membranes in diabetes mellitus. Lab Invest 39: 13–16
Marks J, Raskin P, Stastny P (1981) Increase in capillary basement membrane width in parents of children with Type 1 diabetes mellitus. Diabetes 30: 475–480
Mauer S, Barbosa J, Vernier R, Kjellstrand C, Buselmeier T, Simmons R, Najarian J, Goetz F (1976) Development of diabetic vascular lesions in normal kidneys transplanted into patients with diabetes mellitus. New Engl J Med 295: 916–920
Mauer S, Miller K, Goetz F, Barbosa J, Simmons R, Najarian J, Michael A (1976) Immunopathology of renal extracellular membranes in kidneys transplanted into patients with diabetes mellitus. Diabetes 25: 709–712
Mauer S, Steffes M, Connett J, Najarian J, Sutherland D, Barbosa J (1983) The development of lesions in the glomerular basement membrane and mesangium after transplantation of normal kidneys to diabetic patients. Diabetes 32: 948–952
Mauer S, Steffes M, Sutherland D, Brown D, Goetz F (1984) Structural functional relationships in diabetic nephropathy. J Clin Invest (in press)
Barbosa J, Bach F, Rich S (1982) Genetic heterogeneity of diabetes and HLA. Clin Genet 21: 25–32
Naji A, Silvers W, Barker C (1983) Autoimmunity and Type 1 (insulin-dependent) diabetes mellitus. Transplantation 36: 355–361
Falk R, Dalmasso A, Kim Y, Tsai C, Scheinman J, Gewurz H, Michael A (1983) Neoantigen of the polymerized ninth component of complement. J Clin Invest 72: 560–573
Danielsen R, Helgason T, Arnason A, Jonasson F (1982) HLA and retinopathy in Type 1 (insulin-dependent) diabetic patients in Iceland. Diabetologia 22: 297–298
McCann VJ, McCluskey J, Kay PH, Zilko PJ, Christiansen FT, Dawkins RL (1983) HLA and complement genetic markers in diabetic retinopathy. Diabetologia 24: 221 (Letter)
Bodansky H, Wolf E, Cudworth A, Dean B, Nineham L, Bottazzo G, Matthews J, Kurtz A, Konner E (1982) Genetic and immunologic factors in microvascular disease in Type1 (insulin-dependent) diabetes. Diabetes 31: 70–74
Barbosa J, Ramsay R, Knobloch W, Cantrill H, Noreen H, King R, Yunis E (1980) Histocompatibility antigen frequencies in diabetic retinopathy. Am J Ophthalmol 90: 148–153
Gray R, Starkey I, Rainbow S, Kurtz A, Abdel-Khalik A, Urbaniak S, Elton R, Duncan J, Clarke B (1982) HLA-antigens and other risk factors in the development of retinopathy in Type 1 diabetes. Br J Ophthalmol 66: 280–285
Johnston P, Kidd M, Middleton D, Greenfield A, Archer D, Maguire C, Kennedy L (1982) Analysis of HLA antigen association with proliferative diabetic retinopathy. Br J Ophthalmol 66: 277–279
Dornan T, Ting A, McPherson C, Peckar C, Morris P, Mann J, Turner R (1982) Genetic susceptibility to the development of retinopathy in insulin-dependent diabetes. Diabetes 31: 226–231
Barbosa J, Noreen H, Emme L, Goetz F, Simmons R, de Leiva A, Najarian J, Yunis E (1976) Histocompatibility (HLA) antigens and diabetic microangiopathy. Tissue Antigens 7: 233–237
Barbosa J (1981) Is diabetic microangiopathy genetically heterogeneous? HLA and diabetic nephropathy. Horm Metab Res 11: 77–80
Saner B, Bonney E, Barbosa J (1983) HLA-DR antigens and diabetic nephropathy. Diabetologia 25: 452 (Letter)
Schernthaner G, Ludwig H, Mayr W (1979) Immunoglobulin G-insulin antibodies and immune region-associated alloantigens in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 48: 403–407
Di Mario U, Ventriglia L, Iavicoli M, Guy K, Andreani D (1983) The correlation between insulin antibodies and circulating immune complexes in diabetics with and without microangiopathy. Clin Exp Immunol 52: 575–580
Di Mario U, Iavicoli M, Andreani D (1980) Circulating immune complexes in diabetes. Diabetologia 19: 89–92
Aviner Z, Henley W, Okas S, Leopold I (1976) Leukocyte migration inhibition induced by uveoretinal antigen in patients with diabetic retinopathy. Diabetes 25: 1106–1109
Henley W, Okas S, Leopold I (1975) Leukocyte migration inhibition by choroid and retina in retinal detachement. Ophthalmic Res 7: 129
Bodansky H, Drury P, Cudworth A, Evans D (1981) Acetylator phenotypes and Type 1 (insulin-dependent) diabetics with microvascular disease. Diabetes 30: 907–910
McLaren E, Burden A, Moorhead P (1977) Acetylator phenotype in diabetic neuropathy. Br Med J 2: 291–293
Shenfield G, McCann V, Tjokresetio R (1982) Acetylator status and diabetic neuropathy. Diabetologia 22: 441–444
Permutt M, Rotwein P (1983) Analysis of the insulin gene in non-insulin-dependent diabetes. Am J Med 75: 1–7
Hitman G, Jowett N, Williams L, Humphries S, Winter R, Galton D (1984) Polymorphisms in the 5′-flanking region of the insulin gene and non-insulin-dependent diabetes. Clin Sci 66: 383–388
Jowett N, Williams L, Hitman G, Galton D (1984) Diabetic hyper-triglyceridaemia and related 5′ flanking polymorphism of the human insulin gene. Br Med J 288: 96–99
Mandrup-Poulsen T, Mortensen S, Melnertz H, Owerbach D, Johansen K, Sorensen H, Nerup J (1984) DNA sequences flanking the insulin gene on chromosome 11 confer risk of atherosclerosis. Lancet 1: 250–252
Barbosa J, Rich S, Dunsworth T, Swanson J (1982) Linkage disequilibrium between insulin-dependent diabetes and the Kidd blood group Jkb allele. J Clin Endocrinol Metab 55: 192–195
Lucarelli P, Scacchi R, Corbo R, Palmarino R, Orisini M, Campea L, Carapella E, Pascone R (1975) Genetic polymorphisms in juvenile onset diabetes. Hum Hered 28: 89–95
McCluskey J, McCann V, Kay P, Zilko P, Christiansen F, O'Neill G, Dawkins R (1983) HLA and complement allotypes in Type 1 (insulin-dependent) diabetes. Diabetologia 24: 162–165
Becker B, Shin D, Burgess D, Kilo C, Miller W (1977) Histocom-patability antigens and diabetic retinopathy. Diabetes 26: 997–999
Moller E, Persson B, Sterky G (1978) HLA phenotypes and diabetic retinopathy. Diabetologia 14: 155–158
de Moerloose P, Jeannet M, Bally C (1978) HLA and DRw antigens in insulin-dependent diabetes. Br Med J 1: 823
Standl E, Dexel T, Albert E, Scholz S, Greite J, Mehnert H (1979) Diabetic retinopathy: association with the human leukocyte antigen (HLA) system. Diabetes 28: 396
Jervell J, Solheim B (1979) HLA-antigens in long-standing insulin-dependent diabetics with terminal nephropathy and retinopathy with and without loss of vision. Diabetologia 17: 391 (Letter)
Cove D, Walker J, Mackintosh P, Wells L, Wright A (1980) Are HLA types or Bf alleles markers for diabetic retinopathy? Diabetologia 19: 402–403
Christy M, Anderson AR, Nerup J, Platz P, Ryder L, Thomsen L, Morling M, Svejgaard A (1981) HLA-DR typing in longstanding IDDM with and without nephropathy — evidence for heterogeneity? Diabetologia 21: 259 (Abstract)
Bertrams J, Dewald G, Spitznas M, Rittner C (1979) HLA-A, C, B, DR, Bf, and C2 alleles in insulin-dependent diabetes mellitus with proliferative retinopathy. In: Waldhäusl W, Alberti KGMM (eds) Proceedings of 10th Congress of the International Diabetes Federation, Vienna, September 1979, Excerpta Medica, Amsterdam, pp 213–217
Walton C, Dyer P, Davidson J, Harris R, Mallick N, Oleesky S (1984) HLA antigens and risk factors for nephropathy in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia: 27: 3–7
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Barbosa, J., Saner, B. Do genetic factors play a role in the pathogenesis of diabetic microangiopathy?. Diabetologia 27, 487–492 (1984). https://doi.org/10.1007/BF00290381
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DOI: https://doi.org/10.1007/BF00290381