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. 1968 Sep;47(9):1973–1999. doi: 10.1172/JCI105886

Studies of muscle capillary basement membranes in normal subjects, diabetic, and prediabetic patients

M D Siperstein 1, R H Unger 1, L L Madison 1
PMCID: PMC297361  PMID: 5675423

Abstract

A technique is described for the measurement of muscle capillary basement membranes by electron microscopic examination of needle biopsies of the quadriceps muscle. With this procedure it has been possible to obtain an objective evaluation of the significance of capillary basement membrane hypertrophy in diabetic microangiopathy. The results of such studies of muscle capillary basement membrane thickness in 50 normal, 51 diabetic, and 30 prediabetic patients have demonstrated the following. First, that the average capillary basement membrane width of diabetic patients is over twice that of normal subjects; moreover, such basement membrane thickening is a very constant finding among overtly diabetic patients, in that approximately 98% of individual diabetic subjects demonstrated this lesion. The degree of basement membrane thickening in diabetic patients is, however, unrelated to age, weight, severity, or duration of diabetes. Second, capillary basement membrane hypertrophy has been found in approximately 50% of patients who are genetically prediabetic but who have not yet demonstrated evidence of the manifest carbohydrate disturbances of diabetes mellitus. Third, in contrast to the results obtained in genetically diabetic patients, subjects with severe hyperglycemia due to causes other than genetic diabetes only infrequently show basement membrane hypertrophy.

These results indicate that thickening of the muscle capillary basement membranes is a characteristic of genetic diabetes mellitus, and further, that the hyperglycemia of diabetes is probably not the factor responsible for the microangiopathy characteristic of diabetes mellitus. Finally, the discovery of thickened capillary basement membranes in prediabetic patients suggests that basement membrane hypertrophy is a relatively early lesion of the diabetic syndrome and provides further support for the conclusion that this vascular defect is independent of carbohydrate derangements of diabetes mellitus.

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1973

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Selected References

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  1. AAGENAES O., MOE H. Light- and electron-microscopic study of skin capillaries of diabetics. Diabetes. 1961 Jul-Aug;10:253–259. doi: 10.2337/diab.10.4.253. [DOI] [PubMed] [Google Scholar]
  2. BANSON B. B., LACY P. E. DIABETIC MICROANGIOPATHY IN HUMAN TOES; WITH EMPHASIS ON THE ULTRASTUCTURAL CHANGE IN DERMAL CAPILLARIES. Am J Pathol. 1964 Jul;45:41–58. [PMC free article] [PubMed] [Google Scholar]
  3. BECKER D., MILLER M. Presence of diabetic glomerulosclerosis in patients with hemochromatosis. N Engl J Med. 1960 Aug 25;263:367–373. doi: 10.1056/NEJM196008252630801. [DOI] [PubMed] [Google Scholar]
  4. BELL E. T. A postmortem study of vascular disease in diabetics. AMA Arch Pathol. 1952 May;53(5):444–455. [PubMed] [Google Scholar]
  5. BERGSTRAND A., BUCHT H. Electron microscopic investigations on the glomerular lesions in diabetes mellitus (diabetic glomerulosclerosis). Lab Invest. 1957 Jul-Aug;6(4):293–300. [PubMed] [Google Scholar]
  6. BLOODWORTH J. M., Jr Diabetic microangiopathy. Diabetes. 1963 Mar-Apr;12:99–114. doi: 10.2337/diab.12.2.99. [DOI] [PubMed] [Google Scholar]
  7. BLOODWORTH J. M., Jr EXPERIMENTAL DIABETIC GLOMERULOSCLEROSIS. II. THE DOG. Arch Pathol. 1965 Feb;79:113–125. [PubMed] [Google Scholar]
  8. BLOODWORTH J. M., Jr, HAMWI G. J. Experimental diabetic glomerulosclerosis. Diabetes. 1956 Jan-Feb;5(1):37–43. doi: 10.2337/diab.5.1.37. [DOI] [PubMed] [Google Scholar]
  9. BLOODWORTH J. M., Jr, SOMMERS S. C. "Cirrhotic glomerulosclerosis," a renal lesion associated with hepatic cirrhosis. Lab Invest. 1959 Sep-Oct;8:962–978. [PubMed] [Google Scholar]
  10. BLUMENTHAL H. T., PROBSTEIN J. G., BERNS A. W. INTERRELATIONSHIP OF DIABETES MELLITUS AND PANCREATITIS. Arch Surg. 1963 Nov;87:844–850. doi: 10.1001/archsurg.1963.01310170130022. [DOI] [PubMed] [Google Scholar]
  11. BURSTEIN R., SOULE S. D., BLUMENTHAL H. T. Histogenesis of pathological processes in placentas of metabolic disease in pregnancy. II. The diabetic state. Am J Obstet Gynecol. 1957 Jul;74(1):96–104. doi: 10.1016/s0002-9378(16)37007-7. [DOI] [PubMed] [Google Scholar]
  12. Bencosme S. A., West R. O., Kerr J. W., Wilson D. L. Diabetic capillary angiopathy in human skeletal muscles. Am J Med. 1966 Jan;40(1):67–77. doi: 10.1016/0002-9343(66)90188-4. [DOI] [PubMed] [Google Scholar]
  13. CAMERINI D AVALOS R. A., CAULFIELD J. B., REES S. B., LOZANO CASTANEDA O., NALDJIAN S., MARBLE A. PRELIMINARY OBSERVATIONS ON SUBJECTS WITH PREDIABETES. Diabetes. 1963 Nov-Dec;12:508–518. doi: 10.2337/diab.12.6.508. [DOI] [PubMed] [Google Scholar]
  14. CONN J. W., FAJANS S. S. The prediabetic state. A concept of dynamic resistance to a genetic diabetogenic influence. Am J Med. 1961 Dec;31:839–850. doi: 10.1016/0002-9343(61)90023-7. [DOI] [PubMed] [Google Scholar]
  15. Cerasi E., Luft R. "What is inherited--what is added" hypothesis for the pathogenesis of diabetes mellitus. Diabetes. 1967 Sep;16(9):615–627. doi: 10.2337/diab.16.9.615. [DOI] [PubMed] [Google Scholar]
  16. Colwell J. A., Lein A. Diminished insulin response to hyperglycemia in prediabetes and diabetes. Diabetes. 1967 Aug;16(8):560–565. doi: 10.2337/diab.16.8.560. [DOI] [PubMed] [Google Scholar]
  17. ELLENBERG M. Diabetic nephropathy without manifest diabetes. Diabetes. 1962 May-Jun;11:197–201. [PubMed] [Google Scholar]
  18. ELLENBERG M. Diabetic neuropathy presenting as the initial clinical manifestation of diabetes. Ann Intern Med. 1958 Sep;49(3):620–631. doi: 10.7326/0003-4819-49-3-620. [DOI] [PubMed] [Google Scholar]
  19. FAGERBERG S. E. Studies on the pathogenesis of diabetic neuropathy; survey of the literature and own working hypothesis. Acta Med Scand. 1956 Mar 26;154(2):145–150. doi: 10.1111/j.0954-6820.1956.tb14308.x. [DOI] [PubMed] [Google Scholar]
  20. FARQUHAR M. G., HOPPER J., Jr, MOON H. D. Diabetic glomerulosclerosis: electron and light microscopic studies. Am J Pathol. 1959 Jul-Aug;35(4):721–753. [PMC free article] [PubMed] [Google Scholar]
  21. FOGLIA V. G., MANCINI R. E., CARDEZA A. F. Glomerular lesions in the diabetic rat. Arch Pathol (Chic) 1950 Jul;50(1):75–83. [PubMed] [Google Scholar]
  22. FREEDMAN L. R. Inapparent diabetes mellitus as a cause of renal insufficiency due to Kimmelstiel-Wilson lesions. Bull Johns Hopkins Hosp. 1957 Mar;100(3):132–139. [PubMed] [Google Scholar]
  23. FRIEDENWALD J. S. Diabetic retinopathy. Am J Ophthalmol. 1950 Aug;33(8):1187–1199. doi: 10.1016/0002-9394(50)90988-3. [DOI] [PubMed] [Google Scholar]
  24. FUCHS U. ELEKTRONENMIKROSKOPISCHE UNTERSUCHUNGEN MENSCHLICHER MUSKELCAPILLAREN BEI DIABETES MELLITUS. Frankf Z Pathol. 1964 Jan 22;73:318–327. [PubMed] [Google Scholar]
  25. Friederici H. H., Tucker W. R., Schwartz T. B. Observations on small blood vessels of skin in the normal and in diabetic patients. Diabetes. 1966 Apr;15(4):233–250. doi: 10.2337/diab.15.4.233. [DOI] [PubMed] [Google Scholar]
  26. GOLDENBERG S., ALEX M., JOSHI R. A., BLUMENTHAL H. T. Nonatheromatous peripheral vascular disease of the lower extremity in diabetes mellitus. Diabetes. 1959 Jul-Aug;8(4):261–273. doi: 10.2337/diab.8.4.261. [DOI] [PubMed] [Google Scholar]
  27. HAYNER N. S., KJELSBERG M. O., EPSTEIN F. H., FRANCIS T., Jr CARBOHYDRATE TOLERANCE AND DIABETES IN A TOTAL COMMUNITY, TECUMSEH, MICHIGAN. 1. EFFECTS OF AGE, SEX, AND TEST CONDITIONS ON ONE-HOUR GLUCOSE TOLERANCE IN ADULTS. Diabetes. 1965 Jul;14:413–423. doi: 10.2337/diab.14.7.413. [DOI] [PubMed] [Google Scholar]
  28. Ireland J. T., Patnaik B. K., Duncan L. J. Glomerular ultrastructure in secondary diabetics and normal subjects. Diabetes. 1967 Sep;16(9):628–635. doi: 10.2337/diab.16.9.628. [DOI] [PubMed] [Google Scholar]
  29. Kefalides N. A. A collagen of unusual composition and a glycoprotein isolated from canine glomerular basement membrane. Biochem Biophys Res Commun. 1966 Jan 4;22(1):26–32. doi: 10.1016/0006-291x(66)90597-3. [DOI] [PubMed] [Google Scholar]
  30. Kefalides N. A., Winzler R. J. The chemistry of glomerular basement membrane and its relation to collagen. Biochemistry. 1966 Feb;5(2):702–713. doi: 10.1021/bi00866a043. [DOI] [PubMed] [Google Scholar]
  31. Kimmelstiel P., Osawa G., Beres J. Glomerular basement membrane in diabetics. Am J Clin Pathol. 1966 Jan;45(1):21–31. doi: 10.1093/ajcp/45.1.21. [DOI] [PubMed] [Google Scholar]
  32. LONERGAN P., ROBBINS S. L. Absence of intercapillary glomerulosclerosis in the diabetic patient with hemochromatosis. N Engl J Med. 1959 Feb 19;260(8):367–370. doi: 10.1056/NEJM195902192600804. [DOI] [PubMed] [Google Scholar]
  33. MANN G. V., GODDARD J. W., ADAMS L. The renal lesions associated with experimental diabetes in the rat. Am J Pathol. 1951 Sep-Oct;27(5):857–869. [PMC free article] [PubMed] [Google Scholar]
  34. MARBLE A., STEINKE J. Hämochromatose; Bericht über 42 Fälle mit diabetes. Medizinische. 1959 Jan 3;1(3):19–23. [PubMed] [Google Scholar]
  35. MEIER H., YERGANIAN G. A. Spontaneous hereditary diabetes mellitus in Chinese hamster (Cricetulus griseus). 1. Pathological findings. Proc Soc Exp Biol Med. 1959 Apr;100(4):810–815. doi: 10.3181/00379727-100-24786. [DOI] [PubMed] [Google Scholar]
  36. NILSSON S. E. ON THE HEREDITY OF DIABETES MELLITUS AND ITS INTERRELATIONSHIP WITH SOME OTHER DISEASES. Acta Genet Stat Med. 1964;14:97–124. doi: 10.1159/000151837. [DOI] [PubMed] [Google Scholar]
  37. Nakamura M., Yamada K. Studies on a diabetic (KK) strain of the mouse. Diabetologia. 1967 Apr;3(2):212–221. doi: 10.1007/BF01222198. [DOI] [PubMed] [Google Scholar]
  38. PALADE G. E. A study of fixation for electron microscopy. J Exp Med. 1952 Mar;95(3):285–298. doi: 10.1084/jem.95.3.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. POST R. H. An approach to the question, does all diabetes depend upon a single genetic locus? Diabetes. 1962 Jan-Feb;11:56–65. [PubMed] [Google Scholar]
  40. Pyke D. A., Taylor K. W. Glucose tolerance and serum insulin in unaffected identcal twins of diabetics. Br Med J. 1967 Oct 7;4(5570):21–22. doi: 10.1136/bmj.4.5570.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. RICKETTS H. T., PETERSEN E. S., LINTS H., TUPIKOVA N., STEINER P. E. Degenerative lesions in dogs with experimental diabetes. Diabetes. 1959 Jul-Aug;8(4):298–306. doi: 10.2337/diab.8.4.298. [DOI] [PubMed] [Google Scholar]
  42. STEINBERG A. G., WILDER R. M. A study of the genetics of diabetes mellitus. Am J Hum Genet. 1952 Jun;4(2):113–135. [PMC free article] [PubMed] [Google Scholar]
  43. Siperstein M. D., Norton W., Unger R. H., Madison L. L. Muscle capillary basement membrane width in normal, diabetic and prediabetic patients. Trans Assoc Am Physicians. 1966;79:330–347. [PubMed] [Google Scholar]
  44. Soeldner J. S., Gleason R. E., Williams R. F., Garcia M. J., Beardwood D. M., Marble A. Diminished serum insulin response to glucose in genetic prediabetic males with normal glucose tolerance. Diabetes. 1968 Jan;17(1):17–26. doi: 10.2337/diab.17.1.17. [DOI] [PubMed] [Google Scholar]
  45. Spiro R. G. Studies on the renal glomerular basement membrane. Preparation and chemical composition. J Biol Chem. 1967 Apr 25;242(8):1915–1922. [PubMed] [Google Scholar]
  46. UNGER R. H. The standard two-hour oral glucose tolerance test in the diagnosis of diabetes mellitus in subjects without fasting hyperglycemia. Ann Intern Med. 1957 Dec;47(6):1138–1153. doi: 10.7326/0003-4819-47-6-1138. [DOI] [PubMed] [Google Scholar]
  47. Vracko R., Strandness D. E., Jr Basal lamina of abdominal skeletal muscle capillaries in diabetics and nondiabetics. Circulation. 1967 Apr;35(4):690–700. doi: 10.1161/01.cir.35.4.690. [DOI] [PubMed] [Google Scholar]
  48. YALOW R. S., BERSON S. A. Immunoassay of endogenous plasma insulin in man. J Clin Invest. 1960 Jul;39:1157–1175. doi: 10.1172/JCI104130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. ZACKS S. I., PEGUES J. J., ELLIOTT F. A. Interstitial muscle capillaries in patients with diabetes mellitus: a light and electron microscope study. Metabolism. 1962 Apr;11:381–393. [PubMed] [Google Scholar]
  50. ZALME E., KNOWLES H. C., Jr A PLEA FOR PLASMA SUGAR. Diabetes. 1965 Mar;14:165–166. doi: 10.2337/diab.14.3.165. [DOI] [PubMed] [Google Scholar]

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