Twenty-one young onset Type 1 (insulin dependent) diabetics who developed severe diabetic nephropathy after 14.5±3.3 years (mean ± SD) and 21 age and sex matched Type 1 diabetics without evidence of nephropathy after more than 32 years of disease were compared with particular reference to body build, insulin requirements, stability of diabetes, heart rate and blood pressure before the development of nephropathy. Attempts were made to evaluate the quality of metabolic control during the first 20 years of diabetes from more than 1,600 out-patient measurements of blood and urinary glucose in each group. The renal tubular reabsorption capacity for glucose was calculated in both groups. No differences between the two groups were found for any of the parameters examined, except that the frequency of ketoacidosis was higher in the patients who developed nephropathy. It is concluded that many Type 1 diabetics seem to be protected against the deleterious effect of diabetes on the kidney. The nature of the protecting factors is unknown.

1451 patients with IDDM, onset before 1953 and before the age of 30 were followed until death or until 1976. Survival with diabetes, relative survival and the influence of supervision on survival were examined. It is shown that only 50% of the patients survived more than 30 diabetes years. The patients had an overmortality of more than 600% in relation to age and sex matched non-diabetics. Frequent supervisions in the out-patient clinic reduced as well the overmortality as the prevalence of severe complications significantly.

In 307 patients with diabetes mellitus, developed prior to 1933 and before age 31 it was demonstrated that: (1) frequent contact with a specialized diabetes clinic from an early stage of the disease; (2) a good quality of "metabolic control"; (3) a low insulin dose; (4) a body weight of 10% less than ideal; and (5) a mean blood pressure below 100 mm Hg, all had significantly beneficial effects upon the survival. It was also found that patients domiciled in Copenhagen had a significantly better prognosis than patients domiciled outside Copenhagen. Frequent contact with a diabetes centre was accompanied by an appreciable decrease in disabling late diabetic complications.

The object of this study was to investigate whether outpatient follow-up visits to a subspecialized clinic have a favorable effect upon length of life of juvenile diabetic patients, and to evaluate whether the cost of suchoutpatient supervision is in reasonable proportion to the benefit obtained. The study comprises 180 insulin-dependent diabetic patients in whom a diagnosis had been made before 1933, and before they were 31 years of age. The patients had been admitted to the Steno Memorial Hospital before their fifteenth year of diabetes. Sixteen patients could not be traced after forty years of diabetes, while the others were followed until death or until their fortieth year with diabetes. Seventy-seven patients never attended follow-up in the outpatient clinic, while the others attended one to 145 times in thecourse of their first twenty years of diabetes. From the results it is apparent that the duration of diabetes correlated with increased frequency of outpatient follow-up. With 4.4 annual outpatient follow-up visits, the duration of diabetes was prolonged by 11.9 years. The cost of this was estimated at $10,468 per patient over forty years. The benefit per patient over the entire forty years was $100,656. These findings suggest that outpatient supervision of diabetes in a subspecialized clinic is beneficial for patients and involves relatively little cost.

The morphologic and metabolic effect of a single intracutaneous injection of homologous endocrine pancreas in Freund's complete adjuvant (CFA) was studied in 100 mice and compared with control groups which had been (1) immunized with murine insulin in CFA, (2) injected with CFA alone, or had (3) received no treatment. There were no differences between the control groups as regards the morphology of the pancreatic islets, and the glucose tolerance was normal. Mice immunized with islet homogenate exhibited morphological changes in the form of degranulation and cytoplasmic disintegration. These changes involved B-cells as well as A2-cells and were present from 7 to 18 days after the immunization. A significant reduction in glucose tolerance was observed 14 days after the immunization. Another characteristic finding in the islets from the immunized mice was the extra-vascular presence of mononuclear, agranular cells which on the basis of their morphological criteria appeared to represent lymphocytes.

The influence of August Krogh on the introduction of insulin preparations in Scandinavia is mentioned, and his outstanding physiological background is outlined. Developments in preparation of insulin depending on the progress in protein-chemistry are summarized. The latest step in the purification of insulin extracted from pork pancreas now allows treatment of diabetics with protamine-pork-insulin without causing formation of insulin-antibodies in at least 90 per cent treated with insulin through several months. In only 3 out of 51 diabetics was it possible to demonstrate insulin-antibodies. This new step may be of great interest in two ways 1) it is now possible to make insulin-estimations in the plasma of insulin-treated cases and 2) it will be possible to find out whether elimination of insulin-antibody-formation will reduce the degree of vascular lesions in diabetics, such lesions being the greatest problem in clinical diabetes.

Mice developed degenerative changes of B-cells with loss of insulin granules, extravascularly situated mononuclear cell infiltration of the islets of Langerhans, and glucose intolerance eight and fifteen days after immunization with homologous islets in complete Freund's adjuvant. Murine insulin and adjuvants in comparable preparations did not cause similar changes. The condition was transient, but has the following features in common with juvenile diabetes mellitus in man: glucose intolerance, mononuclear cell infiltration of the islets and organ specific, anti-pancreatic cellular hypersensitivity. It may therefore serve as a useful model in diabetes research.

146 diabetics were HL-A typed, and the results were correlated with age-at-onset, weight, insulin treatment, and the presence of cell-mediated antipancreatic immunity. HL-A8 and W15 were significantly more frequent in the diabetics than in 1967 controls. The increase was found almost exclusively in insulin-dependent diabetes. These findings support the concept that insulin-dependent and insulin-independent diabetes are two different disease entities. Thus, the inherited susceptibility to insulin-dependent diabetes is associated with HL-A8 and W15. The increase of HL-A8 in insulin-dependent diabetes, Graves' disease, and idiopathic Addison's disease is suggestive of a common pathogenesis of these endocrine autoimmune conditions.

AllergyVolume 28, Issue 4 p. 223-230 ANTI-PANCREATIC, CELLULAR HYPERSENSITIVITY IN DIABETES MELLITUS. ANTIGENIC ACTIVITY OF FETAL CALF PANCREAS AND CORRELATION WITH CLINICAL TYPE OF DIABETES JØSRN NERUP, JØSRN NERUP From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorOLE ORTVED ANDERSEN, OLE ORTVED ANDERSEN From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorGUNNAR BENDIXEN, GUNNAR BENDIXEN From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorJØRN EGEBERG, JØRN EGEBERG From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorJACOB E. POULSEN, JACOB E. POULSEN From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this author JØSRN NERUP, JØSRN NERUP From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorOLE ORTVED ANDERSEN, OLE ORTVED ANDERSEN From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorGUNNAR BENDIXEN, GUNNAR BENDIXEN From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorJØRN EGEBERG, JØRN EGEBERG From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this authorJACOB E. POULSEN, JACOB E. POULSEN From Medical Department TA, Laboratory of Clinical Immunology, Rigshospitalet University Hospital, Copenhagen; Steno Memorial Hospital, Gentofte; and Anatomy Department B, University of Copenhagen, Denmark.Search for more papers by this author First published: October 1973 https://doi.org/10.1111/j.1398-9995.1973.tb01443.xCitations: 33AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume28, Issue4October 1973Pages 223-230 RelatedInformation