Diabetes mellitus as analogue of pernicious anemia: a speculation.

Abstract

DIABETES MELLITUS AS ANALOGUE OF PERNICIOUS ANEMIA: A SPECULATION JEROME D. GORMAN, MD* Power of nutriment reaches to bone and to all the parts of bone, to sinew, to artery, to muscle, to membrane, to flesh, fat, blood, phlegm, marrow, brain, spinal marrow, the intestines and all their parts; it reaches also to heat, breath, and moisture. [Hippocrates] There are more than a hundred, indeed more than a thousand, kinds of stomach; consequently, if you gather a thousand persons, each of them will have a different kind of digestion, each unlike the others. [Paracelsus] A speculative induction and deduction is presented regarding food and gut factors in diabetes mellitus and pernicious anemia. No proof or new facts are offered in the hypothesis which concentrates on similarities of form rather than differences in function. Pernicious Anemia Pernicious anemia has juvenile and adult forms [1-3]. In 1926, Minot and Murphy [4] reported therapeutic success with beef liver in pernicious anemia. Castle and Townsend [5] discovered gastric juice intrinsic factor. In 1948, crystalline vitamin B12 was isolated and its structure was determined in 1955. Diabetes Mellitus Diabetes mellitus also has juvenile and adult forms. Episodic hypoglycemia may precede fixed diabetes. Eclampsia, hypertension, and retinopathy occur more often in diabetics. Gepts [6] thought an extrapancreatic factor altered islet cell population as well as the number and size of pancreatic islets. Besides islet hormones, gastrointestinal and other hormones have glucoregulatory roles. * Address: 5713 Penguin Drive South West, Roanoke, Virginia 24018. Perspectives in Biology and Medicine · Winter 1973 I 323 Intersection An association between pernicious anemia and diabetes mellitus has been repeatedly noted. Hepatic dysfunction, gallstones, neuropathies , and polyendocrine and gastric autoantibodies occur in both diseases [7-12]. Discordance may appear in identical twins [13, 14]. Liver Extract In isolating the liver extract effective in pernicious anemia, Cohn et al. [15] found another that lowered blood pressure and still another with hypoglycemic effect. Levin [16] reported useful results in human diabetics given injections of beef-liver extract. Blotner and Murphy Blotner and Murphy [17, 18] compared blood-sugar response in diabetics who ate test meals containing equal amounts of protein (red muscle meat or raw calf liver), carbohydrate, and fat. The meal containing liver (or extracts thereof) was more hypoglycemic than the meal containing muscle (see table 1 and Appendix). Duodenal Extract Moore, Edie and Abram [19] observed therapeutic benefit in decompensated juvenile diabetics treated with an orally administered extract of pork duodenal mucosa. Duncan et al. [20] reported similar results with an orally administered extract of beef duodenal mucosa. In both studies, therapeutic effect persisted beyond acute interaction that may have occurred between gut and islet hormones. Deficiency, Dysfunction, and Dysgenesis Episodic hypoglycemia may onset at various intervals following gastric resection. During pregnancy, a single nutritional store serves both mother and growing fetus. Subclinical hepatic dysfunction and nutritional deficiency are not rare during gestation. Accelerated retinopathy may occur in diabetes, eclampsia, and hyperemesis gravidarum . Stillbirth, neonatal hypoglycemia, respiratory distress, and congenital malformation are more frequent in offspring of diabetic mothers. Hypothesis Though pernicious anemia and diabetes mellitus are functionally dissimilar and have different incidences, they superficially correspond 324 I Jerome D. Gorman · Diabetes Mellitus TABLE 1 Arbitrary Areas under Comparable Blood Sugar Curves when Fasting Blood Sugar Is 100 Percent Muscle Ratio Liver 1929 Crossover 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Mean. 747 996 838 724 264 284 656 766 762 650 756 612 912 1140 1046 940 332 324 844 810 876 931 854 824 .819 .874 .801 .770 .796 .875 .777 .946 .870 .698 .885 .743 .821 1930 Crossover 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 668 466 751 772 646 596 620 620 628 612 620 682 670 643 663 792 702 702 735 757 825 865 1050 744 860 724 836 630 702 732 782 808 751 761 810 786 748 814 .882 .565 .868 .735 .868 .693 .856 .742 .997 .872 .847 .872 .829 .856 .871 .978 .893 .938 .903 Mean. .845 with regard to heredity, age of onset, and involvement of vital polypeptides . Using pernicious anemia as heuristic model, one...