668 DIABETES 



sometimes seen. But, as in phlorhizinized dogs, higher ratios may 

 occur in the human disease. 



If to such a case of diabetes as this we give by mouth 40 grams of 

 glucose there may appear in the urine close to 40 grams of extra 

 sugar. Plainly such extra sugar has escaped utilization of any kind. 

 It cannot have been oxidized or converted into fat, since these proc- 

 esses are irreversible, although it might have existed momentarily in 

 the body as glycogen or other isomer of glucose. What phase in the 

 utilization of this glucose is primaril}' disturbed is another question. 

 To say that 40 grams of ingested glucose causes the appearance of 40 

 grams of extra sugar in the urine does not prove that the diabetic 

 body is inherently incapable of using any sugar or every carbohydrate. 

 It might still be capable of using a two, three, or four carbon atom 

 sugar, some other member of the group of 32 hexoses, or, as some have 

 it (von Noorden), sugar which has first been built up into glycogen, 

 etc., provided these substances could be kept from undergoing trans- 

 formations into the non-utilizable glucose. As a rule, however, when 

 other sugars are fed to complete diabetics, they are transformed into 

 glucose and appear as such in the urine. This phenomenon has much 

 of significance for the general theory of sugar metabolism and is an 

 indication of the nature of the primary disturbance in diabetes, as will 

 now be shown. 



Theory of Diabetes. — What sort of a chemical process is involved 

 when levulose, for example, is converted in the body into glucose? 

 As already stated in the chemical introduction, the reciprocal trans- 

 formations of hexoses one into another in the alkaline solution in 

 liiro depend upon a preliminary ionization of the sugars followed by 

 salt formation, the salts then undergoing dissociation which, according 

 to ^lathews and IMichaelis, is still purely electrolytic with rearrange- 

 ments of the anion ; but which, according to Nef, is a non-electrolytic 

 dissociation of the type which he calls methylene dissociation. Some 

 form of dissociation must he a prelude also to these transformations in 

 the hody. This view is logically just as necessary as it has been found 

 to be for the organic chemist, and, it may be added, that for the oxida- 

 tion of sugars as well as for their polymerization a preliminary dissoci- 

 ation is essential. Now since the diabetic body can transpose other 

 sugars into glucose, it must be able at least to dissociate the former 

 sugars deeply enough for this process. These trans])ositions are ac- 

 complished chiefly in the portal system and perhaj^s in other places 

 too, but certainly- levulose and man}' other substances can be made in 

 the liver into glycogen, whose hj'drolysis then yields glucose. 



The degree or character of the dissociation necessarj'' for reciprocal 

 transfonnations differs from that which is a necessary prelude to 

 destructive reactions such as oxidation. A very weak alkali suffices 

 in vitro for the former, while for the latter it is necessary to use a 



