0(50 METABOLISM 



be found present in at least some of the specimens. In incipient diabetes, 

 however, the condition progresses, until the postprandial hyperglycemia 

 after one meal has not become entirely replaced before the next is taken, 

 so that the increase in sugar produced by the second meal becomes super- 

 added on that following the first meal. The curve of blood sugar rises 

 ever higher and higher, until at last permanent hyperglycemia is estab- 

 lished, or rather the normal level from which the postprandial rise occurs 

 has become permanently raised, so that in blood collected at any time a 

 higher percentage of sugar is found. 



The Relationship Between the Sugar Concentration of the Blood and 

 the Occurrence of Glycosuria. Claude Bernard first pointed out that the 

 percentage of sugar in the blood may rise considerably above its normal 

 level without the appearance of any of the sugar in the urine, or at least 

 without a sufficient amount to give the usual tests for sugar. Even when 

 this limit is reached, as we have seen, the sugar which appears is not all of 

 the excess but only a small part of it. This overflow hypothesis, as it is 

 called, has not been universally accepted because of the many results 

 which are not in conformity with it. Many of these exceptional results 

 have been explained as due to alterations in the permeability of the kidney 

 for sugar, and in general it is probably safe to accept Claude Bernard's 

 hypothesis with certain reservations. 



Strong support has been lent to a modified form of the hypothesis by 

 the recent work of Woodyatt and his collaborators, who have shown by 

 continuous intravenous glucose injections that as much as 0.8 gm. of 

 glucose per kilo body weight can be injected during an hour into an 

 animal without any glycosuria, although under such conditions a very 

 distinct increase occurs in the percentage of sugar in the blood. 



To explain the failure of glucose to pass into the urine under normal 

 conditions, it has been supposed by several investigators that the glucose 

 exists in some form of chemical combination in the blood. This compound 

 is believed to behave like a colloid. One of the recent supporters of this 

 view is Allen, who has observed that, when glucose is injected intrave- 

 nously, it causes diuresis as well as glycosuria; whereas glucose injected 

 subcutaneously or taken by mouth causes neither of these conditions to 

 become developed ; indeed it causes for some time after the administration 

 of the sugar a distinct anuria. To explain these differences in behavior 

 between glucose administered intravenously and that taken in other ways, 

 it is supposed that the glucose molecule in passing through the intervening 

 wall of the capillaries combines with some substance to form a compound 

 which becomes available for incorporation into and utilization by the 

 tissues, glucose in a free state being incapable of utilization. This com- 

 pound is supposed to be of a colloidal nature, and the substance which 



