Diabetes Hyperglycemia

MCPEAK P, RUKMiNi c, REDDY SASTRY c (2001) Supportive therapy for diabetes, hyperglycemia and hypoglycemia. US Patent 6,303,586 Bl. 

Correct answer = A. Elevated blood glucose occurs in type 1 diabetes as a result of a lack of insulin. In type 2 diabetes, hyperglycemia is due to a defect in p cell function and insulin resistance. Both forms of the disease show complex genetics. Ketoacidosis is more common in type 1 disease. 

Fig. 9.1 Schematic model depicting the key events which mediate diabetes-associated vascular complications. Diabetes/hyperglycemia augments the levels of vasoactive peptides including Ang II/ET-1 that enhance the generation of reactive oxygen species (ROS). ROS-induced activation of growth-promoting signaling pathways, such as PKC and MAPK, contributes to aberrant vascular functions.

Hashim, S., Y. Li, and M.B. Anand-Srivastava. 2006. G protein-linked cell signaling and cardiovascular functions in diabetes/hyperglycemia. Cell Biochem. Biophys. 44 51-64. 

Unger, R.H. (1991). Diabetic hyperglycemia Link to impaired glucose transport in pancreatic p cells. Science 251,1200-1205. 

Acyclic cyanomethyl adamantanyl derivatives, (I), prepared by Magnin (3) were effective as DPP-IV inhibitors and used in treating Type II diabetes, hyperglycemia, and hypoglycemia. 

Intracellular redistribution of is illustrated by the fall in plasma IC that occurs following insuiin therapy for diabetic hyperglycemia. The cells must take up as a consequence of glucose transport. Redistribution hypokalemia is also a feature of alkalosis, in which K moves from ECF into the cells as H moves in the opposite direction. In addition, the renal conservation of m the distal tubule occurs at the expense of ions. On the other hand, severe intracellular IC depletion may also cause alkalosis, as shifts intracel-lularly. Catecholamines and states of endogenous or pharmacological P-adrenergic excess have a similar effect. 

Etgen, G.J., Oldham, B.A., Johnson, W.T. et al. (2002) A tailored therapy for the metabolic syndrome the dual peroxisome proliferator-activate receptor-a/y agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in predinical models. Diabetes, 51, 1083-1087. 

The concept that precise control of diabetic hyperglycemia has a part in reducing the microvascular complications in the diabetic comes from several lines of investigation in animals (M8, M15) and man (GIO, L16, S12, S15, V2). Nephropathy is the most serious complication of type I (insulin-dependent) diabetes, and renal failure eventually occurs in some 40%. Within 7 to 10 years of the onset of persistent albuminuria, about 50% of patients will have died. 

Zumoff B, Heilman L. Aggravation of diabetic hyperglycemia by chiordiazepoxide. JAMA (1977) 237, 1960-1. 

In diabetes, hyperglycemia is associated with an excessive oxidative stress leading to cell death in endothelial cells. In an animal model of streptozotocin-induced diabetes, CORM-3 decreased urinary 8-epi-isoprotane PGF (2a), reduced endothelial cell sloughing, and restored vascular function, likely by limiting oxidative stress [67,68]. 

Jarrett RJ, Keen H, Chakrabarti R. Diabetes, hyperglycemia, and arterial disease. In Keen H, Jarrett RJ, eds. Complications of Diabetes. 2nd ed. London Edward Arnold, 1982, pp. 179-204. 

L.-H, Godzala, M.E., and Willsky, G.R. (2005) Aqueous chemistry of the Vanadium " (V ") and the V "-dipicolinate systems and a comparison of the effect of three oxidation states of vanadium compounds on diabetic hyperglycemia in rats. Inorg. Chem., 44, 5416-5427. 

---