Article thumbnail

Disturbance of inorganic phosphate metabolism in diabetes mellitus: temporary therapeutic intervention trials

By Jørn Ditzel and Hans Henrik Lervang


A paradoxical metabolic imbalance in inorganic phosphate occurs from the early onset of diabetes and may lead to a reduction of high energy phosphates and tissue hypoxia. These changes take place in the cells and tissues in which the entry of glucose is not controlled by insulin, and particularly in poorly regulated diabetes patients in whom long-term vascular complications are more likely to occur. Several therapeutic intervention trials have been carried out, including assessment of optimal glucose regulation, the effect of dietary inclusion of calcium diphosphate and pharmaceutical intake of etidronate disodium (EHDP), but none of these modalities wholly overcome the problem. The potential therapeutic application of fructose-1, 6-diphosphate, however, which also acts as human bioenergy, holds a great deal of promise as an efficacious and well-tolerated therapeutic regimen

Topics: Review
Publisher: Dove Medical Press
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. Administration of fructose 1,6-diphosphate during early reperfusion significantly improves recovery of contractile function in the postischemic heart.
  2. An adverse effect of insulin on the oxygen-release capacity of red blood cells in nonacidotic diabetics.
  3. diphosphate as a protective agent for experimental ischemic acute renal failure.
  4. (1986). Does availability of inorganic phosphate regulate cellular oxidative metabolism? News Physiol Sci.
  5. (2000). Does suppression bone turnover impair mechanical properties by allowing microdamage accumulation?
  6. Dysfunction of tubular phosphate reabsorption related to glomerular filtration and blood glucose control in diabetic children.
  7. (1977). Effect of diphosphonate ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on hemoglobin oxygen affinity of diabetic and healthy subjects. Microvasc Res.
  8. (1995). Effect of glycemic control on calcium and phosphorous handling and parathyroid level in patients with non-insulin-depemdemt diabetes mellitus.
  9. Effect of phosphate enhancing the action of triiodothyronine.
  10. (1973). Effect of plasma inorganic phosphate on tissue oxygenation during recovery from diabetic ketoacidosis. Adv Exp Med Biol.
  11. (1981). Elevated glomerular filtration rate in early diabetes may be explained by increased sodium reabsorption secundary to impairment in renal tubular handling of phosphate. Hormone Metab Res.
  12. Evaluation of fructose-1, 6-diphosphate on erythrocyte 2, 3 diphosphoglycerate and ATP in surgical orthopedic patients.
  13. Glucose and alanine inhibition of phosphate transport in renal microvillus membrane vesicles.
  14. (1988). Haemorheological effects of fructose-1, 6-diphosphate in patients with lower extremity ischemia. Curr Med Res Opin.
  15. Hypophosphataemia in the metabolic syndrome. Gender differences in body weight and blood glucose.
  16. Influence of disodium etidronate (EHDPTM) on clinical and laboratory manifestastion of Paget’s disease of bone (osteitis deformans).
  17. Intensive blood glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes.
  18. Is the relationship between plasma concentration of inorganic phosphate and the rate of oxygen consumption of significance in regulating energy metabolism in mammals?
  19. Long-term bone loss in insulin-dependent diabetic patients with microvascular complications.
  20. (1998). Markov AK. In vitro induction of nitric oxide by fructose-1, 6-diphosphate in the cardiovascular system of rats. Mol Cell Biochem.
  21. (2000). Membrane permeability of fructose.1, 6.diphosphate in lipid vesicles and endothelial cells. Mol Cell Biochem.
  22. Metabolic network control of oxidative phosphorylation: Multiple roles of inorganic phosphate.
  23. Metabolic responses of Fructose-1, 6-diphosphate in healthy subjects.
  24. Mineral metabolism in diabetes mellitus. Changes accompanying treatment with portable subcutaneous insulin infusion.
  25. Myocardial metabolism of exogenous FDP is consistent with transport by a dicarboxylate transporter.
  26. Oxidative phosphorylation. Role of inorganic phosphate and acceptor systems in control of metabolic rates.
  27. Plasma Pi and erythrocyte 2, 3DPG concentrations of non-acidotic diabetics in various degree of metabolic control.
  28. (1974). Regulation of fructose metabolism in the perfused rat liver. Interrelation with inorganic phosphate, glucose, ketone body and ethanol metabolism. Biochem Biophys Acta.
  29. The Diabetes Control and Complication Trial Research Group. The effect of intensive treatment of diabetes in insulin-dependent diabetes mellitus.
  30. The effect of chronic insulin therapy on phosphate metabolism in diabetes mellitus.
  31. (1991). The effect of EHDP concentration on enamel demineralization in vitro. J Dent Res.
  32. (1982). The effect of etidronate disodium (EHDP) on retinopathy in insulin-dependent diabetic patients. Graefe’s Arch Clin Exp Ophthalmol.
  33. The effect of oral administration of calcium fructose diphosphate on the serum organic phosphate, inorganic phosphate, calcium protein, and citric acid levels.
  34. The hyperphosphatemic effect of disodium-1-hydroxy-1, 1 diphophonate (EHDPTM): Renal handling of phosphorus and the renal response to parathyroid hormone.
  35. (1993). The influence of a dietary supplement of calcium and phosphate on bone mineral content and mineral homeostasis of diabetic children. Diabetologia.
  36. The problem of tissue oxygenation in diabetes mellitus III. Acta Med Scand. 1975;Suppl 578:S69–S83.
  37. The problem of tissue oxygenation in diabetes mellitus. II Evidence of disordered oxygen release from the erythrocytes of diabetics in various conditions of metabolic control. Acta Med Scand. 1975;Suppl 578:S59–S68.
  38. (1983). Tubular reabsorption rates as related to elevated glomerular filtration in diabetic children. Diabetes.