Diabetes: a pragmatic therapy with a goal to prevent end stage kidney disease and dialysis

Anil KMandal, Nirankar Singh Neki

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DOI: 10.4236/ojim.2011.13017                

Abstract

The pragmatic therapy of diabetes which is to achieve satisfactory glycemic control emerges from author’s laboratory research. Cell culture studies convincingly demonstrated that high glucose levels above 200 mg/dL (> 11.1 mmol/L) cause damage to vascular endothelial cells. The severity of damage increases with duration of exposure of cultured endothelial cells to high glucose. This glucose-induced endothelial cell damage is mitigated by exposure of the endothelial cells to insulin in the presence of high glucose. There is abundant evidence, including that of author, that insulin treatment prevents diabetes-related microvascular complications including nephropathy and renal failure. Even by taking insulin multiple times, glucose level may reach normal level but only for a short time, because endogenous insulin response is insufficient. Manipulation by oral antidiabetic agents to enhance endogenous insulin release, or increase insulin sensitivity, results in exhaustion of the beta cells, thus changing an easily controllable glycemic state to a pathological uncontrollable glycemic state over the years. Even more troublesome is the lack of established information about the glucose levels that are safe for patients who have diabetes. By the term safe glucose level author means a glucose level which is least toxic to microvascular system and not likely to cause neuropathy, foot ulcer, gangrene, sexual dysfunction, and kidney failure. To achieve that glucose control is a formidable task for the patients as well as the doctors and nurses. Nevertheless, persistence is essential in diabetes management. Thus, on one hand patients must be astute in their care and doctors and nurses must be diligent in implementing and maintaining optimal glucose control in their patients. Both parties must be cohesive to achieve only one goal, which is to keep patients learn to cope with diabetes and thrive. Randomized clinical trials of glycemic control comparing one insulin against another, or insulin against oral hypoglycemic agents is not ethical. Such clinical trials will shed no light in improving diabetes care. On the other hand, it may prove to be detrimental.

Keywords

Diabetes; Paradigm Of Therapy; Postprandial Hyperglycemia; Endothelial Cell Injury; Insulin Treatment; Lantus Insulin; Regular Insulin

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Brownlee, M. (2005) Pathobiology of diabetic complications: A unifying mechanism. Diabetes; 54, 1615-1625. doi:10.2337/diabetes.54.6.1615
[2]	Giugliano, D., Ceriello, A. and Paolisso, G. (1996) Oxidative stress and diabetic vascular complications. Diabetes Care; 19, 257-267. doi:10.2337/diacare.19.3.257
[3]	Mandal, A.K., Ping, T., Caldwell, S.J., Bagnell, R. and Hiebert, L.M. (2006)Electron microscopic analysis of glucose-induced endothelial damage in primary cell culture: possible mechanism and prevention. Histology and Histopathology, 21, 941-950.
[4]	Hiebert, L.M. and Liu, J. (1990) Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites. Atherosclerosis, 83, 47-51. doi:10.1016/0021-9150(90)90129-7
[5]	Yokokawa, K., Mandal, A.K., Kohno, M., Horio, T., Murakawa, K., Yasunari, K. and Takeda, T (1992) Heparin suppresses endothelin-1 action and production in spontaneously hypertensive rat. American Journal of Physiology, 263, R1035-R1041.
[6]	Mandal, A.K., Puchalski, J.T., Lemley-Gillespie, S., Taylor, C.A. and Kohno, M. (2000) Effect of insulin and heparin on glucose-induced vascular damage in cell culture. Kidney International, 57, 2492-2501. doi:10.1046/j.1523-1755.2000.00108.x
[7]	Ohkubo, Y., Kishikawa, H., Araki, E., Miyata, T., Isami, S., Motoyoshi, S., et al. (1995) Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: A randomized prospective 6-year study. Diabetes Research and Clinical Practice, 28, 103- 117. doi:10.1016/0168-8227(95)01064-K
[8]	Reichard, P., Nilsson, R.Y. and Rosenqvist, U. (1993) The effect of long-term insulin treatment on the development of microvascular complications of diabetes mellitus. The New England Journal of Medicine, 329, 304- 309. doi:10.1056/NEJM199307293290502
[9]	The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin dependent diabetes mellitus. The New England Journal of Medicine, 329, 977-986. doi:10.1056/NEJM199309303291401
[10]	Fabre, J., Balant, L.P., Dayer, P.G., Fox, H.M. and Vernet, A.T. (1982) The kidney in maturity onset diabetes mellitus: a clinical study of 510 patients. Kidney International, 21, 730-738. doi:10.1038/ki.1982.90
[11]	Kooy, A., de Jager, J., Lehert, P., Bets, D., Wulffelé, M.G., Donker, A.J.M. and Stehouwer, C.D.A. (2009) Long-term effects of metformin on metabolism and micro-vascular and macrovascular disease in patients with Type 2 diabetes mellitus. Archives of Internal Medicine, 169, 616-625. doi:10.1001/archinternmed.2009.20
[12]	Nosadini, R. and Tonolo, G. (2004) Relationship between blood glucose control, pathogenesis and progression of diabetic nephropathy. Journal of the American Society of Nephrology, 15, S1-S5. doi:10.1097/01.ASN.0000093372.84929.BA
[13]	Nathan, D.M., Kuenen, J., Borg, R., Zhengtt, Schoenfeld, D. and Heive, R.J.(2008) Translatingthe A1C assay into estimated average glucose values. Diabetes Care, 31, 1473-1478. doi:10.2337/dc08-0545
[14]	Mandal, A.K., Hiebert, L.M. and Khamis, H. (2011) dGlucose is linked to renal function changes in diabetes. Diabetes Research and Clinical Practice, 91, 190-194. doi:10.1016/j.diabres.2010.11.013
[15]	Palumbo, P.J. (2004) The case for insulin treatment early in type 2 diabetes. Cleveland Clinic Journal of Medicine, 71, 385-405. doi:10.3949/ccjm.71.5.385
[16]	Holman, R.R., Paul, S.K., Bethel, M.A., Mathews, D.R. and Neil, H.A. (2008) 10 year follow up of intensive glucose control in type 2 diabetes. New England Journal of Medicine, 359, 1577-1589. doi:10.1056/NEJMoa0806470
[17]	Heller, S.R., Amiel, S.A., Mansell, P., UK Lispro Study Group (1999) Effect of the fast-acting insulin analog Lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. Diabetes Care, 22, 1607-1611. doi:10.2337/diacare.22.10.1607
[18]	Mandal, A.K., Markert, R.J., Saklayen, M.G., Mankus, R.A. and Yokokawa, K. (1994) Diuretics potentiate angiotensin converting enzyme inhibitor-induced acute renal failure, Clinical Nephrology, 42, 170-174.
[19]	Mandal, A.K. and Hiebert, L.M. (2008) Renal protection in diabetes: Is it affected by glucose control or inhibition of renin-angiotensin pathway. Clinical Nephrology, 69, 169-178.
[20]	Mandal, A.K. (2010) A reversible of acute renal failure associated with renin-angiotensin inhibitor drugs. International Urology and Nephrology, 2, 567-579.
[21]	Hamaty, M. (2011) Insulin treatment for type 2 diabetes: when to start and which to use. Cleveland Clinic Journal of Medicine, 78, 332-342. doi:10.3949/ccjm.78a.10051