Glycemic Control in Diabetic Dialysis Patients and the Burnt-Out Diabetes Phenomenon
- 945 Downloads
Diabetes mellitus (DM) is the most common cause of end-stage kidney disease and a major risk of morbidity and mortality. It is not clear whether medical management of DM has any significant beneficial effect on clinical outcomes at the end-stage of diabetic nephropathy with full-blown micro- and macro-angiopathic complications. Both loss of kidney function and dialysis treatment interfere with glucose homeostasis and confound glycemic control. Given the unique nature of uremic milieu and dialysis therapy related alterations, there have been some debates about reliance on the conventional measures of glycemic control, in particular the clinical relevance of hemoglobin A1c and its recommended target range of <7 % in diabetic dialysis patients. Moreover, a so-called burnt-out diabetes phenomenon has been described, in that many diabetic dialysis patients experience frequent hypoglycemic episodes prompting cessation of their anti-diabetic therapies transiently or even permanently. By reviewing the recent literature we argue that the use of A1c for management of diabetic dialysis patients should be encouraged if appropriate target ranges specific for these patients (e.g. 6 to 8 %) are used. We also argue that “burnt-out diabetes” is a true biologic phenomenon and highly prevalent in dialysis patients with established history and end-stage diabetic nephropathy and explore the role of protein-energy wasting to this end. Similarly, the J- or U-shaped associations between A1c or blood glucose concentrations and mortality are likely biologically plausible phenomena that should be taken into consideration in the management of diabetic dialysis patients to avoid hypoglycemia and its fatal consequences in diabetic dialysis patients.
KeywordsDiabetes mellitus Chronic kidney disease Hemoglobin A1c Glycemic control Maintenance dialysis Burnt-out diabetes Diabetic dialysis
The work is supported by K. Kalantar-Zadeh’s NIH (NIDDK) grants K24-DK091419, R0-DK078106 and R21-DK077341 and by a philanthropic grant from Mr. Harold Simmons. M.Z. Molnar received grants from the National Developmental Agency (KTIA-OTKA-EU 7KP-HUMAN-MB08-A-81231) from the Research and Technological Innovation Fund, and is recipient of the Hungarian Eötvös Scholarship (MÖB/77-2/2012).
Conflicts of interest: J. Park: none; P. Lertdumrongluk: none; M.Z. Molnar: none; C.P. Kovesdy: has been a consultant for Apotex; has received grant support from Abbott, Shire; receives royalties from UpToDate; and has received payment for development of educational presentations including service on speakers’ bureaus from Health Diagnostic Laboratories; K. Kalantar-Zadeh: has been a consultant for Abbott, Amgen, Genzyme, Shire, Vifor; has been an expert witness for law firms; has received grant support from NIH, NKF, Abbott, Shire; receives royalties from UpToDate; and has received payment for development of educational presentations including service on speakers’ bureaus from Abbott, Amgen, Genzyme, Otsuka, Shire.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 3.USRDS. Annual Data Report: Atlas of End-Stage Renal Disease in the United States. 2011. http://www.usrds.org/atlas.asps Accessed 10 April 2012.
- 24.• Kalantar-Zadeh K, Kopple JD, Regidor DL, et al. A1C and survival in maintenance hemodialysis patients. Diabetes Care. 2007;30:1049–55. This is a large study in which A1c is associated with mortality after adjusting possible confounders including demographics, comorbidities, anemia and nutrition. It also shows a significant prevalence of A1c level <6 % in HD patients. PubMedCrossRefGoogle Scholar
- 27.• Williams ME, Lacson Jr E, Wang W, et al. Glycemic control and extended hemodialysis survival in patients with diabetes mellitus: comparative results of traditional and time-dependent cox model analyses. Clin J Am Soc Nephrol. 2010;5:1595–601. The authors supplements their previous observation, in which A1c did not related to mortality in dialysis patients, by extending follow-up to 3 years and using time-dependent survival models. They show only extremes of glycemia are associated with inferior survival, suggesting an aggressive glycemic control is not mandatory in this population. PubMedCrossRefGoogle Scholar
- 30.• Ricks J, Molnar MZ, Kovesdy CP, et al. Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study. Diabetes. 2012;61:708–15. This is a very recent, large, nationally representative study. It demonstrates a J-shaped association between A1c (or glucose) and mortality. Of noteworthy about 40 % of HD patients have A1c levels <6 % linking to inferior survival. PubMedCrossRefGoogle Scholar
- 45.Heaton A, Taylor R, Johnston DG, et al. Hepatic and peripheral insulin action in chronic renal failure before and during continuous ambulatory peritoneal dialysis. Clin Sci (Lond). 1989;77:383–8.Google Scholar
- 53.Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002; 287:2563–2569.Google Scholar
- 55.Kalantar-Zadeh K. A1c remains gold standard outcome predictor in diabetic dialysis patients. Diabetes Care, July 2012 doi: 10.2337/dc12-0483.