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Glycemic Control in Diabetic Dialysis Patients and the Burnt-Out Diabetes Phenomenon

  • Microvascular Complications—Nephropathy (B Roshan, Section Editor)
  • Published:
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Abstract

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.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Kovesdy CP, Sharma K, Kalantar-Zadeh K. Glycemic control in diabetic CKD patients: where do we stand? Am J Kidney Dis. 2008;52:766–77.

    Article  PubMed  Google Scholar 

  2. Kovesdy CP, Kalantar-Zadeh K. Enter the dragon: a Chinese epidemic of chronic kidney disease? Lancet. 2012;379:783–5.

    Article  PubMed  Google Scholar 

  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.

  4. Kalantar-Zadeh K, Derose SF, Nicholas S, et al. Burnt-out diabetes: impact of chronic kidney disease progression on the natural course of diabetes mellitus. J Ren Nutr. 2009;19:33–7.

    Article  PubMed  Google Scholar 

  5. Kovesdy CP, Park JC, Kalantar-Zadeh K. Glycemic control and burnt-out diabetes in ESRD. Semin Dial. 2010;23:148–56.

    Article  PubMed  Google Scholar 

  6. Fluckiger R, Harmon W, Meier W, et al. Hemoglobin carbamylation in uremia. N Engl J Med. 1981;304:823–7.

    Article  PubMed  CAS  Google Scholar 

  7. Kalantar-Zadeh K, Mehrotra R, Fouque D, Kopple JD. Metabolic acidosis and malnutrition-inflammation complex syndrome in chronic renal failure. Semin Dial. 2004;17:445–65.

    Article  Google Scholar 

  8. De Marchi S, Cecchin E, Camurri C, et al. Origin of glycosylated hemoglobin A1 in chronic renal failure. Int J Artif Organs. 1983;6:77–82.

    PubMed  Google Scholar 

  9. Mirani M, Berra C, Finazzi S, et al. Inter-day glycemic variability assessed by continuous glucose monitoring in insulin-treated type 2 diabetes patients on hemodialysis. Diabetes Technol Ther. 2010;12:749–53.

    Article  PubMed  CAS  Google Scholar 

  10. Kazempour-Ardebili S, Lecamwasam VL, Dassanyake T, et al. Assessing glycemic control in maintenance hemodialysis patients with type 2 diabetes. Diabetes Care. 2009;32:1137–42.

    Article  PubMed  Google Scholar 

  11. Riveline JP, Hadjadj S. Assessing glycemic control in maintenance hemodialysis patients with type 2 diabetes: response to Kazempour-Ardebili et al. Diabetes Care. 2009;32:e155–6. author reply.

    Article  PubMed  Google Scholar 

  12. Williams ME, Lacson Jr E, Teng M, et al. Hemodialyzed type I and type II diabetic patients in the US: Characteristics, glycemic control, and survival. Kidney Int. 2006;70:1503–9.

    Article  PubMed  CAS  Google Scholar 

  13. Shurraw S, Majumdar SR, Thadhani R, et al. Glycemic control and the risk of death in 1,484 patients receiving maintenance hemodialysis. Am J Kidney Dis. 2010;55:875–84.

    Article  PubMed  Google Scholar 

  14. Freedman BI, Andries L, Shihabi ZK, et al. Glycated albumin and risk of death and hospitalizations in diabetic dialysis patients. Clin J Am Soc Nephrol. 2011;6:1635–43.

    Article  PubMed  CAS  Google Scholar 

  15. Peacock TP, Shihabi ZK, Bleyer AJ, et al. Comparison of glycated albumin and hemoglobin A(1c) levels in diabetic subjects on hemodialysis. Kidney Int. 2008;73:1062–8.

    Article  PubMed  CAS  Google Scholar 

  16. Kumeda Y, Inaba M, Shoji S, et al. Significant correlation of glycated albumin, but not glycated haemoglobin, with arterial stiffening in haemodialysis patients with type 2 diabetes. Clin Endocrinol (Oxf). 2008;69:556–61.

    Article  CAS  Google Scholar 

  17. Inaba M, Okuno S, Kumeda Y, et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007;18:896–903.

    Article  PubMed  CAS  Google Scholar 

  18. Rubinow KB, Hirsch IB. Reexamining metrics for glucose control. JAMA. 2011;305:1132–3.

    Article  PubMed  CAS  Google Scholar 

  19. Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010;362:800–11.

    Article  PubMed  CAS  Google Scholar 

  20. Wu MS, Yu CC, Yang CW, et al. Poor pre-dialysis glycaemic control is a predictor of mortality in type II diabetic patients on maintenance haemodialysis. Nephrol Dial Transplant. 1997;12:2105–10.

    Article  PubMed  CAS  Google Scholar 

  21. Morioka T, Emoto M, Tabata T, et al. Glycemic control is a predictor of survival for diabetic patients on hemodialysis. Diabetes Care. 2001;24:909–13.

    Article  PubMed  CAS  Google Scholar 

  22. Mcmurray SD, Johnson G, Davis S, Mcdougall K. Diabetes education and care management significantly improve patient outcomes in the dialysis unit. Am J Kidney Dis. 2002;40:566–75.

    Article  PubMed  Google Scholar 

  23. Oomichi T, Emoto M, Tabata T, et al. Impact of glycemic control on survival of diabetic patients on chronic regular hemodialysis: a 7-year observational study. Diabetes Care. 2006;29:1496–500.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  25. Feldt-Rasmussen B. Is there a need to optimize glycemic control in hemodialyzed diabetic patients? Kidney Int. 2006;70:1392–4.

    Article  PubMed  CAS  Google Scholar 

  26. Williams ME, Lacson Jr E, Teng M, et al. Extremes of glycemic control (HbA1c) increase hospitalization risk in diabetic hemodialysis patients in the USA. Am J Nephrol. 2009;29:54–61.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  Google Scholar 

  28. Duong U, Mehrotra R, Molnar MZ, et al. Glycemic control and survival in peritoneal dialysis patients with diabetes mellitus. Clin J Am Soc Nephrol. 2011;6:1041–8.

    Article  PubMed  CAS  Google Scholar 

  29. Molnar MZ, Huang E, Hoshino J, et al. Association of pretransplant glycemic control with posttransplant outcomes in diabetic kidney transplant recipients. Diabetes Care. 2011;34:2536–41.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google Scholar 

  31. Shurraw S, Hemmelgarn B, Lin M, et al. Association between glycemic control and adverse outcomes in people with diabetes mellitus and chronic kidney disease: a population-based cohort study. Arch Intern Med. 2011;171:1920–7.

    Article  PubMed  Google Scholar 

  32. Mak RH. Impact of end-stage renal disease and dialysis on glycemic control. Semin Dial. 2000;13:4–8.

    Article  PubMed  CAS  Google Scholar 

  33. Dzurik R, Spustova V, Lajdova I. Inhibition of glucose utilization in isolated rat soleus muscle by pseudouridine: implications for renal failure. Nephron. 1993;65:108–10.

    Article  PubMed  CAS  Google Scholar 

  34. Mccaleb ML, Izzo MS, Lockwood DH. Characterization and partial purification of a factor from uremic human serum that induces insulin resistance. J Clin Invest. 1985;75:391–6.

    Article  PubMed  CAS  Google Scholar 

  35. Schmitz O. Insulin-mediated glucose uptake in nondialyzed and dialyzed uremic insulin-dependent diabetic subjects. Diabetes. 1985;34:1152–9.

    Article  PubMed  CAS  Google Scholar 

  36. Friedman JE, Dohm GL, Elton CW, et al. Muscle insulin resistance in uremic humans: glucose transport, glucose transporters, and insulin receptors. Am J Physiol. 1991;261:E87–94.

    PubMed  CAS  Google Scholar 

  37. Akmal M, Massry SG, Goldstein DA, et al. Role of parathyroid hormone in the glucose intolerance of chronic renal failure. J Clin Invest. 1985;75:1037–44.

    Article  PubMed  CAS  Google Scholar 

  38. Mak RH, Bettinelli A, Turner C, et al. The influence of hyperparathyroidism on glucose metabolism in uremia. J Clin Endocrinol Metab. 1985;60:229–33.

    Article  PubMed  CAS  Google Scholar 

  39. Ikizler TA. Effects of glucose homeostasis on protein metabolism in patients with advanced chronic kidney disease. J Ren Nutr. 2007;17:13–6.

    Article  PubMed  Google Scholar 

  40. Cusi K, Maezono K, Osman A, et al. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest. 2000;105:311–20.

    Article  PubMed  CAS  Google Scholar 

  41. Lee SW, Dai G, Hu Z, et al. Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidylinositol 3 kinase. J Am Soc Nephrol. 2004;15:1537–45.

    Article  PubMed  CAS  Google Scholar 

  42. Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008;73:391–8.

    Article  PubMed  CAS  Google Scholar 

  43. Cano N. Bench-to-bedside review: glucose production from the kidney. Crit Care. 2002;6:317–21.

    Article  PubMed  Google Scholar 

  44. Arem R. Hypoglycemia associated with renal failure. Endocrinol Metab Clin North Am. 1989;18:103–21.

    PubMed  CAS  Google 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.

    CAS  Google Scholar 

  46. Grodstein GP, Blumenkrantz MJ, Kopple JD, et al. Glucose absorption during continuous ambulatory peritoneal dialysis. Kidney Int. 1981;19:564–7.

    Article  PubMed  CAS  Google Scholar 

  47. Mamoun AH, Anderstam B, Sodersten P, et al. Influence of peritoneal dialysis solutions with glucose and amino acids on ingestive behavior in rats. Kidney Int. 1996;49:1276–82.

    Article  PubMed  CAS  Google Scholar 

  48. Walls EK, Koopmans HS. Differential effects of intravenous glucose, amino acids, and lipid on daily food intake in rats. Am J Physiol. 1992;262:R225–234.

    PubMed  CAS  Google Scholar 

  49. Von Baeyer H, Gahl GM, Riedinger H, et al. Adaptation of CAPD patients to the continuous peritoneal energy uptake. Kidney Int. 1983;23:29–34.

    Article  Google Scholar 

  50. Sharma R, Rosner MH. Glucose in the dialysate: historical perspective and possible implications? Hemodial Int. 2008;12:221–6.

    Article  PubMed  Google Scholar 

  51. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.

    Article  PubMed  CAS  Google Scholar 

  52. Patel A, Macmahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.

    Article  PubMed  CAS  Google Scholar 

  53. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002; 287:2563–2569.

    Google Scholar 

  54. Fioretto P, Steffes MW, Sutherland DE, et al. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med. 1998;339:69–75.

    Article  PubMed  CAS  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.

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Acknowledgments

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).

Disclosure

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.

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Authors and Affiliations

  1. Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA, 90509-2910, USA

    Jongha Park, Paungpaga Lertdumrongluk, Miklos Z. Molnar & Kamyar Kalantar-Zadeh

  2. Division of Nephrology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

    Jongha Park

  3. Institute of Pathophysiology, Semmelweis University, Budapest, Hungary

    Miklos Z. Molnar

  4. Division of Nephrology, University of Virginia, Charlottesville, VA, USA

    Csaba P. Kovesdy

  5. Division of Nephrology, Salem VA Medical Center, Salem, VA, USA

    Csaba P. Kovesdy

  6. David Geffen School of Medicine at UCLA, and Fielding School of Public Health at UCLA, Los Angeles, CA, USA

    Kamyar Kalantar-Zadeh

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  1. Jongha Park
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  2. Paungpaga Lertdumrongluk
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Correspondence to Kamyar Kalantar-Zadeh.

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Park, J., Lertdumrongluk, P., Molnar, M.Z. et al. Glycemic Control in Diabetic Dialysis Patients and the Burnt-Out Diabetes Phenomenon. Curr Diab Rep 12, 432–439 (2012). https://doi.org/10.1007/s11892-012-0286-3

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