The Relationship between Variability in Measured HbA1c Values and Survival in Diabetic Patients Undergoing Hemodialysis Treatment

Öz

Survival of the diabetic patients, which accounts for approximately one-third of hemodialysis patients, is shorter than non-diabetics. Increase in variability of glucose and HbA1c negatively affects survival in diabetic patients. In this study, we aimed to evaluate the relationship between HbA1c variability and survival in diabetic hemodialysis patients. We evaluated diabetic patients receiving hemodialysis for at least one year and had at least four HbA1c measurements retrospectively. The standard deviation (SD) and coefficient of variation (CV) of the HbA1c, hemoglobin and glucose were used as the index of variability for each patient. The mean age of 38 patients (21M, 17F) was 62.1±11.86 (24-81) years, the mean survival time was 67.4±40.6 months. Twenty (52.6%) patients died in the follow-up. The mean values of hemoglobin, glucose and HbA1c was 10.8±1.0 mg/dl, 87±68 mg/dl and 7.1±1.4%, respectively. The variability was greatest in glucose (31.7%), then in HbA1c (12.4%) and least in hemoglobin (10.6%). In Cox regression analysis, age, chronic kidney disease duration, hemoglobin and HbA1c were found to be related with survival (p=0.036, p=0.001, p=0.001, p=0.001, respectively). There was no relationship between the survival and the SD and CV values calculated for HbA1c, glucose and hemoglobin (p> 0.05, for all). The patients were divided into two groups according to HbA1c values (Group 1:<8.5% and group 2:≥8.5%). and a statistically significant difference was found between the groups by Kaplan-Meier method (p=0.021). We found that the increased HbA1c and decreased hemoglobin values in diabetic hemodialysis patients are associated with an increased risk of mortality, but HbA1c variability is not associated with survival unlike diabetic patients with normal renal function.

Anahtar Kelimeler

• Hemodialysis
• diabetes
• HbA1c variability
• chronic renal disease
• survival

Hemodiyaliz Tedavisi Gören Diyabetik Hastalarda Ölçülen HbA1c Değerlerindeki Değişkenliğin Sağkalım ile İlişkisi

Öz

Hemodiyaliz hastalarının yaklaşık üçte birini oluşturan diyabetik grupta sağkalım diyabetik olmayanlara kıyasla daha kısadır. Diyabetik hastalarda glukoz ve HbA1c değişkenliğinin artmasının, sağkalımı olumsuz yönde etkilediği gözlenmiştir. Çalışmamızda hemodiyaliz yapılan diyabetik hastalarda HbA1c ölçümlerindeki değişkenlik ile sağkalım arasındaki ilişkiyi değerlendirmeyi amaçladık. Çalışmamızda Ocak 2006 ile Aralık 2014 tarihleri arasında en az bir yıl süreyle merkezimizde hemodiyaliz yapılmış ve en az dört adet HbA1c ölçümü olan diyabetik böbrek yetmezliği hastaları retrospektif olarak değerlendirildi. Her hasta için değişkenlik ölçütü olarak hemodiyaliz yapıldığı süreçte ölçülen HbA1c, hemoglobin ve glukoz ölçümlerinin standart sapma (SD) ve varyasyon katsayısı (CV) kullanıldı. Çalışmaya dahil edilen 38 hastanın (21E, 17K) yaş ortalaması 62,1±11,86 (24-81) yıl ve ortalama sağkalım süresi 67,4±40,6 ay olup 20’si (%52,6) hayatını kaybetmişti. Hastalarda ortalama hemoglobin 10,8±1,0 mg/dl, glukoz 87±68 mg/dl ve HbA1c %7,1±1,4’tü. Değişkenlik en fazla glukozda (%31,7) sonra HbA1c’de (%12,4) ve en az hemoglobindeydi (%10,6). Cox regresyon analizinde sağkalım süresiyle yaş, kronik böbrek hastalığı süresi, ortalama hemoglobin ve HBA1c ilişkili bulundu (p=0,036, p=0,001, p=0,001, p=0,001, sırasıyla). Hastaların HbA1c, glukoz ve hemoglobin ölçümleri için hesaplanan SD ve CV değerleriyle sağkalım süreleri arasında ilişki saptanmadı (p>0,05, her biri için). Hastalar HbA1c’ye göre iki gruba ayırıldı (Grup 1: <%8,5 ve grup 2: ≥%8,5). Sağkalım hızları Kaplan-Meier yöntemi kullanılarak değerlendirildi ve gruplar arasında istatistiksel olarak anlamlı fark saptandı (p=0,021). Elde ettiğimiz veriler diyabetik hemodiyaliz hastalarında artmış HbA1c ve azalmış hemoglobin değerlerinin mortalite riskinde artış ile ilişkili olduğunu fakat normal böbrek fonksiyonuna sahip diyabetik hastalardakinden farklı olarak HbA1c değişkenliğinin sağkalım süresi ile ilişkili olmadığını desteklemektedir.

Anahtar Kelimeler

• Hemodiyaliz
• diyabet
• HBA1c değişkenliği
• kronik böbrek hastalığı
• sağkalım

Kaynakça

1. Hill NR, Fatoba ST, Oke JL, et al. Global prevalence of chronic kidney disease—a systematic review and meta-analysis. PLoS One. 2016; 11(7): e0158765.
2. Süleymanlar G, Utaş C, Arinsoy T, et al. A population-based survey of Chronic REnal Disease In Turkey – The CREDIT study. Nephrol Dial Transplant. 2011;26(6):1862–71.
3. Mauri JM, Cleries M, Vela E, Catalan Renal Registry: Design and validation of a model to predict early mortality in haemodialysis patients. Nephrol Dial Transplant. 2008;23:1690-6.
4. Goodkin DA, Young EW, Kurokawa K, Prutz KG, Levin NW. Mortality among hemodialysis patients in Europe, Japan, and the United States: case-mix effects. Am J Kidney Dis. 2004;44(2):16–21.
5. Süleymanlar G, Ateş K, Seyahi N. Türkiye’de Nefroloji, Diyaliz ve Transplantasyon Registry 2018. Türk Nefroloji Derneği Yayınları: 2019:13.
6. Schroijen MA, van de Luijtgaarden MW, Noordzij M, et al. Survival in dialysis patients is different between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition. Diabetologia. 2013;56:1949–57.
7. The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes 1996; 45(10): 1289-98.
8. International Expert Committee. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009; 32: 1327–34.

9. KDIGO. Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International Supplements 2013. 2012;3(1):1–163.
10. Takao T, Matsuyama Y, Yanagisawa H, Kikuchi M, Kawazu S. Association between HbA1c variability and mortality in patients with type 2 diabetes. J Diabetes Complications 2014;28:494–9.
11. Penno G, Solini A, Bonora E, et al. Renal Insufficiency and Cardiovascular Events Study Group. HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. Diabetes Care 2013;36: 2301–10
12. Ma WY, Li HY, Pei D, et al. (2012). Variability in hemoglobin A1c predicts all-cause mortality in patients with type 2 diabetes. Journal of Diabetes and Its Complications, 26, 296–300.
13. Kilpatrick ES. The rise and fall of HbA1c as a risk marker for diabetes complications. Diabetologia 2012;55:2089–91.
14. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. 1998;317(7160):703.
15. Hill CJ, Maxwell AP, Cardwell CR, et al. Glycated hemoglobin and risk of death in diabetic patients treated with hemodialysis: A meta-analysis. Am J Kidney Dis 2014;63, 84–94.
16. Shurraw S, Majumdar SR, Thadhani R, Wiebe N, Tonelli M. Glycemic control and the risk of death in 1,484 patients receiving maintenance hemodialysis. Am J Kidney Dis. 2010;55(5):875–84.
17. Robinson TW and Freedman BI. Assessing glycemic control in diabetic patients with severe nephropathy. J Ren Nutr 2013; 23: 199–202.
18. Panzer S, Drorik G, Lechner K, Bettelheim P, Neumann E, Dudezak R. Glycosylated hemoglobins (GHb): an index of red cell survival. Blood 1982;59:1348–50.
19. Konya J, Ng JM, Cox H, et al. Use of complementary markers in assessing glycaemic control in people with diabetic kidney disease undergoing iron or erythropoietin treatment. Diabet Med 2013;30:1250–4.
20. Williams ME, Mittman N, Ma L, et al. The Glycemic Indices in Dialysis Evaluation (GIDE) study: comparative measures of glycemic control in diabetic dialysis patients. Hemodial Int 2015;19:562–71.
21. Muggeo M, Verlato G, Bonora E, Zoppini G, Corbellini M, de Marco R. Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: the Verona Diabetes Study. Circulation 1997;96, 1750–4.
22. Dossett LA, Cao H, Mowery NT, Dortch MJ, Morris JM, May AK. Blood glucose variability is associated with mortality in the surgical intensive care unit. Am Surgeon 2008;74, 679–85.
23. Al-Dorzi HM, Tamim HM, Arabi YM. Glycemic fluctuation predicts mortality in critically ill patients. Anaesth Intens Care 2010;38, 695–702.
24. Eschbach J. Erythropoietin 1991--an overview. Am J Kidney Dis 1991;18(4):3-9.
25. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Inter Suppl 2012;2(4): 279–335.
26. Locatelli F, Pisoni RL, Akizawa T, et al. Anemia management for hemodialysis patients: Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines and Dialysis Outcomes and Practice Patterns Study (DOPPS) findings. Am J Kidney Dis 2004;44: 27–33.
27. Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. The impact of anemia on cardiomyopathy, morbidity, and mortality in end-stage renal disease. Am J Kidney Dis 1996; 28(1): 53-61.