Obesity and Inflammation as Predictors of New-Onset Diabetes Mellitus after Kidney Transplantation

Abstract

Objective: The clinical impact of new-onset diabetes mellitus (DM) after renal transplantation (RT) is frequently underestimated by clinicians. DM after transplantation is a leading risk factor for cardiovascular events. We aimed to identify post-RT risk factors for NODM. Materials and Methods: We retrospectively analyzed 236 non-diabetic patients (mean age 41±12 years; %75 male) between 1995 and 2008. We excluded those diagnosed as DM mellitus at RT time (n=23), greft loss during the two years (n =16), acute rejection, congestive heart failure, active infections (n =19), and those for whom data was not fully available (n=3). At 2 years of follow-up after RT, 34 (19.4%) patients developed DM (group 1). One hundred fourthy one non-diabetic patients were defined as group 2. We have recorded parameters at the time of DM diagnosis such as demographic features, medications, smoking history, blood pressure, daily proteinuria. Results: Age, body mass index, uric acid, sodium, LDL-cholesterol, CRP values were significantly higher in group 1. The percentage of weight gain (6.8%±5.2 vs. 5.2%±2.9, p=0.08) were similar in two groups. The prevalence of DM was similar between patients under CyA and TAC based immunosuppression. Conclusions: Baseline BMI, but not the weight gain at 2 years after RT, is an independent risk factor for DM. Importantly, overweight recipients within the high-risk group had raised inflammatory markers. Tailoring clinical strategies may minimize the impact of this complication.

Keywords

• Renal transplantation, Diabetes mellitus, Obesity.

Böbrek Nakli Sonrası Yeni Diyabetes Mellitus Gelişmesine Etki Eden Faktörler; Obezite ve İnflamasyonun Rolü

Öz

Amaç: Organ naklinden sonra alıcıda yeni gelişen diabetes mellitus (DM) %50'e ulaşan oranda görülen metabolik bir komplikasyondur. Biz bu çalışmada kliniğimizde böbrek nakli sonrası yeni gelişen DM sıklığına katkısı olan faktörleri analiz edildi. Gereç ve Yöntem: Çalışmamızda 1995 ve 2008 yılları arasında böbrek nakli olan ve nakilden 2 yıl sonra greft fonksiyonu devam eden 236 (Ortalama yaş 41±12 yıl; %75 erkek) hastayı retrospektif olarak değerlendirdik. Böbrek nakli sırasında DM tanısı olanlar (n=23), nakil sonrası ilk 2 yıl içinde greft kaybı olanlar (n =16), akut rejeksiyon, konjestif kalp yetmezliği ve aktif enfeksiyonu olanlar (n = 19), ve bilgileri eksik olan hastalar (n=3) çalışma dışı bırakıldı. Böbrek naklinden 2 yıl sonraki takipte 34 hastada (%19.4) yeni gelişen DM tespit edildi (grup 1). DM tanısı almamış kalan 141 hastayı grup 2 olarak kabul ettik. Çalışmaya dahil edilen hastaların başlangıç ve DM tanısı aldığı zamana ait klinik, demografik özellikleri ve tüm laboratuvar özelliklerini kaydettik. Bulgular: Grup 1 hastaların yaş, Beden Kitle İndeksi (BKİ), ürik asit, LDL kolesterol, C-reaktif protein, değerleri istatiksel olarak grup 2 hastalarına göre yüksek bulundu. Her iki grupta 2 yılın sonunda kilo alım oranları eşit tespit edildi. (%6.8±5.2 ve %5.2±2.9, p=0.08). İmmunsupresif tedavilerine göre yapılan incelemede siklosporin ve takrolimus alan hastalarda yeni ortaya çıkan DM oranları eşit bulundu. Sonuç: Böbrek nakli olan hastalarda iki yılın sonunda kilo alım oranları etkili olmazken nakil esnasındaki BKİ oranları yeni ortaya çıkan DMi gelişiminde etkilidir. Risk faktörlerinin yakın takibi ve ortadan kaldırılması bu komplikasyonun görülme sıklığını azaltacaktır.

Anahtar Kelimeler

• Böbrek nakli, Diabetes mellitus, Obezite.

References

1. Cosio FG, Pesavento TE, Osei K, et al. Post-transplant diabetes mellitus: increasing incidence in renal allogreft recipients transplanted in recent years. Kidney Int 2001; 59: 732–7.
2. Davidson J, Wilkinson A, Dantal J, et al. New-onset diabetes after transplantation: 2003 international consensus guidelines. Proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation 2003; 75: 3-24.
3. Rodrigo E, Fernandez-Fresnedo G, Valero R, et al. New-onset diabetes after kidney transplantation: risk factors. J Am Soc Nephrol 2006; 17: 291–5.
4. Kasiske BL, Snyder JJ, Gilbertson D, et al. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 2003; 3: 1–8.
5. Oterdoom L, de Vries A, Gansevort R, et al. Determinants of insulin resistance in renal transplant recipients. Transplantation 2007; 81: 29-35
6. Oetjen E, Baun D, Beimesche S, et al. Inhibition of human insulin gene transcription by the immnosuppressive drugs cyclosporin A and tacrolimus in primary, mature islets of transgenic mice. Mol Pharmacol 2003; 63: 1289-95
7. Johnson C, Gallager-Lapak S, Zhu Y-R et al. Factors influencing weight gain after renal transplantation. Transplantation 1993; 56: 822–7.
8. Mazzali FC, Lalli CA, Alves-Filho G, et al. Posttransplant diabetes mellitus: incidence and risk factors. Transplant Proc 2008; 40: 764–6.

9. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26: 5-20.
10. Arner P, Gunnarsson R, Groth CG. Some characteristics of steroid diabetes: A study in renal transplant recepients receiving high dose corticosteroids therapy. Diabetes Care 1983; 6: 23Sumrani NB, Delaney V, Ding Z, et al. Diabetes mellitus after renal transplantation in cyclosporine era: An analysis of risk factor. Transplantation 1991; 51: 343-7.
11. Depczynski B, Daly B, Campbell LV, Chisholm DJ, Keogh A. Predicting the occurrence of diabetes mellitus in recipients of heart transplants. Diabet Med 2000; 17: 15-9.
12. Kasiske BL, Synder JJ, Gilbertson D, et al. Diabetes mellitus after kidney transplantation in United States. Am J Transplant 2003; 3: 178-85.
13. Montori VM, Velosa JA, Basu A, et al. Posttransplantation diabetes: A systemic rewiev of the literature. Diabetes Care 2002; 25: 583-92.
14. Baltar J, Ortega T, Ortega F et al. Posttransplantation diabetes mellitus: Prevalence and risk factors. Transplant Proc 2005; 37: 3817–8.
15. Fabrizi F, Martin P, Dixit V, et al. Post-transplant DM mellitus and HCV seropositive status after renal transplantation: Metaanalysis of clinical studies. Am J Transplant 2005; 5: 2433–40.
16. Markell M. Clinical impact of posttransplant DM mellitus. Transplant Procc 2001; 33: 19-22.