Review
Copyright ©The Author(s) 2015.
World J Diabetes. Aug 25, 2015; 6(10): 1132-1151
Published online Aug 25, 2015. doi: 10.4239/wjd.v6.i10.1132
Table 1 Selection of studies that reported rates of new-onset diabetes after transplantation or other dysglycemic states
Ref.CriterianRates
Cosio et al[3]Use of medications, F BGL49013% at 1 yr
33% dysglycemic
Hjelmesaeth et al[4]Use of medications, F BGL, oGTT20120% at 3 mo
Vincenti et al[5]oGTT68230% at 6 mo dysglycemic
Delgado et al[6]oGTT, F BGL3746.7% at 4.1 yr
25.1% dysglycemic
Ramesh Prasad et al[7]F BGL or R BGL15120.5%
Luan et al[8]oGTT20311.8% at 10 wk
47.8% dysglycemic
Bayer et al[9]Use of medications, F BGL, R BGL64031.4% at 1 yr
Bergrem et al[10]Use of medications, F BGL, R BGL30113% at 10 wk
Valderhaug et al[11]oGTT141017% at 10 wk
38% dysglycemic
Ciancio et al[12]Use of medications15015%-22% at 4 yr
Israni et al[13]Medications, F BGL184013% at 5 yr
Wauters et al[14]Use of medications, F BGL114614.1% at 1 mo, 11.1% at 4 mo, 13.4% at 1 yr
27%, 34.3% and 29.8% dysglycemic
Chan et al[15]oGTT29224% at 6 mo
Vacher-Coponat et al[16]Use of medications28916.8%-18.8% at 3 yr
Tillman et al[17]oGTT2005% at 39 mo
30.5% dysglycemic
Bonet et al[18]F BGL, R BGL, oGTT13813% at 6 mo
Cole et al[19]Use of medications, F BGL, oGTT494% at 6 mo
Nagaraja et al[20]Use of medications, F BGL11821% at 3 mo, 37% at 1 yr
First et al[21]Use of medications, F BGL, HbA1c63417.8%-36.5% at 1 yr
Nagaraja et al[22]oGTT7613% at 5 yr, 24% at 11 yr
42% and 61% dysglycemic
Tokodai et al[23]Use of medications, F BGL, R BGL14511.7% at 1 yr
Viecelli et al[24]oGTT8317% at 3 mo, 15% at 15 mo
31% and 21% dysglycemic
Weng et al[25]Use of medications, F BGL, R BGL16629.5%
Schweer et al[26]R BGL, HbA1c52616.7%
Prasad et al[27]oGTT43920% at 3 mo
33% dysglycemic
Silva et al[28]HbA1c63821.3%-41.1% at 4 yr
Lv et al[29]F BGL42820.3% at 5.7 yr
Table 2 The rates of unrecognized dysglycemia in patients on the transplant waiting list
Ref.Unrecognised on waiting list - diabetesUnrecognised on waiting list - dysglycemia
Ramesh Prasad et al[7]-15%
Hornum et al[33]-33%
Bergrem et al[30]8.1%45.2%
Iida et al[32]4%30.4%
Caillard et al[31]3.3%15.2%
Bonet et al[18]< 0.1%8.9%
Table 3 Modifiable and non-modifiable risk factors associated with new-onset diabetes after transplantation or dysglycemic state
VariableRef.Comment
ATG-divided doseStevens et al[48]Increased dysglycemia compared to single dose in patients treated with Tac and sirolimus
African AmericanKasiske et al[49] Shah et al[50] Johnston et al[51] Bayer et al[9]OR = 1.68 RR = 1.38 HR = 1.56 HR = 1.35
AgeKasiske et al[49]Strong independent risk factor
RR: 1.9-2.6
Cole et al[52]27707 registry patients OR: 1.33
If > 60 yr
Ghisdal et al[53]OR 1.03 of NODAT for each
6 mo of age
Luan et al[8]Increasing age associated with dysglycemia and new onset metabolic syndrome
Luan et al[46]Analysis of 25837 registry patients, increase in NODAT in each categorised group compared to reference 18-34 years old
Israni et al[13]HR: 1.33 of NODAT at 60 mo
Tillmann et al[17]Increase in dysglycemia at mean of 56 M post-transplant; RR of 1.28 for each 5 yr
Mccaughan et al[54]OR 1.4 per decade in 427 Northern Irish patients
Schweer et al[26]NODAT 56.1 yr vs 47.9 yr; P < 0.01
APCKDde Mattos et al[55]Increased 1 yr incidence in a matched cohort
Hamer et al[56]Multivariate analysis OR 2.4
Johnston et al[51]No increase found in 21564 USRDS patients
Luan et al[46]Multivariate analysis OR: 1.17
Ruderman et al[57]No increased risk found
BasiliximabAasebø et al[58]Basilixmab (n = 134) vs no induction historical control; increased dysglycemic state P = 0.017
Prasad et al[27]In living recipients who elected to receive basiliximab OR 2.34 for NODAT at 3 mo
BMIKasiske et al[49]Increased BMI, NODAT RR: 1.7
Cole et al[52]Multivariate analysis OR 1.76 for NODAT
Luan et al[46]Analysis of 25837 registry patients. increase in NODAT in each categorised group of BMI compared to reference < 20
Israni et al[13]BMI ≥ 30, HR 1.69 for NODAT at 60 mo
CMVHjelmesaeth et al[59]Asymptomatic infection OR: 4.0 for NODAT at 10 wk
CNI –Chan et al[15]NODAT 17% vs 31%, low dose vs standard dose Tac
Higher levelsCole et al[19]Single arm study of 49 patients with a 4% 6 mo incidence of NODAT. Early glucocorticoid reduction and low dose CsA
Suszynski et al[60]Higher Tac levels (plus sirolimus) compared to lower Tac (plus sirolimus) or CsA/MMF higher rates of NODAT with 10 yr FU
CNI –Vincenti et al[5]RCT. Dysglycemia at 6 mo higher in Tac/MMF vs CsA/MMF: P = 0.05
Tac vs CsACole et al[52]27707 registry patients OR 1.51 for NODAT
Luan et al[46]Analysis of 25837 registry patients. Increase in NODAT OR: 1.24
Vacher-Coponat et al[16]No difference in CsA/Aza vs Tac/MMF in RCT (n = 289)
Cotovio et al[44]Retrospective multivariate analysis higher Tac not CsA levels associated with NODAT
Family history of diabetesBora et al[61]Recipients from living related donors
Santos et al[62]Retrospective (n = 303). RR: 3.6 for NODAT
GenderKasiske et al[49]Greater risk in males in registry patients
McCaughan et al[54]OR 2.2 for male gender in 427 Northern Irish patients
Genetic polymorphismsGhisdal et al[53]rs7903146 polymorphism of TCF7L2 OR 1.6 of NODAT at 6 mol/L, but not associated with IGT
Ghisdal et al[63]Summarises known associations
Kurzawski et al[64]Polish Caucasian patients. Increasing SNPs associated with increased risk, OR = 1.37
Yao et al[65]Fok1 vitamin D polymorphism associated with NODAT OR 11.8 P = 0.012
McCaughan et al[54]7 SNPs involved with β-cell apoptosis associated with NODAT
Nicoletto et al[66]Adiponectin gene polymorphism associated with NODAT
Tavira et al[67]Mitochondrial haplogroup H associated with NODAT in Tac treated patients
GlucocorticoidsBoots et al[68]Early glucocorticoid withdrawal associated with reduced NODAT incidence in the first year
Ghisdal et al[53]OR 2.78 of NODAT at 6 mol/L if AR treated with glucocorticoids
Luan et al[46]Analysis of 25837 registry patients. OR 1.42 for NODAT if discharged on maintenance. Glucocorticoid only induction associated with increase in NODAT OR: 1.31
Rizzari et al[69]Significant reduction in NODAT compared with historical control when glucocorticoids rapidly tapered
Cole et al[19]Single arm study of 49 patients with a 4% 6 mo incidence of NODAT. Early glucocorticoid reduction and low dose CsA
Schweer et al[26]Pulse glucocorticoid for BPAR associated with increasing NODAT incidence
HCV +Kasiske et al[49]HCV+, NODAT RR: 1.3
Cole et al[52]27707 registry patients OR for NODAT 1.82
Johnston et al[51]21564 USRDS registry patients, HR: 1.7 for NODAT
Baid-Agrawal et al[70]14 HCV+ 24 HCV- patients. HCV+ increased insulin resistance; P = 0.008
Luan et al[46]Analysis of 25837 registry patients. Increase in NODAT OR: 1.43
Lv et al[29]Cohort of 428 Chinese patients. NODAT associated with HCV at mean 5.6 yr follow up, OR = 2.72
Prasad et al[27]439 Indian patients, OR = 6.37
Hyper-parathyroidism post transplantIvarsson et al[71]PTH > 13.8 pmol/L associated with NODAT at 1 yr, OR = 4.25
Impaired glycemic state pre-transplantRamesh Prasad et al[7]Higher within the normal range random BSL associated with NODAT
Bora et al[61]IGT at time of transplant associated with NODAT
Hornum et al[33]IGT NOT predictive of NODAT
Cotovio et al[44]Higher fasting BGL associated with NODAT
Magnesium post-transplantGarg et al[72]1 mol/L lower Mg associated with dysglycemia; no association with 1M CNI trough level
Magnesium pre-transplantAugusto et al[73]Lower magnesium immediately pre-transplant associated with NODAT; P < 0.02
Metabolic syndrome post-transplantIsrani et al[13]MS in first 6-12 mo associated with NODAT by 60 mo, HR = 3.46
Luan et al[8]10 W dysglycemia associated with MS
Nagaraja et al[22]Development of MS predicts progressive dysglycemia
Metabolic syndrome pre-transplantBayer et al[9]HR: 1.34 for NODAT at 1 yr
SirolimusTeutonico et al[74]No improvement when changing from CNI to sirolimus
Ekberg et al[75]Low dose sirolimus may confer less risk than low dose Tac
Johnston et al[51]20124 registry patients. Compared to CsA + MMF/AZA: Sirolimus + CsA HR 1.61; Sirolimus + Tac HR 1.66; Sirolimus + MMF/AZA HR 1.36
Guerra et al[76]RCT (n = 150) Tac/sirolimus vs Tac/MMF vs CsA/sirolimus. No difference in NODAT
Gyurus et al[77]Retrospective (n = 514). Sirolimus HR 3.5 for NODAT over 10 yr
Veroux et al[78]21 NODAT converted to sirolimus, 80% remission of NODAT on basis of F BGL
Suszynski et al[60]Increased risk with high dose Tac/low dose sirolimus combination
Table 4 Risk of mortality, cardiovascular events and graft loss associated with new-onset diabetes after transplantation or dysglycemic state
MortalityCV event/deathGraft lossRef.
Diabetes at3 mo: 37% at 8 yr (HR = 2.1)20% (death) at 8 yr (HR = 3.5)Hjelmesaeth et al[4]
10 wk: 34% at 6.7 yr (HR = 2.0)Valderhaug et al[11]
1 yr: 44% at 11 yr (HR = 2.2)Death HR: 2.72Nagaraja et al[20]
Dysglycemia at10 wk: 29% at 6.7 yr (HR = 1.78) eachEvents increased with increased F BGLCosio et al[3]
1 mmol/L oGTT: 5% risk increase
4 mo: 0.5 mmol/L increase1 mmol/L oGTT: 6% risk increase in deathValderhaug et al[11]
F BGL: 4% risk increase
12 mo: 0.5 mmol/L increase F BGL: 15% risk increase12 mo: 0.5 mmol/L increase F BGL: 11% risk increase for eventWauters et al[14]
3 mo: RR 3.6 at 6 yrWojtusciszyn et al[41]