Screening strategies and predictive diagnostic tools for the development of new-onset diabetes mellitus after transplantation: an overview

Figures & data

Table 1 WHO and ADA criteria for the diagnosis of diabetes mellitus

Criteria for the diagnosis of DM

Any one of the following:

Classic symptoms of DM ^a + random PG concentrations ≥ 200 mg/dL (11.1 mM) FPG ≥126 mg/dL (7.0 mM). Fasting is defined as no caloric intake for ≥8 hours 2-hour PG ≥ 200 mg/dL (11.1 mM) during an OGTT ^b A1C^c ≥ 6.5% In the absence of unequivocal hyperglycemia accompanied by acute metabolic decompensation, criteria 2–4 must be confirmed by repeat testing on another day.

Criteria for normal FPG and IFG or IGT

FPG WHO criteria FPG < 110 mg/dL (6.1 mM) = normal fasting glucose FPG 110 mg/dL (6.1 mM) and <126 mg/dL (7.0 mM) = IFG 2003 ADA consensus FPG < 100 mg/dL (5.6 mM) = normal fasting glucose FPG ≥ 100 mg/dL (5.6 mM) and <126 mg/dL (7.0 mM) = IFG OR OGTT 2-hour PG < 140 mg/dL (7.8 mM) = normal glucose tolerance 2-hour PG ≥ 140 mg/dL (7.8 mM) and < 200 mg/dl (11.1 nM) = IGT

Prediabetic states based on A1C level

2010 ADA consensus: 5.7%–6.4%

International expert committee: 6.0%–6.4%

Notes:

a Classic symptoms of DM include polyuria, polydipsia, and unexplained weight loss;

b OGTT: the test should be performed as described by WHO, using a glucose load containing equivalent of 75 g anhydrous glucose dissolved in water;

c A1C should be performed using a method certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized to the Diabetes Control and Complications Trial (DCCT) reference assay.

Abbreviations: WHO, World Health Organization; ADA, American Diabetes Association; DM, diabetes mellitus; PG, plasma glucose; FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test.

Table 2 Clinical studies evaluating the utility of FPG, A1C, and OGTT in the screening and diagnosis of NODAT

Study protocols	Demographic characteristics	Study results	Conclusions	References
FPG and OGTT N = 359 All patients completed OGTT 5 days postTx Mean follow-up 42.8 ± 16.9 months	White 91.4% Blacks 1.4% Arabic 7.2%	17.8% developed NODAT A normal (vs diabetic) OGTT at day 5 postTx was associated with ↓NODAT risk (OR = 0.03; P = 0.0002) Sensitivity, 93.4%; Specificity, 71.9% A normal (vs diabetic) FPG on day 5 postTx was associated with ↓NODAT risk (OR = 0.06; P < 0.0001) Sensitivity, 21.6%; Specificity, 97.6%	A normal FPG (vs diabetic) and a normal OGTT (vs diabetic) at 5 days postTx seems to identify patients at ↓NODAT risk	Kuypers et al^Citation4
FPG N = 282 (patients with graft survival > 1 year) FPG at day 5 postTx	Spanish study	16.3% developed NODAT at month 12 A fifth day FPG≥126 mg/dL was associated with a more than fourfold increase in NODAT risk (relative risk: 4.784; P = 0.002) The positive and negative predictive values of a fifth day FPG ≥ 126 mg/dL for predicting NODAT at 1-year were 40% and 89.4%, respectively	A negative predictive value of 89.4% suggests that a FPG < 126 mg/dL may identify patients with a low risk (near 10%) for NODAT	Rodrigo et al^Citation6
FPG and OGTT N = 188 > 6 months postTx, OGTT performed in patients with FPG < 7.0 mmol/L	White > 90%	ROC analyses Optimal FPG predictive of NODAT: 101 mg/dL; 5.6 mmol/L (AUC = 0.70; sensitivity 64%; specificity 67%, positive predictive 20%; negative predictive 93%) Optimal FPG predictive of IGT less well-defined (AUC= 0.54) Prevalence of NODAT (OGTT vs FPG 17% vs 6%, respectively; P < 0.0001)	FPG may not be the optimal screening or diagnostic tool due to lack of sensitivity and specificity OGTT should be considered as a routine screening test in all renal transplant recipients	Armstrong et al^Citation7
FPG and OGTT N = 122 > 6 months postTx OGTT performed in patients with two FPG values between 5.6–6.9 mmol/L	White 96% Asian 3% Afro-Caribbean 1%	OGTT revealed 10% had overt DM, 9% IGT alone, 18% IFG alone, 14% combined IFG and IGT	FPG underestimates IGT and NODAT prevalence Routine use of OGTT is a valuable clinical tool to risk stratify patient for NODAT	Sharif et al^Citation8
FPG and A1C N = 199 ≥3 months postTx All patients had a history of normal FPG prior to study Normal A1C defined as <6.1%	African Americans 81.9%	Twenty (10.1%) had A1C ≥ 6.1% (6 of whom had both ↑A1C and new onset ↑FPG at study entry) and 14 had ↑A1C only Of the 6 patients with both ↑A1C and new onset ↑FPG, 5 were diagnosed with NODAT Of the 14 patients with ↑A1C only, 3 were diagnosed with NODAT and 4 with glucose intolerance The odds of African Americans having ↑A1C were 2.8 times higher than other races High normal FPG was significantly associated with an ↑A1C (P = 0.003) Race effect marginally significant when adjusted for FPG (P = 0.08)	A1C level was a more sensitive test than FPG in detecting NODAT A1C testing should be considered as a screening test for NODAT, especially in African Americans	Hoban et al^Citation9
FPG, A1C, and OGTT N = 929 @ 10-week postTx Patients who had both FPG < 7.0 mmol/L and A1C levels available were evaluated	White 95%	ROC analysis FPG: AUC 0.761 (95% CI: 0.714 0.809) A1C: AUC 0.817 (95% CI: 0.758 0.876) Performing OGTT on patients with FPG ≥ 5.3 mmol/L or A1C ≥ 5.8% predicted NODAT with 81% and 83% sensitivity, requiring 49% and 41% of the patients to be tested, respectively Combined criterion of FPG ≥ 5.0 mmol/L and A1C ≥ 5.7% provided a sensitivity of 79% from testing 29% of the population	OGTT should be considered in patients with FPG between 5.3–6.9 mmol/L or A1C > 5.8% or In those with combined FPG ≥ 5 mmol/L and A1C ≥ 5.7%	Valderhaugh et al^Citation10

Abbreviations: CI, confidence interval; DM, diabetes mellitus; FPG, fasting plasma glucose; OGTT, oral glucose tolerance test; PostTx, posttransplant; ROC, receiver-operating characteristic; AUC, area under the curve.

Table 3 Association of pretransplant risk score with NODAT development

Risk score* (0–7)	N (# of patients)	1-year cumulative incidence of NODAT
Low risk (0–1)	109	13%
Intermediate risk (2–3)	170	29%
High risk (4–7)	39	56%

Notes:

* A risk score of 0–7 was calculated from seven pretransplant risk factors (age, family history of type 2 diabetes, BMI, FPG, triglycerides, use of gout medications, and predicted use of steroids posttransplant).

Abbreviations: BMI, body mass index; FPG, fasting plasma glucose; NODAT, new-onset diabetes after transplantation.

Figure 1 Targeting new onset diabetes after transplantation (NODAT).

Note:^ψOral Glucose Tolerance Testing (OGTT) is the current gold standard test for the diagnosis of NODAT.
Abbreviations: FPG, fasting plasma glucose; iFG, impaired fasting glucose; NODAT, new-onset diabetes after transplantation.

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Rodrigo E Santos L Pinera C Early prediction of new-onset diabetes mellitus by fifth-day fasting plasma glucose, pulse pressure, and proteinuria Transplant Proc 2011 43 6 2208 2210 21839235

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Hoban R Gielda B Temkit M Utility of HbA1c in the detection of subclinical post renal transplant diabetes Transplantation 2006 81 3 379 383 16477224

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Valderhaug TG Jensen T Hartmann A Fasting plasma glucose and glycosylated hemoglobin in the screening for diabetes mellitus after renal transplantation Transplantation 2009 88 429 434 19667949

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