Ana Laura Pimentel

Factors affecting A1C in non-diabetic individuals: Review and meta-analysis.

We carried out a systematic review and meta-analyses of studies that evaluated the possible effects of anemia, variant hemoglobin, and uremia on A1C levels in individuals without diabetes (DM). Medline and Embase were searched for studies that measured A1C values in groups with and without iron deficiency anemia (IDA) and/or iron deficiency (ID), variant hemoglobin and/or uremia by standardized methods. The difference between A1C levels in the groups with and without interferences was obtained by using random-effects meta-analysis and the effect size was presented as absolute difference of means (95% CI). Ten studies fulfilled the inclusion criteria, providing data from 11,176 participants without DM. There were no statistically significant differences in A1C in the presence of IDA/ID, HbS, and uremia by HPLC and uremia by immunoassay [0.79% (95% IC -0.39; 1.97), -0.13% (95% IC -0.51; 0.26), 0.15% (95% CI -0.58; 0.88) and -0.19% (95% CI -0.78; 0.40), respectively]. The effects of HbAS and uremia on A1C levels are within the expected individual variation and should not affect A1C results to diagnose DM. However, the effects of IDA/ID remain inconclusive and further studies are needed to clarify the glycation mechanisms in individuals with IDA/ID without diabetes.

Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis

Aims/Hypothesis Disparities in HbA1c levels have been observed among ethnic groups. Most studies were performed in patients with diabetes mellitus (DM), which may interfere with results due to the high variability of glucose levels. We conducted a systematic review and meta-analysis to investigate the effect of ethnicity on HbA1c levels in individuals without DM. Methods This is a systematic review with meta-analysis. We searched MEDLINE and EMBASE up to September 2016. Studies published after 1996, performed in adults without DM, reporting HbA1c results measured by certified/standardized methods were included. A random effects model was used and the effect size was presented as weighted HbA1c mean difference (95% CI) between different ethnicities as compared to White ethnicity. Results Twelve studies met the inclusion criteria, totalling data from 49,238 individuals. There were significant differences between HbA1c levels in Blacks [0.26% (2.8 mmol/mol); 95% CI 0.18 to 0.33 (2.0 to 3.6), p <0.001; I2 = 90%, p <0.001], Asians [0.24% (2.6 mmol/mol); 95% CI 0.16 to 0.33 (1.7 to 3.6), p <0.001; I2 = 80%, p = 0.0006] and Latinos [0.08% (0.9 mmol/mol); IC 95% 0.06 to 0.10 (0.7 to 1.1); p <0.001; I2 = 0%; p = 0.72] when compared to Whites. Conclusions/Interpretation This meta-analysis shows that, in individuals without DM, HbA1c values are higher in Blacks, Asians, and Latinos when compared to White persons. Although small, these differences might have impact on the use of a sole HbA1c point to diagnose DM in all ethnic populations.

Effect of iron deficiency anaemia on HbA1c levels is dependent on the degree of anaemia

OBJECTIVES Studies suggest that iron deficiency anaemia (IDA) is associated with higher HbA1c levels. We conducted a control–case study to investigate the effect of IDA on HbA1c levels, measured by two commonly used methods, in non-diabetic individuals. DESIGN AND METHODS A total of 122 patients were included, 61 patients with IDA and 61 patients without anaemia. HbA1c was measured by both ion exchange HPLC Variant II Turbo BioRad and immunoturbidimetry (IT) Tina Quant II Roche Diagnostics in each sample. HbA1c results were compared between groups. For correlation analysis, patients were considered altogether. RESULTS There was a significant difference between the results of HbA1c in patients with IDA [HPLC 5.6 ± 0.4% (38 ± 4.4 mmol/mol) and IT 5.7 ± 0.4% (39 ± 4.4 mmol/mol)] and those measured in patients without anaemia [HPLC 5.3 ± 0.4% (34 ± 4.4 mmol/mol) and IT 5.3 ± 0.3% (34 ± 3.3 mmol/mol)], (p < 0.001). Significant negative correlations were observed between total haemoglobin (Hb), haematocrit, mean corpuscular volume (MCV) and ferritin with HbA1c values measured by IT (r = − 0.557; r = − 0.539; r = − 0.488; r = − 0.499; p < 0.01; respectively). These negative correlations were weaker with HbA1c measured by HPLC (r = − 0.272; r = − 0.250; r = − 0.273; r = − 0.229 for Hb, haematocrit, MCV and ferritin; p < 0.05; respectively). HbA1c results were higher in patients with moderate and severe anaemia. However mild anaemia did not show significant effects on HbA1c results measured by both methods. CONCLUSIONS IDA affects HbA1c results and this effect is dependent on anaemia degree. These upward changes are statistically significant but they may be not clinically relevant when the overall variability of the HbA1c test is considered. The presence of slight anaemia is likely to have a minor effect on HbA1c levels favouring its use to diagnose diabetes in patients with mild anaemia.

Role of glycated hemoglobin in the screening and diagnosis of posttransplantation diabetes mellitus after renal transplantation: A diagnostic accuracy study

BACKGROUND The role of glycated hemoglobin (A1C) in the screening and diagnosis of posttransplantation diabetes mellitus (PTDM) is still not entirely understood. We evaluated the use of A1C test in renal transplant recipients at four months after transplantation. METHODS A total of 122 out of 274 patients without previous diabetes that underwent kidney transplantation were enrolled. ROC curve was used to analyze the performance of A1C to diagnose PTDM considering OGTT as the reference standard. RESULTS OGTT identified 32 (26.2%) patients with PTDM, whereas A1C≥6.5% (48 mmol/mol) identified only 16 patients. A1C showed moderate accuracy to detect PTDM in the ROC curve [AUC 0.832 (95% CI 0.740-0.924, p<0.001)]. A1C of 5.8% (40 mmol/mol) was the equilibrium point (sensitivity 75% and specificity 72.2%) and A1C≥6.2% (44 mmol/mol) showed high specificity of 93.3%. CONCLUSIONS A1C≥6.5% (48 mmol/mol) is not enough to be used alone in the diagnosis of PTDM. The combined use of A1C cut-off points of ≤5.8% (40 mmol/mol) and ≥6.2% (44 mmol/mol) would reduce the number of OGTT by 85%. The use of an algorithm with A1C test in combination with FPG and/or 2h-PG proved to be the most efficient strategy to diagnose or rule out PTDM.

Diagnostic accuracy of glycated hemoglobin for post-transplantation diabetes mellitus after kidney transplantation: systematic review and meta-analysis.

Background. Early detection of post‐transplantation diabetes mellitus (PTDM) allows prompt clinical and pharmacological interventions, reducing the chance of adverse outcomes. We conducted a systematic review and meta‐analysis to determine the overall diagnostic accuracy of glycated hemoglobin (HbA1c) for the diagnosis of renal PTDM. Methods. We searched MEDLINE, Embase and SCOPUS up to June 2016. Studies that included adults without previous diabetes were selected if they reported an oral glucose tolerance test as a reference test, HbA1c levels measured by standardized methods and data necessary for drawing 2 × 2 tables. A bivariate model was used to calculate the pooled estimates. Results. Based on 2057 kidney recipients from six studies, an HbA1c cut‐off point of 6.5% in early months after transplant resulted in sensitivity of 0.48 [95% confidence interval (95% CI) 0.31‐0.65], specificity of 0.96 (95% CI 0.95‐0.97), positive likelihood ratio (PLR) of 12.0 (95% CI 7.4‐19.5) and negative likelihood ratio (NLR) of 0.54 (95% CI 0.38‐0.77). Based on 1888 kidney recipients from four studies, an HbA1c cut‐off point of 6.2% early after transplant resulted in sensitivity of 0.76 (95% CI 0.49‐0.91), specificity of 0.89 (95% CI 0.86‐0.92), PLR of 7.18 (95% CI 5.29‐9.75) and NLR of 0.27 (95% CI 0.11‐0.65). Conclusion. HbA1c cut‐off points of 6.5% and 6.2% presented high specificity but low/moderate sensitivity to diagnose PTDM.

Renal posttransplantation diabetes mellitus: An overview

We conducted a literature review about renal posttransplantation diabetes mellitus (PTDM), a glucose metabolism alteration with high incidence. Immunosuppressive therapy, by different diabetogenic mechanisms, is the major risk factor for PTDM. Although corticosteroids and calcineurin inhibitors are the drugs most related to PTDM, the mechanisms of other drugs have been also investigated. Available data in the literature show that, in renal transplant patients, the oral glucose tolerance test presents the highest diagnostic sensitivity for PTDM, although fasting plasma glucose is the most requested test. In addition, we also discussed the possible role of hemoglobin A1C in the diagnosis of PTDM. Renal PTDM is associated with patient survival reduction, increased cardiovascular mortality and has been linked to worsening graft function. As crucial as the screening, the accurate management of the disease can ameliorate graft and patient survival as well as the quality of life of this especial population. Several drugs have been studied in PTDM patients in order to achieve a better glycemic control and, in the best scenario, prevent PTDM. We present proper management approaches that should help to reduce the possible long-term consequences of PTDM.

MP655COLOR DOPPLER ULTRASOUND ASSESSMENT OF JUXTA-ANASTOMOTIC STENOSIS IN RADIOCEPHALIC ARTERIOVENOUS FISTULAS: ENDOVASCULAR OR SURGICAL APPROACH

Background: Juxta-anastomotic stenosis (JAS) is a common complication of radiocephalic arteriovenous fistulas. There is diverging data as to the best therapeutic approach being angioplasty or surgery. Pre-operative color Doppler ultrasound (CDU) is accurately used for initial assessment of the vascular access and follow-up monitoring. The aim of this study was to evaluate immediate and long-term results of endovascular versus open surgical intervention of juxta-anastomotic venous stenosis of forearm radiocephalic fistulas and to test if CDU assessment can be used to ameliorate preoperative strategy and long-term outcomes. Methods: This retrospective cohort study included 63 patients with JAS radiocephalic fistulas referred to vascular access consultation. CDU was used to assess preoperative morphological, functional and hemodynamic stenosis characteristics and according to specific criteria, allocate patients to endovascular or surgical treatment. Results: Surgical revision was proposed in 68.2% of patients (N=43), namely the creation of a new proximal fistula (N=41), while angiographic evaluation was proposed in 31.7% of the cases (N=20). Mean follow-up time was 720±524 days with a maximum follow-up of 4.6 years. In the surgical group, primary patency was 92% and 84% at 6 and 12 months respectively, while in the endovascular group, it was 76% and 47% (p=0.013). There was no significant difference in the assisted primary patency between the interventional groups at 12 months: 94% in the endovascular vs. 93% in the surgical group (p=0.542). Conclusion: Pre-operative CDU assessment of JAS and specific allocation criteria with an access-centered approach choosing the best option in each fistula allowed the correct diagnosis of the lesion, improved the global results of the treatment and optimized the financial resources by reserving PTA for selected cases where surgery could be more difficult with higher risk of access loss.

Variability of glycated hemoglobin levels in the first year post renal transplantation in patients without diabetes

BACKGROUND Glycated hemoglobin (HbA1c) is an alternative test used for the diagnosis and monitoring of diabetes in kidney transplant recipients. Immunosuppressive drugs are the most important risk factors related with changes in the glucose metabolism after transplant. It is still unknown if they impact on the variability of HbA1c. We assessed the variability of HbA1c levels in a group of renal transplant recipients without diabetes during the first year after transplant. METHODS We estimated the variability of HbA1c in a group of 95 Brazilian kidney transplant recipients. Three EDTA whole blood samples were collected from each patient, one every four months for twelve months, totalizing 285 blood specimens. HbA1c values were measured by HPLC (Bio-Rad Variant™ II Turbo analyzer). Estimations were calculated according to Fraser and Harris method. RESULTS There was no difference in HbA1c mean levels between men and women. Within-subject and between-subject biological variations were 4.42% and 7.05%, respectively. The reference change value calculated for HbA1c was 16.15% and the index of individuality was 0.63. CONCLUSIONS Kidney transplant patients without diabetes presented higher HbA1c within-subject variation than individuals without diabetes from the general population. This should be considered when interpreting HbA1c results in the diagnosis and management of diabetes after kidney transplantation.

Are A1C levels at the moment of DM diagnosis associated with renal outcomes

Materials and methods This prospective study evaluated 269 patients screened to DM type 2 at a university hospital between 2008 and 2009. All patients performed an oral glucose tolerance test (OGTT), fasting glucose (FG), urinary albumin and A1C measured by colorimetry, immunoturbidimetry (Advia 1800, Siemens Diagnostica) and HPLC (2.2 Tosoh Plus A1C, Tosoh Corporation), respectively. They were identified with DM according to ADA criteria. Between 2010 and 2012, the patients returned and were re-evaluated. Renal outcomes were measured by urinary albumin levels in the follow up, according with KDIGO guidelines. Poisson regression with robust standard errors was performed in those with DM diagnosis, considering the worsening of renal function, measured by urinary albumin levels, as dependent variable and A1C, FG, 2h plasma glucose after OGTT (G2h) levels, age and hypertension as independent variables. Statistical analysis was performed by SPSS 20.0 and p 0.05). Only age was risk factor (p <0.001; relative risk 1.074 [1.0351.114] to the worsening of renal function, where the increase of one year in age was associated with 7.4% increase in the risk to renal outcomes.

Older patients are at increased risk for renal posttransplantation diabetes mellitus.

Materials and methods All patients without diabetes who underwent renal transplant at a University Hospital between July 2012 and June 2015 were included. PTDM was diagnosed according to current ADA criteria at four months after transplantation. Poisson regression with robust standard errors was performed with PTDM as dependent variable and the possible risk factors under study (age, sex, type of donor, immunosuppressive type, family history of DM, pre-transplant BMI and fasting plasma glucose) as independent variables. P-value <0.05 was considered as statistically significant.