Joiza Lins Camargo

Diabetes Melito: Diagnóstico, Classificação e Avaliação do Controle Glicêmico

Diabetes mellitus and other categories of impaired glucose tolerance are frequent in the adult population and are associated with an increased risk for cardiovascular disease and microvascular complications. The diagnosis of these entities should be performed early and using sensitive and accurate methods, since lifestyle changes and correction of hyperglycemia may delay the incidence of diabetes and its complications. Glucose tolerance test is the reference method and the diagnosis of diabetes and impaired glucose tolerance are established when the 2h plasma glucose after an oral intake of 75g of glucose is ³200mg/dl or ³140 and <200mg/dl, respectively. When it is not possible to perform this test, fasting plasma glucose levels ³126mg/dl or ³110 and <126mg/dl, respectively, are used to establish the diagnosis of diabetes and impaired fasting plasma glucose. Glycohemoglobin should not be used for the diagnosis but it is the reference method for evaluation of the long-term glucose control. The etiological classification of diabetes mellitus includes 4 categories: type 1 diabetes, type 2 diabetes, other specific types of diabetes and gestational diabetes. The assignment of the patient in each category usually is made on clinical grounds, however in some case the measurement of C-peptide and autoantibodies are necessary.

Glomerular filtration rate measurement and prediction equations.

Abstract Chronic kidney disease (CKD) is defined as the presence of kidney damage or a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for three or more months. Measurement of serum creatinine is the most commonly used method to evaluated kidney function, but it must be included in formulas to estimate GFR, adjusting for age, gender and ethnicity, such as the Modification of Diet in Renal Disease (MDRD) study equation. The performance of this equation is acceptable for patients with CKD but appears to under-estimate GFR in populations with unknown kidney status. A new formula has been developed recently. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation appears to perform better than the MDRD equation. Cystatin C has been widely evaluated as a marker for GFR and seems to be more sensitive than creatinine. The aim of this review is to discuss the recommendations for detecting CKD, emphasizing the characteristics and limitations of GFR estimating equations and pitfalls in the evaluation of urinary albumin excretion. Clin Chem Lab Med 2009;47:1023–32.

HbA1c measurement for the diagnosis of diabetes: is it enough?

Diabet. Med. 28, 31–35 (2011)

Comparison between IDMS-traceable Jaffe and enzymatic creatinine assays for estimation of glomerular filtration rate by the CKD-EPI equation in healthy and diabetic subjects.

OBJECTIVES The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals. DESIGN AND METHODS Cross-sectional study conducted in 123 adult southern Brazilians with GFR>60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49±16 years (range of 19-86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the ⁵¹Cr-EDTA single-injection method. RESULTS Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79±0.16 vs. 0.79±0.15 mg/dL, respectively, P=0.76), and diabetic patients (0.96±0.22 vs. 0.92±0.29 mg/dL, respectively, P=0.17). However, the correlation between the two methods was higher in the healthy group (r=0.90 vs. 0.76, P<0.001). The difference between Jaffe creatinine and enzymatic creatinine was <10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P=0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results. CONCLUSION Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better.

Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases

OBJECTIVE The aim of this study was to evaluate the accuracy of the measurement of thyroglobulin in washout needle aspiration biopsy (FNAB-Tg) to detect papillary thyroid cancer (PTC) metastases. SUBJECTS AND METHODS Forty-three patients (51.4 ± 14.6 years) with PTC diagnosis and evidence of enlarged cervical lymph nodes (LN) were included. An ultrasound-guided fine-needle aspiration of suspicious LN was performed, for both cytological examination and measurement of FNAB-Tg. RESULTS The median values of FNAB-Tg in patients with metastatic LN (n = 5) was 3,419 ng/mL (11.1-25,538), while patients without LN metastasis (n = 38) showed levels of 3.7 ng/mL (0.8-7.4). Considering a 10 ng/mL cutoff value for FNAB-Tg, the sensitivity and specificity was 100%. There were no differences on the median of FNAB-Tg measurements between those on (TSH 0.07 mUI/mL) or off levothyroxine (TSH 97.4 mUI/mL) therapy (3.3 vs. 3.8 ng/mL, respectively; P = 0.2). CONCLUSION The results show that evaluation of FNAB-Tg in cervical LN is a valuable diagnostic tool for PTC metastases that can be used independent of the thyroid status.

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.

Glico-hemoglobina (HbA1c): aspectos clínicos e analíticos

Glycohemoglobin (GHb) has a key role in the assessment of glycemic control in diabetic patients. Several studies have clearly shown that improved glycemic control is strongly associated with decreased development and/or progression of diabetic complications in both type 1 and 2 diabetes mellitus. Therefore, accurate determination of GHb concentration is an important issue for clinical laboratories. Several factors may affect and lead to erroneous results. We discuss the problems of standardization of GHb measurements for monitoring glycemic control and also consider the potential interfering factors on GHb measurements. Moreover, GHb assays may be affected by interference in different ways. The effect of interference may be more clinically relevant with poor metabolic control. Laboratory staff must be aware of all pitfalls to avoid adding more confusion to the clinical interpretation of HbA1c values and physicians should contact laboratories if discrepancies between clinical impressions and laboratory data are observed.

Prediction of cardiovascular events, diabetic nephropathy, and mortality by albumin concentration in a spot urine sample in patients with type 2 diabetes

AIMS To analyze in a random urine spot the predictive value of urinary albumin concentration (UAC) for cardiovascular events, diabetic nephropathy (DN), and death in patients with type 2 diabetes. METHODS In this cohort, urinary albumin (immunoturbidimetry) was measured as 24-h urinary albumin excretion (UAE) and, in a random spot urine, as UAC and albumin:creatinine ratio (ACR). Primary outcomes were: 1) cardiovascular events, 2) DN defined as a composite outcome [macroalbuminuria and/or decreased glomerular filtration rate (GFR) <60 ml/min/1.73 m²], and 3) death. RESULTS A total of 199 type 2 diabetic patients, aged 59.9 ± 9.9 years, were followed for 6.1 ± 2.7 years. UAC ≥14.4 mg/l, as determined by ROC curve, predicted DN and prediction for this and other outcomes were compared with traditional microalbuminuria cutoffs for ACR and UAE. The outcomes frequency was: cardiovascular events = 26.4%, DN = 31.7% (23.5% decreased GFR; 13.6% macroalbuminuria) and death = 8.50%. In Cox analyses, UAC ≥14 mg/l increased the risk (hazard ratio, HR) for cardiovascular events 3.25 times (95% CI 1.43-7.38; P = 0.005), 4.30 for DN composite outcome (95% CI 2.22-8.32; P <0.001), and 5.51 for death (95% CI 1.16-26.22; P = 0.032). Corresponding HRs of ACR ≥30 mg/g were: 2.89 (95% CI 1.29-6.45; P = 0.009) for cardiovascular events, 4.67 (95% CI 2.34-9.34; P <0.001) for DN composite outcome and 5.07 (95% CI 1.01-24.88; P = 0.049) for death. HRs of UAE ≥30 mg/24-h were: 2.20 (95% CI 2.08-2.49; P = 0.030) for cardiovascular events, 6.76 (95% CI 3.32-13.77; P <0.001) for DN composite outcome, and 2.47 (95% CI 0.72-8.42; P = 0.150) for death. CONCLUSIONS In conclusion, random UAC ≥14 mg/l predicted cardiovascular events, diabetic nephropathy, and mortality just as well as ACR. UAC may be used to assess cardiovascular and renal risks in patients with type 2 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.

Agreement of Different Immunoassays for Urinary Albumin Measurement

Diagnosis of diabetic nephropathy (DN) is based on measurements of urinary albumin (UALB) by a sensitive analytical method with sufficient analytical precision (CV <15%) to detect changes in UALB concentration(1)(2)(3). We evaluated the comparative diagnostic accuracies of 4 UALB assays for DN. We used urine samples from 98 diabetic outpatients. UALB was measured by 4 immunoturbidimetric (IT) assays: the Urine Pack Immuno method (Bayer) as implemented on a Roche Cobas Mira Plus (method A), Malb Aptec Diagnostic (BioSys) (method B), Albumin Tina-quant (Roche) (method C), and Microalbumin (Randox) (method D). Methods B, C, and D were implemented on a Hitachi 917 analyzer (Roche). Method A was considered as the reference standard (comparison method) because it had been used in our laboratory since 1996 and validated in previous studies(2)(4)(5). Total urinary protein was measured before UALB, and the U/CSF Protein assay (Roche) on the Hitachi 917 analyzer (Roche) was used to estimate the contribution (%) of albumin to total protein for each sample(5). Based on this estimate, we prediluted samples to allow …