HbA1c Alone not a Reliable Diagnostic Tool in Obese Adolescents
New research by Yale University investigators indicates that a hemoglobin A1c (HbA1c) level of 6.5% underestimates the prevalence of prediabetes and diabetes in obese adolescents (Diabetes Care 2011;34:1306–11). The results suggest that HbA1c alone is a poor diagnostic tool in this population, according to the authors.
The researchers investigated the utility of HbA1c in obese adolescents because clinical guidelines recently endorsed HbA1c to diagnose diabetes and identify patients at risk for developing diabetes did not include studies involving adolescent populations. Studies evaluated to make those recommendations all involved adults, and little is known about the use of HbA1c in children and adolescents.
The study involved 1,156 obese adolescents with a mean age of 13.3 years who were not taking medications that might affect glucose metabolism and who were not already known to have type 2 diabetes. All subjects had baseline oral glucose tolerance tests (OGTT) and HbA1c testing, and a subgroup of 218 subjects had repeated testing after a mean of 1.68 years.
At baseline, 77% of subjects had normal glucose tolerance with HbA1c levels <5.7%, 21% were at risk for diabetes with HbA1c concentrations of 5.7–6.4%, and 1% had diabetes with HbA1c levels >6.5%. However, 27% of subjects considered to have normal glucose tolerance based on HbA1c results were classified as being prediabetic based on OGTT. Among subjects placed in the at-risk group by HbA1c results, 53% were considered to have normal glucose tolerance and 47% prediabetes or diabetes based on OGTT. Finally, 12.5% of subjects considered to have diabetes based on HbA1c results were designated as having normal glucose tolerance and 24% to have prediabetes by OGTT.
Based on these findings, the researchers called for further investigation about the role of HbA1c levels in diagnosing prediabetes and diabetes in adolescents and children.
Ovarian Cancer Screening Does Not Reduce Cancer-Related Mortality
Findings from the landmark Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial indicate that for women in a general population, annual screening with CA-125 biomarker testing and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality (JAMA 2011;305:2295–2303). At the same time, this testing algorithm increased invasive medical procedures and associated harms.
The ovarian cancer arm of PLCO involved 78,216 women age 55–74 years at enrollment, 39,105 of whom underwent annual screening, and 39,111 of whom received usual care. Those in the intervention arm had CA-125 testing for 6 years and transvaginal ultrasound for 4 years, with a median follow-up of 12.4 years.
The investigators found 212 and 176 ovarian cancer cases in the intervention arm and usual care arms, respectively. There were 118 ovarian cancer-related deaths in the intervention arm, compared with 100 in the usual care group or 3.1/10,000 person-years versus 2.6/10,000 person-years, respectively. The difference in survival between the intervention and usual care groups was not statistically significant, and no stage shift was observed, meaning that over the course of the study among intervention arm subjects in comparison to normal care subjects, there was not a decline in cases first diagnosed in later stages of the disease.
In addition, there was an approximate 5% false-positive rate for each screening round. Although this rate is comparable to or even lower than false-positive rates for mammography screening, the researchers noted that “the nature of the diagnostic follow-up, which often included invasive procedures, was a serious concern.” They concluded that “even an optimized program of annual screening may be insufficient to detect cancers early enough to reduce mortality.”
Different Centrifugation Conditions Produce Similar Results
An analysis of centrifugation conditions on clinical chemistry and immunology results found that three different conditions delivered identical test results (BMC Clinical Pathology 2011 doi:10.1186/1472–6890-11-6). The results are significant because they suggest that laboratories may be able to reduce centrifugation times and consequently lower their overall turnaround times.
The researchers conducted the investigation because although pre-analytical centrifugation occurs countless times every day in laboratories around the world, the influence of the process on lab results has only rarely and recently been investigated. World Health Organization (WHO) guidelines issued in 2002 recommended a centrifugation time of at least 10 minutes for serum and 15 minutes for plasma with a relative centrifugation force (RCF) of 2,000–3,000g.
The study involved 74 tests on six samples from 44 consecutively admitted patients, for a total of 444 results per patient. The investigators compared three centrifugation conditions, including 15 minutes at 2,180g RCF, 10 minutes at 2,180g RCF, and 7 minutes at 1,870 g RCF, all at 15°C and with a deceleration time of 32 seconds. Two different plasma separators were used for each centrifugation condition.
The researchers found “identical” results in all parameters. They conducted Deming fit, alpha error, and beta error analyses, and found that only 3.6% of statistical test results fell outside the p<0.05 significance level, which was less than the expected 5%. This suggests that the outliers were the result of random variation. The authors conclude that labs that have been following the WHO recommendation might consider shorter centrifugation times, with an eye towards reducing turnaround times.
Copeptin, NT-proBNP Combination Useful in Heart Failure Risk Assessment
Swedish researchers recently reported that among elderly patients with symptoms of heart failure, elevated copeptin levels and the combination of elevated copeptin and N-terminal B-type natriuretic peptide (NT-proBNP) were associated with increased risk of all-cause and cardiovascular mortality (JAMA 2011:305:2088–95). The findings suggest that these two biomarkers, one produced locally in the myocardium, and one a non-cardiac plasma marker of cardiovascular disease, could be used together to assess risk in elderly heart failure patients. The association between outcomes and copeptin, the C-terminal fragment of provasopressin, also point to vasopressin as a potential target for therapeutic intervention in heart failure, according to the authors.
The study involved 470 elderly patients with symptoms of heart failure who were age 65–87 at the time of recruitment in 1996. Patients underwent baseline clinical examination, echocardiography, and NT-proBNP and copeptin measurement, with a subsequent 13-year median follow-up. In all, there were 226 deaths from all causes, and 146 from cardiovascular disease.
Increased copeptin concentration was associated with increased risk of both all-cause mortality, with a hazard ratio of 2.04 from highest to lowest quartile, and cardiovascular mortality, with a hazard ratio of 1.94 from highest to lowest quartile. Likewise, the combination of elevated NT-proBNP and copeptin levels were associated with increased risk of all-cause mortality.