July 2008: Volume 34, Number 7
Even Mildly Elevated Glucose Poses Risk in Pregnancy
A large international study shows a continuum of risk to fetuses as mothers’ glucose levels rise (NEJM 2008; 358: 1991–2002). To settle a controversy about whether maternal hypoglycemia that falls short of diabetes is associated with adverse pregnancy outcomes, a multinational team of researchers tested glucose levels in 25,505 pregnant women at 24 to 32 weeks of gestation at 15 centers in 9 countries. Researchers blinded data for mothers with fasting plasma glucose levels ≤105 mg/dL and 2-hour plasma glucose levels ≤200 mg/dL. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia. For the 23,316 participants with blinded data, the researchers calculated adjusted ORs for adverse pregnancy outcomes associated with an increase of 1 standard deviation in the fasting plasma glucose level (6.9 mg/dL), the 1-hour plasma glucose level (30.9 mg/dL), and the 2-hour plasma glucose level (23.5 mg/dL). For birth weight above the 90th percentile, those ORs (95% CI) were 1.38 (1.32–1.44), 1.46 (1.39–1.53), and 1.38 (1.32–1.44), respectively. For cord-blood serum C-peptide level above the 90th percentile, the ORs were 1.55 (1.47–1.64), 1.46 (1.38–1.54), and 1.37 (1.30–1.44). ORs for primary cesarean delivery were 1.11 (1.06–1.15), 1.10 (1.06–1.15), and 1.08 (1.03–1.12). ORs for neonatal hypoglycemia were 1.08 (0.98–1.19), 1.13 (1.03–1.26), and 1.10 (1.00–1.12). The researchers found no obvious thresholds for increased risk. Associations for secondary outcomes were significant, but weaker.
Longer Cholesterol Testing Intervals Recommended
Physicians should consider a testing interval of 3 years or more for patients who have well-controlled cholesterol levels and adhere to cholesterol-lowering medications, authors of a recent paper suggest (Annals of Internal Medicine 2008; 148: 656–661). Because research has not yet shown an optimal cholesterol monitoring interval and clinical practice varies, researchers from the U.K. and Australia sought to estimate both the variation in initial response to treatment and the long-term drift from initial response. They also aimed to estimate the ability to detect long-term changes in cholesterol levels during treatment (signal), given short-term, within-person variation (noise). The research team analyzed serum cholesterol concentrations at baseline, 6 months, and 12 months, and annually thereafter for the next 4 years in 9,014 patients who participated in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) trial. Researchers randomized the patients, who had past coronary heart disease, to receive pravastatin or placebo. Both the placebo and pravastatin groups showed small increases in within-person variability over time. The estimated within-person standard deviation increased from 15 mg/dL (CV, 7%) to 23 mg/dL (CV, 11%), but it took almost 4 years for the long-term variation to exceed the short-term variation. This slow increase in variation and the modest increase in mean cholesterol level, about 2% per year, suggest that most of the variation in the study is due to short-term biological and analytic variability. The researchers maintained that for patients with levels ≥19 mg/dL under target, monitoring is likely to detect many more false-positive results than true-positive results for at least the first 3 years after treatment.
Minimal Change in Lipids After ACS
Mean lipid levels vary little in the 4 days after an ACS event and can help guide selection of lipid-lowering medication, according to the results a recent study (J Am Coll Cardio. 2008; 51:1440–1445). To help quell a debate over how long changes in lipid levels persist after ACS, researchers from University of Michigan, Ann Arbor, analyzed data from the LUNAR (Limiting UNdertreatment of lipids in ACS with Rosuvastatin) trial to assess lipid changes 1 to 4 days after ACS onset. The prospective, multicenter, randomized, open-label study’s overall goal was to compare efficacy of the two drugs in adults hospitalized for acute ST-segment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina (UA). Before treatment, researchers measured serum lipid levels in blood samples at medians of 26 hours, 43 hours, and 84 hours after onset of ACS symptoms. Of the 507 patients available for analysis, 212 were admitted for STEMI, 176 for non-STEMI, and 119 for UA. The LDL-C levels decreased in the 24 hours after admission, from 136.2 to 133.5 mg/dL, and increased over the subsequent 2 days to 141.8 mg/dL. These changes did not seem to be clinically meaningful, according to the researchers. Similar changes were observed for total cholesterol and smaller changes for HDL-C, but fasting triglyceride levels did not change.
PCA3 Score Predicts Prostate Tumor Volume
A newly published study suggests that the prostate cancer gene 3 (PCA3) test might have clinical application in selecting men with low-grade and low-volume tumors who would be suitable candidates for active surveillance (J Urol 2008 179:1804–1809). To assess association of urinary PCA3 score with prostatectomy tumor volume and other clinical and pathological features, a research team from the University of Texas M.D. Anderson Cancer Center collected urine specimens after digital rectal examinations from 59 men scheduled for prostate biopsy and 83 men scheduled for radical prostatectomy. The researchers evaluated prostatectomy findings from 96 men, using the Gen-Probe DTS 400 System to quantify PCA3 and PSA mRNA, and tabulated PCA3 score as ratio of PCA3 mRNA to PSA mRNA X 100. Scores for the 30 men with negative biopsies and the 29 with positive biopsies differed significantly, with medians of 21.1 and 31.0, respectively. PCA3 scores were significantly correlated with total tumor volume in prostatectomy specimens and with prostatectomy Gleason score, but not with other clinical and pathological features. When researchers compared low volume/low grade cancer (dominant tumor volume less than 0.5 cc, Gleason score 6) and significant cancer, differences in PCA3 scores were significant. In multivariate analysis, PCA3 was the best predictor of total tumor volume in prostatectomy. ROC curve analysis showed that the PCA3 score could discriminate low volume cancer (total tumor volume less than 0.5 cc) well, with AUC of 0.757.
Low Vitamin D Levels Linked to Depression in the Elderly
A large population-based study shows depression status and severity is associated with decreased serum 25-hydroxyvitamin D [25(OH)D] levels and increased serum parathyroid hormone (PTH) levels in older adults (Arch Gen Psychiatry 2008;65: 508–512). A team of researchers from the Netherlands determined if 1,282 community residents ages 65–95 suffered from depression using self reports and diagnostic interviews. They assessed levels of 25(OH)D and PTH and considered potentially confounding factors such as age, sex, smoking, body mass index, and explanatory factors including the season of measurement and physical activity. 25(OH)D levels were 14% lower in 169 persons with minor depression and 14% lower in 26 persons with major depressive disorder, compared with levels in 1,087 controls. Levels of PTH were 5% and 33% higher, respectively. Depression severity was significantly associated with decreased serum 25(OH)D levels and increased serum PTH levels.