Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with Type 2 diabetes uncontrolled by oral agents

ObjectiveProgressive β-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs.Research Design and MethodsThis was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90–110mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups.ResultBoth insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P = 0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P = 0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P = 0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations.ConclusionIn type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study.     

False-positive pregnancy test after passive transfusion of beta-human chorionic gonadotropin from donor red blood cells during erythrocytapheresis

BACKGROUND: Patients transfused with blood products may passively receive soluble antibodies, proteins, and other analytes that persist during the collection, processing, and transfusion of the blood product. In this report, a female patient who received transfusion of five red blood cell (RBC) units during erythrocytapheresis later demonstrated an unexpected positive result in assays for the beta-subunit of human chorionic gonadotropin (bHCG), a screening test for pregnancy. The result caused postponement of an elective surgical procedure. A follow-up test 1 week later was negative. STUDY DESIGN AND METHODS: To investigate the possibility of passive transfusion of the hormone from a donor RBC unit, a sample from each of the units transfused was assayed for the level of bHCG. RESULTS: One of the 5 units transfused to the patient had a high level of bHCG. The observed bHCG level in the recipient was found to be comparable to the predicted level, given the donor's plasma bHCG level and accounting for the dilution factors in the preparation of the RBC unit and the erythrocytapheresis procedure and the in vivo t((1/2)) of the hormone. CONCLUSION: The donor, who was unaware of her pregnancy status at the time of donation, harbored a high bHCG level that caused the positive test result in the recipient patient's serum and urine. If an unexpected analyte or serology is detected in a recipient of a blood transfusion, it is important to consider the possibility of passive transfusion of the analyte.     

First- and second-trimester screening: detection of aneuploidies other than Down syndrome

OBJECTIVE: To evaluate the performance of first- and second-trimester screening methods for the detection of aneuploidies other than Down syndrome. METHODS: Patients with singleton pregnancies at 10 weeks 3 days through 13 weeks 6 days of gestation were recruited at 15 U.S. centers. All patients had a first-trimester nuchal translucency scan, and those without cystic hygroma had a combined test (nuchal translucency, pregnancy-associated plasma protein A, and free beta-hCG) and returned at 15-18 weeks for a second-trimester quadruple screen (serum alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin-A). Risk cutoff levels of 1:300 for Down syndrome and 1:100 for trisomy 18 were selected. RESULTS: Thirty-six thousand one hundred seventy-one patients completed first-trimester screening, and 35,236 completed second-trimester screening. There were 77 cases of non-Down syndrome aneuploidies identified in this population; 41 were positive for a cystic hygroma in the first trimester, and a further 36 had a combined test, of whom 29 proceeded to quadruple screening. First-trimester screening, by cystic hygroma determination or combined screening had a 78% detection rate for all non-Down syndrome aneuploidies, with an overall false-positive rate of 6.0%. Sixty-nine percent of non-Down syndrome aneuploidies were identified as screen-positive by the second-trimester quadruple screen, at a false-positive rate of 8.9%. In the combined test, the use of trisomy 18 risks did not detect any additional non-Down syndrome aneuploidies compared with the Down syndrome risk alone. In second-trimester quadruple screening, a trisomy 18-specific algorithm detected an additional 41% non-Down syndrome aneuploidies not detected using the Down syndrome algorithm. CONCLUSION: First-trimester Down syndrome screening protocols can detect the majority of cases of non-Down aneuploidies. Addition of a trisomy 18-specific risk algorithm in the second trimester achieves high detection rates for aneuploidies other than Down syndrome. LEVEL OF EVIDENCE: II.     

Comparison of serum and plasma measurements of Müllerian inhibiting substance

The authors sought to determine whether measurement of plasma Müllerian inhibiting substance (MIS) is a suitable substitute for measurement of serum MIS. Eighteen samples of serum and plasma were examined that were drawn simultaneously. Levels of MIS were measured with an ELISA kit, and plasma levels were studied in parallel to serum samples. A 98.5% correlation was found between serum and plasma MIS values.