Objective To determine whether the use of insulin glargine during pregnancy is associated with an increase in the incidence of fetal macrosomia or adverse neonatal outcome.Design A matched case-control study.Setting Women's Centre, John Radcliffe Hospital, Oxford, UK.Sample Sixty-four pregnant women treated with insulin during their pregnancies, 20 with type I diabetes and 44 with gestational diabetes.Methods Two groups of women were compared in matched pairs. A study group of 32 pregnant women with diabetes treated with insulin glargine during their pregnancy and a control group of 32 pregnant women treated with an intermediate-acting human insulin (isophane or insulin zinc suspension) and matched for weight at booking, height, gestation at delivery, parity, fetal sex, duration of insulin use in pregnancy and glycaemic control during the third trimester of pregnancy (glycosylated haemoglobin [HbA 1c ] concentration and mean blood glucose concentration).Main outcome measures Birthweight, centile birthweight, the incidence of fetal macrosomia (birthweight > 90th percentile) and neonatal morbidity in the two study groups.Results There was no significant difference between the birthweight or centile birthweight of babies born to the women treated with insulin glargine during pregnancy and that of the babies born to those in the control group treated with intermediate-acting human insulin. The overall incidence of fetal macrosomia was 12/32 (37.5%) in the insulin glargine group and 13/32 (40.6%) in the control group. There was no significant difference in neonatal morbidity between the groups. ConclusionsThe results of this pilot study indicate that insulin glargine treatment during pregnancy does not appear to be associated with increased fetal macrosomia or neonatal morbidity.

Insulin-like growth factor-I (IGF-I) is a known biomarker of recombinant human growth hormone (rhGH) abuse, and is also used clinically to confirm acromegaly. The protein leucine-rich alpha-2-glycoprotein (LRG) was recently identified as a putative biomarker of rhGH administration. The combination of an ACN depletion method and a 5-min ultra-high-performance liquid chromatography/tandem mass spectrometry (uHPLC/MS/MS)-based selected reaction monitoring (SRM) assay detected both IGF-I and LRG at endogenous concentrations. Four eight-point standard addition curves of IGF-I (16-2000 ng/mL) demonstrated good linearity (r(2) = 0.9991 and coefficients of variance (CVs) <13%). Serum samples from two rhGH administrations were extracted and their uHPLC/MS/MS-derived IGF-I concentrations correlated well against immunochemistry-derived values. Combining IGF-I and LRG data improved the separation of treated and placebo states compared with IGF-I alone, further strengthening the hypothesis that LRG is a biomarker of rhGH administration. Artificial neural networks (ANNs) analysis of the LRG and IGF-I data demonstrated an improved model over that developed using IGF-I alone, with a predictive accuracy of 97%, specificity of 96% and sensitivity of 100%. Receiver operator characteristic (ROC) analysis gave an AUC value of 0.98. This study demonstrates the first large scale and high throughput uHPLC/MS/MS-based quantitation of a medium abundance protein (IGF-I) in human serum. Furthermore, the data we have presented for the quantitative analysis of IGF-I suggest that, in this case, monitoring a single SRM transition to a trypsin peptide surrogate is a valid approach to protein quantitation by LC/MS/MS.

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The GH-2000 and GH-2004 projects have developed a method for detecting GH misuse based on measuring insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP). The objectives were to analyze more samples from elite athletes to improve the reliability of the decision limit estimates, to evaluate whether the existing decision limits needed revision, and to validate further non-radioisotopic assays for these markers. The study included 998 male and 931 female elite athletes. Blood samples were collected according to World Anti-Doping Agency (WADA) guidelines at various sporting events including the 2011 International Association of Athletics Federations (IAAF) World Athletics Championships in Daegu, South Korea. IGF-I was measured by the Immunotech A15729 IGF-I IRMA, the Immunodiagnostic Systems iSYS IGF-I assay and a recently developed mass spectrometry (LC-MS/MS) method. P-III-NP was measured by the Cisbio RIA-gnost P-III-P, Orion UniQ™ PIIINP RIA and Siemens ADVIA Centaur P-III-NP assays. The GH-2000 score decision limits were developed using existing statistical techniques. Decision limits were determined using a specificity of 99.99% and an allowance for uncertainty because of the finite sample size. The revised Immunotech IGF-I - Orion P-III-NP assay combination decision limit did not change significantly following the addition of the new samples. The new decision limits are applied to currently available non-radioisotopic assays to measure IGF-I and P-III-NP in elite athletes, which should allow wider flexibility to implement the GH-2000 marker test for GH misuse while providing some resilience against manufacturer withdrawal or change of assays.

The GH-2000 detection method based on IGF-I and P-III-P would be valid in all ethnic groups.