Delayed conception in women with low-urinary iodine concentrations: a population-based prospective cohort study.

STUDY QUESTION: Is iodine deficiency associated with decreased fecundability? SUMMARY ANSWER: Moderate to severe iodine deficiency is associated with a 46% decrease in fecundability. WHAT IS KNOWN ALREADY: Iodine deficiency is common in women of childbearing age but its effect on fecundability has not been investigated. STUDY DESIGN, SIZE, DURATION: The LIFE Study, a population-based prospective cohort study, enrolled 501 women who had discontinued contraception within 2 months to become pregnant between 2005 and 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women reported on risk factors for infertility by interview then kept daily journals of relevant information. Women used fertility monitors to time intercourse relative to ovulation then used home digital pregnancy tests to identify pregnancies on the day of expected menstruation. Urine samples for iodine analysis were collected on enrollment. MAIN RESULTS AND THE ROLE OF CHANCE: Samples were in the deficiency range in 44.3% of participants. The group whose iodine-creatinine ratios were below 50 µg/g (moderate to severe deficiency) had a 46% reduction in fecundity (P = 0.028) compared with the group whose iodine-creatinine ratios were in the adequate range: adjusted fecundability odds ratio of becoming pregnant per cycle, 0.54 (95% confidence interval 0.31-0.94). LIMITATIONS, REASONS FOR CAUTION: Iodine concentrations vary within individuals over time, so the data must be interpreted by group as we have done; residual confounding is possible. WIDER IMPLICATIONS OF THE FINDINGS: Significant delays in becoming pregnant occur at iodine concentrations that are common in women in the USA and parts of Europe. Replicating these findings will be important to determine whether improving iodine status could be beneficial in improving fecundability. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA. Contracts N01-HD-3-3355; N01-HD-3-3356; N01-HD-3-3358 and HHSN275201100001l/HHSN27500007. None of the authors has any conflict of interest to declare.

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review.

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation.

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: a systematic review.

Non-invasive tests for the detection of peripheral artery disease (PAD) among individuals with diabetes mellitus are important to estimate the risk of amputation, ulceration, wound healing and the presence of cardiovascular disease, yet there are no consensus recommendations to support a particular diagnostic modality over another and to evaluate the performance of index non-invasive diagnostic tests against reference standard imaging techniques (magnetic resonance angiography, computed tomography angiography, digital subtraction angiography and colour duplex ultrasound) for the detection of PAD among patients with diabetes. Two reviewers independently screened potential studies for inclusion and extracted study data. Eligible studies evaluated an index test for PAD against a reference test. An assessment of methodological quality was performed using the quality assessment for diagnostic accuracy studies instrument. Of the 6629 studies identified, ten met the criteria for inclusion. In these studies, the patients had a median age of 60-74 years and a median duration of diabetes of 9-24 years. Two studies reported exclusively on patients with symptomatic (ulcerated/infected) feet, two on patients with asymptomatic (intact) feet only, and the remaining six on patients both with and without foot ulceration. Ankle brachial index (ABI) was the most widely assessed index test. Overall, the positive likelihood ratio and negative likelihood ratio (NLR) of an ABI threshold <0.9 ranged from 2 to 25 (median 8) and <0.1 to 0.7 (median 0.3), respectively. In patients with neuropathy, the NLR of the ABI was generally higher (two out of three studies), indicating poorer performance, and ranged between 0.3 and 0.5. A toe brachial index <0.75 was associated with a median positive likelihood ratio and NLRs of 3 and ≤ 0.1, respectively, and was less affected by neuropathy in one study. Also, in two separate studies, pulse oximetry used to measure the oxygen saturation of peripheral blood and Doppler wave form analyses had NLRs of 0.2 and <0.1. The reported performance of ABI for the diagnosis of PAD in patients with diabetes mellitus is variable and is adversely affected by the presence of neuropathy. Limited evidence suggests that toe brachial index, pulse oximetry and wave form analysis may be superior to ABI for diagnosing PAD in patients with neuropathy with and without foot ulcers. There were insufficient data to support the adoption of one particular diagnostic modality over another and no comparisons existed with clinical examination. The quality of studies evaluating diagnostic techniques for the detection of PAD in individuals with diabetes is poor. Improved compliance with guidelines for methodological quality is needed in future studies.

Effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral artery disease: a systematic review.

Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012, a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 to June 2014. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 56 articles were eligible for full-text review. There were no randomized controlled trials, but there were four nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70-89%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular techniques. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of conservatively treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients.

A systematic review of the effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral arterial disease.

In several large recent observational studies, peripheral arterial disease (PAD) was present in up to 50% of the patients with a diabetic foot ulcer and was an independent risk factor for amputation. The International Working Group on the Diabetic Foot therefore established a multidisciplinary working group to evaluate the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. A systematic search was performed for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980-June 2010. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 49 papers were eligible for full text review. There were no randomized controlled trials, but there were three nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70.5-85.5%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular revascularization. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of medically treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients.

Diagnosis and treatment of peripheral arterial disease in diabetic patients with a foot ulcer. A progress report of the International Working Group on the Diabetic Foot.

The International Working Group on the Diabetic Foot (IWDGF) has produced in 2011 a guideline on the diagnosis and treatment of peripheral arterial disease in patients with diabetes and a foot ulcer. This document, together with a systematic review that provided the background information on management, was produced by a multidisciplinary working group of experts in the field and was endorsed by the IWDGF. This progress report is based on these two documents and earlier consensus texts of the IWDGF on the diagnosis and management of diabetic foot ulcers. Its aim is to give the clinician clear guidance on when and how to diagnose peripheral arterial disease in patients with diabetes and a foot ulcer and when and which treatment modalities should be considered, taking both risks and benefits into account.

Placental characteristics and risks of maternal mortality 50 years after delivery.

INTRODUCTION: Adverse pregnancy outcomes such as preterm delivery and preeclampsia are associated with a higher maternal risk for subsequent cardiovascular disease (CVD) and all-cause mortality. While such pregnancy conditions are related to abnormal placentation, little research has investigated whether pathologic placental measures could serve as a risk factor for future CVD mortality in mothers. METHODS: Longitudinal study of 33,336 women from the Collaborative Perinatal Project (CPP; 1959-1966) linked to mortality information through December 2016. Pathologists took extensive morphological and histopathological measures. Apart from assessing associations with morphological features, we derived an overall composite score and specific inflammation-related, hemorrhage-related, and hypoxia-related pathologic placenta index scores. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for mortality adjusting for covariates. RESULTS: Thirty-nine percent of women died with mean (standard deviation, SD) time to death of 39 (12) years. Mean (SD) placental weight and birthweight were 436 g (98) and 3156 g (566), respectively. Placenta-to-birthweight ratio was associated with all-cause mortality (adjusted HR 1.03: 1.01, 1.05 per SD in ratio). In cause-specific analyses, it was significantly associated with respiratory (HR 1.06), dementia (HR: 1.10) and liver (HR 1.04) related deaths. CVD, cancer, diabetes and kidney related deaths also tended to increase, whereas infection related deaths did not (HR 0.94; 0.83, 1.06). Placental measures of thickness, diameters, and histopathological measures grouped by inflammatory, hemorrhagic, or hypoxic etiology were not associated with mortality. DISCUSSION: Placental weight in relation to birthweight was associated with long-term maternal mortality but other histopathologic or morphologic features were not.

Transcobalamin II receptor polymorphisms are associated with increased risk for neural tube defects.

OBJECTIVE: Women who have low cobalamin (vitamin B(12)) levels are at increased risk for having children with neural tube defects (NTDs). The transcobalamin II receptor (TCblR) mediates uptake of cobalamin into cells. Inherited variants in the TCblR gene as NTD risk factors were evaluated. METHODS: Case-control and family-based tests of association were used to screen common variation in TCblR as genetic risk factors for NTDs in a large Irish group. A confirmatory group of NTD triads was used to test positive findings. RESULTS: 2 tightly linked variants associated with NTDs in a recessive model were found: TCblR rs2336573 (G220R; p(corr)=0.0080, corrected for multiple hypothesis testing) and TCblR rs9426 (p(corr)=0.0279). These variants were also associated with NTDs in a family-based test before multiple test correction (log-linear analysis of a recessive model: rs2336573 (G220R; RR=6.59, p=0.0037) and rs9426 (RR=6.71, p=0.0035)). A copy number variant distal to TCblR and two previously unreported exonic insertion-deletion polymorphisms were described. CONCLUSIONS: TCblR rs2336573 (G220R) and TCblR rs9426 represent a significant risk factor in NTD cases in the Irish population. The homozygous risk genotype was not detected in nearly 1000 controls, indicating that this NTD risk factor may be of low frequency and high penetrance. 9 other variants are in perfect linkage disequilibrium with the associated single nucleotide polymorphisms. Additional work is required to identify the disease-causing variant. Our data suggest that variation in TCblR plays a role in NTD risk and that these variants may modulate cobalamin metabolism.

Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development.

The effects of DNA repair and transcription gene abnormalities in human pre-natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10(-6)) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (n = 24) with respect to abnormalities during their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (n = 18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Small for gestational age (SGA) <10th percentile [Relative risk (RR ) = 9.3, 95% CI = 1.4-60.5, p = 0.02], SGA <3rd percentile (RR = 7.2, 95% CI = 1.1-48.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.4-29.5, p = 0.02) occurred more frequently among TTD-affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD-affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.6-92.5, p = 0.0002), elevated mid-trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.0-16.6, p < 0.0001), SGA <3rd percentile (RR = 13.9, 95% CI = 7.4-21.1, p < 0.0001), pre-term delivery (<32 weeks) (RR = 12.0, 95% CI = 4.9-21.6, p < 0.0001), pre-eclampsia (RR = 4.0, 95% CI = 1.6-7.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.6-5.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development.

Testing for genetic association with constrained models using triads.

It has been shown that it is preferable to use a robust model that incorporated constraints on the genotype relative risk rather than rely on a model that assumes the disease operates in a recessive or dominant fashion. Previous methods are applicable to case-control studies, but not to family based studies of case children along with their parents (triads). We show here how to implement analogous constraints while analyzing triad data. The likelihood, conditional on the parents genotype, is maximized over the appropriately constrained parameter space. The asymptotic distribution for the maximized likelihood ratio statistic is found and used to estimate the null distribution of the test statistics. The properties of several methods of testing for association are compared by simulation. The constrained method provides higher power across a wide range of genetic models with little cost when compared to methods that restrict to a dominant, recessive, or multiplicative model, or make no modeling restriction. The methods are applied to two SNPs on the methylenetetrahydrofolate reductase (MTHFR) gene with neural tube defect (NTD) triads.

Degenerative aneurysms of the superficial femoral artery.

PURPOSE: To review the pathogenesis, diagnosis, presentation, diagnosis, management and outcomes (morbidity and mortality) of superficial femoral artery aneurysms. METHODS: A comprehensive review of this entity was performed based on the available literature in all languages and a detailed discussion of our findings is also provided. RESULTS: Our review identified 61 cases of SFA aneurysms. They were most often seen in elderly men, predominately affected the right lower extremity, and were most often located in the middle-third of the artery. At the time of diagnosis, SFA aneurysms were frequently symptomatic because they reached a relative large diameter before the diagnosis was made. The most frequent presentation was localized pain in association with a pulsatile mass. In contrast to popliteal aneurysms, SFA aneurysms more frequently present with rupture than distal ischemia. Angiography was by far the most commonly utilized diagnostic tool. Treatment was primarily by means of an interposition graft, followed by exclusion and surgical bypass. Endovascular repair of SFA aneurysms has only been reported in three instances. SFA aneurysm repair was most often associated with favorable outcomes, with low reported rates of ischemia and limb loss.

Aortic paraprosthetic-colonic fistulae: a review of the literature.

BACKGROUND: Aortic graft-colonic fistulae are a rare complication of aortic reconstructive surgery. METHODS AND FINDINGS: A comprehensive review of this entity was performed based on the available literature from 1950 until 2006. Available reports were analyzed with respect to demographics, prior surgical intervention and its indication, prosthetic material used during the initial intervention, clinical presentation, the time interval in between the initial operation and symptoms, the method of treatment of the aortic graft-colonic fistula and its outcome.

Smoking in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Health-related behaviors are of particular concern in survivors of childhood cancer as they are at increased risk for second cancers and long-term organ dysfunction. The purpose of this study was to compare the smoking behavior and associated factors in young-adult survivors of childhood acute lymphoblastic leukemia (ALL) with those in sibling controls. METHODS: A telephone interview that surveyed smoking behavior was conducted with 592 young-adult survivors, treated before age 20 years on Children's Cancer Group ALL protocols, and 409 sibling controls. Using stratified chi-squared analyses and Cox proportional hazards models, we compared the rates of smoking initiation and smoking cessation between survivors and control subjects. Demographic characteristics (age, sex, race, and education) and psychological factors (mood and self-concept) were examined as predictors interacting with survivorship in logistic regression analyses to try to distinguish a subgroup of survivors who may be at greater risk for smoking. RESULTS: Survivors were significantly less likely to have ever smoked (23.0% versus 35.7%; P<.0001) and thus were less likely to ever be regular, daily smokers than sibling controls (19.1% versus 31.3%; P<.0001). Survivors were less likely to quit smoking than sibling controls (26.6% versus 35.2%), although this result was not statistically significant. There were no interactions between survivor status and either demographic or psychological features on smoking behavior. CONCLUSIONS: Young-adult survivors of childhood ALL are less likely to experiment with smoking but, once having started, are at similar risk for becoming habitual, persistent smokers as sibling controls.

Genome-wide studies of von Willebrand factor propeptide identify loci contributing to variation in propeptide levels and von Willebrand factor clearance.

UNLABELLED: Essentials Variants at ABO, von Willebrand Factor (VWF) and 2q12 contribute to the variation in plasma in VWF. We performed a genome-wide association study of plasma VWF propeptide in 3,238 individuals. ABO, VWF and 2q12 loci had weak or no association or linkage with plasma VWFpp levels. VWF associated variants at ABO, VWF and 2q12 loci primarily affect VWF clearance rates. SUMMARY: Background Previous studies identified common variants at the ABO and VWF loci and unknown variants in a chromosome 2q12 linkage interval that contributed to the variation in plasma von Willebrand factor (VWF) levels. Whereas the association with ABO haplotypes can be explained by differential VWF clearance, little is known about the mechanisms underlying the association with VWF single-nucleotide polymorphisms (SNPs) or with variants in the chromosome 2 linkage interval. VWF propeptide (VWFpp) and mature VWF are encoded by the VWF gene and secreted at the same rate, but have different plasma half-lives. Therefore, comparison of VWFpp and VWF association signals can be used to assess whether the variants are primarily affecting synthesis/secretion or clearance. Methods We measured plasma VWFpp levels and performed genome-wide linkage and association studies in 3238 young and healthy individuals for whom VWF levels had been analyzed previously. Results and conclusions Common variants in an intergenic region on chromosome 7q11 were associated with VWFpp levels. We found that ABO serotype-specific SNPs were associated with VWFpp levels in the same direction as for VWF, but with a much lower effect size. Neither the association at VWF nor the linkage on chromosome 2 previously reported for VWF was observed for VWFpp. Taken together, these results suggest that the major genetic factors affecting plasma VWF levels, i.e. variants at ABO, VWF and a locus on chromosome 2, operate primarily through their effects on VWF clearance.

Comparison of psychologic outcome in adult survivors of childhood acute lymphoblastic leukemia versus sibling controls: a cooperative Children's Cancer Group and National Institutes of Health study.

PURPOSE: To determine psychologic outcome, with the focus on emotional or mood state, of young adult survivors of childhood acute lymphoblastic leukemia (ALL) compared with sibling controls and to identify vulnerable subgroups at highest risk for negative mood. PATIENTS AND METHODS: Adult survivors (n = 580), aged > or = 18 years, who were treated before age 20 years on Children's Cancer Group (CCG) protocols for ALL and 396 sibling controls were administered a structured telephone interview and the Profile of Moods State (POMS), a standardized measure of affective state. RESULTS: Survivors had higher total mood scores (which indicates greater negative mood) than sibling controls (P<.01) and reported more tension (P< .01), depression (P<.01), anger (P<.01), and confusion (P<.01), but not more fatigue or less vigor. Female, minority, and unemployed survivors reported the highest total mood disturbance. Overall, survivors were more likely to be unemployed (P<.05) or working less than half-time (P<.01) compared with controls. CONCLUSION: This large, sibling-controlled, multisite study of young adult survivors of childhood ALL treated on CCG protocols after 1970 found significant increased negative mood in survivors, not accounted for by reported energy level differences, which suggests that these emotional effects are not likely the result of current illness. Survivors are less likely to be fully employed. Female, minority, and unemployed survivors are at greatest risk for emotional sequelae, a finding that indicates the need for targeted, preventive intervention.

Malformations in infants of diabetic mothers occur before the seventh gestational week. Implications for treatment.

In the present study we used a developmental morphologic approach to fix the latest time in development at which the malformations commonly reported in infants of diabetic mothers could occur. Developmental morphologic dating shows that the significantly more common congenital malformations in infants of diabetic mothers occur before the seventh week of gestation. This suggests that any therapeutic intervention aimed at decreasing the incidence of congenital malformations must be instituted during the critical early period.

Effect of normoglycemia before conception on early pregnancy hormone profiles.

Insulin-dependent diabetic women have been shown to have subnormal hormone levels in the first trimester of pregnancy. To determine whether these abnormalities were the result of poor diabetes control, testosterone, androstenedione, human chorionic gonadotropin (HCG), and prolactin were studied longitudinally in diabetic women made normoglycemic before conception (N = 11) and normal (N = 6) control subjects beginning at the fifth week of gestation. HCG levels rose normally in all 11 diabetic and six control subjects and then declined as expected, with peak levels between 8 and 12 wk of gestation. Prolactin levels similarly rose significantly (P less than 0.00001) during the period studied. Plasma androstenedione did not increase during the course of this study, but testosterone levels increased significantly (P = 0.0001). Androgen levels were consistently higher in diabetic subjects despite the normoglycemic state, although the differences reached statistical significance at only one point. This study demonstrates that when normoglycemia is achieved before conception, HCG and prolactin are normal at 5 wk after the last menstrual period. The possibility that androgen levels may be higher in insulin-requiring diabetic women, perhaps due to peripheral hyperinsulinemia, should be explored.

Anti-insulin antibody titers do not influence control or insulin requirements in early pregnancy.

IgG antibodies (AB) to insulin have been reported to influence insulin requirements and control in patients who have taken insulin for prolonged periods of time. Nineteen pregnant type I diabetic patients (C-peptide less than 0.03 pmol/ml) were studied in their fifth week of gestation after the establishment of normoglycemia. Mean age was 27.5 yr and duration of diabetes, 14.2 yr (range: 1-23 yr). IgG AB to beef and pork insulin were measured. IgG AB to insulin were encountered in all diabetic patients (range: 103-6736 microU/ml). None of the nondiabetic pregnant controls in their fifth week of gestation (N = 17) had detectable (greater than 50 microU/ml) AB levels. The antibody titer did not affect the insulin requirement (P greater than 0.2, NS) or ability to achieve normoglycemia. AB levels were correlated with years of treatment with conventional insulin preparations (r = 0.73; P less than 0.001). At 5 wk postmenstruation the mean AB level in the patients with less than 10 yr duration of diabetes (N = 7) was 727 microU/ml and mean insulin requirement was 0.7 U/kg/24 h. In the group of patients with greater than 10 yr duration of diabetes (N = 12) the mean antibody titer was 3716 microU/ml and the insulin requirement was also 0.7 U/kg/24 h. IgG AB to insulin increase with increasing duration of treatment with beef/pork insulin. IgG AB do not affect the insulin requirement or the ability to achieve normoglycemia during early pregnancy.