Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos's along-track orbital velocity component of 2.70 ± 0.10 mm s-1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m-3, we find that the expected value of the momentum enhancement factor, ß, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m-3, [Formula: see text]. These ß values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

You-Me-Us: Results of a Cluster Randomized Trial of a Healthy Relationships Approach to Sexual Risk Reduction.

By middle adolescence, most young people have been involved in at least one romantic relationship, a context in which many sexual interactions occur. Indeed, researchers have suggested the importance of attending to relationships in programs focused on sexual risk, yet few evidence-based programs have a strong relationships focus. Our study examined the impact of a healthy relationship program called You-Me-Us that included a classroom curriculum and a school-wide peer norms approach. We evaluated the intervention using a small group randomized trial that included nine participating urban middle schools (defined as schools that include grades 6-8) in three urban school districts. We invited all 7th grade students within the study schools to enroll. Students completed three surveys during 7th and 8th grades (baseline plus two follow up surveys at 6 and 18 months following baseline). A total of 911 youth with positive consent and assent were enrolled in the study. Follow up survey response rates among those taking the baseline were 92% at 6 months and 80% at 18 months. Multilevel regression models were used to adjust for the correlation among students within the same school, and the correlation of repeated measurements taken on the same student over time. The intervention reduced vaginal sexual initiation by about half at the 6-month follow-up, and this approached significance. Further, youth in the intervention condition were less likely to believe it is okay for people their age to have vaginal sex without using condoms if the girl is on birth control. None of the remaining variables differed significantly by intervention condition. This study provides insights on using a healthy relationship approach for younger urban adolescents. This approach produced a programmatically significant reduction in sexual initiation that did not reach standard levels of statistical significance, and warrants further exploration.

The effect of synthetic method and annealing temperature on metal site preference in Al(1-x)Ga(x)FeO3.

Magnetoelectric materials couple both magnetic and electronic properties, making them attractive for use in multifunctional devices. The magnetoelectric AFeO3 compounds (Pna2(1); A = Al, Ga) have received attention as the properties of the system depend on composition as well as the synthetic method used. Al(1-x)Ga(x)FeO3. (0 ≤ x ≤ 1) was synthesized by the sol-gel and coprecipitation methods and studied by X-ray absorption near-edge spectroscopy (XANES). Al L(2,3-), Ga K-, and Fe K-edge XANES spectra were collected to examine how the average metal coordination number (CN) changes with the synthetic method. Al and Fe were found to prefer octahedral sites, while Ga prefers the tetrahedral site. It was found that composition played a larger role in determining site occupancies than synthetic method. Samples made by the sol-gel or ceramic methods (reported previously; Walker, J. D. S.; Grosvenor, A. P. J. Solid State Chem. 2013, 197, 147-153) showed smaller spectral changes than samples made via the coprecipitation method. This is attributed to greater ion mobility in samples synthesized via coprecipitation as the reactants do not have a long-range polymeric or oxide network during synthesis like samples synthesized via the sol-gel or ceramic method. Increasing annealing temperature increases the average coordination number of Al, and to a lesser extent Ga, while the average coordination number of Fe decreases. This study indicates that greater disorder is observed when the Al(1-x)Ga(x)FeO3. compounds have high Al content, and when annealed at higher temperatures.

Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial.

BACKGROUND: Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes. METHODS: We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (alpha-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045. FINDINGS: Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0.81, 95% CI 0.59-1.12). No adverse maternal or neonatal outcomes were reported. INTERPRETATION: Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing. FUNDING: The Wellcome Trust.

Tumor characteristics of Mohs surgery patients in Ottawa, Canada versus Houston, Texas--a consequence of access to care?

BACKGROUND: Ontario is one of the most underserved provinces in Canada for providing Mohs micrographic surgery (MMS). A new MMS clinic was opened in Ottawa, Ontario, in June 2009 to help combat the increasing incidence of nonmelanoma skin cancer (NMSC) in this region. OBJECTIVE: To prospectively compare MMS cases completed in Ottawa with cases completed in Houston, Texas, and examine the differences in tumor characteristics. MATERIALS AND METHODS: The first 150 cases performed in Ottawa were prospectively compared with 150 consecutive cases performed at a Mohs surgery clinic in Houston, Texas. Patient demographics, tumor diagnosis, primary or recurrent disease, tumor dimension, number of surgical stages, defect size, complexity of the procedure, and closure method were compared. RESULTS: The average preoperative tumor area was three times as great in Ottawa as in Houston. Almost one entire additional stage was required to clear the tumors treated in Ottawa. Postoperative defects were 87% larger in Ottawa. The number of advanced reconstructive repairs was significantly higher in Ottawa (93%) than Houston (14%). CONCLUSIONS: A significantly higher NMSC disease burden and greater surgical complexity was observed in the tumors treated in Ottawa than in Houston.

Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women With Type 1 Diabetes.

OBJECTIVE: To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks' gestation, respectively). RESULTS: FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6-21.4] vs. 12.7 ng/mL [interquartile range 9.6-17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6-25.8] vs. 14.6 ng/mL [interquartile range 10.8-19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24-6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. CONCLUSIONS: Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes.

Microalbuminuria and mortality in long-duration type 1 diabetes.

OBJECTIVE: Microalbuminuria is a recognized risk factor for increased mortality and renal failure in type 1 diabetes. Whether it remains a powerful predictor in patients with a long duration of type 1 diabetes is not known. We ascertained the prognostic significance of abnormal urinary albumin excretion in a cohort of patients with at least 30 years of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 190 patients with a disease duration of type 1 diabetes of at least 30 years with baseline and 5 years of follow-up. RESULTS: At baseline 66% were normoalbuminuric, and at 5 years 11% of this cohort had died. Of the 22% who were microalbuminuric at baseline, 26% had died, and of the 8% with persistent proteinuria at baseline, 44% had died. Of the 4% with end-stage renal failure at baseline, 71% had died within 5 years. Death was attributable to a cardiovascular cause in two-thirds of the cases in all groups. CONCLUSIONS: Even in those with a long duration of type 1 diabetes, the presence of abnormal urinary excretion remains a powerful predictor of increased mortality.

Adiponectin is present in cord blood but is unrelated to birth weight.

OBJECTIVE: In adults, adiponectin is reduced in association with excess adiposity, type 2 diabetes, and hyperinsulinemia. We assessed whether adiponectin was 1) present in the fetal circulation, 2) altered in the fetal circulation in the presence of maternal diabetes, and 3) had relations to fetal cord blood insulin or adiposity. RESEARCH DESIGN AND METHODS: We assessed adiponectin in cord blood in a large cohort of singleton offspring of diabetic mothers (ODM; n = 134) and control mothers (n = 45). RESULTS: Adiponectin was present in cord blood and, in ODM, was higher in those delivered at later gestational ages (Spearman r = 0.18, P = 0.03). Adiponectin was slightly lower in ODM than control subjects (ODM 19.7 +/- 6.1 vs. control 21.8 +/- 5.3 micro g/ml; P = 0.04), although this difference could potentially reflect different gestational ages in the two groups (ODM 37.6 +/- 1.5 and control 40.1 +/- 1.1 weeks). In contrast to adults, adiponectin levels in the fetus were unrelated to the degree of adiposity, blood insulin, or leptin in either control subjects or ODM. CONCLUSIONS: Adiponectin is present in cord blood but does not show expected physiological relations with adiposity as observed in adults.

Glycemic targets in the second and third trimester of pregnancy for women with type 1 diabetes.

OBJECTIVE: To assess the relationship between second and third trimester glycemic control and adverse outcomes in pregnant women with type 1 diabetes, as uncertainty exists about optimum glycemic targets. RESEARCH DESIGN AND METHODS: Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26 and 34 weeks' gestation were categorized into five groups, the lowest, <6.0% (42 mmol/mol), being the reference. Average pre- and postprandial results from an eight-point capillary glucose profile the previous day were categorized into five groups, the lowest (preprandial <5.0 mmol/L and postprandial <6.0 mmol/L) being the reference. RESULTS: An A1C of 6.0-6.4% (42-47 mmol/mol) at 26 weeks' gestation was associated with a significantly increased risk of large for gestational age (LGA) (odds ratio 1.7 [95% CI 1.0-3.0]) and an A1C of 6.5-6.9% (48-52 mmol/mol) with a significantly increased risk of preterm delivery (odds ratio 2.5 [95% CI 1.3-4.8]), pre-eclampsia (4.3 [1.7-10.8]), need for a neonatal glucose infusion (2.9 [1.5-5.6]), and a composite adverse outcome (3.2 [1.3-8.0]). These risks increased progressively with increasing A1C. Results were similar at 34 weeks' gestation. Glucose data showed less consistent trends, although the risk of a composite adverse outcome increased with preprandial glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3-8.0]). CONCLUSIONS: LGA increased significantly with an A1C ≥6.0 (42 mmol/mol) at 26 and 34 weeks' gestation and with other adverse outcomes with an A1C ≥6.5% (48 mmol/mol). The data suggest that there is clinical utility in regular measurement of A1C during pregnancy.

Severe hypercalcaemia secondary to isolated adrenocorticotrophic hormone deficiency and subacute thyroiditis.

Severe hypercalcaemia is usually due to either neoplastic disease or primary hyperparathyroidism. Rarer causes do exist, and exceptionally these may occur concomitantly. We describe the case of a 45-year-old man who presented in a debilitated state with severe hypercalcaemia (total serum calcium 3.56 mmol/L, albumin 35 g/L) and suppressed serum parathyroid hormone concentration. It was initially suspected that he had neoplastic disease, but routine thyroid function tests demonstrated evidence of thyrotoxicosis [thyroid-stimulating hormone <0.05 mU/L (0.15-3.5); free thyroxine 75 pmol/L (8-27); total tri-iodothyronine 7.0 nmol/L (1.0-2.6)], which was probably secondary to a silent or subacute thyroiditis. After extensive investigation, it was established that the patient also had isolated adrenocorticotrophic hormone deficiency, presumably secondary to lymphocytic hypophysitis. Glucocorticoid therapy resulted in a dramatic improvement in the patient's clinical state and 1 year later he remained euthyroid and normocalcaemic.

The role of angiogenic and antiangiogenic factors in the second trimester in the prediction of preeclampsia in pregnant women with type 1 diabetes.

OBJECTIVE: To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial. RESULTS: Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120-423] vs. 365 pg/mL [237-582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108-3,393] vs. 1,193 pg/mL [844-1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9-7.9] vs. 5.1 ng/mL[(4.3-6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17-71] vs. 71 [44-114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4-15.7] vs. 3.1 [1.8-5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001). CONCLUSIONS: These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.

Panhypopituitarism secondary to a macroprolactinoma manifesting with pancytopenia: case report and literature review.

OBJECTIVE: To present a case of pancytopenia associated with hypopituitarism secondary to a macroprolactinoma. METHODS: We report the clinical features on presentation and results of laboratory investigation. Findings on magnetic resonance imaging are illustrated. The response to hormone replacement therapy is summarized. RESULTS: A 46-year-old man was referred with pancytopenia and secondary hypothyroidism. Laboratory investigation revealed hypopituitarism and a substantially increased prolactin level. Magnetic resonance imaging of the head demonstrated a macroprolactinoma. Hematologic investigation disclosed no other cause for the pancytopenia. Hormone replacement therapy was initiated with hydrocortisone, levothyroxine, and testosterone. Cabergoline was used to induce regression of the prolactinoma. A rapid improvement was seen in the cytopenias, with normalization of the blood cell counts after 8 months of treatment. This result has been sustained during 29 months of follow-up. CONCLUSION: Pancytopenia associated with hypopituitarism has been reported in the literature as a rare occurrence limited to isolated case reports, predominantly associated with Sheehan syndrome. To our knowledge, this is the first reported case of pancytopenia associated with a macroprolactinoma. This finding is noteworthy because prolactin alone has been reported to support hematopoiesis in animal studies.

Paintball trauma and mechanisms of optic nerve injury: rotational avulsion and rebound evulsion.

PURPOSE: Ballistic impact studies and supercomputer modeling were performed to elicit the mechanisms of optic nerve rupture that may accompany blunt ocular trauma. METHODS: Paintball ocular impact responses were studied with abattoir-fresh porcine eyes. Physics-based numerical code CTH was used to produce robust geometric and constitutive models of the eye and orbit, providing a comparative 3-D finite volume model to help determine the mechanisms underlying empirical ballistic observations. RESULTS: Among 59 porcine eye specimens submitted to paintball impact in the 1- to 13-J range, 10 (17%) disengaged completely from the orbital mount. In each instance the paintball penetrated the orbit adjacent to the globe, producing rotation and eventual globe repulsion, dramatically evident on high-speed film images. Supercomputer modeling yielded similar globe-expulsive results when orbital constraints were in place, but not when these were removed. In these models, tangential (grazing) impact sheared the nerve flush with the globe via a strain rate effect within 260 µs, with minimal posterior displacement and just 5° of globe rotation. Midperipheral impact produced compressive globe distortion and posterior displacement, followed by rebound and tractional nerve avulsion 10 mm behind the lamina after 700 µs and 20° of globe rotation. CONCLUSIONS: Constitutive modeling studies suggest at least two trajectory-dependent mechanisms for optic nerve rupture with paintball impact on the eye. Tangential glancing blows produce strain-rate rotational avulsion, abscising the optic nerve with minimal internal globe disruption, whereas off-center direct impact produces slower rotational-rebound evulsion, traumatizing the globe and breaching the nerve posteriorly. The latter mechanism would be expected to arise more commonly and would most likely be clinically masked by accompanying intraocular injury.

Blunt eye trauma: empirical histopathologic paintball impact thresholds in fresh mounted porcine eyes.

PURPOSE: Ballistic studies were conducted using gelatin-embedded abattoir-fresh porcine eyes suspended within clear acrylic orbits to discern the energy required to produce specific ocular injuries. Paintball impact provides a robust ballistic model for isolating and quantifying the role of direct blunt force in ocular trauma. METHODS: Fifty-nine porcine orbital preparations received direct blows from 0.68 caliber (16-18 mm diameter/3.8 g) paintballs fired at impact velocities ranging from 26 to 97 meters per second (2-13.5 J). Five additional eyes not subjected to ballistic impact were also evaluated as controls. Impact energies were correlated with histopathologic damage. RESULTS: Minimum impact energies consistently producing damage in experimental eyes unobserved in control specimens were: 2 joules--posterior lens dislocation, zonulysis, capsular rupture, and choroidal detachment; 3.5 joules--moderate angle recession; 4 joules--anterior lens dislocation; 4.8 joules--peripapillary retinal detachment; 7 joules--severe angle recession, iridodialysis, and cyclodialysis; 7.5 joules--corneal stromal distraction; 9.3 joules--choroidal segmentation; and 10 joules--globe rupture. CONCLUSIONS: Impact thresholds correlating traumatic ocular pathology with impact energy followed a positive stepwise progression in severity with impact energies between 2 and 10 joules. Moderate angle recession commensurate with typical clinical traumatic glaucoma was not observed among control eyes, but occurred at relatively low impact energy of 3.5 joules among test eyes. Extensive disruption in and around the angle (iridodialysis/cyclodialysis) consistently occurred at energies >7 joules. Globe rupture required a minimum energy of 10 joules.

Numerical modeling of paintball impact ocular trauma: identification of progressive injury mechanisms.

PURPOSE: To create a computer-based numerical simulation model for comparison with empiric paintball-ocular ballistic study findings, allowing identification of the dynamic physical mechanisms (stress, strain, pressure) responsible for intraocular traumatic injury accompanying blunt ocular impact. Virtual experiments with numerical models could exploit mathematical "instrumentation" to facilitate internal observation impossible with physical experiments alone. METHODS: Models of human eye structures and orbit were implemented into the finite-volume Eulerian numerical hydrocode CTH. Numerical simulation results were compared with dynamic imaging and postimpact histopathology obtained during previous ballistic impact experiments on fresh porcine eyes impacted with paintballs. Forty numerical simulations and 59 impact experiments were conducted as part of the study. RESULTS: Time-lapse correlations showed the CTH models to be dynamically commensurate with orbital penetration and globe deformation measured from ballistic high-speed videos. CTH also predicted the types and levels of damage observed in detailed postimpact pathologic assessments of porcine specimens. High strain in the ciliary body and zonule corresponded with angle recession and lens displacement pathologically. Globe rupture was attained at the highest paintball impact velocities in both the porcine ballistic studies and CTH models, consistent with predicted dynamic intraocular pressures. The simulations also revealed that phenomena such as macular Berlin's edema, midperipheral retinoschisis, and choroidal and retinal detachment might be explained by focal dynamic pressure-wave reflection from the interior surface of the globe. CONCLUSIONS: Significant insight was gained regarding the physical mechanisms responsible for injury. CTH predictions corresponded closely with previous ballistic experimental results, adding intraocular detail otherwise unattainable.

Optimal glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes in the diabetes and pre-eclampsia intervention trial.

OBJECTIVE: To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA(1c) (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks' gestation (n = 592), and at 34 weeks' gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1-6.9%), moderate (7.0-7.9%), and poor (≥8.0%) glycemic control, respectively. RESULTS: Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C ≥ 8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17-11.6]) compared with optimal control. At 26 weeks' gestation, A1C values ≥ 6.1% (good: 2.09 [1.03-4.21]; moderate: 3.20 [1.47-7.00]; and poor: 3.81 [1.30-11.1]) and at 34 weeks' gestation A1C values ≥ 7.0% (moderate: 3.27 [1.31-8.20] and poor: 8.01 [2.04-31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks' gestation, and at 34 weeks' gestation were 0.88 (0.75-1.03), 0.75 (0.64-0.88), 0.57 (0.42-0.78), and 0.47 (0.31-0.70), respectively. Glycemic control was not significantly associated with gestational hypertension. CONCLUSIONS: Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.

Programming of adiposity in offspring of mothers with type 1 diabetes at age 7 years.

OBJECTIVE: The goals of this study were to examine the influence of maternal type 1 diabetes during pregnancy on offspring adiposity and glucose tolerance at age 7 years and to assess whether metabolic factors at birth (neonatal leptin and insulin) predict adverse outcomes. RESEARCH DESIGN AND METHODS: We examined 100 offspring of mothers with type 1 diabetes (OT1DM) and 45 offspring of control mothers. Mothers had previously been recruited during pregnancy, and, where possible, birth weight, umbilical cord insulin, and leptin were measured. Children were classed as overweight and obese using age-specific reference ranges. RESULTS: OT1DM had similar height (control, 1.25 +/- 0. 06 m; OT1DM, 1.24 +/- 0.06 m; P = 0.81) but were heavier (control, 25.5 +/- 3.8 kg; OT1DM, 27.1 +/- 5.7 kg; P = 0.048) and had an increased BMI (control, 16.4 kg/m(2); OT1DM, 17.4 +/- 2.6 kg/m(2), P = 0.005). Waist circumference (control, 56.0 +/- 3.7 cm; OT1DM, 58 +/- 6.8 cm; P = 0.02) and sum of skinfolds were increased (control, 37.5 +/- 17.0 mm [n = 42]; OT1DM, 46.1 +/- 24.2 mm [n = 91]; P = 0.02), and there was a marked increase in the prevalence of overweight and obese children (OT1DM, 22% overweight and 12% obese; control, 0% overweight and 7% obese; chi(2) P = 0.001). Glucose tolerance was not different compared with that in control subjects. BMI at age 7 years correlated with cord leptin (OT1DM, r = 0.25; n = 61, P = 0.047), weakly with adjusted birth weight (r = 0.19; P = 0.06) and hematocrit (r = 0.25; n = 50, P = 0.07), but not cord insulin (OT1DM, r = -0.08; P = 0.54). CONCLUSIONS: OT1DM are at increased risk of overweight and obesity in childhood. This risk appears to relate, in part, to fetal leptin and hematocrit but not insulin.

Inflammation and endothelial activation is evident at birth in offspring of mothers with type 1 diabetes.

OBJECTIVE: Offspring of mothers with diabetes are at risk of obesity and glucose intolerance in later life. In adults, markers of subclinical inflammation (C-reactive protein [CRP] and interleukin [IL]-6) and endothelial activation (intracellular adhesion molecule [ICAM]-1) are associated with obesity and higher risk for incident type 2 diabetes. We examined whether these biomarkers were elevated at birth in offspring of type 1 diabetic mothers (OT1DM). RESEARCH DESIGN AND METHODS: Umbilical cord plasma CRP, IL-6, and ICAM-1 were measured in 139 OT1DM and 48 control offspring, with analysis relative to fetal lipids and hormonal axes. RESULTS: OT1DM had higher median (interquartile range) CRP (OT1DM 0.17 mg/l [0.13-0.22] vs. control subjects 0.14 mg/l [0.12-0.17], P < 0.001) and ICAM-1 (OT1DM 180 ng/ml [151-202] vs. control subjects 166 ng/ml [145-187], P = 0.047). IL-6 was not different after necessary adjustment for mode of delivery. Birth weight was unrelated to inflammatory indexes; however, leptin was correlated with CRP (control subjects r = 0.33, P = 0.02; OT1DM r = 0.41, P < 0.001) and with IL-6 (r = 0.23, P < 0.01) and ICAM-1 (r = 0.29, P < 0.001) in OT1DM. In OT1DM, CRP correlated with maternal glycemic control (A1C at 35-40 weeks; r = 0.28, P = 0.01). In multivariate analysis, leptin was a determinant of CRP (P < 0.001), ICAM-1 (P = 0.003), and IL-6 (P = 0.02) in OT1DM. Inflammatory measures demonstrated positive relationships with triglycerides in OT1DM (CRP, IL-6, and ICAM-1 P < 0.05) and control subjects (ICAM-1 P = 0.001). CONCLUSIONS: Inflammatory markers are increased in OT1DM and are related to measures of fetal adiposity, particularly leptin, and maternal glycemia. Subclinical inflammation is a novel component of the diabetic intrauterine environment and should be considered a potential etiological mechanism for in utero programming of disease.