No abstract

In this large clinical cohort, GDM was not associated with, but maternal pre-pregnancy obesity or overweight and EGWG were independently associated with an increased risk, and breastfeeding ≥6 months was associated with a decreased risk of childhood overweight at age 2 years.

OBJECTIVETo examine the relative importance of maternal preexisting type 1 diabetes (T1D), preexisting type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) on risk of attention deficit/hyperactivity disorder (ADHD) in offspring. RESEARCH DESIGN AND METHODSThis retrospective birth cohort study included 333,182 singletons born in 1995-2012 within Kaiser Permanente Southern California hospitals. Children were prospectively followed through electronic medical records from age 4 years. Relative risks of ADHD associated with diabetes exposures in utero were estimated by hazard ratios (HRs) using Cox regression with adjustment for potential confounders. For GDM, timing of exposure was evaluated by gestational age at diagnosis and severity was assessed by the need for antidiabetes medication treatment during pregnancy. RESULTSA total of 37,878 (11.4%) children were exposed to diabetes (522 exposed to T1D, 7,822 T2D, and 29,534 GDM). During a median of 4.9 years (interquartile range 2.2, 9.6) of follow-up after age 4 years, 17,415 (5.2%) children were diagnosed with ADHD. ADHD risk was not associated with GDM taken as a whole (P = 0.50) or with gestational age at GDM diagnosis (P = 0.16). However, the risk was significantly greater for the GDM requiring versus not requiring antidiabetes medications (P < 0.001). Compared with children unexposed to diabetes, the adjusted HRs for ADHD in children were 1.57 (95% CI 1.09-2.25) for exposure to T1D, 1.43 (1.29-1.60) for T2D, 1.26 (1.14-1.41) for GDM requiring antidiabetes medications, and 0.93 (0.86-1.01) for GDM not requiring medications. CONCLUSIONSThe hierarchy of risks suggests that severity of maternal diabetes (T1D vs. T2D vs. GDM requiring antidiabetes medications) influences the risk of ADHD in offspring of mothers with diabetes.

Maternal preexisting type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) diagnosed by 26 weeks' gestation have been associated with increased risk of autism spectrum disorder (ASD) in offspring. 1 However, little is known about ASD risk associated with maternal preexisting type 1 diabetes (T1D). We extend previous observations by examining the risk of ASD in offspring associated with maternal T1D, T2D, and GDM. Methods | This retrospective cohort study included singleton children born at 28 to 44 weeks' gestation in Kaiser Permanente Southern California (KPSC) hospitals from January 1, 1995, through December 31, 2012. Children were tracked through electronic health records from age 1 year until the first date of the following: clinical diagnosis of ASD, last date of continuous KPSC membership, death, or study end date (December 31, 2017). The KPSC institutional review board approved this study and provided waiver of participant consent. Methods to identify ASD, T2D, and GDM exposure were described previously. 1 GDM exposure was divided into diagnosis by or after 26 weeks' gestation based on a prior finding that risk of ASD was elevated for exposure to GDM by 26 weeks. 1 T1D was identified using the algorithm developed for electronic health records data 2 and confirmed by prescription of insulin during pregnancy. Potential confounders were

In the absence of evidence-based guidelines for high blood pressure screening in asymptomatic youth, a reasonable strategy is to screen those who are at high risk. The present study aimed to identify optimal body mass index (BMI) thresholds as a marker for high-risk youth to predict hypertension prevalence. In a cross-sectional study, youth aged 6 to 17 years (n=237,248) enrolled in an integrated prepaid health plan in 2007 to 2009 were classified according to their BMI and hypertension status. In moderately and extremely obese youth, the prevalence of hypertension was 3.8% and 9.2%, respectively, compared with 0.9% in normal weight youth. The adjusted prevalence ratios (95% confidence intervals) of hypertension for normal weight, overweight, moderate obesity, and extreme obesity were 1.00 (Reference), 2.27 (2.08–2.47), 4.43 (4.10–4.79), and 10.76 (9.99–11.59), respectively. The prevalence of hypertension was best predicted by a BMI-for-age ≥94th percentile. These results suggest that all obese youth should be screened for hypertension.

No abstract

Retinoid signaling is important for patterning the vertebrate hindbrain and midaxial regions. We recently showed that signaling through retinoic acid receptors (RARs) is essential for anteroposterior patterning along the entire body axis. To further investigate the mechanisms through which RARs act, we used microarray analysis to investigate the effects of modulating RAR activity on target gene expression. We identified 334 up-regulated genes (92% of which were validated), including known RA-responsive genes, known genes that have never been proposed as RA targets and many hypothetical and unidentified genes (n ‫؍‬ 166). Sixty-seven validated down-regulated genes were identified, including known RA-responsive genes and anterior marker genes. The expression patterns of selected up-regulated genes (n ‫؍‬ 45) were examined at neurula stages using whole-mount in situ hybridization. We found that most of these genes were expressed in the neural tube and many were expressed in anterior tissues such as neural crest, brain, eye anlagen, and cement gland. Some were expressed in tissues such as notochord, somites, pronephros, and blood islands, where retinoic acid (RA) plays established roles in organogenesis. Members of this set of newly identified RAR target genes are likely to play important roles in neural patterning and organogenesis under the control of RAR signaling pathways, and their further characterization will expand our understanding of RA signaling during development. Developmental Dynamics 232:414 -431, 2005.

OBJECTIVEType 2 diabetes (T2D) results from progressive loss of b-cell function. The BetaFat study compared gastric banding and metformin for their impact on b-cell function in adults with moderate obesity and impaired glucose tolerance (IGT) or recently diagnosed, mild T2D. RESEARCH DESIGN AND METHODSEighty-eight people aged 21-65 years, BMI 30-40 kg/m 2 , with IGT or diabetes known for <1 year, were randomized to gastric banding or metformin for 2 years. Hyperglycemic clamps (11.1 mmol/L) followed by arginine injection at maximally potentiating glycemia (>25 mmol/L) were performed at baseline, 12 months, and 24 months to measure steady-state C-peptide (SSCP) and acute C-peptide response to arginine at maximum glycemic potentiation (ACPRmax) and insulin sensitivity (M/I). RESULTSAt 24 months, the band group lost 10.7 kg; the metformin group lost 1.7 kg (P < 0.01). Insulin sensitivity increased 45% in the band group and 25% in the metformin group (P = 0.30 between groups). SSCP adjusted for insulin sensitivity fell slightly but not significantly in each group (P = 0.34 between groups). ACPRmax adjusted for insulin sensitivity fell significantly in the metformin group (P = 0.002) but not in the band group (P = 0.25 between groups). HbA 1c fell at 12 and 24 months in the band group (P < 0.004) but only at 12 months (P < 0.01) in the metformin group (P > 0.14 between groups). Normoglycemia was present in 22% and 15% of band and metformin groups, respectively, at 24 months (P = 0.66 between groups). CONCLUSIONSGastric banding and metformin had similar effects to preserve b-cell function and stabilize or improve glycemia over a 2-year period in moderately obese adults with IGT or recently diagnosed, mild T2D.Type 2 diabetes (T2D) generally results from a progressive loss of b-cell compensation for chronic insulin resistance, an important measure of b-cell function. There is very strong cross-sectional (1) and longitudinal (2-4) evidence that b-cell compensation declines for years before the development of diabetes, often reaching ,50% of normal in people with impaired glucose tolerance (IGT) or early diabetes. This