Substance Use Disorder in Pregnancy: Improving Care and Reducing Risk in Franklin County with EMPOWER

As part of the mini-symposium entitled Pregnant and Parenting Mothers with History of Opiate Addiction, this presentation describes Project EMPOWER, an innovative hospital-based intervention to improve management of neonatal abstinence syndrome through the use of rooming-in and access to a designated psychotherapist

EMPOWER: A Community-Based Approach to Improve Care for Women and Newborns Affected by Perinatal Substance Use Disorder

New England has the second highest rate of prenatal opioid exposure in the country. This population of women and children is particularly vulnerable and requires a comprehensive, multidisciplinary approach in order to overcome barriers to care and support good outcomes. This webinar will describe how one rural community collaborated to create a screening, referral and support program called EMPOWER (Engaging Mothers for Positive Outcomes with Early Referrals). Learn how this innovative approach helps support women and improve outcomes by identifying and addressing barriers to care for patients, health care providers and their community. Learning Objectives Participants will: Recognize how prenatal opioid exposure affects the health and wellness of women and their newborns. Identify effective strategies to address barriers to care for women and newborns affected by Perinatal Substance Use Disorder and Neonatal Abstinence Syndrome. Understand the benefits of utilizing a comprehensive, community-based approach to improve outcomes

EMPOWER: A Community-Based Approach to Improve Care for Women and Newborns Affected by Perinatal Substance Use Disorder

New England has the second highest rate of prenatal opioid exposure in the country. This population of women and children is particularly vulnerable and requires a comprehensive, multidisciplinary approach in order to overcome barriers to care and support good outcomes. This webinar will describe how one rural community collaborated to create a screening, referral and support program called EMPOWER (Engaging Mothers for Positive Outcomes with Early Referrals). Learn how this innovative approach helps support women and improve outcomes by identifying and addressing barriers to care for patients, health care providers and their community. Learning Objectives Participants will: Recognize how prenatal opioid exposure affects the health and wellness of women and their newborns. Identify effective strategies to address barriers to care for women and newborns affected by Perinatal Substance Use Disorder and Neonatal Abstinence Syndrome. Understand the benefits of utilizing a comprehensive, community-based approach to improve outcomes

Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program

OBJECTIVE: We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss–inducing interventions (lifestyle and metformin) versus placebo. RESEARCH DESIGN AND METHODS: Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end). RESULTS: Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (−0.63 and −0.93 kg/allele, P ≤ 0.005, respectively). Gene–treatment interactions were observed for short-term (LYPLAL1 rs2605100, P$_{lifestyle*SNP}$ = 0.032; GNPDA2 rs10938397, P$_{lifestyle*SNP}$ = 0.016; MTCH2 rs10838738, P$_{lifestyle*SNP}$ = 0.022) and long-term (NEGR1 rs2815752, P$_{metformin*SNP}$ = 0.028; FTO rs9939609, P$_{lifestyle*SNP}$ = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P$_{lifestyle*SNP}$ < 0.05). CONCLUSIONS: Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention

Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: The Diabetes Prevention Program

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss

TCF7L2 Polymorphism, Weight Loss and Proinsulin∶Insulin Ratio in the Diabetes Prevention Program

Aims: TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses. Methods: We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults. Results: We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P, 0.001), higher baseline proinsulin: insulin ratio (p<0.0001) and increased proinsulin: insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms. Conclusions: The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin: insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production

Plasma Dynamics

Contains table of contents for Section 2 and reports on four research projects.Lawrence Livermore National Laboratory Subcontract 6264005National Science Foundation Grant ECS 84-13173National Science Foundation Grant ECS 85-14517U.S. Air Force - Office of Scientific Research Contract AFOSR 89-0082-AU.S. Army - Harry Diamond Laboratories Contract DAAL02-86-C-0050U.S. Navy - Office of Naval Research Contract N00014-87-K-2001Lawrence Livermore National Laboratory Subcontract B108472National Science Foundation Grant ECS 88-22475U.S. Department of Energy Contract DE-FG02-91-ER-54109National Aeronautics and Space Administration Grant NAGW-2048U.S. Department of Energy Contract DE-AC02-ET-51013U.S. Department of Energy Contract DE-AC02-78-ET-5101

Variation in the Glucose Transporter gene <i>SLC2A2 </i>is associated with glycaemic response to metformin

Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear1. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10−14) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine

Plasma Dynamics

Contains table of contents for Section 2 and reports on four research projects.Lawrence Livermore National Laboratory Subcontract 6264005National Science Foundation Grant ECS 84-13173National Science Foundation Grant ECS 85-14517U.S. Air Force - Office of Scientific Research Contract AFOSR 84-0026U.S. Army - Harry Diamond Laboratories Contract DAAL02-86-C-0050U.S. Navy - Office of Naval Research Contract N00014-87-K-2001National Science Foundation Grant ECS 85-15032National Science Foundation Grant ECS 88-22475U.S. Department of Energy Contract DE-AC02-ET-5101