Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). • Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. • Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis.

Objective: To determine whether prenatal cannabis use alone increases the likelihood of fetal and neonatal morbidity and mortality. Study Design: We searched bibliographic databases, such as PubMed, Embase, Scopus, Cochrane reviews, PsycInfo, MEDLINE, Clinicaltrials.gov, and Google Scholar from inception through February 14, 2022. Cohort or case-control studies with prespecified fetal or neonatal outcomes in pregnancies with prenatal cannabis use. Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small-for-gestational-age (SGA), birthweight (grams), and perinatal mortality. Two independent reviewers screened studies. Studies were extracted by one reviewer and confirmed by a second using a predefined template. Risk of bias assessment of studies, using the Newcastle-Ottawa Quality Assessment Scale, and Grading of Recommendations Assessment, Development, and Evaluation for evaluating the certainty of evidence for select outcomes were performed by two independent reviewers with disagreements resolved by a third. Random effects meta-analyses were conducted, using adjusted and unadjusted effect estimates, to compare groups according to prenatal exposure to cannabis use status. Results: Fifty-three studies were included. Except for birthweight, unadjusted and adjusted meta-analyses had similar results. We found very-low- to low-certainty evidence that cannabis use during pregnancy was significantly associated with greater odds of PTB (adjusted odds ratio [aOR], 1.42; 95% confidence interval [CI], 1.19 to 1.69; I2, 93%; p=0.0001), SGA (aOR, 1.76; 95% CI, 1.52 to 2.05; I2, 86%; p<0.0001), and perinatal mortality (aOR, 1.5; 95% CI, 1.39 to 1.62; I2, 0%; p<0.0001), but not significantly different for birthweight (mean difference, -40.69 g; 95% CI, -124.22 to 42.83; I2, 85%; p=0.29). Because of substantial heterogeneity, we also conducted a narrative synthesis and found comparable results to meta-analyses. Conclusion: Prenatal cannabis use was associated with greater odds of PTB, SGA, and perinatal mortality even after accounting for prenatal tobacco use. However, our confidence in these findings is limited. Limitations of most existing studies was the failure to not include timing or quantity of cannabis use. This review can help guide health care providers with counseling, management, and addressing the limited existing safety data. Protocol Registration: PROSPERO CRD42020172343.

Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians (Version 2).

DESCRIPTION: The purpose of this updated guidance statement is to guide clinicians on screening for colorectal cancer (CRC) in asymptomatic average-risk adults. The intended audience is all clinicians. The population is asymptomatic adults at average risk for CRC. METHODS: This updated guidance statement was developed using recently published and critically appraised clinical guidelines from national guideline developers since the publication of the American College of Physicians' 2019 guidance statement, "Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults." The authors searched for national guidelines from the United States and other countries published in English using PubMed and the Guidelines International Network library from 1 January 2018 to 24 April 2023. The authors also searched for updates of guidelines included in the first version of our guidance statement. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to assess the quality of eligible guidelines. Two guidelines were selected for adoption and adaptation by raters on the basis of the highest average overall AGREE II quality scores. The evidence reviews and modeling studies for these 2 guidelines were also used to synthesize the evidence of diagnostic test accuracy, effectiveness, and harms of CRC screening interventions and to develop our guidance statements. GUIDANCE STATEMENT 1: Clinicians should start screening for colorectal cancer in asymptomatic average-risk adults at age 50 years. GUIDANCE STATEMENT 2: Clinicians should consider not screening asymptomatic average-risk adults between the ages of 45 to 49 years. Clinicians should discuss the uncertainty around benefits and harms of screening in this population. GUIDANCE STATEMENT 3: Clinicians should stop screening for colorectal cancer in asymptomatic average-risk adults older than 75 years or in asymptomatic average-risk adults with a life expectancy of 10 years or less. GUIDANCE STATEMENT 4A: Clinicians should select a screening test for colorectal cancer in consultation with their patient based on a discussion of benefits, harms, costs, availability, frequency, and patient values and preferences. GUIDANCE STATEMENT 4B: Clinicians should select among a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years as a screening test for colorectal cancer. GUIDANCE STATEMENT 4C: Clinicians should not use stool DNA, computed tomography colonography, capsule endoscopy, urine, or serum screening tests for colorectal cancer.

Associations of Pregnancy After Bariatric Surgery with Long-Term Weight Trajectories and Birth Weight: LABS-2 Study.

OBJECTIVE: This study aimed to examine whether pregnancy following bariatric surgery affects long-term maternal weight change and offspring birth weight. METHODS: Using data from the Longitudinal Assessment of Bariatric Surgery (LABS)-2 study, linear regression was used to evaluate percent change in total body weight over a 5-year follow-up period among reproductive-aged women who underwent Roux-en-Y gastric bypass or laparoscopic adjustable gastric banding as well as evaluate the association of bariatric procedure type and offspring birth weight. RESULTS: Of 727 women with preoperative age of 36.1 (6.3) years (mean [SD]) and BMI of 46.9 (7.0) kg/m2 , 80 (11%) reported at least one pregnancy. After adjusting for covariates, percent change in total body weight was not significantly different between women who became pregnant and those who did not during a 5-year follow-up period (ß = 2.02; 95% CI: -1.03 to 5.07; P = 0.19). Additionally, mean birth weight was not significantly different between mothers who underwent Roux-en-Y gastric bypass versus laparoscopic adjustable gastric banding (P = 0.99). CONCLUSIONS: Postoperative pregnancy did not diminish long-term weight loss in women in the LABS-2 study. The finding of comparable weight loss is relevant for providers counseling women of reproductive age on weight-loss expectations and family planning following bariatric surgery.

Accelerated Approval of 17α-Hydroxyprogesterone Caproate: A Cautionary Tale.

Before 2011, 17α-hydroxyprogesterone caproate (17P) was used to prevent recurrent preterm birth in women with singleton pregnancies and was compounded at a low cost (∼$15 per injection). In 2011, the U.S. Food and Drug Administration (FDA) approved a commercial version of 17P (trade name "Makena") through their Accelerated Approval Program, and the price of 17P subsequently increased by nearly 100-fold. This approval was largely based on a methodologically limited, placebo-controlled trial, which found that although 17P significantly reduced preterm births, the placebo group had significantly more participants with a history of preterm birth, potentially confounding the results. The FDA required a confirmatory trial for continued approval that demonstrated clinical benefit. Eight years after accelerated approval, the confirmatory trial, PROLONG (Progestin's Role in Optimizing Neonatal Gestation), found no evidence of an effect of Makena for reducing recurrent preterm birth or perinatal mortality. Trial completion triggered an automatic review of Makena by an advisory committee, which voted 9-7 to recommend revoking approval of Makena for preterm birth. Although the FDA created the Accelerated Approval Program to introduce therapies for serious conditions that lacked treatment options, Makena is an example of the limitations of this program. We encourage the FDA to re-evaluate their program and consider improvements, such as shorter timeframes to complete confirmatory trials, potentially revoking approval if the studies are not completed within a predefined timeframe, and to hold manufacturers responsible, in part, for the costs of therapy if they cannot prove a clinical benefit.

Fetal exposure to maternal active and secondhand smoking with offspring early-life growth in the Healthy Start study.

BACKGROUND: Previous studies have modeled the association between fetal exposure to tobacco smoke and body mass index (BMI) growth trajectories, but not the timing of catch-up growth. Research on fetal exposure to maternal secondhand smoking is limited. OBJECTIVES: To explore the associations between fetal exposure to maternal active and secondhand smoking with body composition at birth and BMI growth trajectories through age 3 years. METHODS: We followed 630 mother-child pairs enrolled in the Healthy Start cohort through age 3 years. Maternal urinary cotinine was measured at ~ 27 weeks gestation. Neonatal body composition was measured using air displacement plethysmography. Child weight and length/height were abstracted from medical records. Linear regression models examined the association between cotinine categories (no exposure, secondhand smoke, active smoking) with weight, fat mass, fat-free mass, and percent fat mass at birth. A mixed-effects regression model estimated the association between cotinine categories and BMI. RESULTS: Compared to unexposed offspring, birth weight was significantly lower among offspring born to active smokers (-343-g; 95% CI: -473, -213), but not among offspring of women exposed to secondhand smoke (-47-g; 95% CI: -130, 36). There was no significant difference in the rate of BMI growth over time between offspring of active and secondhand smokers (p = 0.58). Therefore, our final model included a single growth rate parameter for the combined exposure groups of active and secondhand smokers. The rate of BMI growth for the combined exposed group was significantly more rapid (0.27 kg/m2 per year; 95% CI: 0.05, 0.69; p < 0.01) than the unexposed. CONCLUSIONS: Offspring prenatally exposed to maternal active or secondhand smoking experience rapid and similar BMI growth in the first three years of life. Given the long-term consequences of rapid weight gain in early childhood, it is important to encourage pregnant women to quit smoking and limit their exposure to secondhand smoke.

Prenatal Development and Adolescent Obesity: Two Distinct Pathways to Diabetes in Adulthood.

OBJECTIVE: Higher body-mass index (BMI) and lower birth weight (BW) are associated with elevated risk of diabetes in adulthood, but the extent to which they compose two distinct pathways is unclear. METHODS: We used data from the National Longitudinal Study of Adolescent to Adult Health, a cohort of adolescents (1994-1995) followed for 14 years over four waves into adulthood (n = 13,413). Sex-stratified path analysis was used to examine pathways from BW [kg; linear (BW) and quadratic (BW2)] to latent trajectories in BMI from adolescence to adulthood to prevalent diabetes or prediabetes (pre/diabetes) in adulthood, adjusting for sociodemographic characteristics. RESULTS: Two pathways from BW to pre/diabetes were characterized: one from higher BW to elevated BMI and pre/diabetes and a second from lower BW, independent of BMI. In the BMI-independent pathway, greater BW was associated with marginally lower odds of pre/diabetes in women, but not men. Girls born at lower and higher BW exhibited elevated BMI in adolescence [coeff (95% CI): BW: -2.1 (-4.1, -0.05); BW2: 0.43 (0.09, 0.76)]; higher BW predicted marginally faster BMI gain and higher adolescent BMI and faster BMI gain were associated with pre/diabetes [coeff (95% CI): BMI intercept: 0.09 (0.06, 0.11); BMI slope: 0.11 (0.07, 0.15)]. In boys, BW was weakly associated with BMI intercept and slope; BMI slope, but not BMI intercept, was positively associated with pre/diabetes [coeff (95% CI): 0.29 (0.19, 0.39)]. CONCLUSIONS: Findings suggest that in girls, slowing BMI gain is critical for diabetes prevention, yet it may not address distinct pathology stemming from early life.

Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study.

BACKGROUND: Maternal obesity and weight gain during pregnancy are risk factors for child obesity. Associations may be attributable to causal effects of the intrauterine environment or genetic and postnatal environmental factors. OBJECTIVE: We estimated associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) overall and in early pregnancy, midpregnancy, and late pregnancy with neonatal adiposity. DESIGN: Participants were 826 women enrolled in a Colorado prebirth cohort who delivered term infants (2010-2013). GWG to 39 wk of gestation was predicted by using mixed models, and early pregnancy, midpregnancy, and late pregnancy rates of GWG (0-17, 17-27, and 27 wk to delivery) were calculated from repeated weight measures. Neonatal body composition was measured by using air-displacement plethysmography ≤3 d after birth. RESULTS: Each1-kg/m(2) increase in maternal BMI was associated with increased neonatal fat mass (5.2 g; 95% CI: 3.5, 6.9 g), fat-free mass (7.7 g; 95% CI: 4.5, 10.9 g), and percentage of body fat (0.12%; 95% CI: 0.08%, 0.16%). Each 0.1-kg/wk increase in predicted GWG was associated with increased fat mass (24.0 g; 95% CI: 17.4, 30.5 g), fat-free mass (34.0 g; 95% CI: 21.4, 46.6 g), and percentage of body fat (0.55%; 95% CI: 0.37%, 0.72%). No interaction was detected between BMI and GWG in their effects on neonatal body composition. Early pregnancy, midpregnancy, and late pregnancy rates of GWG were independently associated with fat mass and percentage of body fat. Midpregnancy and late pregnancy GWGs were associated with fat-free mass. An observed GWG that exceeded recommendations was associated with higher neonatal fat mass and fat-free mass but not percentage of body fat relative to adequate GWG. CONCLUSIONS: Maternal prepregnancy BMI and GWG, including period-specific GWG, were positively and independently associated with neonatal adiposity. Associations of early and midpregnancy weight gain with neonatal adiposity support the hypothesis that greater maternal weight gain during pregnancy, regardless of prepregnancy BMI, is directly related to offspring adiposity at birth. The Healthy Start study was registered as an observational study at clinicaltrials.gov as NCT02273297.

Exposure to prenatal smoking and early-life body composition: the healthy start study.

OBJECTIVES: To examine associations between exposure to prenatal smoking and early-life changes in fat mass (FM), fat-free mass (FFM), and anthropometrics. METHODS: About 670 mother-offspring pairs were analyzed in the longitudinal Healthy Start study. Maternal smoking data were collected during prenatal research visits. Offspring body composition and size were measured by air displacement plethysmography at delivery and postnatal follow-up (5 months) visits. RESULTS: Comparing exposed and unexposed offspring, exposure to prenatal smoking was significantly associated with reduced neonatal FM (P = 0.007) and FFM (P = 0.02). In contrast, at 5 months, exposed offspring had comparable FM (P = 0.61) and FFM (P = 0.41). After subsequent adjustment for birth weight, offspring exposed to prenatal smoking had significantly greater FFM (154.7 g, 0.5, 309.0; P = 0.049) and sum of skinfolds (2.7 mm, 0.06, 5.3; P = 0.04). From delivery to follow-up, exposed offspring had significantly greater increases in FFM (156.4 g, 2.8, 310.1; P = 0.046) and sum of skinfolds (2.7 mm, 0.06, 5.3; P = 0.04), even after adjustment for respective delivery measures. CONCLUSIONS: Exposure to prenatal smoking was significantly associated with rapid postnatal growth, which may increase the offspring's risk of metabolic diseases.

Interventions for primary prevention of suicide in university and other post-secondary educational settings.

BACKGROUND: Suicide is a leading cause of death among post-secondary students worldwide. Suicidal thoughts and planning are common among post-secondary students. Previous reviews have examined the effectiveness of interventions for symptomatic individuals; however, many students at high risk of suicide are undiagnosed and untreated. OBJECTIVES: We evaluated the effect on suicide and suicide-related outcomes of primary suicide prevention interventions that targeted students within the post-secondary setting. SEARCH METHODS: We searched the following sources up to June 2011: Specialised Registers of two Cochrane Groups, Cochrane Central Register of Controlled Trials, and nine other databases, trial registers, conference proceedings, and websites of national and international organizations. We screened reference lists and contacted authors of included studies to identify additional studies. We updated the search in November 2013; we will include these results in the review's next update. SELECTION CRITERIA: We included studies that tested an intervention for the primary prevention of suicide using a randomized controlled trial (RCT), controlled before-and-after (CBA), controlled interrupted time series (CITS), or interrupted time series (ITS) study design. Interventions targeted students within the post-secondary setting (i.e. college, university, academy, vocational, or any other post-secondary educational institution) without known mental illness, previous suicide attempt or self-harm, or suicidal ideation. Outcomes included suicides, suicide attempts, suicidal ideation, changes in suicide-related knowledge, attitudes and behavior, and availability of means of suicide. DATA COLLECTION AND ANALYSIS: We used standardized electronic forms for data extraction, risk of bias and quality of evidence determination, and analysis. We estimated standardised mean differences (SMD) with 95% confidence intervals (CIs). We analysed studies by intervention type and study design. We summarized RCT effect sizes using random-effects models meta-analyses; and analysed statistical heterogeneity using the Chi(2) test and I(2) statistic. We described narratively the results from studies that used other study designs. MAIN RESULTS: Eight studies met inclusion criteria. They were heterogeneous in terms of participants, study designs, and interventions. Five of eight studies had high risk of bias. In 3 RCTs (312 participants), classroom-based didactic and experiential programs increased short-term knowledge of suicide (SMD = 1.51, 95% CI 0.57 to 2.45; moderate quality evidence) and knowledge of suicide prevention (SMD = 0.72, 95% CI 0.36 to 1.07; moderate quality evidence). The effect on suicide prevention self-efficacy in one RCT (152 participants) was uncertain (SMD = 0.20, 95% CI -0.13 to 0.54; low quality evidence). One CBA analysed the effects of an institutional policy that restricted student access to laboratory cyanide and mandated professional assessment for suicidal students. The incidence of student suicide decreased significantly at one university with the policy relative to 11 control universities, 2.00 vs. 8.68 per 100,000 (Z = 5.90; P < 0.05). Four CBAs explored effects of training 'gatekeepers' to recognize and respond to warning signs of emotional crises and suicide risk in students they encountered. The magnitude of effect sizes varied between studies. Gatekeeper training enhanced short-term suicide knowledge in students, peer advisors residing in student accommodation, and faculty and staff, and suicide prevention self-efficacy among peer advisors. There was no evidence of an effect on participants' suicide-related attitudes or behaviors. One CBA found no evidence of effects of gatekeeper training of peer advisors on suicide-related knowledge, self-efficacy, or gatekeeper behaviors measured four to six months after intervention. AUTHORS' CONCLUSIONS: We found insufficient evidence to support widespread implementation of any programs or policies for primary suicide prevention in post-secondary educational settings. As all evaluated interventions combined primary and secondary prevention components, we were unable to determine the independent effects of primary preventive interventions. Classroom instruction and gatekeeper training increased short-term suicide-related knowledge. We found no studies that tested the effects of classroom instruction on suicidal behavior or long-term outcomes. Limited evidence suggested minimal longer-term effects of gatekeeper training on suicide-related knowledge, while no evidence was found evaluating its effect on suicidal behavior. A policy-based suicide intervention reduced student suicide, but findings have not been replicated. Our findings are limited by the overall low quality of the evidence and the lack of studies from middle- and low-income countries. Rigorously designed studies should test the effects of preventive interventions on important health outcomes, including suicidal ideation and behavior, in varying post-secondary settings.

Quantity and timing of maternal prenatal smoking on neonatal body composition: the Healthy Start study.

OBJECTIVE: To examine the dose-dependent and time-specific relationships of prenatal smoking with neonatal body mass, fat mass (FM), fat-free mass (FFM), and FM-to-FFM ratio, as measured by air-displacement plethysmography (PEA POD system). STUDY DESIGN: We analyzed 916 mother-neonate pairs participating in the longitudinal prebirth cohort Healthy Start study. Maternal prenatal smoking information was collected in early, middle, and late pregnancy by self-report. Neonatal body composition was measured with the PEA POD system after delivery. Multiple general linear regression models were adjusted for maternal and neonatal characteristics. RESULTS: Each additional pack of cigarettes smoked during pregnancy was associated with significant decreases in neonatal body mass (adjusted mean difference, -2.8 g; 95% CI, -3.9 to -1.8 g; P < .001), FM (-0.7 g; 95% CI, -1.1 to -0.3 g; P < .001), and FFM (-2.1 g; 95% CI, -2.9 to -1.3 g; P < .001). Neonates exposed to prenatal smoking throughout pregnancy had significantly lower body mass (P < .001), FM (P < .001), and FFM (P < .001) compared with those not exposed to smoking. However, neonates of mothers who smoked only before late pregnancy had no significant differences in body mass (P = .47), FM (P = .43), or FFM (P = .59) compared with unexposed offspring. CONCLUSION: Exposure to prenatal smoking leads to systematic growth restriction. Smoking cessation before late pregnancy may reduce the consequences of exposure to prenatal smoking on body composition. Follow-up of this cohort is needed to determine the influence of catch-up growth on early-life body composition and the risk of childhood obesity.

Physical activity in pregnancy and neonatal body composition: the Healthy Start study.

OBJECTIVE: To examine associations between pregnancy physical activity and neonatal fat mass and fat-free mass, birth weight, and small for gestational age (SGA). METHODS: We analyzed 826 mother-neonate pairs (term births) participating in the longitudinal Healthy Start study. The Pregnancy Physical Activity Questionnaire was used to assess total energy expenditure and meeting American College of Obstetricians and Gynecologists (College) guidelines for physical activity during early pregnancy, midpregnancy, and late pregnancy. Models were adjusted for maternal and neonatal characteristics. RESULTS: Neonates had mean fat mass of 292.9 g, fat-free mass of 2,849.8 g, and birth weight of 3,290.7 g. We observed 107 (12.9%) SGA and 30 (3.6%) large-for-gestational age neonates. A significant inverse linear trend between total energy expenditure during late pregnancy and neonatal fat mass (Ptrend=.04) was detected. Neonates of mothers in the highest compared with the lowest quartile of total energy expenditure during late pregnancy had 41.1 g less fat mass (249.4 compared with 290.5 g; P=.03). No significant trend was found with total energy expenditure and neonatal fat-free mass or birth weight. Early-pregnancy and midpregnancy total energy expenditure were not associated with neonatal outcomes. No significant trend was observed between late-pregnancy total energy expenditure and SGA (Ptrend=.07), but neonates of mothers in the highest compared with the lowest quartile had a 3.0 (95% confidence interval 1.4-6.7) higher likelihood of SGA. Meeting the College's physical activity guidelines during pregnancy was not associated with differences in neonatal outcomes. CONCLUSION: Increasing levels of late-pregnancy total energy expenditure are associated with decreased neonatal adiposity without significantly reduced neonatal fat-free mass. LEVEL OF EVIDENCE: II.

Role of developmental overnutrition in pediatric obesity and type 2 diabetes.

Childhood obesity continues to be a significant public health burden. Empirical evidence has begun to identify intrauterine and postnatal pathways that increase the likelihood of excess adiposity and increased risk of type 2 diabetes among offspring. Reviewed here is the evidence supporting a transgenerational vicious cycle that increases obesity and diabetes in offspring and contributes substantially to the increases in obesity and type 2 diabetes observed over the past several decades. The public health impact of these findings is discussed and future research opportunities are outlined.