Maternal 24-h movement patterns across pregnancy and postpartum: The LIFE-Moms consortium.

Objective: Time spent among the 24-h movement behaviors (physical activity [PA], sleep, sedentary behavior [SB]) in the perinatal period is important for maternal and child health. We described changes to 24-h movement behaviors and behavior guideline attainment during pregnancy and postpartum and identified correlates of behavior changes. Methods: This secondary data analysis included the standard of care group (n = 439) from the U.S.-based Lifestyle Interventions For Expectant Moms (LIFE-Moms) consortium, including persons with overweight and obesity. Wrist-worn accelerometry was used to measure movement behaviors early (9-15 weeks) and late (35-36 weeks) pregnancy, and âˆ¼ 1-year postpartum. Sleep and moderate-to-vigorous PA (MVPA) were compared to adult and pregnancy-specific guidelines, respectively. SB was classified into quartiles. PA and SB context were quantified using questionnaires. Mixed models were used to examine changes in behaviors and guidelines and identify correlates. Results: Participants were 31.3 ± 3.5 years, 53.5 % were Black or Hispanic, and 45.1 % had overweight. Sleep duration decreased across time, but participants consistently met the guideline (range: 85.0-93.6 %). SB increased during pregnancy and decreased postpartum, while light PA and MVPA followed the inverse pattern. Participants met slightly fewer guidelines late pregnancy (1.2 ± 0.7 guidelines) but more postpartum (1.7 ± 0.8 guidelines) than early pregnancy (1.4 ± 0.8 guidelines). Black or Hispanic race/ethnicity, higher pregravid body mass index, and non-day work-shift (e.g., night-shift) were identified correlates of lower guideline adherence and varying PA and SB context. Conclusion: Perinatal interventions should consider strategies to prevent SB increase and sustain MVPA to promote guideline adherence.

The association of self-reported sleep and circadian measures with glycemic control and diabetes complications among young adults with type 2 diabetes.

We aim to examine the association of sleep duration, sleep quality, late chronotype, and circadian misalignment with glycemic control and risk of complications in young adults with youth-onset type 2 diabetes followed in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Self-reported sleep duration, quality, timing, and circadian misalignment were assessed via a modified Pittsburgh Sleep Quality Index (PSQI) questionnaire, and chronotype was assessed via the Morningness-Eveningness Questionnaire (MEQ). We examined diabetes complications including loss of glycemic control (defined as hemoglobin A1c ≥8%), hypertension, dyslipidemia, albuminuria, and diabetic peripheral neuropathy. Multivariable logistic regression models were constructed to assess associations between sleep and circadian measures with outcomes of interest, such as loss of glycemic control and diabetes complications. A total of 421 participants (34.2% male), mean age 23.6 ± 2.5 yr, mean body mass index (BMI) of 36.1 ± 8.3 kg/m2, and mean diabetes duration of 10.0 ± 1.5 yr were evaluated. Self-reported short sleep duration, daytime sleepiness, and sleep quality were not associated with loss of glycemic control or diabetes complications. Late self-reported bedtime (after midnight) on work/school nights, rather than self-expressed chronotype or circadian misalignment, was independently associated with loss of glycemic control. An association was seen between late bedtimes and albuminuria but was attenuated after adjusting for depression. In conclusion, late bedtime on work/school days, rather than short sleep duration, daytime sleepiness, or poor sleep quality, was independently associated with loss of glycemic control in this longitudinal cohort of young adults with youth-onset type 2 diabetes.NEW & NOTEWORTHY The prevalence of type 2 diabetes in youth is increasing at an alarming rate. Identifying potentially modifiable factors modulating glycemic control is critically important to reduce micro and macrovascular complications. In a large cohort of youth-onset type 2 diabetes, self-reported late bedtime on work/school days was independently associated with loss of glycemic control in this longitudinal cohort of young adults with youth-onset type 2 diabetes.

Major adverse events in youth-onset type 1 and type 2 diabetes: The SEARCH and TODAY studies.

AIMS: To determine contemporary incidence rates and risk factors for major adverse events in youth-onset T1D and T2D. METHODS: Participant interviews were conducted once during in-person visits from 2018 to 2019 in SEARCH (T1D: N = 564; T2D: N = 149) and semi-annually from 2014 to 2020 in TODAY (T2D: N = 495). Outcomes were adjudicated using harmonized, predetermined, standardized criteria. RESULTS: Incidence rates (events per 10,000 person-years) among T1D participants were: 10.9 ophthalmologic; 0 kidney; 11.1 nerve, 3.1 cardiac; 3.1 peripheral vascular; 1.6 cerebrovascular; and 15.6 gastrointestinal events. Among T2D participants, rates were: 40.0 ophthalmologic; 6.2 kidney; 21.2 nerve; 21.2 cardiac; 10.0 peripheral vascular; 5.0 cerebrovascular and 42.8 gastrointestinal events. Despite similar mean diabetes duration, complications were higher in youth with T2D than T1D: 2.5-fold higher for microvascular, 4.0-fold higher for macrovascular, and 2.7-fold higher for gastrointestinal disease. Univariate logistic regression analyses in T1D associated age at diagnosis, female sex, HbA1c and mean arterial pressure (MAP) with microvascular events. In youth-onset T2D, composite microvascular events associated positively with MAP and negatively with BMI, however composite macrovascular events associated solely with MAP. CONCLUSIONS: In youth-onset diabetes, end-organ events were infrequent but did occur before 15 years diabetes duration. Rates were higher and had different risk factors in T2D versus T1D.

Healthful Eating Behaviors among Couples Contribute to Lower Gestational Weight Gain.

Through longitudinal analysis from the GLOWING cohort study, we examined the independent and joint relationships between couples' eating behaviors and gestational weight gain (GWG). Pregnant persons (n = 218) and their non-pregnant partners (n = 157) completed an Eating Inventory. GWG was calculated as gestation weight at 36 weeks minus that at 10 weeks. General linear models were used to examine the relationships between GWG and the pregnant persons, non-pregnant partners, and couples (n = 137; mean of pregnant persons and non-pregnant partners) cognitive restraint (range 0-21), dietary disinhibition (range 0-18), and perceived hunger (range 0-14), with higher scores reflecting poorer eating behaviors. The adjusted models included race/ethnicity, education, income, marital status, and age. The pregnant persons and their non-pregnant partners' cognitive restraint, dietary disinhibition, and perceived hunger scores were 9.8 ± 4.7, 4.8 ± 3.2, and 4.4 ± 2.5 and 6.6 ± 4.6, 5.4 ± 3.4, and 4.7 ± 3.2, respectively. Higher cognitive restraint scores among the pregnant persons and couples were positively associated with GWG (p ≤ 0.04 for both). Stratified analyses revealed this was significant for the pregnant persons with overweight (p ≤ 0.04). The non-pregnant partners' eating behaviors alone were not significantly associated with GWG (p ≥ 0.31 for all). The other explored relationships between GWG and the couples' eating behaviors were insignificant (p ≥ 0.12 for all). Among the pregnant persons and couples, reduced GWG may be achieved with higher levels of restrained eating. Involving non-pregnant partners in programs to optimize GWG may be beneficial.

Impact of youth onset type 2 diabetes during pregnancy on microvascular and cardiac outcomes.

AIMS: To examine the impact of pregnancy on microvascular and cardiovascular measures in women with youth-onset T2D. METHODS: Microvascular and cardiovascular measures were compared in in a cohort of 116 women who experienced a pregnancy of ≥ 20 weeks gestation and 291 women who did not among women in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. RESULTS: Cox regression models adjusted for participant characteristics at baseline including age, race/ethnicity, household income, diabetes duration, HbA1c (>6%), and BMI, demonstrated those who experienced pregnancy had 2.76 (1.38-5.49; p = 0.004) fold increased risk of hyperfiltration (eGFR ≥ 135 ml/min/1.73 m2), compared to those without a pregnancy. No differences were observed in rates of retinopathy (48.9% vs. 41.1%) or neuropathy (23.3% vs. 16.3%) in women who experienced pregnancy vs. women who did not, respectively. In fully adjusted models, pregnancy did not impact changes in echocardiographic or arterial stiffness compared to changes in women who were never pregnant. CONCLUSIONS: These results indicate that pregnancy increases the risk of hyperfiltration in women with youth-onset T2D, but not other micro or macrovascular complications. The rates of vascular complications are very high in youth-onset T2D potentially obscuring micro- and macrovascular changes attributable to pregnancy. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov numbers,NCT01364350andNCT02310724.

Plasma neurofilament light chain concentrations are elevated in youth-onset type 2 diabetes and associated with neuropathy.

BACKGROUND AND AIMS: The lack of easily measurable biomarkers remains a challenge in executing clinical trials for diabetic neuropathy (DN). Plasma Neurofilament light chain (NFL) concentration is a promising biomarker in immune-mediated neuropathies. Longitudinal studies evaluating NFL in DN have not been performed. METHODS: A nested case-control study was performed on participants with youth-onset type 2 diabetes enrolled in the prospective Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Plasma NFL concentrations were measured at 4-year intervals from 2008 to 2020 in 50 participants who developed DN and 50 participants with type 2 diabetes who did not develop DN. RESULTS: NFL concentrations were similar in the DN and no DN groups at the first assessment. Concentrations were higher in DN participants at all subsequent assessment periods (all p < .01). NFL concentrations increased over time in both groups, with higher degrees of change in DN participants (interaction p = .045). A doubling of the NFL value at Assessment 2 in those without DN increased the odds of ultimate DN outcome by an estimated ratio of 2.86 (95% CI: [1.30, 6.33], p = .0046). At the final study visit, positive Spearman correlations (controlled for age, sex, diabetes duration, and BMI) were observed between NFL and HbA1c (0.48, p < .0001), total cholesterol (0.25, p = .018), and low-density lipoprotein (LDL (0.30, p = .0037)). Negative correlations were observed with measures of heart rate variability (-0.42 to -0.46, p = <.0001). INTERPRETATION: The findings that NFL concentrations are elevated in individuals with youth-onset type 2 diabetes, and increase more rapidly in those who develop DN, suggest that NFL could be a valuable biomarker for DN.

Retinal Thickness and Morphology Changes on OCT in Youth with Type 2 Diabetes: Findings from the TODAY Study.

Objective: To evaluate changes in retinal thickness and morphology using OCT in youth with type 2 diabetes (T2D) and to identify systemic biomarkers correlating with these changes. Design: Retrospective subgroup analysis of a prospective study. Participants: Participants who underwent OCT imaging in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial and its follow-up study TODAY2. Methods: In 2010-2011 (TODAY) and 2017-2018 (TODAY2), 6 × 6-mm macular volume OCT scans were acquired, segmented, and analyzed to generate total retinal thickness, inner retinal thickness, and outer retinal thickness. The main retinal morphologies graded were intraretinal cystoid spaces, subretinal fluid, and posterior vitreous detachment (PVD). Main Outcome Measures: Changes in total and individual retinal layer thickness and development of abnormal vitreomacular morphology between TODAY and TODAY2. Results: Participants had a mean age of 17.9 ± 2.4 years and glycated hemoglobin (HbA1c) of 8.2 ± 2.8% in TODAY and a mean age of 25.0 ± 2.4 years and mean HbA1c of 9.5 ± 2.8% in TODAY2. Longitudinally between assessments, there were overall decreases in outer retinal thickness from 167.2 ± 11.5 microns to 158.4 ± 12.8 microns (P < 0.001) and in photoreceptor thickness from 30.3 ± 2.9 microns to 29.8 ± 4.1 microns (P = 0.04) in the central subfield, while in the inner subfield, we noted a decrease in outer retinal thickness from 150.5 ± 10.1 microns to 144.9 ± 10.5 microns (P < 0.001) and an increase in inner retinal thickness from 136.9 ± 11.5 microns to 137.4 ± 12.6 microns (P = 0.01). Multivariate analysis showed that in the center subfield, HbA1c increases were associated with increases in total retinal thickness (r: 0.67, P = 0.001), whereas fasting glucose was positively correlated with inner retinal thickness (r: 0.02, P = 0.02). In the inner subfield, both systolic (r: -0.22, P < 0.001) and diastolic (r: -0.22, P = 0.003) blood pressures were negatively correlated with total retinal thickness. There was an increase in PVD (18.9%) and cystoid spaces (4.2%). Conclusions: Youth with T2D develop retinal thickness changes on OCT, including increases in total retinal and inner retinal thickness in the center subfield that correlate with HbA1c and fasting glucose, respectively. Taken together with the increased prevalence of abnormal vitreomacular morphology in this cohort at risk, these findings emphasize the importance of controlling risk factors to prevent the development of sight-threatening retinal complications.

Association of psychosocial factors with medication adherence in emerging adults with youth-onset type 2 diabetes: The iCount study.

AIMS: To assess associations of psychosocial factors with medication adherence in young adults with youth-onset type 2 diabetes in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY2) cohort. METHODS: Participants (mean age 26 years) completed validated psychosocial measures. Adherence to oral hypoglycemia agents (OHAs) was assessed with 3-monthly unannounced phone pill counts; insulin adherence by self-report. Logistic and linear regressions identified factors associated with "low-adherence" (<80% of pills/insulin) controlling for confounders. RESULTS: Of 212 participants taking OHAs (67% female, 39% Hispanic, 36% non-Hispanic Black), 69.8% were low-adherent. After adjustment, beliefs that medicines are necessary was associated with lower odds of low-adherence (p = 0.040, dichotomous). Less self-management support (p = 0.008), no healthcare coverage (p = 0.001), ≥1 (p = 0.008)/≥2 (p = 0.045) need insecurities were associated with higher odds of low-adherence. Factors associated with lower % adherence (continuous) were beliefs that medicines are harmful (p < 0.001)/overused (p = 0.007)/less necessary (p = 0.022), low self-management support (p = 0.003), food insecurity (p = 0.036), no healthcare coverage (p < 0.001), ≥1 (p = 0.003)/≥2 (p = 0.018) need insecurities. Of 192 taking insulin (69% female, 36% Hispanic, 41% non-Hispanic Black, 16% non-Hispanic white), 37.0% were low-adherent. Beliefs that medicines are overused (p = 0.009), that diabetes is not serious (p = 0.010), low diabetes self-efficacy (p = 0.035), high distress (p = 0.027), low self-management support (p = 0.001), food insecurity (p = 0.020), ≥1 (p = 0.011)/≥2 (p = 0.015) insecurities increased odds of insulin low-adherence. CONCLUSIONS: Poor medication adherence, common in young adults with youth-onset type 2 diabetes, is associated with interfering beliefs, diabetes distress and social factors. We must address these factors to develop tailored interventions for this vulnerable group.

The obesity paradox: Retinopathy, obesity, and circulating risk markers in youth with type 2 diabetes in the TODAY Study.

AIM: To understand the relationship of obesity and 27 circulating inflammatory biomarkers to the prevalence of non-proliferative diabetic retinopathy (NPDR) in youth with type 2 diabetes. METHODS: Youth with type 2 diabetes who participated in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study were followed for 2-6.5 years. Digital fundus photographs were obtained in the last year of the study. Blood samples during the study were processed for inflammatory biomarkers, and these were correlated with obesity tertiles and presence of retinopathy. RESULTS: Higher BMI was associated with an increase in circulating levels of metabolic biomarkers including high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, LDL-cholesterol (LDL-C) and Apolipoprotein B (ApoB), tumor necrosis factor receptors 1 and 2 (TNFR-1 and -2), interleukin 6 (IL-6), E-selectin, and homocysteine, as well as a decrease in the metabolic risk markers HDL-cholesterol (HDLC), and insulin-like growth factor binding protein 1 (IGFBP-1). Although NPDR risk decreased with increasing obesity, it was not associated with any of the measured biomarkers. CONCLUSIONS: Circulating levels of measured biomarkers did not elucidate the "obesity paradox" of decreased NPDR in the most obese participants in the TODAY study. TRIAL REGISTRATION: clinicaltrials.govNCT00081328.

ZnT8 autoantibody prevalence is low in youth with type 2 diabetes and associated with higher insulin sensitivity, lower insulin secretion, and lower disposition index.

Aim: ZnT8 autoantibody positivity (ZnT8+) is associated with risk for type 1 diabetes and with metabolic complications in adults. Our aim was to assess prevalence of ZnT8 + in the Treatment of T2D in Adolescents and Youth (TODAY) cohort and describe associated phenotypic outcomes. Methods: TODAY participants were 13.98 ± 2.03 years with a confirmed diagnosis of T2D, BMI percentile of 97.69 ± 3.32 (64% female), and GAD- and IA2- at baseline. ZnT8 autoantibodies were measured at baseline and end of study. Results: 3 of 687 participants (0.29%) were ZnT8 + and there was one conversion (0.15%) from ZnT8- to ZnT8 + during the study. ZnT8A + individuals had higher HbA1c, HDL and LDL cholesterol, and IL-1ß concentrations, and lower BMI, IL-6, and triglyceride concentrations compared to the TODAY cohort and ZnT8A- individuals. They also had higher insulin sensitivity with lower insulin secretion and disposition index, metabolically resembling T1D. All ZnT8 + participants experienced loss of glycemic control on randomized treatment, but exhibited lower rates of diabetic complications than other groups. Conclusion: Given the low rate of complications in ZnT8 + individuals, ZnT8 likely does not impact the clinical course of the disease in this population.

Medication adherence in young adults with youth-onset type 2 diabetes: iCount, an observational study.

AIMS: To assess prevalence of, and factors associated with, medication adherence of young adults with youth-onset type 2 diabetes. METHODS: Oral hypoglycaemia agent (OHA) adherence was measured with unannounced telephone pill counts, insulin adherence was self-reported. Those taking ≥ 80% of pills/insulin were classified "high-adherent," <80% of pills/insulin "low-adherent." Analyses included unadjusted, and adjusted linear and logistic regressions assessing associations of participant factors with adherence. RESULTS: For people taking OHAs (N = 212, mean age 26 yrs, 67% women, 18% non-Hispanic White, 35% non-Hispanic Black, 41% Hispanic), 69.8% were low-adherent. HbA1c was lower in the high-adherent group (9.2%/77 mmol/mol vs. 10.0%/86 mmol/mol, p < 0.04). More non-Hispanic Blacks were low-adherent (85.7%) than Hispanics (60.2%) and non-Hispanic whites (55.3%, p < 0.002); 91.4% of participants without healthcare coverage were low-adherent vs. 65.5% of those with coverage (p < 0.004). After adjustment, gender (p = 0.024), race/ethnicity (p < 0.001) and healthcare coverage (p = 0.001) remained related to OHA adherence. For insulin (N = 192), 37% were low-adherent. HbA1c was associated with insulin adherence (low = 11.2%/99 mmol/mol vs. high = 10.0%/86 mmol/mol, p < 0.001) with and without adjustment. CONCLUSIONS: Young adults with youth-onset type 2 diabetes, especially females, non-Hispanic Blacks and those without healthcare coverage, commonly had low-OHA adherence. Glycaemic control was also poor. Interventions to improve medication adherence are needed for this vulnerable group.

Long-Term Complications in Youth-Onset Type 2 Diabetes.

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood. METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated. RESULTS: At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up. CONCLUSIONS: Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.).

Identification of changes in sleep across pregnancy and the impact on cardiometabolic health and energy intake in women with obesity.

This prospective, observational study investigated changes in sleep and the effect on energy intake, gestational weight gain, and cardiometabolic health across pregnancy in 52 healthy pregnant women with obesity. Habitual sleep was assessed by wrist-worn actigraphy (time spent in bed; TIB, total sleep time; TST, and sleep efficiency) in early (130-156 weeks) and late (350-366) pregnancy. A change to habitual sleep was defined as change of one-half of the standard deviation of TIB and TST across six consecutive nights from early pregnancy. Energy intake and changes in weight, fasting glucose, insulin, and lipids across pregnancy were compared between women who changed sleep. During early pregnancy, TIB was 9:24 ± 0:08 h and varied by 1:37 ± 0:07 h across the six nights. TST and sleep efficiency significantly declined from early to late pregnancy (7:03 ± 0:08 h to 6:28 ± 0:09 h, p < 0.001) and (76 ± 0.1% to 71 ± 0.2%, p < 0.001), respectively. For women who increased TIB (n = 11), fasting glucose decreased (-11.6 ± 4.3%, p < 0.01) across pregnancy and they had a trend towards decreased insulin (-57.8 ± 33.5%; p = 0.09) and HOMA-IR (-72.4 ± 37.3%; p = 0.06) compared to women who decreased TIB (n = 13). Women who increased TIB had a significantly lower daily energy intake across pregnancy (-540 ± 163 kcal; p < 0.01) and tended to have less gestational weight gain (-147 ± 88 g/week; p = 0.10). Changes in TST did not affect plasma markers, energy intake or weight gain. The positive relationship between sleep and cardiometabolic health during pregnancy is explained in part by lower energy intake. We hypothesize lower energy intake is due to a prolonged overnight fast and a decrease in the time available for eating.

Attenuated early pregnancy weight gain by prenatal lifestyle interventions does not prevent gestational diabetes in the LIFE-Moms consortium.

AIMS: To examine the effect of lifestyle (diet and physical activity) interventions on the prevalence of GDM, considering the method of GDM ascertainment and its association with early pregnancy characteristics and maternal and neonatal outcomes in the LIFE-Moms consortium. METHODS: LIFE-Moms evaluated the effects of lifestyle interventions to optimize gestational weight gain in 1148 pregnant women with BMI ≥ 25 kg/m2 and without known diabetes at enrollment, compared with standard care. GDM was assessed between 24 and 31-weeks gestation by a 2-hour, 75-gram OGTT or by local clinical practice standards. RESULTS: Lifestyle interventions initiated prior to 16 weeks reduced early excess GWG compared with standard care (0.35 ± 0.24 vs 0.43 ± 0.26 kg per week, p=<0.0001) but did not affect GDM diagnosis (11.1% vs 11.6%, p = 0.91). Using the 75-gram, 2-hour OGTT, 13. 0% of standard care and 11.0% of the intervention group had GDM by the IADPSG criteria (p = 0.45). The 'type of diagnostic test' did not change the result (p = 0.86). Women who developed GDM were significantly heavier, more likely to have obesity, and more likely to have dysglycemia at baseline. CONCLUSION: Moderate-to-high intensity lifestyle interventions grounded in behavior change theory initiated between 9 and 16-weeks gestation did not affect the prevalence of GDM despite reducing early GWG. CLINICALTRIALS.GOV: NCT01545934, NCT01616147, NCT01771133, NCT01631747, NCT01768793, NCT01610752, NCT01812694.

One-year postpartum anthropometric outcomes in mothers and children in the LIFE-Moms lifestyle intervention clinical trials.

BACKGROUND/OBJECTIVES: Excess gestational weight gain (GWG) is a risk factor for maternal postpartum weight retention and excessive neonatal adiposity, especially in women with overweight or obesity. Whether lifestyle interventions to reduce excess GWG also reduce 12-month maternal postpartum weight retention and infant weight-for-length z score is unknown. Randomized controlled trials from the LIFE-Moms consortium investigated lifestyle interventions that began in pregnancy and tested whether there was benefit through 12 months on maternal postpartum weight retention (i.e., the difference in weight from early pregnancy to 12 months) and infant-weight-for-length z scores. SUBJECTS/METHODS: In LIFE-Moms, women (N = 1150; 14.1 weeks gestation at enrollment) with overweight or obesity were randomized within each of seven trials to lifestyle intervention or standard care. Individual participant data were combined and analyzed using generalized linear mixed models with trial entered as a random effect. The 12-month assessment was completed by 83% (959/1150) of women and 84% (961/1150) of infants. RESULTS: Compared with standard care, lifestyle intervention reduced postpartum weight retention (2.2 ± 7.0 vs. 0.7 ± 6.2 kg, respectively; difference of -1.6 kg (95% CI -2.5, -0.7; p = 0.0003); the intervention effect was mediated by reduction in excess GWG, which explained 22% of the effect on postpartum weight retention. Lifestyle intervention also significantly increased the odds (OR = 1.68 (95% CI, 1.26, 2.24)) and percentage of mothers (48.2% vs. 36.2%) at or below baseline weight at 12 months postpartum (yes/no) compared with standard care. There was no statistically significant treatment group effect on infant anthropometric outcomes at 12 months. CONCLUSIONS: Compared with standard care, lifestyle interventions initiated in pregnancy and focused on healthy eating, increased physical activity, and other behavioral strategies resulted in significantly less weight retention but similar infant anthropometric outcomes at 12 months postpartum in a large, diverse US population of women with overweight and obesity.

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10-3) and candidate genes from knockout mice (P = 5.2 × 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.

Lifestyle Interventions Limit Gestational Weight Gain in Women with Overweight or Obesity: LIFE-Moms Prospective Meta-Analysis.

OBJECTIVE: This study aimed to evaluate the effects of varied lifestyle intervention programs designed to ameliorate excess gestational weight gain (GWG) in pregnant women with overweight or obesity compared with standard care, including effects on pregnancy outcomes. METHODS: Seven clinical centers conducted separate randomized clinical trials to test different lifestyle intervention strategies to modify GWG in diverse populations. Eligibility criteria, specific outcome measures, and assessment procedures were standardized across trials. The results of the separate trials were combined using an individual-participant data meta-analysis. RESULTS: For the 1,150 women randomized, the percent with excess GWG per week was significantly lower in the intervention group compared with the standard care group (61.8% vs. 75.0%; odds ratio [95% CI]: 0.52 [0.40 to 0.67]). Total GWG from enrollment to 36 weeks' gestation was also lower in the intervention group (8.1 ± 5.2 vs. 9.7 ± 5.4 kg; mean difference: -1.59 kg [95% CI:-2.18 to -0.99 kg]). The results from the individual trials were similar. The intervention and standard care groups did not differ in preeclampsia, gestational diabetes, cesarean delivery, or birth weight. CONCLUSIONS: Behavioral lifestyle interventions focusing primarily on diet and physical activity among women with overweight and obesity resulted in a significantly lower proportion of women with excess GWG. This modest beneficial effect was consistent across diverse intervention modalities in a large, racially and socioeconomically diverse US population of pregnant women.

Multicenter Comparison of Lung and Oral Microbiomes of HIV-infected and HIV-uninfected Individuals.

RATIONALE: Improved understanding of the lung microbiome in HIV-infected individuals could lead to better strategies for diagnosis, therapy, and prophylaxis of HIV-associated pneumonias. Differences in the oral and lung microbiomes in HIV-infected and HIV-uninfected individuals are not well defined. Whether highly active antiretroviral therapy influences these microbiomes is unclear. OBJECTIVES: We determined whether oral and lung microbiomes differed in clinically healthy groups of HIV-infected and HIV-uninfected subjects. METHODS: Participating sites in the Lung HIV Microbiome Project contributed bacterial 16S rRNA sequencing data from oral washes and bronchoalveolar lavages (BALs) obtained from HIV-uninfected individuals (n = 86), HIV-infected individuals who were treatment naive (n = 18), and HIV-infected individuals receiving antiretroviral therapy (n = 38). MEASUREMENTS AND MAIN RESULTS: Microbial populations differed in the oral washes among the subject groups (Streptococcus, Actinomyces, Rothia, and Atopobium), but there were no individual taxa that differed among the BALs. Comparison of oral washes and BALs demonstrated similar patterns from HIV-uninfected individuals and HIV-infected individuals receiving antiretroviral therapy, with multiple taxa differing in abundance. The pattern observed from HIV-infected individuals who were treatment naive differed from the other two groups, with differences limited to Veillonella, Rothia, and Granulicatella. CD4 cell counts did not influence the oral or BAL microbiome in these relatively healthy, HIV-infected subjects. CONCLUSIONS: The overall similarity of the microbiomes in participants with and without HIV infection was unexpected, because HIV-infected individuals with relatively preserved CD4 cell counts are at higher risk for lower respiratory tract infections, indicating impaired local immune function.

Metabolic syndrome is common and persistent in youth-onset type 2 diabetes: Results from the TODAY clinical trial.

OBJECTIVE: To examine the prevalence of metabolic syndrome (MetS) in youth-onset type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. METHODS: Prevalence of MetS (ATP III definition) was compared at baseline (n = 679) and at 6 (n = 625) and 24 months (n = 545) using chi-square tests. Laboratory data were examined between MetS classifications at each time point using ANOVA. RESULTS: Baseline prevalence of MetS was 75.8% and did not differ by treatment group or change over time. MetS was more common in females (83.1%) than males (62.3%; P < 0.0001) at baseline; this difference persisted over 24 months. Prevalence of MetS was similar between ethnic groups at baseline but greater in Hispanics (82.7%) vs. non-Hispanic Whites (67.5%; P = 0.0017) and non-Hispanic Blacks (72.7%; P = 0.0164) at 24 months. Although MetS was common in participants with hemoglobin A1c < 7.0% (74.4% at baseline; no significant change over 24 months), it was more common in those who did not maintain glycemic control at 6 months (80.3%; P = 0.0081). Elevated C-reactive protein, ALT, IL-6, and PAI-1 levels were more frequent with MetS. CONCLUSIONS: Persistent high prevalence of MetS in youth-onset diabetes, even with excellent glycemic control, is of concern given the associated increased cardiovascular risk.