Daniel S. Hsia

With the rising prevalence of type 2 diabetes (T2D) among children and adolescents, the ability to predict the progression of prediabetes to T2D in youth is imperative, as it significantly affects long-term health and quality of life. A number of biological and social risk factors have been identified in literature. Additionally, a growing body of literature illustrates the use of machine learning techniques to identify those with prediabetes or T2D in adults. A prediction model identifying adults with prediabetes who are most likely to progress to T2D has been suggested; however, to date, no such predictive algorithm in youth with prediabetes, a population with a high rate of spontaneous regression to normoglycemia, has been developed. Machine learning (ML) techniques can be applied to potentially identify novel risk factors for youth-onset T2D progression. The use of ML techniques with longitudinal data would enrich the prediction models to accurately identify children with prediabetes who are at the most risk of developing T2D without intervention. This narrative review summarizes the literature on biological and social risk factors for T2D progression and the use of ML to predict progression to T2D.

Background: Household chaos is an emerging risk factor for childhood obesity development, especially in families with lower socioeconomic status (SES). It is unclear if changes in household chaos, especially in pregnancy, may mediate the effectiveness of weight-related behavioral interventions. Objective: This study aimed to describe how household chaos changed across gestation and determine whether household chaos mediated the effect of an eHealth behavioral gestational weight gain (GWG) intervention in pregnant people with low SES. Methods: Pregnant people who were enrolled in the US Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) were recruited for a randomized controlled trial testing the effectiveness of an eHealth-based pragmatic intervention for GWG management. The usual care group received the standard WIC program guidance and monthly health coach support with general pregnancy recommendations. The intervention group received the standard WIC program plus health information via email and weekly health coach discussions to promote healthy eating and adequate physical activity. Weight and household chaos were measured at baseline (early pregnancy, 10+0 to 16+6 weeks gestation) and at the end of the intervention (late pregnancy, 35+0 to 37+6 weeks gestation). Household chaos changes across time were examined using a paired t test for the continuous score and using the McNemar test for household chaos category (improved or no change vs declined). Serial linear regression models and mediation analyses assessed the relationship between the intervention group (predictor), household chaos change (mediator), and GWG (outcome) with adjustment for covariates. Results: Among 258 participants, 53.9% (n=139) were Black, 43.4% (n=112) were nulliparous, 36.0% (n=93) were obese, and almost half (n=124, 48.1%) were classified as low household chaos at baseline. Overall, there were minimal changes in household chaos scores from early to late pregnancy (P=.34), although scores and categories tended to be higher in late pregnancy. Household chaos changes were divided; some improved or had no change (n=140, 54.3%), and some declined (n=118, 45.7%) across gestation. Household chaos did not mediate the effect of the intervention on GWG. Conclusions: In this sample, household chaos did not change across gestation and did not explain the effect of an eHealth behavioral GWG intervention in pregnant people with lower SES. Routine-focused and multilevel interventions may improve upon these findings to support an organized home for future parent and child health. Trial Registration: ClinicalTrials.gov NCT04028843; https://www.clinicaltrials.gov/study/NCT04028843

Background: Underserved pregnant women have a greater risk of excessive or inadequate gestational weight gain (GWG) and adverse perinatal outcomes. In the United States, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides supplemental nutrition and is uniquely positioned to deliver equitable interventions that support recommended GWG. Yet to date, no randomized controlled trials have evaluated behavioral strategies for managing GWG in this setting. Objective: The primary objective was to examine the effects of a statewide randomized multicomponent mobile eHealth lifestyle intervention trial on change in physical activity and sedentary time across pregnancy. The secondary objective was to explore associations between changes in physical activity, sedentary time, and GWG. Methods: A total of 351 pregnant women were recruited from the Louisiana WIC clinics and were randomly assigned to a multicomponent mobile eHealth intervention for GWG management (N=179) or usual care (N=172; standard in-person WIC care) prior to 16 weeks of gestation. The multicomponent mobile intervention included daily weighing, step tracking, counseling, exercise videos, health coach interactions, and social support. For the first objective, physical activity, including movement duration and movement context, and sedentary time were assessed at baseline (early pregnancy) and at the end of the intervention (late pregnancy) using accelerometry and the Pregnancy Physical Activity Questionnaire. For the second objective, GWG was determined based on weight collected at study visits in early and late pregnancy. Linear mixed models assessed intervention effects on physical activity and GWG. Results: Both the Intervention Group and the Usual Care Group significantly increased sedentary time from early to late pregnancy (adjusted effect estimate [95% CI] 62 minutes per day (42-83), P<.001 and 52 minutes per day (31-72), P<.001, respectively). Both the Intervention Group and the Usual Care Group significantly decreased moderate activity (–13 minutes per day (–20 to –6), P<.001 and –10 minutes per day (–17 to –3), P=.01, respectively) and total moderate to vigorous physical activity (–14 minutes per day (–21 to –7), P<.001 and –10 minutes per day (–18 to –3), P=.01, respectively) from early to late pregnancy. For the Pregnancy Physical Activity Questionnaire, the Intervention Group reported an increase in sports participation across pregnancy compared with the Usual Care Group (+4 metabolic equivalent task (MET)–hours per week (2-7); P=.002). There were no associations between physical activity (–7 g (–32 to 18), P=.57) or sedentary time measures (4 g (–4 to 12), P=.31) and GWG. Conclusions: The first of its kind mobile eHealth multicomponent behavioral lifestyle intervention that included guidance to increase physical activity toward national guidelines did not meaningfully impact physical activity outcomes in pregnant women who were enrolled in Louisiana WIC. Trial Registration: ClinicalTrials.gov NCT04028843; https://www.clinicaltrials.gov/study/NCT04028843 International Registered Report Identifier (IRRID): RR2-10.2196/18211

OBJECTIVE: To compare rates of and risk factors for hospitalizations among Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants taking metformin and randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin. RESEARCH DESIGN AND METHODS: Intention-to-treat (ITT) (N = 5,047) and on-assigned-treatment (AT) (N = 4,830) data sets were used. Baseline differences between those hospitalized versus those not hospitalized were assessed. Kaplan-Meier analysis was used to determine incidence for time to first hospitalization, and log-rank tests were used to determine treatment group differences. Time-to-event analyses were used to examine factors affecting subsequent hospitalization risk. RESULTS: During GRADE, 1,636 participants (32.4%) were hospitalized at least once and 751 (14.9%) were hospitalized more than once. Hospitalized participants were older, less likely to be Hispanic, more likely to be White, and more likely to have a history of hypertension and had higher baseline BMI. There were no treatment group differences in incidence for time to first hospitalization in the ITT data set (P = 0.148), but a reduced hazard rate was observed for those taking liraglutide versus those taking glimepiride in the AT data set (hazard ratio 0.78 [95% CI 0.66, 0.92]; P = 0.022). Factors increasing the risk for subsequent hospitalizations included meeting the secondary outcome (HbA1c >7.5%, confirmed), each prior hospitalization, and change from assigned treatment (29%, 41%, and 56% increase in risk, respectively). Assignment to liraglutide versus glimepiride reduced this risk by 13%. CONCLUSIONS: Hospitalizations were common in GRADE, and rates were nearly identical across treatment groups. The small, but significant, reduction in risk for subsequent hospitalizations among participants assigned to liraglutide versus glimepiride may influence treatment decisions in populations similar to GRADE participants.

BACKGROUND Household chaos is an emerging risk factor for childhood obesity development, especially in families with lower socioeconomic status (SES). It is unclear if changes in household chaos, especially in pregnancy, may mediate the effectiveness of weight-related behavioral interventions. OBJECTIVE This study aimed to describe how household chaos changed across gestation and determine whether household chaos mediated the effect of an eHealth behavioral gestational weight gain (GWG) intervention in pregnant people with low SES. METHODS Pregnant people who were enrolled in the US Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) were recruited for a randomized controlled trial testing the effectiveness of an eHealth-based pragmatic intervention for GWG management. The usual care group received the standard WIC program guidance and monthly health coach support with general pregnancy recommendations. The intervention group received the standard WIC program plus health information via email and weekly health coach discussions to promote healthy eating and adequate physical activity. Weight and household chaos were measured at baseline (early pregnancy, 10+0 to 16+6 weeks gestation) and at the end of the intervention (late pregnancy, 35+0 to 37+6 weeks gestation). Household chaos changes across time were examined using a paired t test for the continuous score and using the McNemar test for household chaos category (improved or no change vs declined). Serial linear regression models and mediation analyses assessed the relationship between the intervention group (predictor), household chaos change (mediator), and GWG (outcome) with adjustment for covariates. RESULTS Among 258 participants, 53.9% (n=139) were Black, 43.4% (n=112) were nulliparous, 36.0% (n=93) were obese, and almost half (n=124, 48.1%) were classified as low household chaos at baseline. Overall, there were minimal changes in household chaos scores from early to late pregnancy (P=.34), although scores and categories tended to be higher in late pregnancy. Household chaos changes were divided; some improved or had no change (n=140, 54.3%), and some declined (n=118, 45.7%) across gestation. Household chaos did not mediate the effect of the intervention on GWG. CONCLUSIONS In this sample, household chaos did not change across gestation and did not explain the effect of an eHealth behavioral GWG intervention in pregnant people with lower SES. Routine-focused and multilevel interventions may improve upon these findings to support an organized home for future parent and child health. CLINICALTRIAL ClinicalTrials.gov NCT04028843; https://www.clinicaltrials.gov/study/NCT04028843

BACKGROUND Underserved pregnant women have a greater risk of excessive or inadequate gestational weight gain (GWG) and adverse perinatal outcomes. In the United States, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides supplemental nutrition and is uniquely positioned to deliver equitable interventions that support recommended GWG. Yet to date, no randomized controlled trials have evaluated behavioral strategies for managing GWG in this setting. OBJECTIVE The primary objective was to examine the effects of a statewide randomized multicomponent mobile eHealth lifestyle intervention trial on change in physical activity and sedentary time across pregnancy. The secondary objective was to explore associations between changes in physical activity, sedentary time, and GWG. METHODS A total of 351 pregnant women were recruited from the Louisiana WIC clinics and were randomly assigned to a multicomponent mobile eHealth intervention for GWG management (N=179) or usual care (N=172; standard in-person WIC care) prior to 16 weeks of gestation. The multicomponent mobile intervention included daily weighing, step tracking, counseling, exercise videos, health coach interactions, and social support. For the first objective, physical activity, including movement duration and movement context, and sedentary time were assessed at baseline (early pregnancy) and at the end of the intervention (late pregnancy) using accelerometry and the Pregnancy Physical Activity Questionnaire. For the second objective, GWG was determined based on weight collected at study visits in early and late pregnancy. Linear mixed models assessed intervention effects on physical activity and GWG. RESULTS Both the Intervention Group and the Usual Care Group significantly increased sedentary time from early to late pregnancy (adjusted effect estimate [95% CI] 62 minutes per day (42-83), P<.001 and 52 minutes per day (31-72), P<.001, respectively). Both the Intervention Group and the Usual Care Group significantly decreased moderate activity (–13 minutes per day (–20 to –6), P<.001 and –10 minutes per day (–17 to –3), P=.01, respectively) and total moderate to vigorous physical activity (–14 minutes per day (–21 to –7), P<.001 and –10 minutes per day (–18 to –3), P=.01, respectively) from early to late pregnancy. For the Pregnancy Physical Activity Questionnaire, the Intervention Group reported an increase in sports participation across pregnancy compared with the Usual Care Group (+4 metabolic equivalent task (MET)–hours per week (2-7); P=.002). There were no associations between physical activity (–7 g (–32 to 18), P=.57) or sedentary time measures (4 g (–4 to 12), P=.31) and GWG. CONCLUSIONS The first of its kind mobile eHealth multicomponent behavioral lifestyle intervention that included guidance to increase physical activity toward national guidelines did not meaningfully impact physical activity outcomes in pregnant women who were enrolled in Louisiana WIC. CLINICALTRIAL ClinicalTrials.gov NCT04028843; https://www.clinicaltrials.gov/study/NCT04028843 INTERNATIONAL REGISTERED REPORT RR2-10.2196/18211

Objective: Hypoglycemia is a major concern in type 2 diabetes (T2DM), but little is known about its likelihood compared across common therapies. We compared the likelihood of hypoglycemia among metformin-treated patients with T2DM randomized to the addition of one of 4 common therapies. Research design & methods: Randomized, controlled trial of 5,047 participants with T2DM of 7.5% (>58.5 mmol/mol) was confirmed, rescue glargine and/or aspart insulin was added. We conducted a per-protocol analysis of 4,830, who attended at least one post-baseline visit and took at least one dose of assigned study medication. We assessed severe hypoglycemia events reported throughout the entire study. At quarterly visits, all participants were asked about hypoglycemic symptoms within the last 30 days, and those in the glargine and glimepiride groups were asked for any measured glucose <70 mg/dL (3.9 mmol/L) within this time period. Results: While participants were taking their assigned medications, severe hypoglycemia occurred in 10 (0.8%), 16 (1.3%), 6 (0.5%), and 4 (0.3%), (p<0.05) and hypoglycemic symptoms in 659 (54.2%), 833 (68.3%), 375 (32.4%), and 361 (29.1%) of participants following randomization to glargine, glimepiride, liraglutide, and sitagliptin, respectively (p<0.001). Conclusions: In metformin-treated patients with T2DM who add a second medication, hypoglycemia is most likely with addition of glimepiride, less with glargine, and least likely with liraglutide and sitagliptin. Trial registration: ClinicalTrials.gov Identifier: NCT01794143.