Approach to Obesity Treatment in Primary Care: A Review.

Importance: More than 40% of US adults have obesity, which increases the risks for multiple chronic diseases and premature mortality. Historically, nonsurgical interventions often have not led to sufficient weight loss and maintenance to improve health, but highly effective antiobesity medications (AOMs) have recently become available, and additional effective therapeutics are under development. Given that most medical care for adults with obesity is delivered in primary care settings, guidance for integrating weight-management approaches is needed. Observations: Lifestyle interventions can lead to a mean weight loss of 2% to 9% of initial weight at 1 year and increase the likelihood of weight loss of 5% or more, but weight regain over time is common even with continued treatment. Adjunctive treatments, including AOMs and surgical approaches, can lead to larger, more sustained weight loss and improvements in numerous obesity-associated medical conditions. Highly effective AOMs, including nutrient-stimulated hormone-based therapies, induce mean weight loss of 15% or more. Barriers to intervention, including access to care, have a disproportionate influence on populations most affected by obesity and its consequences. Conclusions and Relevance: Primary care clinicians play a vital role in the assessment, management, and support of patients with obesity. With careful clinical assessment and shared decision-making, a flexible treatment plan can be developed that reflects evidence of treatment efficacy, patient preference, and feasibility of implementation. Adjunctive therapies to lifestyle interventions, including more effective pharmacotherapeutics for obesity, offer hope to patients and the potential for considerable improvements in health and quality of life.

Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop.

Obesity in children remains a major public health problem, with the current prevalence in youth ages 2-19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29-30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.

A Prospective Cohort of Alcohol Use and Alcohol-related Problems Before and After Metabolic and Bariatric Surgery in Adolescents.

OBJECTIVE: To describe alcohol use, alcohol-related harm, and alcohol-related problems preoperatively and up to 8 years following metabolic and bariatric surgery (MBS) in adolescents. BACKGROUND: Risk for alcohol use and alcohol use disorders (AUD) increases post-Roux-en-Y gastric bypass and vertical sleeve gastrectomy in adults. However, data are lacking in adolescents who undergo MBS. METHODS: This study includes 217 adolescents (aged 13-19 y) enrolled in a 5-center prospective cohort study who underwent Roux-en-Y gastric bypass or vertical sleeve gastrectomy (2007-2011) and reported alcohol use preoperatively and annually postoperatively for up to 8 years. Time to elevated Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score, alcohol-related harm, and alcohol-related problems were analyzed with Kaplan-Meier estimates of cumulative incidence. RESULTS: Preoperatively, the median age was 17 years; the median body mass index was 51 kg/m 2 . Alcohol use frequency and average quantity of drinks per drinking day increased postoperatively (2% consumed alcohol 2-4 times/month 6 months versus 24% 8 years postoperatively, P <0.001; 2% consumed≥3 drinks per drinking day 6 months versus 35% 8 years postoperatively, P <0.001). Cumulative incidence of postoperative onset elevated AUDIT-C score, alcohol-related harm, and alcohol-related problems at year 8 were 45% (95% CI:37-53), 43% (95% CI:36-51), and 47% (95% CI:40-55), respectively. CONCLUSIONS: Nearly half of those who underwent MBS as adolescents screened positively for AUD, symptoms of alcohol-related harm, or alcohol-related problems 8 years post-MBS, highlighting the risk for alcohol use and AUD after MBS in adolescents. AUD evaluation and treatment should be integrated into routine long-term care for adolescents undergoing MBS.

State negative affect in relation to loss-of-control eating among children and adolescents in the natural environment.

Affect regulation theory proposes that loss-of-control (LOC)-eating is preceded by increases and followed by decreases in negative affect (NA), but empirical tests of this theory among pediatric samples in the natural environment are needed. Using an ecological momentary assessment approach, we conducted post-hoc analyses to examine LOC-eating severity reported during post-meal surveys in relation to the intensity of composite NA and NA components (anger, anxiety, depression, guilt) throughout the day for two weeks in a cohort of healthy children and adolescents. Multilevel models tested the associations among LOC-eating severity and NA components reported at pre-meal surveys (t-1), post-meal surveys (t), and lagged post-meal surveys (t+1). Models were adjusted for sex, age, race/ethnicity, height, fat mass, socioeconomic status, and time between the occurrence and report of eating episodes; post-meal analyses were also adjusted for pre-meal NA. Participants age 8-17 (N = 100; 55% female; 45% male; 12.83 ± 2.73y; 24% with overweight/obesity) recorded 2410 eating episodes. Pre-meal composite NA and NA components were not associated with LOC-eating severity at the subsequent meal. LOC-eating severity was positively associated with post-meal depression (ß = 0.042, 95% CI = 0.007, 0.076) and guilt (ß = 0.056, 95% CI = 0.017, 0.095), but not composite negative affect, anger, or anxiety. The positive association among LOC-eating severity and guilt persisted in lagged post-meal analyses (ß = 0.075, 95% CI = 0.021, 0.128). Contrary to affect regulation theory and laboratory data, but consistent with prior ecological momentary assessment data in children and adolescents, pre-meal NA was not linked to subsequent LOC-eating. Increased guilt following meals may be a mechanism for the development of exacerbated disordered eating. Longitudinal studies may elucidate how NA is implicated in the etiology of pediatric eating disorders.

Impact of COVID-19 on life experiences reported by a diverse cohort of older adults with diabetes and obesity.

OBJECTIVE: This study aimed to measure the impact of the COVID-19 pandemic on self-reported life experiences in older adults with diabetes and obesity. METHODS: Participants were surveyed in 2020 regarding negative and positive impacts of the pandemic across domains of personal, social, and physical experiences. A cumulative negative risk index (a count of all reported negative impacts of 46 items) and a positive risk index (5 items) were characterized in relation to age, sex, race/ethnicity, BMI, and multimorbidity. RESULTS: Response rate was high (2950/3193, 92%), average age was 76 years, 63% were women, and 39% were from underrepresented populations. Women reported more negative impacts than men (6.8 vs. 5.6; p < 0.001 [of 46 items]) as did persons with a greater multimorbidity index (p < 0.001). Participants reporting African American/Black race reported fewer negative impacts than White participants. Women also reported more positive impacts than men (1.9 vs. 1.6; p < 0.001 [of 5 items]). CONCLUSIONS: Older adults with diabetes and obesity reported more positive impacts of the pandemic than negative impacts, relative to the number of positive (or negative) items presented. Some subgroups experienced greater negative impacts (e.g., for women, a greater multimorbidity index). Efforts to reestablish personal, social, and physical health after the pandemic could target certain groups.

Use of prescription medications associated with weight gain among US adults, 1999-2018: A nationally representative survey.

OBJECTIVE: This study aimed to evaluate trends in the use of obesogenic medications among adults. METHODS: Cross-sectional data on adults aged ≥20 years are from the 1999 to 2018 National Health and Nutrition Examination Survey (n = 52,340). Obesogenic medications were defined according to the 2015 Endocrine Society guidelines on the pharmacological management of obesity. Weight status was categorized according to BMI. Trends in prior 30-day use were evaluated. RESULTS: In NHANES 2017-2018, 20.3% of US adults used an obesogenic medication. Beta-blockers (9.8%) and antidiabetics (5.7%) were the most common; antipsychotics (1.0%) were the least common. Most common indications were disorders of glucose metabolism, hypertension, neuralgia or neuritis, heart disease, and musculoskeletal pain and/or inflammation. From 1999 to 2018, the proportional use of obesogenic medications increased for anticonvulsants (34.4% to 55.0%) but decreased for antidepressants (32.1% to 18.8%), antidiabetics (82.9% to 52.5%), and beta-blockers (83.9% to 80.7%). The proportional use of obesogenic medications was not associated with weight status, except for antipsychotics. CONCLUSIONS: Use of obesogenic medications was common. Differences in the proportional use of obesogenic medication may reflect changing availability of obesogenic versus nonobesogenic medications over time. The decision to prescribe a nonobesogenic alternative, if one exists, is guided by weighing the risks and benefits of available treatments.

Changes in the Prevalence of Symptoms of Depression, Loneliness, and Insomnia in U.S. Older Adults With Type 2 Diabetes During the COVID-19 Pandemic: The Look AHEAD Study.

OBJECTIVE: To evaluate changes in the prevalence of depressive symptoms, loneliness, and insomnia among older adults with type 2 diabetes from 2016 to 2020 and to assess risk factors for these conditions including demographics, multimorbidity, BMI, treatment group, and pre-coronavirus 2019 (COVID-19) measure scores. RESEARCH DESIGN AND METHODS: This was a prospective, observational study of participants from the Look AHEAD (Action for Health in Diabetes) cohort study. Data were from two assessments before COVID-19 (visit 1: April 2016-June 2018 and visit 2: February 2018-February 2020) and one assessment during COVID-19 (visit 3: July-December 2020). Surveys were administered to assess depressive symptoms, loneliness, and insomnia. RESULTS: The study included 2829 adults (63.2% female, 60.6% White, mean [SD] age 75.6 [6.0] years). The prevalence of mild or greater depressive symptoms did not change significantly between the two pre-pandemic visits (P = 0.88) but increased significantly from pre- to during COVID-19 (19.3% at V2 to 30.4% at V3; P < 0.001). Higher odds of mild or greater depressive symptoms at V3 were associated with being female (adjusted odds ratio [OR] 1.4 [95% CI 1.1-1.7]), identifying as non-Hispanic White (OR 1.4 [95% CI 1.1-1.7]), having obesity (OR 1.3 [95% CI 1.0-1.5]), and reporting mild or greater depressive symptoms at V1 (OR 4.0 [95% CI 2.9-5.4]), V2 (OR 4.4 [95% CI 3.2-5.9]), or both visits (OR 13.4 [95% CI 9.7-18.4]). The prevalence of loneliness increased from 12.3% at V1 to 22.1% at V3 (P < 0.001), while the prevalence of insomnia remained stable across visits at 31.5-33.3%. CONCLUSIONS: The prevalence of mild or greater depressive symptoms in older adults with diabetes was more than 1.6 times higher during COVID-19 than before the pandemic.

Changes in Smoking Behavior Before and After Gastric Bypass: A 7-year Study.

OBJECTIVE: To evaluate smoking history and change in smoking behavior, from 1 year before through 7 years after Roux-en-Y gastric bypass (RYGB) surgery, and to identify risk factors for post-surgery smoking. BACKGROUND: Smoking behavior in the context of bariatric surgery is poorly described. METHODS: Adults undergoing RYGB surgery entered a prospective cohort study between 2006 and 2009 and were followed up to 7 years until ≤2015. Participants (N = 1770; 80% female, median age 45 years, median body mass index 47 kg/m2) self-reported smoking history pre-surgery, and current smoking behavior annually. RESULTS: Almost half of participants (45.2%) reported a pre-surgery history of smoking. Modeled prevalence of current smoking decreased in the year before surgery from 13.7% [95% confidence interval (CI) = 12.1-15.4] to 2.2% (95% CI = 1.5-2.9) at surgery, then increased to 9.6% (95% CI = 8.1-11.2) 1-year post-surgery and continued to increase to 14.0% (95% CI = 11.8-16.0) 7-years post-surgery. Among smokers, mean packs/day was 0.60 (95% CI = 0.44-0.77) at surgery, 0.70 (95% CI = 0.62-0.78) 1-year post-surgery and 0.77 (95% CI = 0.68-0.88) 7-years post-surgery. At 7-years, smoking was reported by 61.7% (95% CI = 51.9-70.8) of participants who smoked 1-year pre-surgery (n = 221), 12.3% (95% CI = 8.5-15.7) of participants who formerly smoked but quit >1 year pre-surgery (n = 507), and 3.8% (95% CI = 2.1-4.9) of participants who reported no smoking history (n = 887). Along with smoking history (ie, less time since smoked), younger age, household income <$25,000, being married or living as married, and illicit drug use were independently associated with increased risk of post-surgery smoking. CONCLUSION: Although most adults who smoked 1-year before RYGB quit pre-surgery, smoking prevalence rebounded across 7-years, primarily due to relapse.

Associations of sleep with food cravings and loss-of-control eating in youth: An ecological momentary assessment study.

BACKGROUND: Inconsistent sleep patterns may promote excess weight gain by increasing food cravings and loss-of-control (LOC)-eating; however, these relationships have not been elucidated in youth. OBJECTIVE: We tested whether sleep duration and timing were associated with food cravings and LOC-eating. METHOD: For 14 days, youths wore actigraphy monitors to assess sleep and reported severity of food cravings and LOC-eating using ecological momentary assessment. Generalized linear mixed models tested the associations between weekly and nightly shifts in facets of sleep (i.e., duration, onset, midpoint, and waketime) and next-day food cravings and LOC-eating. Models were re-run adjusting for relevant covariates (e.g., age, sex, adiposity). RESULTS: Among 48 youths (12.88 ± 2.69 years, 68.8% female, 33.3% with overweight/obesity), neither weekly nor nightly facets of sleep were significantly associated with food cravings (ps = 0.08-0.93). Youths with shorter weekly sleep duration (est. ß = -0.31, p = 0.004), earlier weekly midpoints (est. ß = -0.47, p = 0.010) and later weekly waketimes (est. ß = 0.49, p = 0.010) reported greater LOC-eating severity; findings persisted in adjusted models. CONCLUSIONS: In youth, weekly, but not nightly, shifts in multiple facets of sleep were associated with LOC-eating severity; associations were not significant for food cravings. Sleep should be assessed as a potentially modifiable target in paediatric LOC-eating and obesity prevention programs.

Longitudinal associations between facets of sleep and adiposity in youth.

OBJECTIVE: Beyond sleep duration, other facets of sleep such as variability and timing may be associated with obesity risk in youth. However, data are limited. Using a longitudinal design, this study tested whether multiple facets of sleep were associated with fat mass gain over 1 year. METHODS: A convenience sample of non-treatment-seeking youth (age 8-17 years) wore actigraphy monitors for 14 days. Average weekly sleep duration, within-person sleep duration variability, weekend catch-up sleep, bedtime and wake time shift, social jet lag, bedtime, wake time, and sleep midpoint were calculated. The association of each facet of baseline sleep with 1-year fat mass, adjusting for baseline fat mass and height, was examined. RESULTS: A total of 137 youths (54.0% female; mean [SD], age 12.5 [2.6] years; 28.4% non-Hispanic Black or African American; baseline fat mass = 15.3 [8.9] kg; 1-year fat mass = 17.0 [10.0] kg; 28.5% with baseline overweight or obesity) were studied. Wake time (p = 0.03) and sleep midpoint (p = 0.02) were inversely associated with 1-year fat mass, such that earlier wake time and midpoint were associated with higher 1-year fat mass. No other facet of sleep was significantly associated with 1-year fat mass (p > 0.09). CONCLUSIONS: Using objective measures, youth with earlier wake times and sleep midpoints had greater gains in fat mass. Additional research is needed to determine whether sleep timing may be a modifiable target to prevent pediatric obesity.

Changes in mood and health-related quality of life in Look AHEAD 6 years after termination of the lifestyle intervention.

OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. METHODS: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. RESULTS: ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. CONCLUSIONS: Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.

Food cravings and loss-of-control eating in youth: Associations with gonadal hormone concentrations.

OBJECTIVE: Among youth with overweight, food cravings (FC) are associated with loss-of-control (LOC)-eating, but the impact of sex-associated biological characteristics on this relationship is unknown. We examined whether sex and gonadal hormone concentrations moderated the relationships between FC and LOC-eating severity among healthy boys and girls across the weight strata in natural and laboratory environments. METHOD: Using ecological momentary assessment (EMA), FC, and LOC-eating severity were reported 3-5 times a day for 2 weeks. In the laboratory, participants reported FC, consumed lunch from a buffet test meal designed to simulate LOC-eating, and rated LOC-eating severity during the meal. RESULTS: Eighty-seven youth (13.0 ± 2.7 years, 58.6% female, 32.2% with overweight/obesity) participated. EMA measured general and momentary FC were positively associated with LOC-eating severity (ps < .01), with no differences by sex (ps = .21-.93). Estradiol and progesterone significantly moderated the relationships between FC and LOC-eating such that general FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) estradiol (p = .01), and momentary FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) progesterone (p = .01). Boys' testosterone did not significantly moderate the associations between FC and LOC-eating severity (ps = .36-.97). At the test meal, pre-meal FC were positively related to LOC-eating severity (p < .01), without sex or hormonal moderation (ps = .20-.64). DISCUSSION: FC were related to LOC-eating severity in boys and girls. In the natural environment, gonadal hormones moderated this relationship in girls, but not boys. The mechanisms through which gonadal hormones might affect the relationship between FC and LOC-eating warrant investigation.

Physiology of the Weight-Reduced State: A Report from a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Preventing regain of lost weight is the most difficult challenge in the treatment of obesity. The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop, "The Physiology of the Weight-Reduced State," on June 3 to 4, 2019, in order to explore the physiologic mechanisms of appetitive and metabolic adaptation that take place in the weight-reduced state and counter an individual's efforts to maintain reduced weight following weight loss.

Within-Trial Cost-Effectiveness of a Structured Lifestyle Intervention in Adults With Overweight/Obesity and Type 2 Diabetes: Results From the Action for Health in Diabetes (Look AHEAD) Study.

OBJECTIVE: To assess the cost-effectiveness (CE) of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, as implemented in the Action for Health in Diabetes study. RESEARCH DESIGN AND METHODS: Data were from 4,827 participants during their first 9 years of study participation from 2001 to 2012. Information on Health Utilities Index Mark 2 (HUI-2) and HUI-3, Short-Form 6D (SF-6D), and Feeling Thermometer (FT), cost of delivering the interventions, and health expenditures was collected during the study. CE was measured by incremental CE ratios (ICERs) in costs per quality-adjusted life year (QALY). Future costs and QALYs were discounted at 3% annually. Costs were in 2012 U.S. dollars. RESULTS: Over the 9 years studied, the mean cumulative intervention costs and mean cumulative health care expenditures were $11,275 and $64,453 per person for ILI and $887 and $68,174 for DSE. Thus, ILI cost $6,666 more per person than DSE. Additional QALYs gained by ILI were not statistically significant measured by the HUIs and were 0.07 and 0.15, respectively, measured by SF-6D and FT. The ICERs ranged from no health benefit with a higher cost based on HUIs to $96,458/QALY and $43,169/QALY, respectively, based on SF-6D and FT. CONCLUSIONS: Whether ILI was cost-effective over the 9-year period is unclear because different health utility measures led to different conclusions.

Weight-based teasing in youth: Associations with metabolic and inflammatory markers.

BACKGROUND: Research among adults suggests that weight stigma is associated with worsened cardiometabolic health. However, these relationships have not been examined among youth. OBJECTIVE: Assess associations between weight-based teasing (WBT) and metabolic and inflammatory markers among two samples of youth: (1) a non-treatment-seeking sample and (2) a weight loss treatment-seeking sample with obesity. METHOD: Weight, height, adiposity, waist circumference and blood pressure were measured. Fasting blood samples were collected for metabolic (triglycerides, glucose, high-density lipoprotein cholesterol) and inflammatory analytes (high-sensitivity C-reactive protein in Study 1 and erythrocyte sedimentation rate in both studies). Youths completed the Perception of Teasing Scale, a measure of WBT. Metabolic and inflammatory indices were compared between those with and without teasing, adjusting for demographics and body composition. RESULTS: Study 1 enrolled 201 non-treatment-seeking youth (Mage = 13.1y; 54.2% female; 44.8% non-Hispanic White; 32.8% with overweight/obesity); 15.4% reported WBT. Study 2 enrolled 111 treatment-seeking adolescents with obesity (Mage = 14.0y; 66.7% female; 37.8% non-Hispanic White); 73.0% reported WBT. Adjusting for covariates, WBT was not associated with cardiometabolic risk factors in either study. CONCLUSIONS: WBT was not associated with worsened cardiometabolic health. Longitudinal research is needed to elucidate associations between WBT and health in youth.

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.

Cross-Sectional and Longitudinal Examination of Insulin Sensitivity and Secretion across Puberty among Non-Hispanic Black and White Children.

BACKGROUND: Few studies using criterion measures of insulin sensitivity (SI) and insulin secretory capacity (ISC) have been conducted across puberty to adulthood. We examined how SI and ISC change from pre-puberty through adulthood. METHODS: Hyperglycemic clamp studies were performed in a convenience sample of non-Hispanic Black (NHB) and White children evaluated at age 6 to 12 years and at approximately 5-year intervals into adulthood (maximum age 27 years). SI and ISC (first-phase and steady-state insulin secretion) were determined cross-sectionally in 133 unique participants across puberty and in adulthood. Additionally, longitudinal changes in SI and ISC were compared at two timepoints among three groups defined by changes in pubertal development: pre-pubertal at baseline and late-pubertal at follow-up (n=27), early-pubertal at baseline and late-pubertal at follow-up (n=27), and late-pubertal at baseline and adult at follow-up (n=24). RESULTS: Cross-sectionally, SI was highest in pre-puberty and early puberty and lowest in mid-puberty (analysis of covariance [ANCOVA] P=0.001). Longitudinally, SI decreased from pre-puberty to late puberty (P<0.001), then increased somewhat from late puberty to adulthood. Cross-sectionally, first-phase and steady-state ISC increased during puberty and decreased in adulthood (ANCOVA P<0.02). Longitudinally, steady-state and first-phase ISC increased from pre-puberty to late puberty (P<0.007), and steady-state ISC decreased from late puberty to adulthood. The NHB group had lower SI (P=0.003) and greater first-phase and steady-state ISC (P≤0.001), independent of pubertal development. CONCLUSION: This study confirms that SI decreases and ISC increases transiently during puberty and shows that these changes largely resolve in adulthood.