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Diabetes-related gastroparesis is a challenging complication of diabetes that often results in flares of intractable vomiting and recurrent hospitalizations. Currently, there is no standard of care or guidelines for the management of diabetes-related gastroparesis in the acute care setting, leading to inconsistent and suboptimal care for these patients. Consequently, patients with diabetes-related gastroparesis may have prolonged inpatient lengths of stay and frequent readmissions affecting their overall health and well-being. Successful management of diabetes-related gastroparesis requires a coordinated multimodal approach to address the different components of an acute flare, including nausea and vomiting, pain, constipation, nutrition, and dysglycemia. This case report demonstrates how the development and implementation of an acute care diabetes-related gastroparesis treatment protocol demonstrates efficacy and promise for better quality of care for this population.

Achieving target inpatient glycemic management outcomes has been shown to influence important clinical outcomes such as hospital length of stay and readmission rates. However, arguably the most profound, lasting impact of inpatient diabetes management is achieved at the time of discharge—namely reconciling and prescribing the right medications and making referrals for follow-up. Discharge planning offers a unique opportunity to break through therapeutic inertia, offer diabetes self-management education, and institute an individualized treatment plan that prepares the patient for discharge and promotes self-care and engagement. However, the path to a successful discharge plan can be fraught with potential pitfalls for clinicians, including lack of knowledge and experience with newer diabetes medications, costs, concerns over insurance coverage, and lack of time and resources. This article presents an algorithm to assist clinicians in selecting discharge regimens that maximize benefits and reduce barriers to self-care for patients and a framework for creating an interdisciplinary hospital diabetes discharge program.

Background Studies have shown the predictive value of hemoglobin A1c (HbA1c) on inpatient glycemic control, and its value for discharge planning. There is little data on HbA1c testing adherence to American Diabetes Association (ADA) guidelines among inpatient providers, and anecdotal evidence suggests that most inpatient providers do not have a standardized approach to HbA1c measurement. The Lean Six Sigma method is a management system that originated in the automobile industry and has become widely used in healthcare to improve the efficiency of processes. The objective of this study was to determine the impact utilizing Lean Six Sigma methodology to increase frequency of HbA1c measurements among hospitalized patients with a known history of diabetes, in line with ADA guidelines. Methods This was a quality improvement study performed in a 240-bed community hospital, evaluating inpatients (≥16 years) consecutively admitted with a diagnosis of diabetes (ICD-10 code E8-E13 and O24) between January 2016-June 2021. Patients were excluded if they had a HbA1c in the health system electronic health record (EHR) in the prior 3 months. The Lean Six Sigma approach was utilized to define the problem and implement solutions. The intervention bundle delivered between November 2017 and February 2018 included 1) provider and nursing education on the utility of HbA1c in patient care, 2) change in laboratory protocols for more rapid turnaround of HbA1c, 3) modifications to the EHR including a glucose management tab and insulin order set that included HbA1c. Hospital encounter and patient-level data were extracted from the EHR via bulk query. Demographic characteristics were calculated. Frequency of HbA1c lab sent while inpatient was compared pre- (Jan 2016-Nov 2017) and post-intervention (March 2018-June 2021) using chi-square analysis. Results 17,869 patients were included (7,332 pre- and 10,537 post-intervention). Demographics did not differ between pre and post intervention periods (mean age [range]: 78.1 [16-106] years, sex: 52.3% male, race: 52.1% White, 25.1% Black). Only 53.5% of patients who met criteria had a HbA1c measured during hospitalization before intervention. This frequency increased to 70.2% postintervention. The improvement in the frequency of HbA1c measurement was sustained more than two years following the initial interventions and continued to improve over time. Conclusion This novel approach was successful in improving adherence to guideline-based measurement of HbA1c in hospitalized patients. This is the first quality improvement project in a community hospital utilizing the Lean Six Sigma process for this purpose and may represent a valuable methodology for community hospitals to improve inpatient diabetes care. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Background: Community hospitals account for over 84% of all hospitals and over 94% of hospital admissions in the United States. In academic settings, implementation of an Inpatient Diabetes Management Service (IDMS) model of care has been shown to reduce rates of hyper- and hypoglycemia, hospital length of stay (LOS), and associated hospital costs. However, few studies to date have evaluated the implementation of a dedicated IDMS in a community hospital setting. Methods: This retrospective study examined the effects of changing the model of inpatient diabetes consultations from a local, private endocrine practice to a full-time endocrine hospitalist on glycemic control, LOS, and 30-day readmission rates in a 267-bed community hospital. Results: Overall diabetes patient days for the hospital were similar pre- and post-intervention (20,191 vs 20,262); however, the volume of patients seen by IDMS increased significantly after changing models. Rates of hyperglycemia decreased both among patients seen by IDMS (53.8% to 42.5%, P < .0001) and those not consulted on by IDMS (33.2% to 29.9%; P < .0001). When examined over time, rates of hypoglycemia steadily decreased in the 24 months after dedicated IDMS initiation ( P = .02); no such time effect was seen prior to IDMS ( P = .34). LOS and 30DRR were not significantly different between IDMS models. Conclusions: Implementation of an endocrine hospitalist-based IDMS at a community hospital was associated with significantly decreased hyperglycemia, while avoiding concurrent increases in hypoglycemia. Further studies are needed to investigate whether these effects are associated with improvements in clinical outcomes, patient or staff satisfaction scores, or total cost of care.

Background: The American Diabetes Association (ADA) recommends measuring A1C in all inpatients with diabetes if not performed in the prior three months. Our objective was to determine the impact of utilizing Lean Six Sigma to increase the frequency of A1C measurements in hospitalized patients. Methods: We evaluated inpatients with diabetes mellitus consecutively admitted in a community hospital between January 2016 and June 2021, excluding those who had an A1C in the electronic health record (EHR) in the previous three months. Lean Six Sigma was utilized to define the extent of the problem and devise solutions. The intervention bundle delivered between November 2017 and February 2018 included (1) provider education on the utility of A1C, (2) more rapid turnaround of A1C results, and (3) an EHR glucose-management tab and insulin order set that included A1C. Hospital encounter and patient-level data were extracted from the EHR via bulk query. Frequency of A1C measurement was compared before (January 2016-November 2017) and after the intervention (March 2018-June 2021) using χ2 analysis. Results: Demographics did not differ preintervention versus postintervention (mean age [range]: 70.9 [18-104] years, sex: 52.2% male, race: 57.0% white). A1C measurements significantly increased following implementation of the intervention bundle (61.2% vs 74.5%, P < .001). This level was sustained for more than two years following the initial intervention. Patients seen by the diabetes consult service (40.4% vs 51.7%, P < 0.001) and length of stay (mean: 135 hours vs 149 hours, P < 0.001) both increased postintervention. Conclusions: We demonstrate a novel approach in improving A1C in hospitalized patients. Lean Six Sigma may represent a valuable methodology for community hospitals to improve inpatient diabetes care.

STRUCTURED ABSTRACTBackground and ObjectivesMuscular dystrophies associated with decreased sarcolemma integrity lack validated clinical measures of sarcolemma fragility that can be used to assess disease progression and the effects of therapies designed to reduce sarcolemma fragility. We conducted a pilot study to test the hypothesis that physical activity leads to significant changes in muscle-derived plasma enzymes in participants with “fragile sarcolemmal muscular dystrophies” (FSMD).MethodsWe enrolled ambulatory individuals clinically affected with genetically confirmed FSMD neither taking anti-inflammatory medications nor having relevant co-morbidities for an inpatient study. Over five days, blood samples at 20 time points were obtained. Plasma enzymes alanine and aspartate aminotransferase (ALT, AST), creatine kinase (CK), and lactate dehydrogenase (LDH), all found in muscle, were measured before and after routine morning activities and motor function testing. Analysis of Z-transformed time series data led to feature and kinetic models that revealed activity-dependent feature and kinetic parameters.ResultsAmong the 11 enrolled participants, (LGMD Type 2B/R2 Dysferlin-related (4F/1M), LGMD Type 2L/R12 Anoctamin-5-related (3F/2M), LGMD Type 2I/R9 FKRP-related (1M)), plasma enzymes increased with activity. The average % change +/- SEM with morning activity across all participants was ALT 12.8 ± 2.8%, AST 11.6 ± 2.9%, CK 12.9 ± 2.8%, and LDH 12.2 ± 3.9%, suggesting the increases originate from the same stimulated source, presumably skeletal muscle. For ALT, AST, CK, and LDH, characteristic kinetic features include (a) elevated enzyme activities on arrival that decreased overnight; (b) a longer decay trend observed over the week, and (c) for ALT, AST, and CK, a similar decay trend observed with post-morning activity blood draws.DiscussionControlled activity-dependent changes in plasma ALT, AST, and CK on time scales of days to weeks can serve as common outcome measures for sarcolemma integrity and may be efficient and effective tools for monitoring disease progression and treatment efficacy for both individuals and patient populations. In addition, this study provides data that may benefit patient management as it can inform guidance on duration and type of activity that minimizes muscle damage.

Biochemical characterization of primary bilateral macronodular adrenocortical hyperplasia (PBMAH) by distinct plasma steroid profiles and its putative correlation to disease has not been previously studied. LC-MS/MS–based steroid profiling of 16 plasma steroids was applied to 36 subjects (22 females, 14 males) with PBMAH, 19 subjects (16 females, 3 males) with other forms of adrenal Cushing's syndrome (ACS), and an age and sex-matched control group. Germline ARMC5 sequencing was performed in all PBMAH cases. Compared to controls, PBMAH showed increased plasma 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol, and aldosterone, but lower progesterone, DHEA, and DHEA-S with distinct differences in subjects with and without pathogenic variants in ARMC5. Steroids that showed isolated differences included cortisol and 18-oxocortisol with higher (P ARMC5 was achieved in 91.7% of subjects with PBMAH. Subjects with PBMAH show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

Objective Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine’s effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS). Methods Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini–Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing. Results At baseline, age (48.0 ± 13.8 vs. 44.7 ± 10.3 years) and BMI (39.8 ± 6.4 vs. 41.8 ± 8.2 kg/m2) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis. Conclusions In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine’s IL-6 suppressive effects may be beneficial in COVID-19.

Health-deteriorating effects of obesity include chronic inflammation and insulin resistance (IR). A recent pilot human trial reported reduced IR in colchicine-treated vs. placebo-treated adults with obesity. Thus, we examined anti-inflammatory and metabolic effects of two commonly employed dosing regimens of colchicine, 0.2 mg/kg and 0. 02mg/kg, in a high-fat diet (HFD; 45%) mouse obesity model. We placed male C57BL/6J mice on HFD from ages 8 through 16 weeks. At age 12 weeks, mice were randomized to: high-dose colchicine (CHD 0.2 mg/kg, n=28), low dose colchicine (CLD, 0. 02mg/kg, n=26) or vehicle (V, n=26), injected intraperitoneally (IP) for 4 weeks. Serum CRP was measured by ELISA. Dual-energy X-ray absorptiometry (DXA) scans and fasting IP glucose tolerance (GTT) and insulin-tolerance (ITT) tests were performed at baseline and following treatment. Hepatic tissue was processed for immunoblotting to determine expression of NLRP3 and caspase-1. Changes in pre- vs. post-treatment serum CRP were significantly different in the CHD group (Mean±SD: -0.57±3.1µg/mL) vs. V (+3.64±2.9µg/mL; p Presentation: No date and time listed

OBJECTIVE: To examine if colchicine’s anti-inflammatory effects would improve measures of lipolysis and distribution of leukocyte populations in subcutaneous adipose tissue (SAT). METHODS: We conducted a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6mg or placebo twice-daily for 3 months. Noninsulin-suppressible (l(0)), insulin-suppressible (l(2)), and maximal (l(0)+l(2)) lipolysis rates were calculated by minimal model analysis. Body composition was determined by dual-energy x-ray absorptiometry. SAT leukocyte populations were characterized by flow cytometry analysis from biopsied samples obtained pre- and post-intervention. RESULTS: Colchicine treatment significantly decreased l(2) and l(0)+l(2) versus placebo (p’s 0.05). CONCLUSIONS: In adults with obesity and MetS, colchicine appears to improve insulin regulation of lipolysis and reduce markers of systemic inflammation independent of an effect on local leukocyte distributions in SAT. Further studies are needed to better understand the mechanisms by which colchicine affects adipose tissue metabolic pathways in adults with obesity and MetS.

Knockout mice for the kisspeptin receptor, Kiss1r (Kiss1r−/−) and its ligand kisspeptin, Kiss1 (Kiss1−/−) replicate the phenotype of isolated hypogonadotropic hypogonadism (IHH) associated with variants of these genes in humans. A recent report suggests that kisspeptin may be involved in human fetal adrenocortical development and function. Herein, we characterized the adrenal function and morphology in Kiss1−/− mice that do not go through normal puberty. Two fetal markers were expressed in eosinophilic cells potentially derived from the X-zone that should disappear at puberty in male mice and during the first pregnancy in female animals. Although the hypercorticosteronism observed in Kiss1−/− females corrected overtime, hyperaldosteronism persisted at 14 months and correlated with the overexpression of Star. To determine if KISS1 and KISS1R genes are involved in the development of primary aldosteronism (PA) and hypercortisolism [Cushing’s syndrome (CS)] in humans, we sequenced these 2 genes in 65 patients with PA and/or CS. Interestingly, a patient with CS presented with a germline KISS1 variant (p.H90D, rs201073751). We also found three rare variants in the KISS1R gene in three patients with PA: p.C95W (rs141767649), p.A189T (rs73507527) and p.R229R (rs115335009). The two missense variants have been previously associated with IHH. Our findings suggest that KISS1 may play a role in adrenal function in mice and possibly adrenocortical steroid hormone secretion in humans, beyond its recently described role in human fetal adrenocortical development.

Recent studies examining the genetic underpinnings of obesity have suggested that the melanocortin 3 receptor (MC3R) plays a role in body composition and nutrient partitioning (Chen et al., 2000, Demidowich et al., 2017). In mice, inactivating Mc3r causes increased feeding efficiency leading to obesity with increased fat mass, but with reduced lean mass (Chen et al., 2000, Kumar et al., 2009, Butler et al., 2017, Renquist et al., 2011). The common minor human MC3R C17A+G241A haplotype, which leads to 2 amino acid substitutions Thr6Lys and Val81Ile in the protein translated from the first start site of the human gene, leads to a partially inactive protein transcript (Feng et al., 2005). In a large pediatric cohort, individuals homozygous for the MC3R C17A+G241A haplotype were reported to have greater BMI, body fat, plasma leptin, and insulin concentrations, with reduced lean mass when compared to those who were heterozygous (Het) for the C17A + G241A haplotype and homozygous for the wild-type MC3R gene (WT) (Feng et al., 2005). The greater adiposity and reduced signal transduction associated with homozygosity for the C17A+G241A haplotype has since been replicated in other pediatric cohorts (Savastano et al., 2009, Lee et al., 2007, Aris et al., 2015). Supportive data for the effects of this haplotype have also been reported in mice. When the murine Mc3r was replaced with the human MC3R C17A+G241A haplotype, homozygous knockin mice also displayed increased feeding efficiency, greater adiposity, and reduced lean mass (Lee et al., 2016). Among adult human cohorts, however, the MC3R C17A+G241A haplotype has not been associated with greater BMI (Li et al., 2000, Hani et al., 2001, Wong et al., 2002, Rutanen et al., 2007, Calton et al., 2009, Matsuoka et al., 2007) and scant data exist for its effects on other anthropometric or metabolic parameters (Hani et al., 2001, Rutanen et al., 2007). A major limitation of most of these prior studies is the low number of homozygous participants (Calton et al., 2009, Li et al., 2000, Hani et al., 2001, Wong et al., 2002, Rutanen et al., 2007); consequently, many prior conclusions were based largely on the assumption that heterozygotes and homozygotes are phenotypically identical or there would be additive effects from each minor allele/haplotype. Although labelled as a common variant, the MC3R C17A+G241A haplotype is relatively rare in most races and ethnicities, with an estimated prevalence of homozygous individuals between 0.4–3.5% (Obregon et al., 2010, Lee et al., 2007, Rutanen et al., 2007, Hani et al., 2001). Individuals of predominately African ancestry are the exception, as over half carry at least one copy of the haplotype, and 12–16% are homozygous for C17A+G241A (Li et al., 2000, Feng et al., 2005, Savastano et al., 2009). As such individuals have been underrepresented in most adult cohort studies examining MC3R polymorphisms, it remains unclear if homozygous individuals have a different anthropometric and metabolic phenotype than Het or WT adults. To our knowledge, this is the first study of a large cohort of adults that has assessed the association of the MC3R C17A+G241A haplotype with body composition data such as fat mass and lean mass. Our primary hypothesis was that homozygosity for the MC3R C17A+G241A haplotype would be associated with greater BMI and fat mass in African American adults. We additionally hypothesized that this increase in adiposity would be associated with greater insulin resistance and inflammation in homozygous individuals as compared to Het and WT.

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include KCNJ5 , ATP1A1 , ATP2B3 , and CACNA1D . Based on independent studies, there appears to be racial differences in the prevalence of somatic KCNJ5 mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population. In the present study, we investigated genetic characteristics of APAs in blacks using a CYP11B2 (aldosterone synthase) immunohistochemistry-guided next-generation sequencing approach. The adrenal glands with adrenocortical adenomas from 79 black patients with primary aldosteronism were studied. Seventy-three tumors from 69 adrenal glands were confirmed to be APAs by CYP11B2 immunohistochemistry. Sixty-five of 73 APAs (89%) had somatic mutations in aldosterone-driver genes. Somatic CACNA1D mutations were the most prevalent genetic alteration (42%), followed by KCNJ5 (34%), ATP1A1 (8%), and ATP2B3 mutations (4%). CACNA1D mutations were more often observed in APAs from males than those from females (55% versus 29%, P =0.033), whereas KCNJ5 mutations were more prevalent in APAs from females compared with those from males (57% versus 13%, P CACNA1D . Determination of racial differences in the prevalence of aldosterone-driver gene mutations may facilitate the development of personalized medicines for patients with primary aldosteronism.

Background: Hospitalized patients who are receiving antihyperglycemic agents are at increased risk for hypoglycemia. Inpatient hypoglycemia may lead to increased risk for morbidity, mortality, prolonged hospitalization, and readmission within 30 days of discharge, which in turn may lead to increased costs. Hospital-wide initiatives targeting hypoglycemia are known to be beneficial; however, their impact on patient care and economic measures in community nonteaching hospitals are unknown. Methods: This retrospective quality improvement study examined the effects of hospital-wide hypoglycemia initiatives on the rates of insulin-induced hypoglycemia in a community hospital setting from January 1, 2016, until September 30, 2019. The potential cost of care savings has been calculated. Results: Among 49 315 total patient days, 2682 days had an instance of hypoglycemia (5.4%). Mean ± SD hypoglycemic patient days/month was 59.6 ± 16.0. The frequency of hypoglycemia significantly decreased from 7.5% in January 2016 to 3.9% in September 2019 ( P = .001). Patients with type 2 diabetes demonstrated a significant decrease in the frequency of hypoglycemia (7.4%-3.8%; P < .0001), while among patients with type 1 diabetes the frequency trended downwards but did not reach statistical significance (18.5%-18.0%; P = 0.08). Based on the reduction of hypoglycemia rates, the hospital had an estimated cost of care savings of $98 635 during the study period. Conclusions: In a community hospital setting, implementation of hospital-wide initiatives targeting hypoglycemia resulted in a significant and sustainable decrease in the rate of insulin-induced hypoglycemia. These high-leverage risk reduction strategies may be translated into considerable cost savings and could be implemented at other community hospitals.

Context Diabetes is a leading metabolic disorder with a substantial cost burden, especially in inpatient settings. The complexity of inpatient glycemic management has led to the emergence of inpatient diabetes management service (IDMS), a multidisciplinary team approach to glycemic management. Objective To review recent literature on the financial and clinical impact of IDMS in hospital settings. Methods We searched PubMed using a combination of controlled vocabulary and keyword terms to describe the concept of IDMS and combined the search terms with a comparative effectiveness filter for costs and cost analysis developed by the National Library of Medicine. Findings In addition to several improved clinical endpoints such as glycemic management outcomes, IDMS implementation is associated with hospital cost savings through decreased length of stay, preventing hospital readmissions, hypoglycemia reduction, and optimizing resource allocation. There are other downstream potential cost savings in long-term patient health outcomes and avoidance of litigation related to suboptimal glycemic management. Conclusion IDMS may play an important role in helping both academic and community hospitals to improve the quality of diabetes care and reduce costs. Clinicians and policymakers can utilize existing literature to build a compelling business case for IDMS to hospital administrations and state legislatures in the era of value-based healthcare.

Background: Obesity-associated inflammation promotes adipose tissue (AT) dysfunction and contributes to the progression of type 2 diabetes and cardiovascular disease. Recent clinical studies have demonstrated that colchicine may improve metabolic and cardiovascular outcomes; however, colchicine’s effects on metabolic and inflammatory measures within AT remain unclear. Methods: The aim of this study was to examine if colchicine’s anti-inflammatory effects would improve measures of lipolysis and immune cell populations in subcutaneous AT (SAT). This is a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 nondiabetic adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6mg or placebo twice daily for 3 months. Blood samples for insulin, glucose, and free fatty acids were collected in the fasted state and during a frequently-sampled intravenous glucose tolerance test. Noninsulin-suppressible (l0), insulin-suppressible (l2), and maximal (l0+l2) lipolysis rates were calculated by minimal model analysis. Body composition was determined by DXA. SAT immune cell populations were characterized by flow cytometry fluorescence-activated single cell sorting of the stromovascular fractions obtained after collagenase digestion of SAT samples obtained using a mini-liposuction technique pre- and post-intervention. Results: Data from 18 subjects in the colchicine group (Mean ± SD: age 48.4 ± 13.5 y; BMI 39.3 ± 6.3 kg/m2; sex: female 72.2%) and 18 subjects in the placebo group (age 44.7 ± 10.2 y; BMI 41.8 ± 8.2 kg/m2; sex: female 77.8%) were available for this study. Colchicine treatment significantly reduced l2 (p = 0.04) and l0+l2 (p = 0.04) versus placebo. These changes were significantly associated with reductions in systemic inflammation, including the changes in high-sensitivity C-reactive protein concentrations, white blood cell count, circulating monocyte and neutrophil populations, and the neutrophil-lymphocyte ratio (p’s < 0.015). Colchicine did not significantly alter SAT immune cell population distributions (p’s > 0.05). Conclusions: In adults with obesity and MetS, colchicine may improve insulin action at the level of AT. These improvements were positively associated with the suppression of systemic inflammation. However, no local AT inflammatory cell populations were significantly affected by colchicine use in our study, suggesting that colchicine’s systemic, rather than local, anti-inflammatory effects may be more consequential in ameliorating AT metabolic pathways in MetS. Further studies are warranted to elucidate the biological mechanisms underlying colchicine’s effects in AT, as these investigations could potentially shed light on treatments to improve metabolic outcomes in human obesity.

Context Radiological characterization of adrenal size in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) has not been previously investigated. Objective We hypothesized that volumetric modeling of adrenal gland size may correlate with biochemical disease severity in patients with PBMAH. Secondary analysis of patients with concurrent primary aldosteronism (PA) was performed. Design A retrospective cross-sectional analysis of 44 patients with PBMAH was conducted from 2000 to 2019. Setting Tertiary care clinical research center. Patients Patients were diagnosed with PBMAH based upon clinical, genetic, radiographic and biochemical characteristics. Intervention Clinical, biochemical, and genetic data were obtained. Computed tomography scans were used to create volumetric models by manually contouring both adrenal glands in each slice using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota). Main Outcome and Measures 17-hydroxycorticosteroids (17-OHS), ARMC5 genetics, and aldosterone-to-renin ratio (ARR) were retrospectively obtained. Pearson test was used for correlation analysis of biochemical data with adrenal volume. Results A cohort of 44 patients with PBMAH was evaluated, with a mean age (±SD) of 53 ± 11.53. Eight patients met the diagnostic criteria for PA, of whom 6 (75%) were Black. In the Black cohort, total adrenal volumes positively correlated with midnight cortisol (R = 0.76, P = 0.028), urinary free cortisol (R = 0.70, P = 0.035), and 17-OHS (R = 0.87, P = 0.0045), with a more pronounced correlation with left adrenal volume alone. 17-OHS concentration positively correlated with total, left, and right adrenal volume in patients harboring pathogenic variants in ARMC5 (R = 0.72, P = 0.018; R = 0.65, P = 0.042; and R = 0.73, P = 0.016, respectively). Conclusions Volumetric modeling of adrenal gland size may associate with biochemical severity in patients with PBMAH, with particular utility in Black patients.

BACKGROUND: Primary aldosteronism (PA) is associated with increased risk for dysglycemia. However, the effects of hyperaldosteronism on insulin sensitivity and β-cell function are unclear. METHODS: Using a cross-sectional study design, we assessed insulin sensitivity and pancreatic β-cell function from an oral glucose tolerance test (OGTT) in patients from two cohorts: subjects with PA (n=21) and essential hypertension control (EHC) subjects (n=22). Age, sex, BMI, and mean arterial pressure adjusted measures of insulin sensitivity and β-cell function were compared between the groups. RESULTS: PA individuals were less insulin sensitive compared to EHC subjects (Quantitative insulin sensitivity check index [QUICKI]: 0.340 ± 0.006 vs. 0.374 ± 0.013, p

Background: Primary Aldosteronism (PA) is the most common cause of endocrine hypertension in US. Diagnostic techniques such as a 24 hour urine collection or saline suppression test (SST) can be laborious for both patients and staff. Our group previously showed that human hair cortisol measurements correlated with urine and serum cortisol levels in patients with endogenous cortisol excess. In this study, we explored whether human hair aldosterone correlated with other measures of aldosterone production. Methods: 41 adult subjects were evaluated at the NIH Clinical Center for adrenal disorders. A pencil-width of hair near the occiput was removed, and the 1cm segment closest to the scalp was analyzed by enzyme immunoassay for aldosterone, reported as pg aldosterone/mg dry hair. Not all subjects underwent complete workup for PA. Data were transformed as necessary to maintain assumptions of normality. Student’s t-test and Pearson correlations were used for statistical analysis. Results: Of the evaluated subjects, 18 were diagnosed with PA, 22 subjects did not have PA, and 1 subject was indeterminate. The mean hair weight was 33.0±13.7mg. For hair samples weighing greater than 10mg, hair weight was not correlated with hair aldosterone concentration (p=0.40). There was no difference in measured hair aldosterone between the subjects with and without PA (2.01±1.09 vs. 2.52±2.45 pg/mg; p=0.82). Among all subjects, hair aldosterone did not correlate with serum aldosterone (p=0.92), aldosterone-to-renin ratio (ARR; p=0.94), 24 hour urine aldosterone (Ualdo; p=0.85), or the serum aldosterone at the 4 hour time point of a SST (4hrAldo; p=0.98). Serum aldosterone, ARR, Ualdo, and 4hrAldo all correlated highly amongst each other (all p’s Conclusions: Hair aldosterone levels do not correlate with other markers of PA. Further work is needed to understand whether optimization of study conditions could improve the usefulness of hair aldosterone measurements in the evaluation of PA.

AIMS: Hemolysis of serially-collected insulin serum samples frequently causes falsely-low measured concentrations due to release of intracellular insulin degrading enzyme (IDE). We investigated if bacitracin, an in vitro IDE inhibitor, could prevent hemolysis-induced insulin degradation during insulin sensitivity testing. MATERIALS AND METHODS: Blood samples were collected from adults undergoing serial sampling for insulin sensitivity. A dose-finding study measured insulin from experimentally-hemolyzed samples containing five bacitracin concentrations (0–2.5g/L) and from non-experimentally-hemolyzed samples. To confirm utility of bacitracin in the clinical setting, we compared insulin in samples collected with and without 1g/L bacitracin from a frequently sampled intravenous glucose tolerance test (FSIVGTT), where hemolysis often occurs accidentally. RESULTS: In the dose-finding study, bacitracin 0.25g/L, 1g/L, and 2.5g/L all maximally prevented insulin degradation in experimentally-hemolyzed samples. Among FSIVGTT unintentionally-hemolyzed samples, insulin concentrations from bacitracin-containing samples were significantly higher than from those without bacitracin (p

Objective Pediatric loss-of-control (LOC) eating is associated with, and predictive of, gains in adiposity and adverse metabolic outcomes. In addition, some preliminary data suggest that anxiety may exacerbate the relationship of LOC eating with weight and metabolic syndrome (MetS)-related measures. We therefore examined whether anxiety moderated the relationship between LOC eating and body mass index z (BMIz), adiposity, and MetS-related measures in youth. Methods A convenience sample of non-treatment-seeking boys and girls of varying weight strata were interviewed to determine the presence of LOC eating and completed a questionnaire assessing trait anxiety. BMIz and MetS-related measures (blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, and insulin) were measured after an overnight fast. Adiposity was assessed by air displacement plethysmography or dual-energy x-ray absorptiometry. Analyses adjusted for age, sex, race, height, fat mass, and depressive symptoms, as appropriate. Results In all, 379 youths (13.0 ± 2.8 years; 53% female; BMIz = 0.8 ± 1.1; 22% with LOC eating) were studied. Anxiety was not significantly related to BMIz, adiposity, or MetS-related measures. However, anxiety and LOC eating interacted such that only among youth with LOC eating, anxiety was positively associated with fasting insulin (p = .02) and insulin resistance (p = .01). The interaction of anxiety and LOC eating was not significantly related to BMIz, adiposity, or any other MetS-related measure (ps = ns). Conclusions Only among non-treatment-seeking youth with LOC eating, anxiety may be associated with increased insulin secretion and insulin resistance. Longitudinal studies are required to confirm these findings and explore mechanisms for these relationships.

Background Depression is associated with poor insulin sensitivity. We evaluated the long-term effects of a cognitive behavioral therapy (CBT) program for prevention of depression on insulin sensitivity in adolescents at risk for type 2 diabetes (T2D) with depressive symptoms. Methods One-hundred nineteen adolescent females with overweight/obesity, T2D family history, and mild-to-moderate depressive symptoms were randomized to a 6-week CBT group (n = 61) or 6-week health education (HE) control group (n = 58). At baseline, posttreatment, and 1 year, depressive symptoms were assessed, and whole body insulin sensitivity (WBISI) was estimated from oral glucose tolerance tests. Dual energy X-ray absorptiometry assessed fat mass at baseline and 1 year. Primary outcomes were 1-year changes in depression and insulin sensitivity, adjusting for adiposity and other relevant covariates. Secondary outcomes were fasting and 2-hr insulin and glucose. We also evaluated the moderating effect of baseline depressive symptom severity. Results Depressive symptoms decreased in both groups (P < .001). Insulin sensitivity was stable in CBT and HE (ΔWBISI: .1 vs. .3) and did not differ between groups (P = .63). However, among girls with greater (moderate) baseline depressive symptoms (N = 78), those in CBT developed lower 2-hr insulin than those in HE (Δ-16 vs. 16 μIU/mL, P < .05). Additional metabolic benefits of CBT were seen for this subgroup in post hoc analyses of posttreatment to 1-year change. Conclusions Adolescent females at risk for T2D decreased depressive symptoms and stabilized insulin sensitivity 1 year following brief CBT or HE. Further studies are required to determine if adolescents with moderate depression show metabolic benefits after CBT.

OBJECTIVE Interpersonal psychotherapy (IPT) prevents weight gain in adults with obesity and binge-eating-disorder, and is especially effective among those with increased psychosocial problems. However, IPT was not superior to health education (HE) to prevent excess weight gain at 1-year follow-up in 113 adolescent girls at high-risk for excess weight gain because of loss-of-control eating and high body mass index (BMI; kg/m2; Tanofsky-Kraff et al., 2014). METHOD Participants from the original trial were recontacted 3 years later for assessment. At baseline, adolescent- and parent-reported social-adjustment problems and trait anxiety were evaluated. At baseline and follow-ups, BMIz and adiposity by dual-energy x-ray absorptiometry were obtained. RESULTS Nearly 60% were reassessed at 3 years, with no group differences in participation (ps ≥ .70). Consistent with 1 year, there was no main effect of group on change in BMIz/adiposity (ps ≥ .18). In exploratory analyses, baseline social-adjustment problems and trait-anxiety moderated outcome (ps < .01). Among girls with high self-reported baseline social-adjustment problems or anxiety, IPT, compared to HE, was associated with the steepest declines in BMIz (p < .001). For adiposity, girls with high or low anxiety in HE and girls with low anxiety in IPT experienced gains (ps ≤ .03), while girls in IPT with high anxiety stabilized. Parent-reports yielded complementary findings. CONCLUSION In obesity-prone adolescent girls, IPT was not superior to HE in preventing excess weight gain at 3 years. Consistent with theory, exploratory analyses suggested that IPT was associated with improvements in BMIz over 3 years among youth with high social-adjustment problems or trait anxiety. Future studies should test the efficacy of IPT for obesity prevention among at-risk girls with social-adjustment problems and/or anxiety. (PsycINFO Database Record

Loss of control (LOC) eating in youth is associated with excess body weight and adiposity. After adjusting for fat mass, youth with LOC eating have higher blood pressure and higher low-density lipoprotein cholesterol compared to youth without LOC eating. Increased inflammation may account for this relationship, although few data have examined this hypothesis. Therefore, this study explored the association between LOC eating and high-sensitivity C-reactive protein (hsCRP), a marker of inflammation.We investigated hsCRP concentrations in relation to LOC eating in a convenience sample of 194 youth (age 14.3 ± 2.1 years; 63.9% female; BMI-z 1.64 ± 1.06). The presence of LOC eating in the past month was assessed by the Eating Disorder Examination interview. Serum hsCRP was measured by enzyme-linked immunosorbent assay. Adiposity was measured by air displacement plethysmography or dual-energy x-ray absorptiometry. We compared hsCRP in those with and without LOC eating in analyses accounting for sex, adiposity, height, depressive symptoms, and eating psychopathology.Youth with LOC eating had significantly greater hsCRP than youth without LOC eating (p = 0.02), after accounting for all covariates. The number of LOC eating episodes in the past month was positively associated with hsCRP (p = 0.01). The relationship between LOC eating and hsCRP was not mediated by depressive symptoms or eating psychopathology (ps 0.05).Youth with disinhibited eating may manifest increased chronic inflammation. Those with LOC eating may be an important subgroup at risk for adverse health outcomes associated with both chronic inflammation and obesity. Future research should examine whether hsCRP concentrations mediate the relationship between LOC eating and its association with cardiometabolic risk.

Background/Aims: Animal studies suggest that leptin may adversely affect bone mineral density (BMD). Clinical studies have yielded conflicting results. We therefore investigated associations between leptin and bone parameters in children. Methods: 830 healthy children (age = 11.4 ± 3.1 years; 75% female; BMI standard deviation score [BMIz] = 1.5 ± 1.1) had fasting serum leptin measured with ELISA and body composition by dual-energy X-ray absorptiometry. The main effects for leptin and BMIz plus leptin’s interactions with sex and BMIz were examined using hierarchical linear regressions for appendicular, pelvis, and lumbar spine BMD as well as bone mineral content (BMC), and bone area (BA). Results: Accounting for demographic, pubertal development, and anthropometric variables, leptin was negatively and independently associated with lumbar spine BMC and BA, pelvis BA, and leg BA (p < 0.05 for all). Sex, but not BMIz, moderated the associations of leptin with bone parameters. In boys, leptin was negatively correlated with leg and arm BMD, BMC at all bone sites, and BA at the subtotal and lumbar spine (p < 0.01 for all). In girls, leptin was positively correlated with leg and arm BMD (p < 0.05 for both). Conclusion: Independent of body size, leptin is negatively associated with bone measures; however, these associations are moderated by sex: boys, but not girls, have a negative independent association between leptin and BMD.

Introduction: Increased circulating free fatty acid (FFA) due to impaired control of adipocyte triglyceride lipolysis contributes to the development of obesity-related insulin resistance (IR). However, it is less clear whether there are differences in the relationship between lipolysis and skeletal muscle vs hepatic IR, or how these relationships are influenced by age, race, sex, body composition, or inflammation. We investigated the associations of lipolytic rate (LR) with skeletal muscle insulin sensitivity, as evidenced by insulin sensitivity index (SI), and hepatic IR, as measured by HOMA-IR. Methods: 46 healthy, non-diabetic adults with obesity (BMI 39.8±6.9 kg/m2) and 11 lean (BMI 25.6±2.1 kg/m2) adults (40% NHB, 20% HISP, 37% NHW, 3% Asian; 65% female; age 45.8±12.6y) underwent fasting blood draws and an insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT). LR was calculated by a mathematical minimal model that estimated basal lipolysis and insulin-mediated lipolysis stimulated by insulin modulation of FFA during the FSIVGTT; SI was derived from Bergman’s minimal model. Body composition was determined by DXA. Using ANCOVA, we examined how LR was related to SI and HOMA-IR, controlling for age, race, and sex. Secondary analyses examined if the differences seen could be accounted for by differences in total fat mass or hsCRP. Results: As expected, LR was significantly elevated in adults with obesity (Mean±SD: 0.069±0.047 vs. 0.0052±0.00084 mEq/L*min, p.05), LR remained correlated with SI (B= -.24, p.05). By contrast, for HOMA-IR, even after including total fat mass and hsCRP in the model, the effect of LR was still observed (B= +.30, p

Background: Biochemical characterization of primary bilateral macronodular adrenocortical hyperplasia (PBMAH) by distinct plasma steroid profiles and its putative correlation to disease has not been previously studied. Methods: LC-MS/MS-based steroid profiling of 16 plasma steroids was applied to 36 subjects (22 females, 14 males) with PBMAH, 19 subjects (16 females, 3 males) with other forms of adrenal CS (ACS), and an age and sex-matched control group. Germline ARMC5 sequencing was performed in all PBMAH cases. Results: The steroids showing the most dramatic differences between subject groups included 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol, progesterone and DHEA/DHEA-S. Steroids that showed isolated differences included cortisol and 18-oxocortisol with higher (P

Insulin sensitivity and pancreatic beta-cell function are primary determinants of glucose tolerance. Primary aldosteronism (PA) is associated with increased risk for glucose intolerance. However, its effects on insulin sensitivity and β-cell function have shown mixed results. In this study, we compared indices of insulin sensitivity and pancreatic β-cell function derived from an oral glucose tolerance test (OGTT) in patients from two cohorts: subjects with PA (n=25) and essential hypertension control (EHC) subjects. The EHC controls (n=25) were similar in age and BMI range, gender composition (female, n=14), and number of subjects with type 2 diabetes (n=3). Group comparisons were performed after adjusting for age, sex, and BMI; data is presented as unadjusted mean ± SD. As expected, the PA group show lower potassium concentrations compared to the EHC group, as well as elevated aldosterone and reduced renin levels. Mean arterial pressure was not significantly different between the groups (PA:100.6 ± 11.7, EHC: 96.7 ± 15.5 mm Hg, p=0.22). The area under the curve (AUC) for insulin during an OGTT, but not glucose, was higher in the PA group (insulin AUC: 14831 ± 9545 vs. 8582 ± 4948, μU/mL∙min, p

Background: Mesenchymal tumors represent around 1% of all thyroid neoplasms. Schwannoma is one such tumor that arises from the peripheral nerve sheath within the thyroid gland. Case: A 40-year-old lady was referred to our center for evaluation of a thyroid mass that was initially noticed 2 years prior and had been rapidly enlarging over the past several months. The patient experienced occasional dysphagia, but no shortness of breath nor change in voice. There was no family history of thyroid cancer or exposure to head and neck radiation. On physical exam, a firm, non-tender, 3 cm nodule was palpated in the right thyroid lobe. There was no cervical lymphadenopathy. Pemberton sign was negative. There was no evidence of café-au-lait spots or cutaneous neurofibromas on skin exam. The thyroid function tests were normal (NL), with serum TSH of 2.06 µIU/mL (NL: 0.27 - 4.2) and free thyroxine of 1.2 ng/dL (NL: 0.9 - 1.7), anti-TPO antibody was elevated (483 IU/mL; NL: 0 - 34.9), serum calcitonin was undetectable (

Introduction: Low-grade chronic inflammation, due in part to activation of the NLRP3 inflammasome, increases with increasing adiposity and plays a significant role in the development of type 2 diabetes and cardiovascular disease. However, to date, the efficacy of anti-inflammatory medications to improve aspects of the metabolic syndrome (MetS) is not well established. As colchicine has been shown to prevent assembly of the NLRP3 inflammasome and ameliorate other inflammatory conditions, we aimed to evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in adults with obesity and MetS. Materials and Methods: We conducted a randomized, double-blind, placebo-controlled pilot trial in which 40 non-diabetic adults with obesity, MetS, and elevated high-sensitivity C-reactive protein (hsCRP≥ 2.0 mg/L) were randomized to colchicine 0.6 mg or placebo twice daily for three months. Fasting labs, insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT), and body composition by DXA were performed at baseline and 3-month follow up. The primary outcome was change in FSIVGTT insulin sensitivity (SI) as measured by Bergman’s minimal model. Secondary outcomes included changes in other metabolic parameters and inflammatory markers. ANCOVA was used to examine differences between treatment arms, with age, sex, baseline body fat%, and Δbody fat% as covariates. Data were analyzed according to intention-to-treat and reported as mean±SD. Results: Colchicine significantly reduced inflammatory indices, including hsCRP (-2.8±2.9 vs. 0.4±2.8 mg/L, p=.002), ESR (-5.5±6.4 vs. 0.6±6.3 mm/hr, p=.007), white blood cell count (-1.09±1.23 vs. 0.29±1.16 K/µL, p=.002), and absolute neutrophil count (-1.06±1.05 vs. 0.12±0.93 K/µL, p

AIM To evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS). MATERIALS AND METHODS Adults with obesity and MetS, but who did not have diabetes, were randomized to colchicine 0.6 mg or placebo capsules twice daily for 3 months. The primary outcome was change in insulin sensitivity (SI ) as estimated by insulin-modified frequently sampled intravenous glucose tolerance tests. Secondary outcomes included changes in other metabolic variables and inflammatory markers. RESULTS Of 40 participants randomized (21 colchicine, 19 placebo), 37 completed the trial. Compared with placebo, colchicine significantly reduced C-reactive protein (P

This chapter will discuss in detail the background, evaluation, and management of adrenal tumours, with an additional focus on the role of endocrine nursing in the care of these patients. It is divided into three parts, each providing a comprehensive outline of: A) Adrenocortical functioning adenomas and adrenal hyperplasia, B) Pheochromocytomas and Paragangliomas, and C) Adrenal incidentaloma and adrenocortical cancer (ACC).

Background: Hospitalized patients with diabetes are at risk of complications and longer length of stay (LOS). Inpatient Diabetes Management Services (IDMS) are known to be beneficial; however, their impact on patient care measures in community, non-teaching hospitals, is unknown. Objectives: To evaluate whether co-managing patients with diabetes by the IDMS team reduces LOS and 30-day readmission rate (30DR). Methods: This retrospective quality improvement cohort study analyzed LOS and 30DR among patients with diabetes admitted to a community hospital. The IDMS medical team consisted of an endocrinologist, nurse practitioner, and diabetes educator. The comparison group consisted of hospitalized patients with diabetes under standard care of attending physicians (mostly internal medicine-trained hospitalists). The relationship between study groups and outcome variables was assessed using Generalized Estimating Equation models. Results: 4,654 patients with diabetes (70.8 ± 0.2 years old) were admitted between January 2016 and May 2017. The IDMS team co-managed 18.3% of patients, mostly with higher severity of illness scores (p

Background: Insulin pen injectors (“pens”) are intended to facilitate a patient’s self-administration of insulin and can be used in hospitalized patients as a learning opportunity. Unnecessary or duplicate dispensation of insulin pens is associated with increased healthcare costs. Methods: Inpatient dispensation of insulin pens in a 240-bed community hospital between July 2018 and July 2019 was analyzed. We calculated the percentage of insulin pens unnecessarily dispensed for patients who had the same type of insulin pen assigned. The estimated cost of insulin pen waste was calculated. A pharmacist-led task force group implemented hospital-wide awareness and collaborated with hospital leadership to define goals and interventions. Results: 9516 insulin pens were dispensed to 3121 patients. Of the pens dispensed, 6451 (68%) were insulin aspart and 3065 (32%) were glargine. Among patients on insulin aspart, an average of 2.2 aspart pens was dispensed per patient, but only an estimated 1.2 pens/patient were deemed necessary. Similarly, for inpatients prescribed glargine, an average of 2.1 pens/patient was dispensed, but only 1.3 pens/patient were necessary. A number of gaps were identified and interventions were undertaken to reduce insulin pen waste, which resulted in a significant decrease in both aspart (p = 0.0002) and glargine (p = 0.0005) pens/patient over time. Reductions in pen waste resulted in an estimated cost savings of $66 261 per year. Conclusions: In a community hospital setting, identification of causes leading to unnecessary insulin dispensation and implementation of hospital-wide staff education led to change in insulin pen dispensation practice. These changes translated into considerable cost savings and facilitated diabetes self-management education.

Objective Adolescent emotional-eating, referring to eating in response to negative affective states, is frequently reported by those with loss of control (LOC) eating. Although LOC eating has been shown to predict exacerbated disordered eating and excess weight/adiposity gain, the extent to which emotional-eating, either alone or in combination with LOC, predicts adverse outcomes has not been determined. Thus, we examined associations of baseline emotional-eating with changes in disordered eating, BMI, and adiposity over 1-year, and to what degree the presence or absence of baseline LOC moderated these associations. Methods 189 non-treatment-seeking youth (15.4 ± 1.4y; 66% female; 67% non-Hispanic White, 38% overweight [BMI ≥85th %ile]) completed the emotional-eating Scale for Children/Adolescents and the Eating Disorder Examination interview at baseline and again at 1-year. Air displacement plethysmography assessed adiposity at both time points. Results Baseline emotional-eating alone was not significantly associated with the development of objective binge eating or changes in disordered eating attitudes, BMI or adiposity 1-year later. However, baseline emotional-eating interacted with the presence of baseline LOC in the prediction of 1-year outcomes. Among adolescents with LOC eating, greater baseline emotional-eating was related to increased disordered eating attitudes (P = 0.03), BMI (P = 0.04), and adiposity (P = 0.04) at 1-year, after correcting for false discovery rate. Discussion Emotional-eating among youth also reporting LOC was associated with adverse outcomes over 1-year. Adolescents who report both behaviors may represent a subset of individuals at especially high risk for exacerbated disordered eating and excess weight gain. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016)

The influence of insulin and insulin resistance (IR) on children's weight and fat gain is unclear.To evaluate insulin and IR as predictors of weight and body fat gain in children at high risk for adult obesity. We hypothesized that baseline IR would be positively associated with follow-up body mass index (BMI) and fat mass.Two hundred and forty-nine healthy African American and Caucasian children aged 6-12 years at high risk for adult obesity because of early-onset childhood overweight and/or parental overweight were followed for up to 15 years with repeated BMI and fat mass measurements. We examined baseline serum insulin and homeostasis model of assessment-IR (HOMA-IR) as predictors of follow-up BMI Z-score and fat mass by dual-energy X-ray absorptiometry in mixed model longitudinal analyses accounting for baseline body composition, pubertal stage, sociodemographic factors and follow-up interval.At baseline, 39% were obese (BMI⩾95th percentile for age/sex). Data from 1335 annual visits were examined. Children were followed for an average of 7.2±4.3 years, with a maximum follow-up of 15 years. After accounting for covariates, neither baseline insulin nor HOMA-IR was significantly associated with follow-up BMI (Ps0.26), BMIz score (Ps0.22), fat mass (Ps0.78) or fat mass percentage (Ps0.71). In all models, baseline BMI (P0.0001), body fat mass (P0.0001) and percentage of fat (P0.001) were strong positive predictors for change in BMI and fat mass. In models restricted to children without obesity at baseline, some but not all models had significant interaction terms between body adiposity and insulinemia/HOMA-IR that suggested less gain in mass among those with greater insulin or IR. The opposite was found in some models restricted to children with obesity at baseline.In middle childhood, BMI and fat mass, but not insulin or IR, are strong predictors of children's gains in BMI and fat mass during adolescence.

Prospective data suggest depressive symptoms worsen insulin resistance and accelerate type 2 diabetes (T2D) onset.We sought to determine whether reducing depressive symptoms in overweight/obese adolescents at risk for T2D would increase insulin sensitivity and mitigate T2D risk.We conducted a parallel-group, randomized controlled trial comparing a 6-week cognitive-behavioral (CB) depression prevention group with a 6-week health education (HE) control group in 119 overweight/obese adolescent girls with mild-to-moderate depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D] ≥16) and T2D family history. Primary outcomes were baseline to post-intervention changes in CES-D and whole body insulin sensitivity index (WBISI), derived from 2-h oral glucose tolerance tests. Outcome changes were compared between groups using ANCOVA, adjusting for respective baseline outcome, puberty, race, facilitator, T2D family history degree, baseline age, adiposity, and adiposity change. Multiple imputation was used for missing data.Depressive symptoms decreased (p 0.001) in CB and HE from baseline to posttreatment, but did not differ between groups (ΔCESD = -12 vs. -11, 95 % CI difference = -4 to +1, p = 0.31). Insulin sensitivity was stable (p 0.29) in CB and HE (ΔWBISI = 0.1 vs. 0.2, 95 % CI difference = -0.6 to +0.4, p = 0.63). Among all participants, reductions in depressive symptoms were associated with improvements in insulin sensitivity (p = 0.02).Girls at risk for T2D displayed reduced depressive symptoms following 6 weeks of CB or HE. Decreases in depressive symptoms related to improvements in insulin sensitivity. Longer-term follow-up is needed to determine whether either program causes sustained decreases in depressive symptoms and improvements in insulin sensitivity.The trial was registered with clinicaltrials.gov (NCT01425905).

Summary Background In adults, obesity is associated with abnormalities of thyroid function; there are fewer studies in paediatric cohorts. Objectives To examine associations of weight and adiposity with indices of thyroid function and thyroid-related metabolic factors in children. Design/Methods A sample of 1203 children without obesity (body mass index [BMI]

Purpose Extant research indicates that some of the comorbidities associated with adult obesity may be adversely affected by the stress resulting from negative body image and weight-related stigma. This study examined the association between weight-related pressure and insulin sensitivity in adolescents, who are vulnerable to both weight-based teasing and the onset of metabolic dysregulation. Methods Participants were 215 adolescent healthy volunteers (55% female; 59% white; 35% overweight/obese; mean ± standard deviation age = 15.4 ± 1.4 year), who completed a self-report measure of pressure to be thin from parents, friends, and romantic partners. Fasting blood samples were obtained to assess serum insulin and glucose, which were used to calculate insulin sensitivity; fat mass (kg) and fat-free mass (%) were measured with air-displacement plethysmography. Pubertal stage was determined by physical examination. Results Pressure to be thin was positively associated with fasting insulin ( p = .01) and negatively associated with insulin sensitivity ( p = .02), after controlling for pubertal stage, sex, race, height, fat-free mass, and adiposity. Pressure to be thin was associated with a greater odds of having hyperinsulinemia (fasting insulin ≥ 15 μIU/mL; odds ratio (95% confidence interval): 1.65 [1.08–2.50], p = .02), adjusting for the same covariates. Conclusions Results indicate that adolescents perceiving more pressure to be thin have greater elevations of fasting insulin and poorer insulin sensitivity above and beyond the effect of fat mass. Future research is warranted to elucidate the mechanisms responsible for this relationship.

Summary Background Adults with binge eating disorder may have an exaggerated or blunted cortisol response to stress. Yet, limited data exist among youth who report loss of control (LOC) eating, a developmental precursor to binge eating disorder. Methods We studied cortisol reactivity among 178 healthy adolescents with and without LOC eating. Following a buffet lunch meal adolescents were randomly assigned to watch a neutral or sad film clip. After, they were offered snacks from a multi-item array to assess eating in the absence of hunger. Salivary cortisol was collected at −80, 0, 30 and 50 min relative to film administration, and state mood ratings were reported before and after the film. Results Adolescents with LOC had greater increases in negative affect during the experimental paradigm in both conditions (ps > 0.05). Depressive symptoms, but not LOC, related to a greater cortisol response in the sad film condition (ps > 0.05). Depressive symptoms and state LOC were related to different aspects of eating behaviour, independent of film condition or cortisol response (ps > 0.05). Conclusions A film clip that induced depressed state affect increased salivary cortisol only in adolescents with more elevated depressive symptoms. Adolescents with and without LOC were differentiated by greater increases in state depressed affect during laboratory test meals but had no difference in cortisol reactivity. Future studies are required to determine if adolescents with LOC manifest alterations in stress reactivity to alternative stress-inducing situations.