Effects of preprandial versus postprandial nutritional insulin administration in the inpatient setting.

AIMS: Hospitalized patients can have inconsistent nutritional intake due to acute illness, changing diet, or unpredictable meal delivery. The aim of this study was to evaluate whether implementation of a hospital-wide policy shifting nutritional insulin administration from pre-meal to post-meal was associated with changes in glycemic control or length of stay (LOS). METHODS: This retrospective study performed at a community hospital evaluated adult inpatients receiving nutritional insulin across three time periods. pre-intervention, immediate post-intervention, and distant post-intervention. Outcomes included rates of hypoglycemia (glucose ≤ 70 mg/dL), moderate hypoglycemia (< 54 mg/dL), severe hypoglycemia (≤ 40 mg/dL), severe hyperglycemia (≥ 300 mg/dL), daily mean glucose level, and LOS. RESULTS: The number of patient-days analyzed across the cohorts were 1948, 1751, and 3244, respectively. After multivariate adjustment, risk of developing any hypoglycemia and severe hypoglycemia significantly decreased over time (p = 0.001 and p = 0.009, respectively). Daily mean glucose increased over time (194.6 ± 62.5 vs 196.8 ± 65.5 vs 199.3 ± 61.5 mg/dL; p = 0.003), but there were no significant differences among rates of severe hyperglycemia (p = 0.10) or LOS (p = 0.74). CONCLUSIONS: Implementing a hospital-wide shift to postprandial nutritional insulin administration significantly reduced hypoglycemia rates without increasing severe hyperglycemia. This suggests a promising strategy for improving patient safety, but further prospective randomized controlled trials are warranted to confirm these findings.

Colchicine effects on the gut microbiome in adults with metabolic syndrome.

Obesity-induced inflammation plays a substantial role in the development of insulin resistance and type 2 diabetes. The altered gut flora in obesity can also contribute to metabolic dysregulation and systemic inflammation. However, it remains unclear how dysregulation of systemic inflammation in obesity affects the gut microbiome. We hypothesized that colchicine's systemic anti-inflammatory effects in obesity would be associated with improvements in gut microbial diversity. We conducted a secondary analysis of a double-blind randomized placebo-controlled trial, in which 40 adults with obesity, high C-reactive protein (CRP) (≥2.0 mg/L), insulin resistance (homeostatic model of insulin resistance: HOMA-IR ≥2.6 mg/L), and metabolic syndrome (MetS) were randomized to three months of colchicine 0.6 mg or placebo tablets twice daily. Serum and stool samples were collected at baseline and final visit. Gut microbiota composition was characterized from stool DNA by dual-index amplification and sequencing of 16S ribosomal RNA. Pre- and post-intervention stool samples were available for 15 colchicine- and 12 placebo-treated subjects. Circulating high sensitivity CRP (hsCRP), interleukin-6, resistin, white blood count, and neutrophils were significantly decreased in the colchicine arm as compared to placebo. However, changes in stool microbiome alpha diversity, as assessed by the Chao1, Shannon, and Pielou indices, were not significant between groups. Amplicon sequence variant counts were unchanged among all examined phyla or families. Oscillibacter was the only genus to demonstrate even a nominally significant change. Among adults with obesity and MetS, colchicine significantly improved systemic inflammation. However, this anti-inflammatory effect was not associated with significant changes in the gut microbiome. Further studies are warranted to investigate this relationship.

Effects of the COVID-19 booster vaccine on glycemia and insulin resistance in people with type 1 diabetes: A prospective pilot study.

AIMS: Inflammation can trigger hyperglycemia in people with type 1 diabetes (T1D). Vaccines purposefully intend to cause an acute immunogenic response, and booster vaccines may cause even more potent immunologic responses. However, the effects of vaccines on glycemic control and insulin requirements in the days immediately post-vaccination remains poorly understood. The aim of this study was to examine the changes in glycemic control and insulin usage immediately preceding and following a COVID-19 booster vaccine among adults with T1D. METHODS: In this prospective cohort study of adults with T1D, participants wore blinded Dexcom G6 Pro continuous glucose monitors for 10 days. After a baseline period, participants received a COVID-19 booster vaccine, and subsequent changes in glycemic indices were evaluated. RESULTS: Among the 21 enrolled participants, 38% received a Moderna and 62% Pfizer-BioNTech booster. Compared to baseline (162.9 ± 44.1 mg/dL), mean glucose was significantly increased at Day 2 (172.8 ± 47.0 mg/dL; p = 0.04) and Day 3 (173.1 ± 45.0 mg/dL; p = 0.02) post-vaccination. Insulin resistance was also increased on Day 2 (p = 0.03). There were no differences in outcome metrics between booster vaccine manufacturers. CONCLUSIONS: These results suggest that adults with type 1 diabetes may experience transient mild glycemic elevations after receiving a COVID-19 booster vaccination. Studies examining the effects of other vaccines are warranted.

Diabetes-Related Gastroparesis in the Acute Care Setting: A Case Report.

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.

Increasing Frequency of Hemoglobin A1C Measurements in Hospitalized Patients With Diabetes: A Quality Improvement Project Using Lean Six Sigma.

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.

Immunomodulatory effects of colchicine on peripheral blood mononuclear cell subpopulations in human obesity: Data from a randomized controlled trial.

OBJECTIVE: Colchicine is known to reduce inflammation and improve endothelial cell function and atherosclerosis in obesity, but there is little knowledge of the specific circulating leukocyte populations that are modulated by colchicine. METHODS: A secondary analysis of a double-blind randomized controlled trial of colchicine 0.6 mg or placebo twice daily for 3 months on circulating leukocyte populations and regulation of the immune secretome in 35 adults with obesity was performed. RESULTS: Colchicine altered multiple innate immune cell populations, including dendritic cells and lymphoid progenitor cells, monocytes, and natural killer cells when compared with placebo. Among all subjects and within the colchicine group, changes in natural killer cells were significantly positively associated with reductions in biomarkers of inflammation, including cyclooxygenase 2, pulmonary surfactant-associated protein D, myeloperoxidase, proteinase 3, interleukin-16, and resistin. Changes in dendritic cells were positively correlated with changes in serum heart-type fatty acid-binding protein concentrations. Additionally, colchicine treatment reduced cluster of differentiation (CD) CD4+ T effector cells and CD8+ T cytotoxic cells. Conversely, colchicine increased CD4+ and CD8+ T central memory cells and activated CD38High CD8+ T cells. Changes in CD4+ T effector cells were associated with changes in serum heart-type fatty acid-binding protein. CONCLUSIONS: In adults with obesity, colchicine significantly affects circulating leukocyte populations involved in both innate and adaptive immune systems along with the associated inflammatory secretome.

Instituting a Successful Discharge Plan for Patients With Type 2 Diabetes: Challenges and Solutions.

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.

Primary adrenal insufficiency.

Primary adrenal insufficiency is a potentially life-threatening condition. We report a case of a 49-year-old female patient who presented to the hospital for evaluation of dizziness, nausea, and vomiting. Darkening of the palmar creases and tongue was noted. The adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency.

Effects of colchicine on lipolysis and adipose tissue inflammation in adults with obesity and metabolic syndrome.

OBJECTIVE: The aim of this study was to examine whether colchicine's anti-inflammatory effects would improve measures of lipolysis and distribution of leukocyte populations in subcutaneous adipose tissue (SAT). METHODS: A secondary analysis was conducted for a double-blind, randomized, placebo-controlled pilot study in which 40 adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Non-insulin-suppressible (l0 ), insulin-suppressible (l2 ), and maximal (l0 +l2 ) 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 before and after the intervention. RESULTS: Colchicine treatment significantly decreased l2 and l0 +l2 versus placebo (p < 0.05). These changes were associated with a significant reduction in markers of systemic inflammation, including high-sensitivity C-reactive protein, resistin, and circulating monocytes and neutrophils (p < 0.01). Colchicine did not significantly alter SAT leukocyte population distributions (p > 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.

Inpatient Insulin Pen Implementation, Waste, and Potential Cost Savings: A Community Hospital Experience.

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.

Retrospective Quality Improvement Study of Insulin-Induced Hypoglycemia and Implementation of Hospital-Wide Initiatives.

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.

Effects of a Dedicated Inpatient Diabetes Management Service on Glycemic Control in a Community Hospital Setting.

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.

The Financial Impact of an Inpatient Diabetes Management Service.

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.

Insulin sensitivity and pancreatic ß-cell function in patients with primary aldosteronism.

BACKGROUND: Primary aldosteronism (PA) is associated with an increased risk for dysglycemia. However, the effects of hyperaldosteronism on insulin sensitivity and ß-cell function are unclear. METHODS: Using a cross-sectional study design, we assessed insulin sensitivity and pancreatic ß-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 ß-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 < 0.001; Matsuda index: 4.14 ± 0.49 vs. 7.87 ± 1.42, p < 0.001; SI: 11.45 ± 4.85 vs. 21.23 ± 6.11 dL/kg/min per µU/mL, p = 0.02). The hepatic insulin resistance index (HIRI) was higher in PA subjects (PA: 5.61 ± 1.01 vs. EHC: 4.13 ± 0.61, p = 0.002). The insulinogenic index (IGI), an index of ß-cell function was higher in the PA cohort (PA: 1.49 ± 0.27 vs. 1.11 ± 0.21 µU/mL/mg/dL, p = 0.03). However, the oral disposition index (DI) was similar between the groups (PA: 4.77 ± 0.73 vs. EHC: 5.46 ± 0.85, p = 0.42), which likely accounts for the similar glucose tolerance between the two cohorts, despite lower sensitivity. CONCLUSIONS: In summary, insulin sensitivity is significantly lower in PA with an appropriately compensated ß-cell function. These results suggest that excess aldosterone and/or other steroids in the context of PA may negatively affect insulin action without adversely impacting ß-cell function.

Volumetric Modeling of Adrenal Gland Size in Primary Bilateral Macronodular Adrenocortical Hyperplasia.

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 ±â€…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.

Kisspeptin deficiency leads to abnormal adrenal glands and excess steroid hormone secretion.

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.

Associations of GlycA and high-sensitivity C-reactive protein with measures of lipolysis in adults with obesity.

BACKGROUND: Obesity-associated inflammation promotes metabolic dysfunction. However, it is unclear how different inflammatory biomarkers predict dysregulation in specific tissues/organs, particularly adipose tissue. OBJECTIVE: The aim of our study was to examine whether GlycA, a nuclear magnetic resonance-measured biomarker of inflammation, is a better predictor of insulin-suppressible lipolysis and other measures of metabolic dysfunction compared with high-sensitivity C-reactive protein (hsCRP) in human obesity. METHODS: This was a cross-sectional study of 58 nondiabetic adults with obesity (body mass index: 39.8 ± 7.0 kg/m2, age 46.5 ± 12.2 years, 67.2% female) who underwent a frequently sampled intravenous glucose tolerance test in the fasted state. Noninsulin-suppressible (l0), insulin-suppressible (l2), and maximal (l0+l2) lipolysis rates, as well as insulin sensitivity and acute insulin response to glucose, were calculated by minimal model analysis. Nuclear magnetic resonance was used to measure GlycA. Body composition was determined by dual-energy X-ray absorptiometry. RESULTS: GlycA was strongly correlated with hsCRP (r = +0.46; P < .001). GlycA and hsCRP were positively associated with l2, l0+l2, and fat mass (Ps < .01). In linear regression models accounting for age, race, sex, and fat mass, GlycA remained significantly associated with l2 and l0+l2 (Ps < .05), whereas hsCRP did not (Ps ≥ .20). Neither GlycA nor hsCRP was associated with l0, insulin sensitivity, or acute insulin response to glucose. CONCLUSIONS: GlycA was associated with elevated lipolysis, independent of adiposity, in adults with obesity. Our findings suggest that GlycA and hsCRP have distinct inflammation-mediated metabolic effects, with GlycA having a greater association with adipose tissue dysfunction. Further studies are warranted to investigate the mechanisms underlying these associations.

Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial.

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.