Elevated Adiponectin Research Articles

Combined detection of serum adiponectin and pregnancy-associated plasma protein A for early prediction of gestational diabetes mellitus.

Early diagnosis of gestational diabetes mellitus (GDM) reduces the risk of adverse perinatal and maternal outcomes. At present, the value of serum adiponectin (ADP) and pregnancy-associated plasma protein A (PAPP-A) in clinical practice for the diagnosis of GDM in early pregnancy is unclear. To investigate the predictive value of serum ADP and PAPP-A in GDM. The electronic medical record data of all pregnant women from Zhongshan People's Hospital from 2018 to 2021 were retrospectively collected and divided into GDM group and control group according to whether GDM occurred. ADP and PAPP-A levels of the 2 groups were detected in early pregnancy, and the related factors of GDM were analyzed by binary logistic regression analysis. Receiver operating characteristic (ROC) curves of ADP and PAPP-A in predicting GDM in the early pregnancy were plotted and their clinical predictive value was analyzed. The significance level for all statistical tests is 0.05. Compared with the non-GDM group, the ADP of the GDM group was significantly lower than that of the non-GDM group [(8.19 ± 2.24) vs. (10.04 ± 2.73)]mg/L, the difference between groups was statistically significant (P < .05), and the multiple of median (MoM) of PAPP-A was significantly lower than that of the non-GDM group (1.13 ± 0.52) versus (1.45 ± 0.61) (P < .05). Binary logistic regression analysis showed that elevated serum ADP and PAPP-A levels were negatively correlated with the subsequent development of GDM [odds ratio (OR) 95% confidence interval (95% CI)] was 0.626 (0.536, 0.816), 0.934 (0.908, 0.961), respectively, P < .05.ROC curve analysis showed that the sensitivity and specificity of ADP and PAPP-A in predicting gestational diabetes were79.1% and 58.6%, respectively, 92.7% and 73.1%, and respectively. The area under curve (AUC) is 0.755 for ADP and 0.770 for PAPP-A. The AUC of the combined detection was 0.867, both of which were higher than that of single index diagnosis, and the sensitivity and specificity of the combined detection were 0.958 and 0.853, respectively. In summary, PAPP-A and ADP levels are independent related factors affecting the occurrence of GDM. The combined detection of PAPP-A and ADP should be utilized in diagnosing GDM to improve pregnancy outcomes for pregnant women.

Serum Adiponectin Is Elevated in Critically Ill Patients with Liver Disease and Associated with Decreased Overall Survival.

Adiponectin, an adipokine with anti-inflammatory properties, has been implicated in various liver diseases. This study aimed to elucidate the prognostic value of serum adiponectin levels in critically ill patients with liver disease. This observational study included 161 critically ill patients admitted to the medical ICU of RWTH Aachen University Hospital due to acute liver failure or decompensated advanced chronic liver disease. Serum adiponectin levels were measured at ICU admission and after 48 h. Clinical parameters and outcomes, including transplant-free survival, were analyzed. Serum adiponectin concentrations were significantly elevated compared to healthy controls (p < 0.001). Levels were particularly high in patients with sepsis compared to those with gastrointestinal bleeding as the precipitating factor of acute decompensation (p = 0.045) and were higher in female patients (p = 0.023). Adiponectin concentrations correlated with the Model of End-Stage Liver Disease (MELD) score and Child-Pugh score. Multivariate analysis confirmed a significant correlation with total bilirubin (r = 0.292, p < 0.001) and serum sodium (r = -0.265, p = 0.028). Higher adiponectin concentrations were associated with a trend towards poorer 30- and 180-day survival. Cox regression analysis identified a significant association between increased adiponectin concentration and reduced transplant-free survival (p = 0.037), supported by a Kaplan-Meier analysis using a cutoff of 119 ng/mL (log-rank 5.145, p = 0.023). Elevated serum adiponectin concentrations are associated with liver dysfunction and poor outcomes in critically ill patients. Higher adiponectin levels at ICU admission may predict poorer transplant-free survival. Further research in larger, multicenter cohorts is warranted to validate these findings and explore the underlying mechanisms.

Genetic polymorphisms (FTO rs9939609 and TMEM18 rs6548238), adipokines (leptin and adiponectin) and adiposity in children and adolescents with asthma

ObjectiveTo describe independent factors related to the interaction of FTO rs9939609, TMEM18 rs6548238, leptin, and adiponectin in children/adolescents with asthma, under the influence of obesity. MethodsThe authors performed a cross-sectional study with 57 children/adolescents, ages 8–19 years, at a tertiary hospital, from 2017 to 2018. Participants were classified by nutritional status, performed spirometry with a bronchodilator test and completed an asthma questionnaire, higher scores indicated more asthma symptoms. Two asthma groups were formed: Group 1(G1)-normal-weight; Group 2(G2)-overweight/obese. Serum was collected for adipokines (n = 32) and genetic polymorphisms (n = 53) dosages. ResultsAge and body mass index (BMI) correlated directly in normal-weight (p = 0.009) and obese participants (p = 0.004). Girls reported more asthma complaints (p = 0.044). Participants with negative bronchodilator responses presented lower BMI (14.55–17.16) than responders (19.4–26.84) (p = 0.049). Leptin dosages are related directly to BMI (5,34–40 ng/ml in obese × 0,54–42 ng/ml in nonobese) (p = 0.003). Levels were high in girls (4.78–17.55 µg/ml) (p = 0.029) and low in nonobese boys (0.54–6.92 µg/ml) (p = 0.006). In obese, low leptin levels (< 10 ng/ml) were found in small airway dysfunction carriers (p = 0.025); elevated adiponectin (> 5 µg/ml) correlated with FEV1/FVC > 80 % (p = 0.035) and positive bronchodilator tests (8.84–13 µg/ml) (p = 0.039); and FTO A allele correlated with low adiponectin 0–8.84 µg/ml (p = 0.021) and low FEV1/FVC (46 %-88 %) (p = 0.023). ConclusionBMI correlated directly with age and leptin levels. Obese participants presented high serum levels of leptin and FTO A allele correlated with low FEV1/FVC. Larger cohorts are necessary for better elucidation of the role of adipokines and polymorphisms in the pathophysiology of asthma and obesity.

Plasma Adiponectin Levels in Relation to Chronic Hepatitis B Infection Progression to Liver Cancer Milestones: A Prospective Study

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Among 3,931 HBsAg(+)/anti-HCV(−) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 10&lt;sup&gt;5&lt;/sup&gt; IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55–3.28; OR = 2.11, 95% CI: 1.47–3.04; and OR = 1.92, 95% CI: 1.47–2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27–0.85), HBsAg (HR = 0.69, 95% CI: 0.49–0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43–0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98–4.20, HCC (HR = 2.38, 95% CI: 1.52–3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51–3.54). HBV genotype significantly modified the adiponectin-HCC (P&lt;sub&gt;interaction&lt;/sub&gt; = 0.005) and adiponectin-liver death associations (P&lt;sub&gt;interaction&lt;/sub&gt; = 0.0157), with higher risk among genotype C. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.

Mediating effect of adiponectin between free fatty acid and tumor necrosis factor-α in patients with diabetes

Background/ObjectivesIncreased free fatty acid (FFA) promotes adiponectin secretion in healthy subjects and induces inflammation in diabetes. Given the potential pro-inflammatory role of adiponectin in “adiponectin paradox”, we performed this study in patients with type 2 diabetes mellitus (T2DM) to assess the association of FFA with adiponectin and to investigate whether adiponectin mediates FFA-related inflammation.MethodsThis cross-sectional study consisted of adult patients with T2DM. FFA, adiponectin, and tumor necrosis factor-α (TNF-α) were assayed from fasting venous blood after overnight fasting for at least 8 h. Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between FFA and adiponectin. Mediation analysis was performed to determine the mediating effect of adiponectin on the association between FFA and TNF-α.ResultsThis study included 495 participants, with 332 males (67.1%) and a mean age of 47.0 ± 11.2 years. FFA was positively associated with adiponectin (b = 0.126, 95%CI: 0.036–0.215, P = 0.006) and was the main contributor to the increase of adiponectin (standardized b = 0.141). The RCS analysis demonstrated that adiponectin increased with FFA when FFA was less than 0.7 mmol/L but did not further increase thereafter (Poverall < 0.001 and Pnon-linear < 0.001). In addition, adiponectin mediated the association between FFA and TNF-α. The mediating effect was 0.08 (95%CI: 0.03–0.13, P = 0.003) and the mediating effect percentage was 26.8% (95%CI: 4.5–49.2, P = 0.02).ConclusionsIn patients with T2DM, FFA was positively associated with adiponectin when FFA was less than 0.7 mmol/L. Elevated adiponectin mediated FFA-related inflammation. This study may provide insights into the pro-inflammatory effect of adiponectin in T2DM.

Obesity-associated inflammatory macrophage polarization is inhibited by capsaicin and phytolignans.

Obesity is often accompanied by increased adipose tissue inflammation, a process that is partially driven by adipose tissue-resident macrophages. In this study, we explored the potential for plant-derived dietary compounds to exert anti-inflammatory effects in macrophages that alleviate obesity-associated adipocyte dysfunction. Capsaicin (CAP), schisandrin A (SA), enterodiol (END), and enterolactone (ENL) treatment polarized J774 macrophages to an "M2" or anti-inflammatory phenotype and inhibited responses to stimulation with lipopolysaccharide (LPS). Furthermore, these compounds blocked inflammasome activation when administered just before ATP-induced NLRP3 activation, as evidenced by the abrogation of IL-1β release in mouse macrophages and human peripheral blood monocytes. The addition of CAP, SA, or ENL during the differentiation of bone marrow-derived macrophages was also sufficient to inhibit LPS-induced IL-6 and TNFα production. Finally, CAP, END, and ENL treatment during differentiation of 3T3-L1 adipocytes induced an adiponectin-high phenotype accompanied by increases in thermogenic gene expression, and conditioned media from these adipocytes inhibited LPS-induced production of IL-1β, IL-6, and TNFα from J774 macrophages. These polarizing effects were partially mediated by the elevated adiponectin and decreased syndecan-4 in the adipocyte-conditioned media. These results implicate the contribution of plant-derived dietary components to the modulation of macrophages and adipocytes in obesity.NEW & NOTEWORTHY The utility of food-based products to prevent or alleviate chronic conditions such as obesity and its associated comorbidities is an attractive approach. Capsaicin, schisandrin A, enterodiol, and enterolactone, phytochemicals present in traditional medicinal food, decreased proinflammatory cytokine production from macrophages that, in turn, reduced obesity-associated adipocyte dysfunction. These results implicate the contribution of plant-derived dietary components to the modulation of macrophages and adipocytes in obesity.

Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model

Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects.

Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction.

The adiponectin (APN) levels in obesity are negatively correlated with chronic subclinical inflammation markers. The hypertrophic adipocytes cause obesity-linked insulin resistance and metabolic syndrome. Furthermore, macrophage polarization is a key determinant regulating adiponectin receptor (AdipoR1/R2) expression and differential adiponectin-mediated macrophage inflammatory responses in obese individuals. In addition to decrease in adiponectin concentrations, the decline in AdipoR1/R2 messenger ribonucleic acid (mRNA) expression leads to a decrement in adiponectin binding to cell membrane, and this turns into attenuation in the adiponectin effects. This is defined as APN resistance, and it is linked with insulin resistance in high-fat diet-fed subjects. The insulin-resistant group has a significantly higher leptin-to-APN ratio. The leptin-to-APN ratio is more than twofold higher in obese individuals. An increase in expression of AdipoRs restores insulin sensitivity and β-oxidation of fatty acids via triggering intracellular signal cascades. The ratio of high molecular weight to total APN is defined as the APN sensitivity index (ASI). This index is correlated to insulin sensitivity. Homeostasis model of assessment (HOMA)-APN and HOMA-estimated insulin resistance (HOMA-IR) are the most suitable methods to estimate the metabolic risk in metabolic syndrome. While morbidly obese patients display a significantly higher plasma leptin and soluble (s)E-selectin concentrations, leptin-to-APN ratio, there is a significant negative correlation between leptin-to-APN ratio and sP-selectin in obese patients. When comparing the metabolic dysregulated obese group with the metabolically healthy obese group, postprandial triglyceride clearance, insulin resistance, and leptin resistance are significantly delayed following the oral fat tolerance test in the first group. A neuropeptide, Spexin (SPX), is positively correlated with the quantitative insulin sensitivity check index (QUICKI) and APN. APN resistance together with insulin resistance forms a vicious cycle. Despite normal or high APN levels, an impaired post-receptor signaling due to adaptor protein-containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1)/APPL2 may alter APN efficiency and activity. However, APPL2 blocks adiponectin signaling through AdipoR1 and AdipoR2 because of the competitive inhibition of APPL1. APPL1, the intracellular binding partner of AdipoRs, is also an important mediator of adiponectin-dependent insulin sensitization. The elevated adiponectin levels with adiponectin resistance are compensatory responses in the condition of an unusual discordance between insulin resistance and APN unresponsiveness. Hypothalamic recombinant adeno-associated virus (rAAV)-leptin (Lep) gene therapy reduces serum APN levels, and it is a more efficient strategy for long-term weight maintenance.

Elevated plasma adiponectin in risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: observational and mendelian randomization studies

Abstract Background and purpose Adiponectin, an adipocyte-secreted protein-hormone, may play an important protective role in heart failure and associated cardiovascular diseases through insulin-sensitizing, anti-atherogenic, and anti-inflammatory properties. We hypothesized that plasma adiponectin is associated observationally and causal, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. Methods In the Copenhagen General Population Study (CGPS), we examined 30,045 individuals with plasma adiponectin measurements observationally and 96,903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants. In the HERMES, UK Biobank, The Nord-Trøndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1,030,836 individuals using 12 genetic variants. Results In observational analyses, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37–1.66) for heart failure, 1.63 (1.50–1.78) for atrial fibrillation, 1.21 (1.03–1.41) for aortic valve stenosis, and 1.03 (0.93–1.14) for myocardial infarction; levels above the median was also associated with increased risk of myocardial infarction. Corresponding genetic, causal risk ratios were 0.92 (0.65–1.29), 0.87 (0.68–1.12), 1.55 (0.87–2.76), and 0.93 (0.67–1.30) in one-sample Mendelian randomization analyses, while corresponding causal risk ratios were 0.99 (0.89–1.09), 1.00 (0.92–1.08), 1.01 (0.79–1.28), and 0.99 (0.86–1.13) in two-sample Mendelian randomization analyses, respectively. Conclusion Elevated plasma adiponectin was associated with increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for those associations.Observational associationObservational and genetic association

Adiponectin stimulates Sca1+CD34−-adipocyte precursor cells associated with hyperplastic expansion and beiging of brown and white adipose tissue

BackgroundThe adipocyte hormone adiponectin improves insulin sensitivity and there is an inverse correlation between adiponectin levels and type-2 diabetes risk. Previous research shows that adiponectin remodels the adipose tissue into a more efficient metabolic sink. For instance, mice that overexpress adiponectin show increased capacity for hyperplastic adipose tissue expansion as evident from smaller and metabolically more active white adipocytes. In contrast, the brown adipose tissue (BAT) of these mice looks “whiter” possibly indicating reduced metabolic activity. Here, we aimed to further establish the effect of adiponectin on adipose tissue expansion and adipocyte mitochondrial function as well as to unravel mechanistic aspects in this area. MethodsBrown and white adipose tissues from adiponectin overexpressing (APN tg) mice and littermate wildtype controls, housed at room and cold temperature, were studied by histological, gene/protein expression and flow cytometry analyses. Metabolic and mitochondrial functions were studied by radiotracers and Seahorse-based technology. In addition, mitochondrial function was assessed in cultured adiponectin deficient adipocytes from APN knockout and heterozygote mice. ResultsAPN tg BAT displayed increased proliferation prenatally leading to enlarged BAT. Postnatally, APN tg BAT turned whiter than control BAT, confirming previous reports. Furthermore, elevated adiponectin augmented the sympathetic innervation/activation within adipose tissue. APN tg BAT displayed reduced metabolic activity and reduced mitochondrial oxygen consumption rate (OCR). In contrast, APN tg inguinal white adipose tissue (IWAT) displayed enhanced metabolic activity. These metabolic differences between genotypes were apparent also in cultured adipocytes differentiated from BAT and IWAT stroma vascular fraction, and the OCR was reduced in both brown and white APN heterozygote adipocytes. In both APN tg BAT and IWAT, the mesenchymal stem cell-related genes were upregulated along with an increased abundance of Lineage−Sca1+CD34− “beige-like” adipocyte precursor cells. In vitro, the adiponectin receptor agonist Adiporon increased the expression of the proliferation marker Pcna and decreased the expression of Cd34 in Sca1+ mesenchymal stem cells. ConclusionsWe propose that the seemingly opposite effect of adiponectin on BAT and IWAT is mediated by a common mechanism; while reduced adiponectin levels are linked to lower adipocyte OCR, elevated adiponectin levels stimulate expansion of adipocyte precursor cells that produce adipocytes with intrinsically higher metabolic rate than classical white but lower metabolic rate than classical brown adipocytes. Moreover, adiponectin can modify the adipocytes' metabolic activity directly and by enhancing the sympathetic innervation within a fat depot.

Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: large-scale observational and Mendelian randomization evidence.

Adiponectin may play an important protective role in heart failure and associated cardiovascular diseases. We hypothesized that plasma adiponectin is associated observationally and causally, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. In the Copenhagen General Population Study, we examined 30 045 individuals with plasma adiponectin measurements observationally and 96 903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants explaining 3% of the variation in plasma adiponectin. In the HERMES, UK Biobank, The Nord-Trøndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1 030 836 individuals using 12 genetic variants explaining 14% of the variation in plasma adiponectin.In observational analyses modelled linearly, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37-1.66) for heart failure, 1.63 (1.50-1.78) for atrial fibrillation, 1.21 (1.03-1.41) for aortic valve stenosis, and 1.03 (0.93-1.14) for myocardial infarction; levels above the median were also associated with an increased risk of myocardial infarction, and non-linear U-shaped associations were more apparent for heart failure, aortic valve stenosis, and myocardial infarction in less-adjusted models. Corresponding genetic, causal risk ratios were 0.92 (0.65-1.29), 0.87 (0.68-1.12), 1.55 (0.87-2.76), and 0.93 (0.67-1.30) in one-sample Mendelian randomization analyses, and no significant associations were seen for non-linear one-sample Mendelian randomization analyses; corresponding causal risk ratios were 0.99 (0.89-1.09), 1.00 (0.92-1.08), 1.01 (0.79-1.28), and 0.99 (0.86-1.13) in two-sample Mendelian randomization analyses, respectively. Observationally, elevated plasma adiponectin was associated with an increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for these associations.

Association of Adipocytokines and Vitamin D Status in Tuberculosis

Leptin and Adiponectin are considered principal indicators of tuberculosis (TB). They are critical parts of the pathophysiological processes to which treatment can be applied. Thus, this research aimed at finding out the role of Adipocytokines and 25-dihydroxy vitamin D in the aetiology of tuberculosis. The research sample included (90) participants divided into (50) tuberculosis patients and (40) healthy subjects representing the control group who were age and sex-matched. Circulating levels of adipocytokines and 25- dihydroxy vitamin D were analysed by using ELISA techniques. Compared to the subjects of control group, tuberculosis subjects had significantly (P&lt;0.0001) lower levels of serum leptin (5.84±1.83 pg/mL) and vitamin D (2.77±0.52 ng/mL). However, compared to their control counterparts, tuberculosis patients had significantly (P&lt;0.0001) higher levels of adiponectin (16.30±1.23 ng/mL). The ROC curve analysis of Leptin, Adiponectin, and 25-dihydroxy vitamin D indicated a high diagnostic value in predicting the risk of tuberculosis. The present study findings revealed that elevated serum adiponectin with decreased serum leptin levels and hypovitaminosis D are strongly correlated with the pathogenesis and state of tuberculosis.

THU381 A Case of Severe Type B Insulin Resistance Successfully Treated With Combined Immunosuppressive Therapy

Abstract Disclosure: A.K. Sumal: None. D.S. Martinez: None. Background: Type B insulin resistance is a rare autoimmune disorder caused by autoantibodies against the insulin receptor and is characterized by markedly high insulin requirements, severe catabolism, and a mortality rate over 50%. Clinical Case: A 50-year-old woman with Sjogren’s syndrome and a one-year history of diabetes treated with insulin presented with diabetic ketoacidosis (DKA) and was found to have type B insulin resistance. Initial laboratory workup demonstrated DKA with a blood glucose of 464 mg/dL (n: 65–99 mg/dL), CO2 8 mmol/L (n: 20–30 mmol/L), anion gap 16 (n: 8–12), pH 7.08 (n: 7.30–7.40) on venous blood gas, 2+ ketonuria, and a hemoglobin A1c of 11.7% (n: &amp;lt;5.7%). Additional workup revealed negative glutamic acid decarboxylase-65, insulin antigen-2, and insulin antibodies, positive C-peptide 2.7 ng/mL (n: 1.1–4.3 ng/mL), and elevated adiponectin 41 ug/mL (n: 5–28 ug/mL). Her physical exam was notable for 100 lb weight loss and extensive acanthosis nigricans, facial acne, and hirsutism. She was started on IV insulin infusion with resolution of her DKA but required more than 5000 units of insulin per day to obtain glycemic control. Due to the suspicion of type B insulin resistance, she was treated with metformin 1000 mg twice daily and pioglitazone 45 mg daily to reverse her hypercatabolic state and combined immunosuppressive therapy consisting of 2 cycles of rituximab 750 mg/m2 infusion, cyclophosphamide 100 mg daily, and dexamethasone 40 mg for 4 days administered 14 days apart based on a 2018 NIH protocol. Her serum was sent for confirmatory insulin receptor autoantibody testing, which is pending. Over the next 30 days, her insulin requirements improved immensely, and she was ultimately discharged without insulin in clinical remission. To prevent recurrence and hypoglycemia associated with low titers of insulin receptor autoantibodies, she was started on azathioprine 100 mg daily as maintenance therapy. Three months later, she was seen in endocrine clinic in sustained remission with a hemoglobin A1c of 6.0% and resolution of her acanthosis nigricans and hyperandrogenism. Review of her continuous glucose monitor showed no episodes of hypoglycemia. Conclusion: This rare case demonstrates the successful treatment of type B insulin resistance using metformin, pioglitazone, and combination immunosuppressive therapy with rituximab, cyclophosphamide, and pulse-dose steroids, followed by maintenance azathioprine. With a mortality rate over 50%, the use of combined immunosuppressive therapy has transformed this condition into a curable form of diabetes and should be recommended in all patients with type B insulin resistance. Presentation: Thursday, June 15, 2023

Relationship between chronic obstructive pulmonary disease and adiponectin concentrations: An updated meta-analysis and single-cell RNA sequencing.

Adipose tissue, being an organ of the endocrine system, can influence the severity of chronic obstructive pulmonary disease (COPD). Even though several inflammatory markers can potentially significantly influence lung function, the precise function of adipokines, like adiponectin, in COPD is still disputed. To analyze the association of COPD with adiponectin concentrations, a meta-analysis of the most recent literature and single-cell sequencing data were conducted. Studies in Embase, PubMed, Cochrane Library, and Web of Science were browsed to obtain relevant data, which were then assessed with the aid of R 4.1.3 and STATA 11.0 software. Standardized mean differences and correlation coefficients aided the analysis of effect values. Moreover, a single-cell sequencing GSE136831 dataset was retrieved to ascertain the mRNA expression of adiponectin gene (ADIPOQ) in the lung tissue of COPD patients to confirm the difference in the expression of adiponectin between the case and control groups. This meta-analysis comprised 18 publications involving 24 studies. The overall combined data established the concentration of plasma/serum adiponectin as significantly higher in patients with COPD compared to healthy subjects. Subgroup analyses based on disease status, specimen type, ethnicity, study design method, measurement method, and age of COPD patients demonstrated that all patients with COPD had elevated levels of adiponectin compared to healthy controls. When subgroup analysis was performed for gender alone, the results depicted that male COPD patients had significantly higher adiponectin than healthy males, while female patients of COPD had elevated adiponectin compared to healthy females. Furthermore, it was found that plasma/serum adiponectin appeared to be positively correlated with tumor necrosis factor-α, and it was negatively correlated with FEV1% and FEV1/FVC. The results of single-cell sequencing data suggested that ADIPOQ mRNA was mainly expressed in alveolar epithelial cells, and the level of ADIPOQ mRNA was higher in lung tissues of patients with COPD than in lung tissues of healthy subjects. This meta-analysis suggests that the levels of plasma/serum adiponectin are significantly elevated in patients with COPD versus controls. Tumor necrosis factor-α, FEV1/FVC, and FEV1% may all be associated with the concentrations of adiponectin.

The association of serum adiponectin level with activities of daily living in hospitalized elderly patients with heart failure

BackgroundSeveral studies have reported a relationship between elevated serum adiponectin levels and poor outcomes in patients with heart failure (HF). However, data on the activities of daily living (ADL) in elderly patients with HF are limited. MethodsWe evaluated 218 hospitalized elderly (≥65 years) patients with HF who underwent a comprehensive cardiac rehabilitation (CR) program during hospitalization. Serum adiponectin levels were measured before discharge. The Barthel index (BI) score was evaluated at discharge. Low ADL was defined as a BI score < 85. ResultsSerum adiponectin levels were significantly associated with low ADL [p = 0.03; odds ratio (OR), 1.024, per 1.0 μg/mL increase]. In logistic or regression analyses adjusted for age, sex, body mass index, and estimated glomerular filtration rate, high adiponectin levels (≥16.2 μg/mL) were significantly associated with low ADL (p = 0.04; OR, 2.53), malnutrition (p < 0.01; OR, 2.88), and 6-min walk distance (p = 0.04; β = −17.5). In the multivariate analysis adjusted for conventional risk factors of low ADL, high adiponectin levels were also significantly associated with low ADL (p = 0.03; OR, 2.68). In the stepwise forward selection procedure, a high adiponectin level was an independent determinant of low ADL (p = 0.02; R2 = 0.0262). Both net reclassification improvement (0.53; p < 0.01) and integrated discrimination improvement (0.02; p = 0.01) improved significantly after the addition of high adiponectin level to conventional risk factors. In the regression analysis adjusted for age and sex, serum adiponectin levels were significantly (p < 0.0025) negatively associated with abdominal visceral and subcutaneous adipose tissue areas, body weight, body mass index, and serum triglyceride levels. ConclusionsHigh serum adiponectin levels were not only significantly associated with an increased risk of low ADL, but also with an increased risk of malnutrition and low physical activity in elderly patients with HF after the in-hospital CR program.

WISER Survivor Trial: Combined Effect of Exercise and Weight Loss Interventions on Adiponectin and Leptin Levels in Breast Cancer Survivors with Overweight or Obesity.

Adipocyte dysregulation is one mechanism linking overweight and breast cancer recurrence. Exercise and weight loss are associated with a decreased risk of breast cancer recurrence in breast cancer survivors with overweight or obesity, which may be mediated through reduced leptin levels, increased adiponectin levels, and an elevated adiponectin to leptin (A:L) ratio. The four-arm randomized controlled WISER Survivor trial examined the 12-month intervention effects of exercise, weight loss, and the combination of exercise and weight loss on adipokine levels among breast cancer survivors (n = 339) with overweight or obesity. Compared with Control, the Combination of Exercise and Weight Loss decreased leptin levels (-35.9%; 95% CI: -46.8%, -25.0%) and increased A:L ratio (11.6%; 95% CI: 5.6%, 17.6%) but did not change adiponectin levels (4.1%; 95% CI: -3.1%, 11.2%). Compared with Control, Weight Loss Alone decreased leptin levels (-35.6%; 95% CI: -46.6%, -24.5%) and increased A:L ratio (10.6%; 95% CI: 4.7%, 16.5%) but did not change adiponectin levels (0.9%; 95% CI: -6.0%, 7.9%). Compared with Control, Exercise Alone did not change leptin levels, adiponectin levels, or A:L ratio. In analyses that consolidated intervention groups, compared with Control, weight loss of ≥5% decreased leptin levels (p trend < 0.01) and increased A:L ratio (p trend < 0.01) but did not alter adiponectin levels (p trend = 0.53). Weight loss, with or without exercise, was associated with decreased leptin levels in breast cancer survivors with overweight or obesity. Improvements in the adipokine secretion profile (A:L ratio) were primarily driven by a weight loss-induced change in leptin levels.

Elevated plasma adiponectin in risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: Observational and mendelian randomization studies

Elevated plasma adiponectin in risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: Observational and mendelian randomization studies

Pre-procedural high serum visfatin and tumor necrosis factor-α might predict recurrent atrial fibrillation after catheter ablation

BackgroundMany patients would require repeated ablation procedures owing to recurrent atrial fibrillation with its associated symptoms. Identifying those who are at risk of recurrent AF could assist us to develop preventive strategies and to properly select those who will benefit more from catheter ablation. Our aim is to study the role of preprocedural serum level of certain biomarkers in the prediction of AF recurrence after catheter ablation.ResultsThe present study included 117 patients: 26 patients with persistent and 91 patients with paroxysmal AF. Blood samples for estimation of serum levels of studied cytokines were obtained prior to the procedure. Pulmonary vein isolation was performed in all patients through point-by point radiofrequency ablation guided by 3D electroanatomical mapping system. Patients were followed for 12 months for AF recurrence. Forty-one (35%) patients developed AF recurrence. Those patients were significantly older, had significantly higher BMI, lower ejection fraction, and wider maximal left atrial diameter (LAD). Serum hs-CRP, IL-6, TNF-α, visfatin, and adiponectin levels were significantly higher compared to those who did not develop AF recurrence. Correlation analysis showed positive correlations between the incidence of RAF and patients’ age, BMI, and maximum LAD and elevated cytokine levels and maximal LAD showed significant correlations with the type of AF and elevated serum TNF-α, visfatin, and adiponectin. Statistical analyses defined elevated serum levels of TNF-α, visfatin, and adiponectin as positive predictors for RAF, and automatic linear modeling analysis showed that elevated serum visfatin, TNF-α, and adiponectin can predict RAF by accuracy rates of 50%, 34%, and 16%, respectively.ConclusionsRAF is most probably an outcome of the interplay between patients' clinical data, obesity, and inflammation. Pre-procedural estimation of serum levels of visfatin and TNF-α might determine patients with probability for RAF.

Elevated baseline adiponectin level predicting an increased risk of disease activity in idiopathic nephrotic syndrome and chronic kidney disease in children

Adiponectin, an adipocyte-derived protein, is present abundantly in circulation and has anti-atherogenic and anti-inflammatory effects, so we aimed to assess the role of adiponectin in idiopathic nephrotic syndrome and chronic kidney disease in children. Overall of 290 children, 95 patients with the steroid-responsive idiopathic nephrotic syndrome (50 in remission and 45 in relapse). Another 95 patients with chronic kidney disease (50 on hemodialysis and 45 on conservative therapies) and 100 apparently healthy matched children were enrolled into the study. Serum adiponectin levels, blood chemistry (protein/albumin, serum creatinine, blood urea and electrolytes levels) and 24-hour proteinuria w studied as well. There was highly significant increasing differences in adiponectin level between the relapsed idiopathic nephrotic syndrome (26.93±6.79 µg/mL) compared to remission (10.96±3.33 µg/mL) and control group (4.89±1.01 µg/mL) and between remission in comparing to control group (P<0.001). Also there was significant negative correlation between adiponectin level and serum albumin level in the relapse group (r=-0.60, P≤0.05), and highly positive correlation between adiponectin level and 24-hour proteinuria in relapse (r=0.98, P≤0.001) and remission group (r=0.92, P≤0.001). Regarding children with chronic kidney disease, There were high significant increasing differences in adiponectin levels in conservative (13.88±4.27 µg/mL) and dialysis (15.09±6.14 µg/mL) groups compared to controls (6.05±5.83 µg/mL) with P<0.001. Furthermore, there was a significant positive correlation between adiponectin and serum creatinine and blood urea levels in both conservative and dialysis groups with P<0.05. Adiponectin can be considered as an important useful biomarker for chronic kidney diseases in children.

Circulating adipokine concentrations and the risk of venous thromboembolism: A Mendelian randomization and mediation analysis.

Background: Previous observational studies have suggested that circulating adipokine concentrations are related to a greater risk of venous thromboembolism (VTE). However, it remained unclear whether these observations reflect causality. Objective: This study aimed to investigate the causal relationship between circulating adipokine concentrations (including adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN) and the risk of VTE and its subtypes (DVT and PE) and to determine whether circulating adipokine concentrations are a mediator of venous thromboembolic events in obese patients. Methods: We used Mendelian randomization (MR) analyses to determine the effects of the body mass index (BMI), adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN levels on VTE, DVT, and PE in a cohort of 11,288 VTE cases, 5,632 DVT cases, 5,130 PE cases, and 254,771 controls. We then assessed the proportion of the effect of obesity on VTE, DVT, and PE explained by circulating leptin levels. Result: Genetically predicted higher BMI was related to increased VTE (OR = 1.45, p < 0.001), DVT (OR = 1.63, p < 0.001), and PE (OR = 1.37, p < 0.001) risk, and higher circulating leptin levels increase odds of VTE (OR = 1.96, q < 0.001), DVT (OR = 2.52, q < 0.001), and PE (OR = 2.26, q = 0.005). In addition, we found that the causal effect between elevated serum adiponectin and the decreased risk of VTE (OR = 0.85, p = 0.013, q = 0.053) and PE (OR = 0.81, p = 0.032, q = 0.083) and between MCP-1 and the reduced risk of VTE (OR = 0.88, p = 0.048, q = 0.143) is no longer significant after FDR adjustment. In MR mediation analysis, the mediation effect of circulating leptin levels in the causal pathway from BMI to PE was estimated to be 1.28 (0.95-1.71, p = 0.10), accounting for 39.14% of the total effect. Conclusion: The circulating leptin level is a risk factor for VTE, DVT, and PE, but it might be a potential mediator of BMI on the risk of PE, and thus, interventions on the circulating leptin level in obesity might reduce the risk of PE. Adiponectin is a potential protective factor for both VTE and PE.