Metabolic Comorbid Conditions Research Articles

392 Pathogenic relationship between Psoriasis and Obesity:an ex vivo study

Psoriasis is a chronic inflammatory skin disease associated with metabolic comorbid conditions, including obesity. The crosstalk between adipose tissue-derived products and psoriasis signature cytokines may contribute to the pathogenesis of both psoriasis and metabolic syndrome. To date, pathogenic relationship between psoriasis and obesity has not been fully elucidated. Our study aimed to investigate adipose tissue response to psoriasis-signature cytokines and the potential contribution of adipose tissue to psoriasis pathogenesis.

183-LB: High Daily Doses of Insulin in Type 2 Diabetes—Predictors beyond Weight

In clinical practice, needing ≥ 200 units insulin/day is defined as severe insulin resistance. This study seeks to identify predictive characteristics of those with type 2 diabetes and severe insulin resistance (≥ 200 units insulin/day) vs. those using <100 units insulin/day. This retrospective cross-sectional study analyzed data for a six-month period gathered from a diabetes clinic electronic database. Compared were 59 patients using >200 units daily (high insulin users - HIU) vs. 59 patients using <100 units (low insulin users - LIU) . For the entire study group (n=118) , mean age was 57.7 ± 9.5 years, 66% were female and 52% Hispanic. Comparing groups, no differences seen in age, race, ethnicity, and A1c. Compared to LIU, HIU had more men (26 vs. 14, P=0.032) , higher BMI (41.8 ± 9.5 vs. 35.1 ± 6.6 kg/m2, p<0.001) , less physically active (42.5 (0.0, 120.0) vs. 140.0 (80.0, 180.0) min/week, p<0.001) , lower HDL (37.5 (32.0, 46.0) vs. 43.0 (37.0, 52.0) mg/dL, p=0.005) , higher insulin units/kg/day (2.3 ± 0.7 vs. 0.9 ± 0.3, p<0.001) , higher use of GLP1-RA medication (16 vs. 6, p=0.018) , higher incidence diabetic neuropathy (36 vs. 18, P<0.001) and co-morbid metabolic conditions like hypertension (58 vs. 50, p=0.024) , congestive heart failure (13 vs. 4, p=0.018) , metabolic liver disease (12 vs. 4, p=0.031) , and obstructive sleep apnea (18 v 7, p=0.013) . Per stepwise multivariate analysis, significant predictors of needing more insulin were being less active, lower HDL, co-morbid conditions like hypertension, neuropathy, obstructive sleep apnea, use of GLP1-RA and higher insulin/kg/day. Factors responsible for high insulin requirements go beyond weight alone as evidenced by higher insulin/kg/day in HIU. Insulin resistance may be exaggerated in the HIU by physical inactivity. Beta cell secretory dysfunction in HIU may also play a role as implied by their longer diabetes duration and higher rate of metabolic comorbid conditions. Disclosure J. Duron tabora: None. A. Amblee: n/a. B. Tahsin: n/a. L. Fogelfeld: Research Support; Lilly, Sanofi.

Metabolic comorbidities among patients with peripheral artery disease: a national population-based study

Peripheral artery disease (PAD) is a chronic disease which is associated with old age. PAD was known as an age-related chronic condition. Metabolic comorbid conditions which include hypertension, diabetes, and hyperlipidemia can have negative impacts on blood vessels aggravating PAD in elderly patients. Therefore, metabolic comorbidities need be considered in order to develop intervention for patients with PAD. The aim of this study is to find the characteristics of PAD patients with metabolic comorbidities. This is a retrospective study that used the national claim data of South Korea from 2009 to 2018. The inclusion criteria were adults (20+) and patients diagnosed with PAD as a primary or secondary diagnosis from 2011 to 2017. The frequency of hypertension, hyperlipidemia, diabetes, and metabolic comorbidities in PAD patients was examined. In addition, the difference in the number of metabolic comorbidities according to sex was identified using the chi-squared test. Among the total PAD adult patients(n=8,478,876), the number of elderly patients over 60 years old was 4,124,592(48.7%). Among the total patients, PAD patients with hypertension were the most common at 958,329 (11.30%). Sex was significantly related to having metabolic comorbidities and women showed higher proportion of metabolic comorbidities compared to men (χ2 =5.02, p<.001). As the frequency of PAD patients with hypertension were the highest, it is necessary to develop a health management program that considers metabolic comorbidities, especially hypertension, in order to manage PAD disease. In addition, there is a need for special interest in intervening metabolic conditions of female patients with PAD.

Adult but not childhood onset asthma is associated with the metabolic syndrome, independent from body mass index

IntroductionAdult-onset asthma (AOA) is usually more severe compared to childhood onset asthma (CoA). Given the increasing evidence that AoA is associated with obesity, we investigated the relationship of other related metabolic comorbid conditions with AoA compared to CoA. Study design and methodsThis cross-sectional study compared the metabolic syndrome and lipid derived inflammatory markers in patients with AoA, CoA and age- and sex-matched control subjects without asthma. Participants were asthma patients visiting the outpatient clinic of two teaching hospitals in Rotterdam, The Netherlands. All participants underwent lung function tests, blood tests and physical activity tracking. AoA was defined as asthma age of onset after the age of 18 years. Metabolic syndrome was defined according to the international joint interim statement criteria. ResultsEighty-one participants were included (27 AoA, 25 CoA, 29 controls). AoA was associated with the metabolic syndrome (Odds Ratio = 3.64 95% CI (1.16–11.42) p = 0.03, Nagelkerke R2 = 0.26), adjusted for age, sex, body mass index and smoking habits. AoA patients had higher median serum IL-6 and leptin-adiponectin (LA) ratio compared to controls (IL-6 (pg/mL): 3.10 [1.11–4.30] vs. 1.13 [0.72–1.58], p = 0.002 and LA ratio (pg/mL): 6.21 [2.45–14.11] vs. 2.24 [0.67–4.71], p = 0.0390). This was not observed in CoA and controls. ConclusionAoA was associated with the metabolic syndrome and its related pro-inflammatory endocrine and cytokine status. This may suggest adipose tissue derived inflammatory markers play a role in the pathophysiology of AoA.

Familial combined hyperlipidemia: current knowledge about pathophysiology, diagnostics and correction

The review is devoted to the current knowledge about pathophysiology, diagnostics and correction of familial combined hyperlipidemia (FCHL) that is considered to be the most frequent among primary dyslipidemias in general population (1 — 3 %) as well as among the patients survived after myocardial infarction (20 — 38 %). The current knowledge about genetic characterization of FCHL and its pathophysiology are adduced. FCHL is emphasized to be a heterogenic state and many of genetic determinants are involved in its development. Excessive concentration of apolipoprotein B (ApoB) — containing lipoproteins is shown to be the main biochemical sign of FCHL and hence, the genes of proteins participated in their metabolism could be claimed for genes‑candidates of FCHL. A special attention is paid to the diagnostics of FCHL, the most valuable diagnostic signs of FCHL are emphasized because FCHL is not monogenic disorder and due to its phenotype characterized by high levels of low‑density lipoprotein cholesterol and/or triglyceride (TG), this lipid disorder is not frequently diagnosed. A combination of concentrations of ApoB &gt; 120 mg/dl and TG &gt; 1.5 mmol/l (&gt; 133 mg/dl) with a family history of early cardiovascular debut could be used today for revelation of patients with a probable diagnosis of FCHL. The influence of FCHL on cardiovascular risk (CVR) that is partly realized through its association with metabolic comorbid conditions such as type 2 diabetes mellitus, metabolic syndrome, nonalcoholic fatty liver disease is considered. These comorbid conditions could play a role of etiological causes of cardiovascular disease and could increase a CVR through some common pathophysiological mechanisms such as insulin resistance of muscular and fat tissues and hepatic overproduction of very low‑density lipoproteins. The current approaches to FCHL correction in accordance with acting recommendations are elucidated. They consider its correction to be necessary as a primary atherogenic dyslipidemia and propose to start intervention from the influence on modified factors of CVR (smoking, alcohol consumption, excessive body mass, obesity). Some differential approaches to correction of lipid exchange disorders in FCHL from the beginning of the first line hypolipidemic agent (statin of fibrate) or their combined usage depended on dyslipidemia phenotype revealed during diagnostics of FCHL are discussed. Update combinations of hypolipidemic agents with an addition to statin and fibrate omega‑3 fatty acids, ezetimibe and inhibitors of PCSK9 (alirocumab, evolocumab) from the point of their influence on a reduction of CVR as well as on the components of dyslipidemia phenotype occurred in FCHL are considered.

Metabolic syndrome, metabolic comorbid conditions and risk of early-onset colorectal cancer

ObjectiveFactors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC...

The incidence of COVID-19 in patients with metabolic syndrome and non-alcoholic steatohepatitis: A population-based study

BackgroundThe novel coronavirus disease (COVID-19) emerged from China in 2019 and rapidly spread worldwide. Patients with metabolic comorbid conditions are more susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Metabolic syndrome is a constellation of interlinked metabolic risk factors that predispose patients to increased risk of complications. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and non-alcoholic steatohepatitis (NASH) is the aggressive form of NAFLD. ObjectiveThe aim of this study is to determine the relationship between metabolic syndrome components and the risk of COVID-19. MethodsWe reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED-CT), we identified adults with the diagnosis of metabolic syndrome and its individual components from 1999 to 2019. We included patients with the diagnosis of COVID-19 from December 2019 to May 2020. Comorbidities known to be associated with COVID-19 and metabolic syndrome such as obesity, diabetes mellitus, dyslipidemia, smoking, male gender, African American, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether metabolic syndrome or its individual components are independently associated with the risk of COVID-19. ResultsOut of 61.4 million active adult patients in the database, 8885 (0.01%) had documented COVID-19. The cumulative incidence of COVID-19 was higher if metabolic syndrome was the primary diagnosis (0.10% vs 0.01%, OR 7.00 [6.11–8.01]). The adjusted odds (aOR) of having COVID-19 was higher in patients if they were African Americans (aOR 7.45 [7.14–7.77]), hypertensive (aOR 2.53 [2.40–2.68]), obese (aOR 2.20 [2.10–2.32]), diabetic (aOR 1.41 [1.33–1.48]), hyperlipidemic (aOR 1.70 [1.56–1.74]), or diagnosed with NASH (aOR 4.93 [4.06–6.00]). There was a slight decrease in the adjusted odds of having COVID-19 in males as compared to females (aOR 0.88 [0.84–0.92]). ConclusionThe incidence of COVID-19 in patients with metabolic syndrome is high. Among all comorbid metabolic conditions, NASH had the strongest association with COVID-19.

Metabolic syndrome, metabolic comorbid conditions, and risk of early-onset colorectal cancer.

1571 Background: The etiology and contributors to the rising incidence of early-onset colorectal cancer (CRC diagnosed under age 50), driven largely by distal and rectal cancer, remain largely unknown. Metabolic syndrome is associated with higher risk of CRC diagnosed at older ages; however, its association with early-onset CRC remains unclear. Methods: We conducted a nested case-control study among participants aged 18-50 years with ≥2 years of enrollment and prescription drug coverage in the IBM MarketScan Commercial Databases (2006-2015). Incident CRC cases were identified using ICD-9-CM diagnosis codes. Controls without any cancer were identified using frequency matching on age, sex, geographical region, and duration of insurance enrollment. Metabolic syndrome was defined using either ICD-9-CM diagnosis codes or the presence of at least 3 of the following: obesity, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes. In addition to ICD-9-CM codes, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes were also defined based on regular use of medications. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 4,673 early-onset CRC and 40,832 controls were included. Metabolic syndrome was associated with increased risk of early-onset CRC (OR: 1.33, 95% CI 1.16-1.52), after adjusting for a range of potential confounders. The number of metabolic comorbid conditions was positively associated with risk of early-onset CRC in a dose-response fashion. Compared to individuals without any conditions, individuals with 1, 2, ≥3 metabolic conditions had a 13% (OR: 1.13, CI 1.04-1.22), 18% (OR: 1.18, CI 1.07-1.31), and 40% (OR: 1.40, CI 1.22-1.61) higher risk of early-onset CRC (Ptrend&lt;0.001), respectively. These associations were driven by proximal (OR for ≥2 vs 0 metabolic comorbid conditions: 1.40, CI 1.15-1.69) and distal colon cancer, OR ≥2 vs 0: 1.25, CI 1.03-1.53), but not rectal cancer (OR≥2 vs 0: 1.07, CI 0.92-1.24). Conclusions: Metabolic syndrome and metabolic comorbid conditions were associated with increased risk of early-onset CRC, largely driven by proximal and distal colon cancer. Metabolic dysregulations may contribute to the rising incidence of early-onset CRC.

Nonalcoholic Fatty Liver Disease and the Development of Metabolic Comorbid Conditions in Patients With Human Immunodeficiency Virus Infection

Cardiovascular and liver disease are main causes of death in people with human immunodeficiency virus (HIV) (PWH). In HIV-uninfected patients, nonalcoholic fatty liver disease (NAFLD) is associated with incident metabolic complications. We investigated the effect of NAFLD on development of metabolic comorbid conditions in PWH. We included PWH undergoing a screening program for NAFLD using transient elastography. NAFLD was defined as a controlled attenuation parameter ≥248 dB/m with exclusion of other liver diseases. Incident diabetes, hypertension, dyslipidemia, and chronic kidney disease were investigated using survival analysis and Cox proportional hazards. The study included 485 HIV-monoinfected patients. During a median follow-up of 40.1 months (interquartile range, 26.5-50.7 months), patients with NAFLD had higher incidences of diabetes (4.74 [95% confidence interval, 3.09-7.27] vs 0.87 [.42-1.83] per 100 person-years) and dyslipidemia (8.16 [5.42-12.27] vs 3.99 [2.67-5.95] per 100 person-years) than those without NAFLD. With multivariable analysis, NAFLD was an independent predictor of diabetes (adjusted hazard ratio, 5.13; 95% confidence interval, 2.14-12.31) and dyslipidemia (2.35; 1.34-4.14) development. HIV-monoinfected patients with NAFLD are at higher risk of incident diabetes and dyslipidemia. Early referral strategies and timely management of metabolic risk may improve outcomes.

Impact of Human Immunodeficiency Virus-Related Gut Microbiota Alterations on Metabolic Comorbid Conditions.

We aimed to identify a human immunodeficiency virus (HIV)-related microbiota signature, independent of sexual preferences and demographic confounders, in order to assess a possible impact of the microbiome on metabolic comorbid conditions. Bacterial 16S ribosomal RNA analyses were performed on stool samples from 405 HIV-infected and 111 uninfected participants of the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Individuals were stratified according to sexual behavior (men who have sex with men [MSM] vs non-MSM). After excluding MSM-associated microbiota traits and adjusting for confounders, we identified an HIV-related microbiota signature, consisting of lower biodiversity, increased relative abundance of the bacterial clades Gammaproteobacteria and Desulfovibrionaceae and decrease in several Clostridia. This microbiota profile was associated with a 2-fold excess risk of metabolic syndrome, driven by increase in Desulfovibrionaceae and decrease in Clostridia (Butyrivibrio, Coprococcus 2, Lachnospiraceae UCG-001 and CAG-56). This association was accentuated (5-fold excess risk) in individuals with previous severe immunodeficiency, which also modified the association between HIV-related microbiota signature and visceral adipose tissue (VAT) area (P for interaction = .01). Accordingly, HIV-related microbiota was associated with 30-cm2 larger VAT in individuals with history of severe immunodeficiency, but not in those without. The HIV-related microbiota was associated with increased risk of metabolic syndrome and VAT accumulation, particularly in individuals with previous severe immunodeficiency, driven by increased Desulfovibrionaceae and lower abundance of several Clostridia. Our findings suggest a potential interplay between HIV-related microbiota, immune dysfunction and metabolic comorbid conditions. Interventions targeting the gut microbiome may be warranted to reduce cardiovascular risk, particularly in individuals with previous immunodeficiency.

The prevalence and predictors of resistant hypertension in high‐risk overweight and obese patients: A cross‐sectional study based on the 2017 ACC/AHA guidelines

Obesity is significantly associated with uncontrolled blood pressure and resistant hypertension (RH). There are limited studies on the prevalence and determinants of RH in patients with higher body mass index (BMI) values. Since the hypertension guidelines changed in 2017, the prevalence of RH has become unknown and now is subject to be estimated by further studies. We conducted a cross-sectional study in an urban Federally Qualified Health Center in New York City aiming to estimate the prevalence of RH in high-risk overweight and obese patients based on the new hypertension definition, BP threshold ≥130/80mm Hg, and also to describe the associated comorbid conditions in these patients. We identified 761 eligible high-risk overweight and obese subjects with hypertension between October 2017 and October 2018. Apparent treatment-RH was found in 13.6% among the entire study population. This represented 15.4% of those treated with BP-lowering agents. True RH confirmed with out-of-office elevated BP was found in 6.7% of the study population and 7.4% among patients treated with BP-lowering agents. Prevalence was higher with higher BMI values. Those with true RH were more likely to be black, to have diabetes mellitus requiring insulin, chronic kidney disease stage 3 or above and diastolic heart failure. In conclusion, obesity is significantly associated with RH and other significant metabolic comorbid conditions.

Laparoscopic sleeve gastrectomy for morbidly obese adolescents in Singapore.

Laparoscopic sleeve gastrectomy (LSG) outcomes among adolescents and factors associated with adolescent obesity in Singapore were evaluated. Prospectively collected data of patients aged 16-19 years who underwent LSG was retrospectively reviewed. A lifestyle questionnaire, Berlin and Epworth scores, and Patient Health Questionnaire-9 scores were collected. Preoperative anthropometrics, comorbidities, weight loss and body composition outcomes were recorded. Among 208 LSGs, 13 (6.3%) were performed on obese adolescents. Mean age and body mass index (BMI) at first presentation were 19.1 ± 0.9 (range 16.8-19.8) years and 46.2 ± 6.3 (range 36-57) kg/m2, respectively. There was family history of obesity (n = 7) and regular consumption of high-calorie drinks (n = 12). Most patients had comorbidities (n = 12), including hypertension (n = 5), asthma (n = 4), diabetes mellitus (n = 3), hernia (n = 3) and obstructive sleep apnoea requiring continuous positive airway pressure support (n = 3). At one year, excess weight loss was 64.3% ± 34.7% (range 21.8%-101.5%), while BMI and fat mass dropped to 31.2 ± 7.6 (range 23-40) kg/m2 and 17.4 kg, respectively. Pain score was 2/10 at 24 hours after surgery. Mean postoperative stay was 2.7 days. No complications or readmissions occurred. Remission of diabetes mellitus and hypertension was reported in two of three and four of five adolescents, respectively, within one year of surgery. LSG is a safe option for adolescents with good short-term weight loss outcomes and remission of metabolic comorbid conditions.

A surgical rat model of human Roux-en-Y gastric bypass.

Obesity affects 30% of the United States population and its detrimental effects are obesity-related metabolic diseases. For patients refractory to conventional weight loss therapy, gastric bypass surgery is one of the proven methods for inducing a sustained weight loss and reversing the metabolic sequelae of obesity. To understand the mechanisms of weight loss and the amelioration of related metabolic comorbid conditions, a reproducible animal model is needed. We report our developmental experience with rat models of sequential Roux-en-Y gastric bypass after reproducing the diet-induced obesity that characterizes the hallmarks of human obesity. Four experiments were performed to induce weight reduction through successive modifications: In Experiment 1 a 20% stapled gastric pouch with a 16 cm biliary-pancreatic limb and a 10 cm alimentary limb accomplished sufficient weight loss within 10 days to ameliorate metabolic changes associated with obesity, but the occurrence of gastrogastric fistulas prevented sustained weight loss; in Experiment 2 the model was improved by dividing the stomach to avoid gastrogastric fistula, but again sustained weight loss was not achieved; in Experiment 3 the biliary-pancreatic limb was lengthened from 16 to 30 cm, reducing the common channel to approximately 18 cm. Sustained weight loss was achieved for 28 days. In Experiment 4 the model in Experiment 3 was modified by dividing the stomach between two rows of staples. Sustained weight loss was observed for 67 days. We developed a reproducible rat model of Roux-en-Y gastric bypass. The existence of this model opens a new field of research in which to study the metabolic sequelae of obesity and the mechanisms of weight loss.