scholarly journals POS0561 OBESITY PHENOTYPES IN EARLY RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 515.1-515
Author(s):  
Y. Gorbunova ◽  
T. Popkova ◽  
L. Kondrateva ◽  
M. Cherkasova ◽  
E. Nasonov ◽  
...  

Background:Patients with rheumatoid arthritis (RA) and obesity have a lower risk of early death than patients with normal weight due to the so-called “obesity paradox”. Available publications discuss three phenotypes of obesity: classical obesity, metabolically healthy overweight/obesity, and latent obesity (normal weight associated with metabolic disorders, most importantly - with insulin resistance and adipocytokines imbalance).Objectives:To clarify the prevalence of obesity phenotypes and to identify factors predisposing to «latent obesity» in early RA without diabetes mellitus or hyperglycemia.Methods:The study included 35 pts (23 women, 12 men) with early RA (criteria ACR / EULAR, 2010), 56 [43,0; 60,0] years old, naïve to treatment with glucocorticoids and disease-modifying anti-rheumatics, without established diabetes mellitus. Pts were seropositive for IgM RF and anti-CCP, with highly active RA (DAS28 5,9 [5,2; 6,4]; SDAI 35,4 [27,0; 45,8], and CDAI 31,0 [26,0; 44,0]) scores, and median disease duration of 8.0 [6,0;15.0] months. Electrochemiluminescence assay Elecsys (Roche Diagnostics) was used to measure patients’ insulin levels, and ELISA (DBS – Diagnostics Biochem Canada Inc.) - for evaluation of serum leptin concentrations. Insulin resistance (IR) was defined as Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR) ≥2,77. Leptin levels were considered elevated at values ≥11,1 ng/ml for women, ≥5,6 ng/ml for men. The overweight/obesity status was determined by World Health Organization criteria in pts with body mass index (BMI) ≥25kg/m2.Results:Overweight/obesity were documented in 19 (54, 3%) pts with early RA, 4/19 (21%) had high leptin levels and IR, 11/19 (58%) had isolated hyperleptinemia. Normal BMI was found in 16 (45,7%) pts with early RA, 2/16 (12,5%) had elevated leptin levels and IR, and 6/16 (37,5%) – only hyperleptinemia. Four (21%) out of 19 overweight and 8 (50%) out of 16 pts with normal BMI did not show any metabolic disorders (p=0,02). Сlassical obesity was found in 15 (43%), and latent obesity – in 8 (23%) pts with early RA. Leptin levels correlated with waist circumference (r=0,58, p=0,02), BMI (r=0,71, p=0,0006), ESR (r=0,5, p=0,02) in the overweight/obese pts, and with waist circumference (r=0,59, p=0,03), IgM RF (r=0,58, p=0,03), triglyceride levels (r=0,77, p=0,003), and atherogenic index (r=0,62, p=0,03) in pts with normal weight.Conclusion:The classical obesity phenotype associated with abdominal obesity and inflammation was the most common and prevailing over other phenotypes in early RA. Latent obesity was less common and was associated with an unfavorable lipid profile and accumulation of abdominal fat, therefore increasing the risk of cardiovascular diseases in RA. Metabolically healthy overweight/obesity in early RA was really a rare phenotype.Disclosure of Interests:None declared

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1179.1-1179
Author(s):  
L. Kondrateva ◽  
T. Panafidina ◽  
T. Popkova ◽  
M. Cherkasova ◽  
A. Lila ◽  
...  

Background:The so-called “obesity paradox” when cardiovascular risk is lower in overweight compared to lean patients accompanies some chronic conditions. A possible explanation for this phenomenon comes from variability of obesity phenotypes, i.e., “classical” obesity as exemplary perception of obesity is equal to increased body mass index (BMI) and metabolic disorders; but there are also “metabolically healthy” overweight individuals (increased BMI without metabolic disorders), and “latent” obesity phenomenon (when normal weight is associated with metabolic disorders, especially with insulin resistance (IR) and adipocytokines imbalance). Serum leptin concentrations increase has been established in obese, therefore, this adipocytokine synthesized in adipose tissue, can be used as a marker of body fat mass. Higher cardiovascular risks are known even in young patients with systemic lupus erythematosus (SLE), but obesity phenotypes have not been studied.Objectives:To find out the rate of various obesity phenotypes and to identify factors contributing to “latent” obesity in SLE pts without diabetes mellitus (DM) or hyperglycemia.Methods:A total of 49 SLE pts (46 women, 3 men, 40 [33;48] years old) without established DM or hyperglycemia were enrolled in the study. The median disease duration was 3,0[0,7;8,0] years, SLEDAI-2K was 5[2;8]. SLE pts were treated with glucocorticoids (GC) (84%) and hydroxychloroquine (78%), immunosuppressive drugs (20%) and biological agents (10%). Insulin levels were measured using electrochemiluminescence assay Elecsys (Roche Diagnostics), serum leptin concentrations were estimated using ELISA (DBS-Diagnostics Biochem Canada Inc.). IR was defined as Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR) ≥2,77. Leptin levels were considered elevated at values ≥11,1 ng/ml for women, ≥5.6 ng/ml for men. The overweight / obesity status was determined by World Health Organization criteria in patients with body mass index (BMI) ≥25kg/m2.Results:Overweight / obesity were established in 45% of pts, normal BMI was in 55% of SLE pts. The combination of IR and high leptin levels was found in 32% of overweight / obese pts and 11% of pts with normal BMI (p=0,2), an isolated increased leptin levels - in 64% and 41%, respectively (p=0,1). Metabolic disturbances were absent in 4% of overweight pts and 48% of pts with a normal BMI (p=0,001). Thus, “classical” obesity was found in 43% of cases, “metabolically healthy” obesity - in 2%, and “latent” obesity - in 29% of SLE pts. Leptin levels correlated with BMI (r=0,5, p=0,02), waist circumference (r=0,5, p=0,02) in the overweight / obesity group, and with disease duration (r=0,5, p=0,02), SLEDAI-2K (r=-0,6, p=0,002), anti-dsDNA (r=-0,7, p<0,001), C3 complement (r=0,5, p=0,01), maximum (r=0,7, p<0,001) and current GCs doses (r=0,4, p=0,03) in patients with normal weight. There was a trend to association between leptin levels and duration of GCs therapy in SLE pts with normal BMI (r=0,4, p=0,06).Conclusion:Metabolic disorders - most often increased leptin levels - were diagnosed in the majority of overweight / obese patients, as well as in about 50% of SLE patients with normal weight. There were only isolated cases of “metabolically healthy” obesity in SLE patients. Metabolically obese normal weight (“latent” obesity) phenotype was strongly associated with GCs therapy and decreased disease activity.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.3-989
Author(s):  
A. Jitaru ◽  
C. Pomirleanu ◽  
M. M. Leon-Constantin ◽  
F. Mitu ◽  
C. Ancuta

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly


2019 ◽  
Vol 13 (3) ◽  
pp. 2041-2047 ◽  
Author(s):  
Diego Urrunaga-Pastor ◽  
Luciana De La Fuente-Carmelino ◽  
Carlos J. Toro-Huamanchumo ◽  
Miriam Pérez-Zavala ◽  
Vicente A. Benites-Zapata

2018 ◽  
Vol 50 (3) ◽  
pp. 169-178 ◽  
Author(s):  
Lam O. Huang ◽  
Ruth J. F. Loos ◽  
Tuomas O. Kilpeläinen

Obesity has evolved into a global pandemic that constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for Type 2 diabetes and cardiovascular disease. However, many obese individuals, often called metabolically healthy obese (MHO), seem to be protected from these cardiometabolic complications. Conversely, there is a group of individuals who suffer from cardiometabolic complications despite being of normal weight; a condition termed metabolically obese normal weight (MONW). Recent large-scale genomic studies have provided evidence that a number of genetic variants show an association with increased adiposity but a favorable cardiometabolic profile, an indicator for the genetic basis of the MHO and MONW phenotypes. Many of these loci are located in or near genes that implicate pathways involved in adipogenesis, fat distribution, insulin signaling, and insulin resistance. It has been suggested that a threshold for subcutaneous adipose tissue expandability may be at play in the manifestation of MHO and MONW, where expiry of adipose tissue storage capacity could lead to ectopic lipid accumulation in non-adipose tissues such as liver, muscle, heart, and pancreatic beta cells. Understanding the genetic aspects of the mechanisms that underpin MHO and MONW is crucial to define appropriate public health action points and to develop effective intervention measures.


2016 ◽  
Vol 175 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Akaal Kaur ◽  
Desmond G Johnston ◽  
Ian F Godsland

Objective Overweight and obese individuals may be metabolically healthy, but attention needs to be given to long-term persistence of this trait and any associated variation in cardiovascular risk. Design Cross-sectional and longitudinal variation in metabolic health and associated cardiovascular mortality were analysed in 1099 white European-origin normal-weight and overweight or obese males followed for 20years. Methods Definitions of metabolic health were based on LDL and HDL cholesterol, triglycerides, blood pressure, fasting glucose and cardiovascular risk. Insulin resistance (e.g. HOMA-IR) and sub-clinical inflammation (ESR and white blood cell count) were explored. Cardiovascular mortality risks and persistence of metabolic health status were evaluated. Results There were 87 cardiovascular deaths. Insulin resistance was increased in metabolically healthy overweight or obese participants (median HOMA-IR 2.63, 95% CI: 1.79–3.65, P<0.001) relative to normal-weight participants (median HOMA-IR 1.67, 95% CI: 1.08–2.67, P<0.001) as was sub-clinical inflammation but metabolically healthy overweight or obese individuals were not at increased risk of cardiovascular mortality compared with the metabolically healthy normal-weight individuals (hazard ratio 1.13, 95% CI: 0.34–3.72, P=0.8). The proportions of initially metabolically healthy overweight or obese who remained metabolically healthy for visits 2, 3 and 4 were 54, 48 and 39% respectively, and for initially normal-weight individuals, 68, 51 and 41%. A lower proportion of metabolically healthy overweight or obese individuals remained metabolically healthy at visit 2 compared with normal-weight individuals (P=0.007), but proportions converged thereafter. Conclusions Despite being insulin resistant and having greater sub-clinical inflammation, and despite instability in metabolic health status, metabolically healthy overweight or obese individuals were at no greater risk of cardiovascular mortality than their normal-weight equivalents.


2017 ◽  
Vol 126 (05) ◽  
pp. 309-315
Author(s):  
Katarína Šebeková ◽  
Melinda Csongová ◽  
Radana Gurecká ◽  
Zora Krivošíková ◽  
Jozef Šebek

AbstractWe investigated whether metabolically healthy normal weight adults with central obesity display worse cardiometabolic profile compared with their centrally lean counterparts. This retrospective, cross-sectional study, comprised 1 135 subjects (64% females) aged 18-to-81 years, presenting ≤2 components of metabolic syndrome. They were classified as centrally lean (waist-to-height ratio (WHtR)<0.5 and waist circumference<80 cm in females and<94 cm in males) or presenting central obesity (WHtR ≥0.5, regardless of waist circumference). Data on blood pressure, glucose homeostasis, lipid profile, renal function, high-sensitive C-reactive protein (hsCRP), uric acid, adiponectin, leptin, and soluble receptor for advanced glycation end products were compared between the groups, separately in males and females. 5.7% of males and 6.9% of females presented WHtR ≥0.5. Compared with centrally lean subjects, those with central obesity had higher BMI-adjusted fasting plasma glucose (p<0.001), and leptin levels (p<0.05); females also presented higher blood pressure (p<0.001), while males had higher hsCRP concentrations (p=0.021). These changes associated with significantly higher BMI-adjusted odds to present fasting plasma glucose >5.6 mmol/l in both genders, higher odds to present hsCRP >3 mg/l in males, and those to present elevated blood pressure in females. Our analysis suggests that in metabolically healthy normal weight subjects WHtR ≥0.5 might indicate “early increased health risk”.


2020 ◽  
Vol 96 (7) ◽  
pp. 529-535
Author(s):  
Yu. A. Sorokina ◽  
O. V. Zanozina ◽  
A. D. Postnikova

The article provides a review of the literature on the possibilities of using various indices of insulin resistance in type 2 diabetes (T2DM) treatment. The main mechanisms of insulin resistance and its role in the formation of type 2 diabetes mellitus and other metabolic disorders are described. The main indices of insulin resistance, used in real clinical practice nowadays, are considered. Methods of their calculation are given. The effect of metformin and incretin active medications on insulin resistance is described. It was shown that the combination of these medications improves tissue sensitivity to insulin in patients with T2DM. Standard indicators for assessing glycemic control, such as fasting glucose and glycosylated hemoglobin (HbA1c), do not reflect the patient’s lipid metabolism. The use of insulin resistance assessment indices in patients with type 2 diabetes mellitus allows both, exercising glycemic control, and the metabolic disorders, often associated with carbohydrate metabolism disorders, monitoring. Using insulin resistance indices, it is possible to select the optimal treatment regimen for type 2 diabetes mellitus for a particular patient, to predict and evaluate the effectiveness of treatment in dynamics. Simple, generally available laboratory indicators and anthropometric data are used to calculate the indices of insulin resistance, and they are easy to measure. In this regard, the use of insulin resistance indices is possible in routine clinical practice.


2021 ◽  
Vol 27 (3) ◽  
pp. 279-290
Author(s):  
M. A. Boyarinova ◽  
O. P. Rotar ◽  
A. M. Erina ◽  
N. A. Paskar ◽  
A. S. Alieva ◽  
...  

Objective. The purpose of the study was to determine the dynamics of the metabolically healthy obesity (MHO) status according to the Meigs criteria, and to establish the predictors of the transformation of healthy obesity phenotype into an unhealthy (MUHO) one in the population of residents of St Petersburg (Russia) at 6,5-year follow-up. Design and methods. Within the epidemiology study ESSE-RF a random sample of 1600 St Petersburg inhabitants stratified according to gender and age was formed. Examination of participants included anthropometry with measurement of waist circumference and calculation of body mass index (BMI), measurement of blood pressure (BP), fasting blood glucose, insulin (index of insulin resistance was calculated), creatinine, cortisol, lipid spectrum, C-reactive protein, adiponectin, leptin, and uric acid. Meigs MHO criteria (2006) were used in obese subjects (BMI > 30 kg/m²). Obese patients, who were identified as metabolically healthy in 2012–2013, were invited for follow-up in 2018–2019. Results. At the first stage obesity was diagnosed in 430 (26,9 %) participants, according to the BMI, 116 (27,0 %) of them were metabolically healthy according to the Meigs criteria. At follow-up, 44,4% individuals with the MHO phenotype transformed to the MUHO category on average after 6,5 years. Individuals who retained the MHO phenotype over time had significantly lower baseline systolic BP and diastolic BP levels, more favorable lipid levels and lower levels of uric acid, insulin, and index of insulin resistance. Glucose increase by every 0,5 mmol/l and higher was associated with elevated probability of transformation MHO to MUHO phenotype by 10,9 times (adjusted for sex and age). Conclusions. Significantly higher levels of BP, insulin resistance, low density lipoprotein and uric acid at baseline, as well as an increase in glucose levels over time, were associated with the transformation of the metabolically healthy to the unhealthy phenotype in obese individuals at 6,5-year follow-up. In all individuals with the MHO phenotype, there was a significant increase in waist circumference over time, accompanied by an increase in BMI only in those who transformed into the MUHO status.


2021 ◽  
Vol 2 (6) ◽  
pp. 53-56
Author(s):  
Irina A. Novikova ◽  
◽  
Tatiana M. Panina ◽  

Type 2 diabetes mellitus is a violation of carbohydrate metabolism caused by insulin resistance and relative insulin insufficiency or a violation of insulin secretion with or without insulin resistance. The number of people with diabetes increased from 108 million in 1980 to 422 million in 2014. The World Health Organization (WHO) predicts that by 2030 this number will increase to 439 million, which is almost 10% of the adult population. A dentist is often the first to encounter manifestations of diabetes mellitus in the oral cavity, such as caries, candidiasis, dryness, inflammatory periodontal diseases, etc. Therefore, timely diagnosis and close interaction of doctors of different specialties is crucial for the treatment of this disease.


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