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The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE.
Lee, AK, Woodward, M, Wang, D, Ohkuma, T, Warren, B, Sharrett, AR, Williams, B, Marre, M, Hamet, P, Harrap, S, et al
The Journal of clinical endocrinology and metabolism. 2020;105(1)
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Type 2 diabetes is characterized by metabolic dysregulation resulting in an increased risk of cardiovascular disease The objectives of this study were: a. to determine whether weight change over 2 years was associated with subsequent cardiovascular outcomes and death in adults with diabetes, and b. to examine whether this association was modified by baseline body mass index (BMI), age, or type of glucose-lowering medications. This study is a large prospective study of adults with type 2 diabetes. One arm tested the effects of intensive glucose lowering versus standard glucose control. Whereas the second arm tested the effects of blood pressure-lowering medication versus a placebo. Results showed that that >10% weight loss was associated with >2 times higher risk of cardiovascular and all-cause mortality and was associated with 75% greater risk of major macrovascular events, compared with adults with stable weight. These associations were not significantly modified by metformin use, age, or baseline BMI. Authors conclude that unless patients specifically report lifestyle changes to lose weight, even modest weight loss may be a marker of declining health for which further clinical investigation is merited.
Abstract
CONTEXT Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. OBJECTIVE To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. DESIGN AND SETTING The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. RESULTS Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. CONCLUSIONS In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.
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Brain-Behavior-Immune Interaction: Serum Cytokines and Growth Factors in Patients with Eating Disorders at Extremes of the Body Mass Index (BMI) Spectrum.
Caroleo, M, Carbone, EA, Greco, M, Corigliano, DM, Arcidiacono, B, Fazia, G, Rania, M, Aloi, M, Gallelli, L, Segura-Garcia, C, et al
Nutrients. 2019;11(9)
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Eating disorders such as anorexia, binge eating and night-time eating cause great fluctuations in body mass and have also been shown to alter the immune system, and more specifically markers of inflammation called cytokines. In this observational study of 90 patients with known eating disorders, the researchers tried to identify how much BMI, ‘underweightness’ and malnutrition influenced the body’s pro-inflammatory response and upset the normal immune response. They found that many inflammatory cytokines were elevated in the blood samples taken, a likely response to the conditions of stress in the body. These cytokines are known to interact with the nervous system and were also influenced by other common symptoms such as depression. They were able to group the differences in cytokines for anorexia nervosa, binge-eating disorder, post-dinner eating, night-eating, sweet-eating and fasting. These markers of dysfunctional eating behaviours may help form part of a therapeutic approach to treating eating disorders based on supporting the immune response and reducing inflammation to stabilise metabolic processes. Future studies in a larger population of patients is necessary to determine the relevance of these findings.
Abstract
Alterations of the immune system are known in eating disorders (EDs), however the importance of cytokine balance in this context has not been clarified. We compared cytokines and growth factors at opposite ends of BMI ranges, in 90 patients classified in relation to BMI, depressive and EDs comorbidities. Serum concentrations of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were determined by a biochip analyzer (Randox Labs). Differences were calculated through ANOVA. Possible predictors of higher cytokine levels were evaluated through regression analysis. IL-1α, IL-10, EGF, and IFN-γ were altered individuals with anorexia nervosa (AN) and binge eating disorder (BED). Night-eating was associated with IL-8 and EGF levels, IL-10 concentrations with post-dinner eating and negatively with sweet-eating, long fasting with higher IFN-γ levels. IL-2 increase was not linked to EDs, but to the interaction of depression and BMI. Altogether, for the first time, IL-1α, IL-10, EGF, and IFN-γ were shown to differ between AN and HCs, and between AN and individuals with obesity with or without BED. Only IL-2 was influenced by depression. Dysfunctional eating behaviors predicted abnormal concentrations of IL-10, EGF, IL-8 and IFN-γ.
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Visceral obesity, skeletal muscle mass and resistin in metabolic syndrome development.
Rodríguez-López, CP, González-Torres, MC, Cruz-Bautista, I, Nájera-Medina, O
Nutricion hospitalaria. 2019;36(1):43-50
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Obesity is a growing public health problem at a national and global level. Visceral adipose tissue (VAT) is the most bioactive component that is related with the release of inflammatory mediators which gives rise to insulin resistance, mainly local, and subsequently in liver and skeletal muscle. The aim of this study was to determine the relationship of body components with the concentration of resistin as an inflammatory marker in patients with overweight and obesity. The study is an observational, cross-sectional clinical study which analysed 40 participants with an age range between 18 and 40 years. Results indicate that: - as body mass index and VAT increased, anthropometric measurements, body composition, and biochemical indicators were altered. - persons with obesity and increased VAT had the highest proportions of metabolic syndrome (MS). - an increase in skeletal muscle is related with increased BMI and with the presence of increased VAT. - there was a significant increase in resistin concentration in individuals without MS and increased VAT compared to those without MS and normal VAT. Authors conclude that resistin might be acting as an inflammatory adipocytokine [a bioactive product produced by adipose tissue], contributing to the increase in frequency of MS in those persons who present increased levels of this cytokine.
Abstract
INTRODUCTION Background: obesity implies an increase in the visceral adipose tissue (VAT), which is a risk factor for various metabolic diseases. VAT releases proinflammatory mediators, like resistin. In addition, it has been noted that the skeletal muscle mass (SMM) is involved in the development of metabolic syndrome (MS). Objective: this study was designed to determine the relationship of body components (VAT and SMM) with MS and resistin in patients with obesity. Methods: body composition and anthropometric and biochemical measurements to assess MS, and ELISA tests for resistin were carried out in 40 patients aged 18-40 years. Results: overweight and obesity were observed in 72% of patients; visceral obesity was found in 53% and 35% had MS. A positive correlation between VAT and SMM in patients with MS was detected. In the entire population, an increase of 1 kg of SMM was found to be associated with an increase of 3 cm2 of VAT, and an increase of 4 cm2 of VAT was observed in individuals with MS. According to resistin, people with increased VAT had higher concentration than persons with normal VAT. Furthermore, an increase of 1 cm2 of VAT accounted for a person entertaining a 3.3 fold greater risk of MS for different values of SMM and resistin. Conclusion: the transcendence and significance of VAT as a main factor in triggering the chronic inflammatory process and MS, the SMM and resistin were also related. INTRODUCCIÓN: Introducción: la obesidad implica un aumento del tejido adiposo visceral (TAV), el cual es un factor de riesgo para varias enfermedades metabólicas. El VAT se relaciona con mediadores proinflamatorios, como la resistina. Además, se ha observado que la masa musculoesquelética (MME) interviene en el desarrollo del síndrome metabólico (SM). Objetivo: este estudio fue diseñado para determinar la relación de la composición corporal (TAV y MME) con el SM y la resistina en pacientes con obesidad. Métodos: se realizaron medidas antropométricas, de composición corporal y bioquímica para determinar el SM y prueba de ELISA para resistina en 40 pacientes de 18 a 40 años de edad. Resultados: se observó sobrepeso y obesidad en el 72% de los participantes, obesidad visceral en el 53% y el 35% presentó SM. Se detectó una correlación positiva entre el TAV y la MME en pacientes con SM. En el grupo de estudio encontramos que un aumento de un 1 kg de MME se asociaba con un incremento de 3 cm2 de TAV y en individuos con SM, con un incremento de 4 cm2 de TAV. En relación con la resistina, las personas con TAV incrementado presentan concentraciones más altas que las personas con TAV normal. Además, se observó que un aumento de 1 cm2 de TAV representa un riesgo 3,3 veces mayor que para las personas de padecer SM para diferentes valores de MME y de resistina. Conclusión: además de la trascendencia y la importancia del TAV como factor principal para desencadenar el proceso inflamatorio crónico y el SM, se observó que la MME y la resistina también están relacionadas.
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Vitamin D nutritional status and its relationship with metabolic changes in adolescents and adults with severe obesity.
Teixeira, JS, Bull Ferreira Campos, A, Cordeiro, A, Pereira, SE, Saboya, CJ, Ramalho, A
Nutricion hospitalaria. 2018;35(4):847-853
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In adolescents, severe obesity may lead to a high risk of premature mortality and morbidity in adult life. Increased vitamin D deficiency (VDD) occurs together with obesity. The main aim of this study was to assess the nutritional status of vitamin D and metabolic profile in adolescents and adults with obesity. The study is a comparative observational study which included 128 individuals. A total of 60 participants comprised the adolescent group (G1), (63.3% female) whereas 68 participants comprised the adult group (G2), (75% female). Results indicate: - a high prevalence of inadequacy of Vitamin D in both groups. - a trend of association of elevated blood glucose with the inadequacy of Vitamin D in the adolescent group. - a high prevalence of VDD and non-alcoholic fatty liver disease in both groups. - no relationship between Vitamin D and high blood pressure or metabolic syndrome in any of the groups evaluated. Authors conclude that strategies for the prevention and control of obesity and for the fight against the inadequacy of the nutritional status of vitamin D should be developed.
Abstract
INTRODUCTION increased vitamin D deficiency occurs together with obesity and the association between these conditions has been observed. OBJECTIVE to assess the nutritional status of vitamin D and metabolic profile in adolescents and adults with obesity, and the relationship between complications arising from severe class of obesity with vitamin D nutritional status, and to compare the differences between these groups. METHODS observational comparative study. Population comprises adolescents and adults with severe obesity. Waist circumference (WC) and body mass index (BMI) were measured. Analysis of vitamin D (25(OH)D), lipid profile, C-reactive protein (CRP), blood glucose, fasting insulinemia, insulin sensitivity, blood pressure and diagnoses of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) were performed. RESULTS a total of 60 adolescents (G1) and 68 adults (G2) were evaluated. The percentage of vitamin D inadequacy was observed in 90% in G1 and 79.4% in G2. There was a negative and significant correlation of BMI with the values of 25(OH)D in the group of adults (r = -0.244; p = 0.045). Individuals with inadequacy of vitamin D showed higher values of CRP in both groups (p = 0.000). HOMA-IR showed a negative correlation with 25(OH)D in G1 (r = -0.832; p = 0.000) and G2 (r = -0.589; p = 0.000). The inadequacy of this vitamin showed association with high total cholesterol in G1 (p = 0.029) and higher values of LDL-c in G2 (p = 0.003). CONCLUSION high prevalence of deficiency and insufficiency of vitamin D were observed, associated with metabolic changes both in obese adults and adolescents. It is necessary to develop strategies for the prevention and control of obesity and vitamin D deficiency.
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Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative.
Stout, AC, Barbe, MF, Eaton, CB, Amin, M, Al-Eid, F, Price, LL, Lu, B, Lo, GH, Zhang, M, Pang, J, et al
BMC musculoskeletal disorders. 2018;19(1):1
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Individuals with osteoarthritis (OA) typically present with greater systemic inflammation and impaired glucose homeostasis. Currently it is unclear whether these factors are associated with early-stage OA, namely bone marrow lesions and swelling. The purpose of this cross-sectional study was to investigate the role of inflammation and glucose homeostasis in early-stage OA. Using baseline data from the Osteoarthritis Initiative, 343 participants were enrolled and tested for markers of inflammation and impaired glucose homeostasis. Bone marrow lesions and swelling were also assessed through imaging results. Results indicate that among individuals without OA, those with greater systemic inflammation were more likely to have bone marrow lesions and knee swelling. According to these results, the authors conclude that systemic inflammation and glucose homeostasis are related to structural features of osteoarthritis. Future studies should explore whether these factors are predictive of OA in order to identify therapeutic targets to prevent or delay the onset of knee OA.
Abstract
BACKGROUND Greater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features. We examined if serum concentrations of glucose homeostasis (glucose, glycated serum protein [GSP]) or inflammation (C-reactive protein [CRP]) were associated with prevalent knee bone marrow lesions (BMLs) or effusion among adults without knee OA. METHODS We conducted a cross-sectional study using baseline data from the Osteoarthritis Initiative. We selected participants who had no radiographic knee OA but were at high risk for knee OA. Blinded staff conducted assays for CRP, GSP, and glucose. Readers segmented BML volume and effusion using semi-automated programs. Our outcomes were prevalent BML (knee with a BML volume > 1 cm3) and effusion (knee with an effusion volume > 7.5 cm3). We used logistic regression models with CRP, GSP, or glucose concentrations as the predictors. We adjusted for age, sex, body mass index (BMI), and Physical Activity Scale for the Elderly (PASE) scores. RESULTS We included 343 participants: mean age = 59 ± 9 years, BMI = 27.9 ± 4.5 kg/m2, PASE score = 171 ± 82, and 64% female. Only CRP was associated with BML prevalence (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09 to 1.87). For effusion, we found an interaction between BMI and CRP: only among adults with a BMI <25 kg/m2 was there a significant trend towards a positive association between CRP and effusion (OR = 1.40, 95% CI = 1.00 to 1.97). We detected a U-shaped relationship between GSP and effusion prevalence. Fasting glucose levels were not significantly associated with the presence of baseline effusion or BML. CONCLUSIONS Among individuals without knee OA, CRP may be related to the presence of BMLs and effusion among normal weight individuals. Abnormal GSP may be associated with effusion. Future studies should explore whether inflammation and glucose homeostasis are predictive of symptomatic knee OA.