Publications by Year: 2013

2013
Dalamaga M, Papadavid E. Metabolic co-morbidities and psoriasis: The chicken or the egg?. World J Dermatol. 2013;2(4):32-35.Abstract
Accumulating evidence supports that psoriasis may be a potential multisystem inflammatory disease associated with a range of co-morbidities showing an overlapping pathology and an important health impact such as metabolic diseases.   Psoriasis is associated with an increased risk of obesity, metabolic syndrome (Mets) and diabetes mellitus type 2 (t2DM), following a “dose-response” relationship from mild to severe psoriasis. Conversely, recent evidence from large prospective studies suggests that obesity constitutes a risk factor for psoriasis and psoriatic arthritis. Also, a dyslipidemic profile may precede psoriasis onset. Both obesity, Mets and psoriasis, characterized as chronic inflammatory states, stem from a shared underlying pathophysiology exhibiting common genetic predisposition and risk factors such as high caloric intake, physical inactivity and psychological stress. Excess weight may potentiate the inflammation of psoriasis through the deregulation of adipocytokines while, at the same time, it may help the development of Mets. Interestingly, recent translational data has shown that psoriasis, through increased T-helper inflammatory cytokines in skin and sera, may exert a plethora of effects on insulin regulation and lipid metabolism. Larger population-based prospective cohort and longitudinal studies are needed to unravel the association between psoriasis and metabolic co-morbidities. The recognition of the intricate complex interplay between psoriasis and metabolic co-morbidities may help dermatologists to be aware of associated metabolic co-morbidities in order to screen for metabolic diseases and manage holistically and effectively the psoriatic patient.
Dalamaga M, Papadavid E. Adipocytokines and psoriasis: Insights into mechanisms linking obesity and inflammation to psoriasis. World J Dermatol. 2013;2(4):27-31.Abstract
Psoriasis has been lately seen as a potential systemic inflammatory disease associated with a range of co-morbidities exhibiting an overlapping pathology and presenting a great social health impact such as cardiovascular disease and metabolic diseases, including obesity. Adipose tissue is considered a genuine endocrine organ producing a variety of bioactive adipocytokines, such as leptin, adiponectin, resistin and visfatin, participating in physiological and pathological processes, such as energy balance, insulin sensitivity and resistance, immunity, inflammation, hematopoiesis and angiogenesis. Adipocytokines could serve as a missing link in the association between psoriasis, obesity and metabolic co-morbidities. In chronic inflammatory disease states such as psoriasis, adipocytokines may be implicated in psoriasis onset, progression, severity as well as in the pathogenesis of co-morbidities. Measuring serum adipocytokine levels in the future may be useful in predicting psoriasis severity, progression, treatment outcome and risk of any co-morbidities. Interventions to decrease pro-inflammatory adipocytokine levels could offer preventive and therapeutic options for improving psoriasis severity and protecting against its co-morbidities. Candidate strategic interventions incorporate increased physical activity, weight control and pharmacologic approaches such as metformin. However, the mechanisms underlying the actions of adipocytokines in psoriasis as well as their potential diagnostic, prognostic and/or therapeutic utility require further investigation with larger prospective, longitudinal and mechanistic studies.
Kassi E, Dimas C, Dalamaga M, Panagiotou A, Papoutsi Z, Spilioti E, Moutsatsou P. Sideritis euboea extract lowers total cholesterol but not LDL cholesterol in humans: A randomized controlled trial. Clinical Lipidology [Internet]. 2013;8(6):627 - 634. Website
Trakakis E, Papadavid E, Dalamaga M, Koumaki D, Stavrianeas N, Rigopoulos D, Creatsas G, Kassanos D. Prevalence of non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Greek women with acne: a hospital-based cross-sectional study. J Eur Acad Dermatol Venereol. 2013;27(11):1448-51.Abstract
AIM: To determine the prevalence and frequency of non classical congenital adrenal hyperplasia (NC-CAH) due to 21-OHD at the time of clinical presentation and at the peripubertal period in a substantial sample of Greek women with acne and to investigate the correlation of serum T, 17-OHP and DHEA-S with acne appearance at the time of clinical presentation. METHODS: One hundred and twenty-three unselected women with hyperandrogenemic symptoms were examined. After the ACTH stimulation test, 6 (4.9%) women were diagnosed with NC-CAH due to 21-OHD. RESULTS: There was not any statistical significant difference in the frequency of peripubertal acne between NC-CAH group of patients (6.4%) and patients with hyperandrogenemia of other aetiology (93%), mainly ovarian (P = 0.41). However, there was a statistical significant difference in the prevalence of acne at the time of clinical examination between the two groups (P = 0.04). Acne was present in 83.3% of women with NC-CAH vs. 41.02% of women in the hyperandrogenic group without NC-CAH. A statistically significant decrease of acne from the peripubertal time to the time of clinical examination in the group of women with hyperandrogenemia of other aetiology (-21.37%) was observed compared to women with NC-CAH (P < 0.001). CONCLUSION: We have shown that acne persists from peripubertal period to adult life in NC-CAH women whereas it tends to diminish in women with hyperandrogenemia of other aetiology. Acne is a prominent finding in women with NC-CAH. Serum concentrations of 17-OHP after ACTH stimulation (17-OHP6O ) should be investigated in women with persistent acne in adult life.
Papadavid E, Vlami K, Dalamaga M, Giatrakou S, Theodoropoulos K, Gyftopoulos S, Stavrianeas N, Papiris S, Rigopoulos D. Sleep apnea as a comorbidity in obese psoriasis patients: a cross-sectional study. Do psoriasis characteristics and metabolic parameters play a role?. J Eur Acad Dermatol Venereol. 2013;27(7):820-6.Abstract
BACKGROUND: Psoriasis is associated with a variety of comorbidities such as obesity and cardiovascular disease. OBJECTIVE: In a cross-sectional study, we explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is associated with psoriasis characteristics and metabolic parameters. METHODS: Thirty-five patients with chronic plaque psoriasis underwent a nocturnal polysomnography study and were analysed for Apnoea-Hypopnoea Index to assess OSAHS severity and Framigham score to predict the absolute risk of coronary artery disease at 10 years. The association of OSAHS with psoriasis was examined according to psoriasis characteristics (PASI and DLQI scores, disease duration and previous use of systemic treatments), metabolic parameters (Body Mass Index - BMI, waist to hip ratio - WHR, lipid profile) and other comorbidities (obesity, hypertension, arthritis and cardiovascular disease). RESULTS: There was no correlation between psoriasis characteristics and OSAHS. Psoriasis patients with OSAHS presented more frequent snoring and lower sleep quality compared with those without OSAHS. In univariate analyses, OSAHS was associated with increased BMI and hypertension in psoriasis patients. In multivariable logistic regression models, there was statistically significant evidence that only BMI and hypertension were associated with increased risk of OSAHS, adjusting for psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR, and smoking were not significant risk factors for OSAHS. In subgroup analyses, OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and with Framigham score in men (P = 0.035). CONCLUSION: OSAHS may be a comorbidity in obese psoriasis patients with hypertension. Treatment with continuous positive airway pressure and weight loss interventions should be initiated.
Dalamaga M, Papadavid E, Basios G, Vaggopoulos V, Rigopoulos D, Kassanos D, Trakakis E. Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study. J Am Acad Dermatol. 2013;69(6):922-30.Abstract
BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. OBJECTIVE: In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. LIMITATION: There was no performance of skin biopsies. CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities.
Dalamaga M, Kousoulis AA. Remembering Louis Tribondeau (1872-1918). JAMA Dermatol. 2013;149(8):934.
Dalamaga M, Chou SH, Shields K, Papageorgiou P, Polyzos SA, Mantzoros CS. Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab. 2013;18(1):29-42.Abstract
Since its discovery as an adipocyte-secreted hormone, leptin has been found to impact food intake, energy homeostasis, and metabolism through its effects on the central nervous system and peripheral organs. Recent research indicates that leptin may also be involved in cognition, immune function, and bone metabolism. These findings place leptin at the intersection of neuroendocrinology and metabolism, and possibly immune function, and render it an appealing therapeutic target for several niche areas of unmet clinical need. Current evidence regarding classic and emerging roles of leptin as well as the pros and cons of its potential clinical use are summarized herein.
Papadavid E, Evangelia P, Panayiotides I, Ioannis P, Makris M, Michael M, Giatrakou S, Sophia G, Dalamaga M, Maria D, et al. Pityriasis rosea-like eruption associated with lamotrigine. J Am Acad Dermatol. 2013;68(6):e180-1.
Dalamaga M, Karmaniolas K, Papadavid E, Pelekanos N, Sotiropoulos G, Lekka A. Hyperresistinemia is associated with postmenopausal breast cancer. Menopause. 2013;20(8):845-51.Abstract
OBJECTIVE: The constellation of obesity, insulin resistance, and serum adipocytokine levels is associated with the risk and prognosis of postmenopausal breast cancer (PBC). Altered secretion of resistin may underlie the association between overweight/obesity and PBC. We thus explored the association of serum resistin with PBC, taking into account established risk factors, including adipokines and anthropometric, metabolic, and inflammatory markers. METHODS: In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control participants matched on age and time of diagnosis between 2003 and 2010 at the Veterans' Administration General Hospital of Athens (NIMTS Hospital). Serum resistin, adiponectin, leptin, metabolic (homeostasis model assessment score of insulin resistance) and inflammatory (tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein) parameters, and tumor markers (carcinoembryonic antigen and CA 15-3) were determined. RESULTS: The mean serum resistin level was significantly higher in case participants than in control participants (P < 0.001) in both univariate and multivariable analyses, adjusting for age, date of diagnosis, education, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, physical activity, reproductive markers, metabolic markers, anthropometric (body mass index and weight circumference) markers, inflammatory markers, and adipokines (odds ratio, 1.17; 95% CI, 1.03-1.34; P = 0.02). In case participants, resistin level correlated significantly with tumor markers and inflammatory parameters, but not with metabolic and anthropometric variables. CONCLUSIONS: Further prospective, longitudinal, and mechanistic studies are needed to determine whether hyperresistinemia is involved in the development of PBC or reflects changes during PBC progression and therefore could be used as a biomarker for PBC. Targeting resistin inhibition could be an effective therapeutic strategy in breast cancer by down-regulating the inflammatory microenvironment in breast tissue.
Moon H-S, Dalamaga M, Kim S-Y, Polyzos SA, Hamnvik O-P, Magkos F, Paruthi J, Mantzoros CS. Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals. Endocr Rev. 2013;34(3):377-412.Abstract
Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.
Dalamaga M, Sotiropoulos G, Karmaniolas K, Pelekanos N, Papadavid E, Lekka A. Serum resistin: a biomarker of breast cancer in postmenopausal women? Association with clinicopathological characteristics, tumor markers, inflammatory and metabolic parameters. Clin Biochem. 2013;46(7-8):584-90.Abstract
OBJECTIVE: Previous few studies have shown that resistin is significantly elevated in breast cancer (BC) patients. Therefore, we investigated whether serum resistin could be used as a potential diagnostic and prognostic tool for postmenopausal BC (PBC), taking into account clinicopathological features, serum tumor markers, anthropometric, metabolic, and, for the first time, inflammatory parameters. METHODS: Serum resistin, tumor markers (CA 15-3 and CEA), metabolic, anthropometric and inflammatory parameters (TNF-α, IL-6, hsCRP) were determined in 103 postmenopausal women with incident, pathologically confirmed, invasive BC, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL). RESULTS: Mean serum resistin was significantly higher in cases than in controls and patients with BBL (p<0.001). In patients, resistin was significantly associated with tumor and inflammatory markers, cancer stage, tumor size, grade and lymph node invasion but not with anthropometric, metabolic parameters and hormone receptor status. Multivariable regression analysis revealed that serum IL-6 (p=0.02) and cancer stage (p=0.048) were the strongest determinants of serum resistin in cases adjusting for demographic, metabolic and clinicopathological features. Although resistin's diagnostic performance was low based on ROC curve analysis [0.72, 95% CI: 0.64-0.79], it could, however, represent a BC biomarker reflecting advanced disease stage and inflammatory state. CONCLUSION: Further prospective and longitudinal studies are needed to evaluate whether serum resistin could be used as a prognostic tool in BC monitoring and management. More research is essential to elucidate resistin's ontological role in the association between obesity, representing a chronic low-grade subclinical inflammation, and PBC.
Dalamaga M, Papadavid E, Vlami K. Unmasking the Janus face of the association between psoriasis, metabolic syndrome and obstructive sleep apnea. Sleep Breath. 2013;17(2):449-50.
Dalamaga M. Obesity, insulin resistance, adipocytokines and breast cancer: New biomarkers and attractive therapeutic targets. World J Exp Med. 2013;3(3):34-42.Abstract
Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyl-transferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy.
Dalamaga M. Interplay of adipokines and myokines in cancer pathophysiology: Emerging therapeutic implications. World J Exp Med. 2013;3(3):26-33.Abstract
Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding of the mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.
Evangelopoulos AA, Dalamaga M, Panoutsopoulos K, Dima K. Nomenclature and basic concepts in automation in the clinical laboratory setting: a practical glossary. Clin Lab. 2013;59(11-12):1197-214.Abstract
In the early 80s, the word automation was used in the clinical laboratory setting referring only to analyzers. But in late 80s and afterwards, automation found its way into all aspects of the diagnostic process, embracing not only the analytical but also the pre- and post-analytical phase. While laboratories in the eastern world, mainly Japan, paved the way for laboratory automation, US and European laboratories soon realized the benefits and were quick to follow. Clearly, automation and robotics will be a key survival tool in a very competitive and cost-concious healthcare market. What sets automation technology apart from so many other efficiency solutions are the dramatic savings that it brings to the clinical laboratory. Further standardization will assure the success of this revolutionary new technology. One of the main difficulties laboratory managers and personnel must deal with when studying solutions to reengineer a laboratory is familiarizing themselves with the multidisciplinary and technical terminology of this new and exciting field. The present review/glossary aims at giving an overview of the most frequently used terms within the scope of laboratory automation and to put laboratory automation on a sounder linguistic basis.
Marouga A, Dalamaga M, Kastania AN, Antonakos G, Thrasyvoulides A, Kontelia G, Dimas C, Vlahakos DV. Correlates of serum resistin in elderly, non-diabetic patients with chronic kidney disease. Clin Lab. 2013;59(9-10):1121-8.Abstract
BACKGROUND: Renal function may be a major determinant of resistin levels, since most studies revealed association between elevated resistin levels and decreased glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD). The aim of the present study was to test the hypothesis whether serum resistin is associated with markers of malnutrition and inflammation in elderly non-diabetic adults in different stages of CKD including hemodialysis. METHODS: This was a cross-sectional study of 80 elderly patients divided in four groups of 20 patients each according to eGFR and matched for age (+/- 5 years) and gender. Patients with eGFR more than 1.5 mL/second served as controls. Multivariate regression was used to evaluate the association of resistin with eGFR, demographic, metabolic and inflammatory markers, and insulin resistance. Hematological, biochemical, and immunochemical analyses were performed using commercially available enzyme immunoassays. RESULTS: Our results showed that: 1) serum resistin levels were two times higher in patients with advanced CKD especially those undergoing hemodialysis compared to controls, 2) in univariate analysis, resistin levels correlated directly with Tumor Necrosis Factor-alpha (TNF-alpha), high sensitive C-Reactive Protein (hsCRP), and serum phosphate and inversely correlated with albumin, eGFR, and hematocrit levels. We failed to reveal any relationship between resistin levels and Homeostasis Model Assessment Score of Insulin Resistance (HOMA-IR), body mass index (BMI), cholesterol and leptin levels, 3) in multivariate analysis, only TNF-alpha (p < 0.001) and hsCRP (p = 0.032) were the most important independent determinants of serum resistin levels. CONCLUSIONS: These results indicate that resistin increases as GFR declines and may be involved in the malnutrition-inflammation state and the reverse epidemiology phenomenon present in elderly, non-diabetic patients with CKD.
Dalamaga M, Karmaniolas K, Chamberland J, Nikolaidou A, Lekka A, Dionyssiou-Asteriou A, Mantzoros CS. Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome. Metabolism. 2013;62(12):1830-9.Abstract
OBJECTIVE: Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. MATERIALS & METHODS: In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. RESULTS: Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. CONCLUSION: Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications.