Referrals For Gender-Affirming Hormone Treatment in Croatia's National Network for Transgender Healthcare.

A network of healthcare professionals specializing in transgender care was established in Croatia in 2011, and legal advancements were subsequently made in 2014. Both achievements made gender transition more transparent and thus more attainable in Croatia. This observational study was conducted to assess the number of transgender individuals initiating gender-affirming hormone treatment (GAHT) in Croatia and describes trends in age and sex assigned at birth. Between 2011 and 2022, a total of 111 transgender individuals initiated GAHT. Within the cohort, 52 were assigned male at birth (AMAB) and 59 were assigned female at birth (AFAB). The overall annual incidence rate of transgender individuals initiating GAHT was 0.52 per 100,000 age-adjusted individuals. There was a statistically significant increase (p < 0.01) in transgender individuals commencing GAHT before the COVID-19 pandemic. Furthermore, a rising trend toward masculinizing rather than feminizing treatment was identified (p < 0.05), particularly among younger transgender individuals. The COVID-19 pandemic disrupted these trends in 2020, except for the trend of initiating therapy at a younger age (p < 0.01). The annual incidence and age distribution trends of transgender individuals initiating GAHT in Croatia closely mirrored those in other European countries, with a higher prevalence of individuals assigned female at birth. The study underscores a significant rise in the number of individuals initiating gender-affirming hormone treatment, emphasizing the need for proper legal regulation and healthcare system response.

The Role of Continuous Glucose Monitoring in Detecting Early Dysglycemia and Clinical Outcomes in Patients with Cystic Fibrosis.

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). CFRD has been correlated with important clinical outcomes, including poor nutrition, reduced pulmonary function, and earlier mortality. However, clinical decline due to abnormalities of blood glucose (dysglycemia) begins early in CF, before the diagnosis of CFRD by the gold-standard oral glucose tolerance test (OGTT). Continuous glucose monitoring (CGM) has been validated in patients with CF and has been recognized as a valuable tool in detecting early glucose abnormalities in patients with CF. Several CGM parameters have been used to predict CFRD in some but not all studies, and there is no consensus regarding CGM use for diagnostic purposes. Thus, it remains a complementary test to OGTT in CFRD diagnosis. The aim of this review is to provide an update on the pathophysiological mechanisms of CFRD, recent advances in the use of CGM for CFRD screening, and the association between CGM measures and CF-related clinical outcomes.

The Impact of Modern Anti-Diabetic Treatment on Endothelial Progenitor Cells.

Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are mononuclear cells that are derived from different tissues. Circulating EPCs contribute to regenerating the vessel's intima and restoring vascular function. The ability of EPCs to repair vascular damage depends on their number and functionality. Diabetic patients have a decreased circulating EPC count and impaired EPC function. This may at least partially explain the increased risk of diabetic complications, including the increased cardiovascular risk in these patients. Recent studies have confirmed that many currently available drugs with proven cardiovascular benefits have beneficial effects on EPC count and function. Among these drugs are also medications used to treat different types of diabetes. This manuscript aims to critically review currently available evidence about the ways anti-diabetic treatment affects EPC biology and to provide a broader context considering cardiovascular complications. The therapies that will be discussed include lifestyle adjustments, metformin, sulphonylureas, gut glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor analogs, sodium-glucose transporter 2 inhibitors, and insulin.

The Role of Endothelial Progenitor Cells in Atherosclerosis and Impact of Anti-Lipemic Treatments on Endothelial Repair.

Cardiovascular complications are associated with advanced atherosclerosis. Although atherosclerosis is still regarded as an incurable disease, at least in its more advanced stages, the discovery of endothelial progenitor cells (EPCs), with their ability to replace old and injured cells and differentiate into healthy and functional mature endothelial cells, has shifted our view of atherosclerosis as an incurable disease, and merged traditional theories of atherosclerosis pathogenesis with evolving concepts of vascular biology. EPC alterations are involved in the pathogenesis of vascular abnormalities in atherosclerosis, but many questions remain unanswered. Many currently available drugs that impact cardiovascular morbidity and mortality have shown a positive effect on EPC biology. This review examines the role of endothelial progenitor cells in atherosclerosis development, and the impact standard antilipemic drugs, including statins, fibrates, and ezetimibe, as well as more novel treatments such as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulating agents and angiopoietin-like proteins (Angtpl3) inhibitors have on EPC biology.

Count Ivan VIII Draskovic: a case of Graves' orbitopathy?

There is a possibility that Count Ivan VIII Draskovic (1740-1787), a member of one of the oldest and most famous Croatian noble families, had Graves' disease and suffered from a thyroid disorder. Our suspicions were aroused by certain data, including his personal history, his lifestyle, including use of tobacco and iodine, as well as stress, and, finally, two portraits. If he was affected by Graves' disease and orbitopathy, his poor health might have been a consequence of thyroid disease, which was further worsened by injury and tobacco use. Later spontaneous remission could have been induced by higher iodine intake and bed rest.

Stress Hyperglycaemia Indicates Embolus Size and Localization in Patients with Acute Pulmonary Embolism.

OBJECTIVE: Acute pulmonary embolism is a life-threatening form of venous thromboembolism often causing stress hyperglycaemia. The aim of this study was to determine the prognostic value of stress hyperglycaemia in acute pulmonary embolism, providing new insights into the presumed embolus size and localization, clinical parameters (Pulmonary Embolism Severity Index, PESI), and in-hospital mortality. Design and Methods. Among a total of 95,454 patients referred to the Emergency Department of the Sestre Milosrdnice University Hospital Centre between 2014 and 2016, all patients with acute pulmonary embolism were included into this observational cohort study. The study group consisted of 190 patients aged 25-96. Relevant patient history, clinical data, and laboratory findings were collected during the entire hospitalization period. Data were analyzed for the entire group of patients, as well as separately for patients without diabetes, using the Fisher exact test and logistic regression. RESULTS: Analysis of embolus localization as an indirect parameter of embolus size showed that patients with stress hyperglycaemia more often had emboli located in proximal parts of the pulmonary circulation (i.e., main artery or lobar branches) (p < 0.05). Furthermore, stress hyperglycaemia correlated with PESI score and diabetes (p < 0.05) in the entire patient group. Stress hyperglycaemia showed independent association with in-hospital mortality in patients (p < 0.05). CONCLUSION: Stress hyperglycaemia in patients with acute pulmonary embolism is associated with embolus localization in larger arteries of the pulmonary circulation and higher PESI score and therefore could serve as an independent in-hospital mortality predictor.

GLUCAGON-LIKE PEPTIDE-1 AFFECTS TASTE PERCEPTION DIFFERENTLY IN WOMEN: A RANDOMIZED, PLACEBO-CONTROLLED CROSSOVER STUDY.

Gastrointestinal tract is an important connector between food intake and body weight, it senses basic tastes in a similar manner as the tongue. The aim of the study was to find out how gut hormone glucagon-like peptide-1 (GLP-1) influences taste preference. Fourteen healthy participants (six male and eight female) were included in this double-blind, placebo-controlled crossover study. After overnight fast and salty fluid (oral sodium load), participants were randomized to receive placebo (500 mL of 0.9% saline) or GLP-1 infusion (1.5 pmol/kg/min) over a 3-hour period. At the end of infusion, participants chose food preferences from illustrations of food types representing 5 tastes. After 7 days, the protocol was repeated, this time those that had received placebo first got GLP-1 infusion, and those having received GLP-1 first got placebo. Change of taste preference after GLP-1 infusion but not after placebo was reported as response, and non-response was reported in case of taste persistence. A statistically significant difference in response type was found between genders, with women being more likely to change their taste preference after GLP-1 than men. The change of taste upon GLP-1 infusion observed in women might be ascribed to estrogen weight-lowering effects accomplished by receptor-mediated delivery.

[CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES]. / HRVATSKE SMJERNICE ZA FARMAKOLOSKO LIJECENJE SECERNE BOLESTI TIPA 2.

INTRODUCTION: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. PARTICIPANTS: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. EVIDENCE: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. CONCLUSIONS: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes.

Endothelial progenitor cells (EPCs) in ageing and age-related diseases: How currently available treatment modalities affect EPC biology, atherosclerosis, and cardiovascular outcomes.

Endothelial progenitor cells (EPCs) are mononuclear cells that circulate in the blood and are derived from different tissues, expressing cell surface markers that are similar to mature endothelial cells. The discovery of EPCs has lead to new insights in vascular repair and atherosclerosis and also a new theory for ageing. EPCs from the bone marrow and some other organs aid in vascular repair by migrating to distant vessels where they differentiate into mature endothelial cells and replace old and injured endothelial cells. The ability of EPCs to repair vascular damage depends on their number and functionality. Currently marketed drugs used in a variety of diseases can modulate these characteristics. In this review, the effect of currently available treatment options for cardiovascular and metabolic disorders on EPC biology will be discussed. The various EPC-based therapies that will be discussed include lipid-lowering agents, antihypertensive agents, antidiabetic drugs, phosphodiesteraze inhibitors, hormones, as well as EPC capturing stents.

Nebivolol Induced Hyperkalemia: Case Report

In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation. Our patient, a 47-year-old woman taking nebivolol for hypertension developed persistent hyperkalemia, with serum potassium levels up to 6.4 mmol/L. After extensive diagnostic evaluation and exclusion of other known conditions leading to hyperkalemia, its cause remained occult. Since hyperkalemia coincided with increased doses of nebivolol, dose reduction and discontinuation were attempted, resulting in normalized serum potassium. Poor drug metabolism could not explain this adverse effect, since pharmacogenetic testing showed no relevant aberrations. In conclusion, hyperkalemia is a harmful adverse event with possible lethal outcome, and it may be caused by nebivolol. Therefore, medical professionals have to be aware of this side effect and hyperkalemia should be listed as an adverse event in nebivolol SmPC.

Comparative Effects of Sunscreens Alone vs Sunscreens Plus DNA Repair Enzymes in Patients With Actinic Keratosis: Clinical and Molecular Findings from a 6-Month, Randomized, Clinical Study.

Recent experimental irradiation studies have shown that the addition of DNA repair enzymes (photolyase and endonuclease) to traditional sunscreens may reduce ultraviolet radiation (UVR)-induced molecular damage to the skin to a greater extent than sunscreens alone. In this 6-month, randomized, clinical study, we sought to compare the clinical and molecular effects of sunscreens plus DNA repair enzymes vs. those of traditional sunscreens alone in patients with actinic keratosis (AK). A total of 28 AK patients were randomized to topically apply sunscreens plus DNA repair enzymes (enzyme group; n = 14) or sunscreens alone (sunscreen group; n = 14) for 6 months. The main outcome measures included 1) hyperkeratosis, 2) field cancerization (as measured by fluorescence diagnostics using methylaminolaevulinate), and 3) levels of cyclobutane pyrimidine dimers (CPDs) in skin biopsies. Both regimens produced a significant reduction of hyperkeratosis at 6 months, with no difference between the two groups. Field cancerization was significantly reduced by both regimens, but the decrease observed in the enzyme group was significantly more pronounced than in the sunscreen group (P < 0.001). At 6 months, CPDs decreased by 61% in the enzyme group and by 35% in the sunscreen group compared with baseline values (P < 0.001). These findings indicate that, despite a similar effect on hyperkeratosis, the addition of DNA repair enzymes to sunscreens was more effective in reducing field cancerization and CPDs than sunscreens alone. Taken together, our findings indicate that sunscreens plus DNA repair enzymes may be superior to traditional sunscreens alone in reducing field cancerization and UVR-associated molecular signatures (CPDs) in AK patients, potentially preventing malignant transformation into invasive squamous cell carcinoma in a more efficient manner.

Anti-ghrelin antibodies in appetite suppression: recent advances in obesity pharmacotherapy.

Obesity is a medical condition caused by accumulated excess body fat with negative impact on patients' health, including decreased life expectancy. It has become a major health problem in most developed and developing countries, since the worldwide prevalence of obesity nearly doubled during the last 30 years. Consequently, novel treatments focusing on obesity are being investigated. Potential targets include several pathophysiological mechanisms involved in appetite control affecting multiple organ systems, like adipose tissue; some cell types in the stomach and gut; pancreas; thyroid gland; several hypothalamic areas; and centers located in the brainstem. One of the most important orexigenic neuropeptides is ghrelin, which is produced and secreted primarily by ghrelin cells located in the stomach and duodenum. In humans, plasma ghrelin levels rise when the stomach is empty and fall shortly after meal ingestion. In fat tissue, ghrelin increases fat storage. In the brain, it exerts its orexigenic action through activation of NPY/AgRP neurons in the arcuate nucleus. From the pharmacological point of view, it seems that opposing ghrelin activity could be used as a therapeutic principle in treating obesity. The principal idea of antiobesity drugs is to augment anorexigenic and lipolytic signaling, or to block orexigenic and lipogenic mediators. Recent studies have shown that therapeutic vaccines could be a new approach in the development of antiobesity medications. A vaccine should provoke an immune response to a specific causal factor for a particular disease. Several types of anti-ghrelin vaccines have been developed so far, with significant immune response in terms of rising anti-ghrelin antibodies. However, in the only clinical trial performed yet, the results were disappointing, showing no additional weight loss in the study group. Until now, several studies have demonstrated the "proof of concept", but more studies are required to develop prophylactic and therapeutic vaccines to prevent and/or cure obesity.

Topical application of preparations containing DNA repair enzymes prevents ultraviolet-induced telomere shortening and c-FOS proto-oncogene hyperexpression in human skin: an experimental pilot study.

The exposure to ultraviolet radiation (UVR) is one of the most important risk factors for skin aging and increases the risk of malignant transformation. Telomere shortening and an altered expression of the proto-oncogene c-FOS are among the key molecular mechanisms associated with photoaging and tumorigenesis. Photolyase from A. nidulans and endonuclease from M. luteus are xenogenic DNA repair enzymes which can reverse the molecular events associated with skin aging and carcinogenosis caused by UVR exposure. Therefore, the purpose of this study was to investigate whether the topical application of preparations containing DNA repair enzymes may prevent UVR-induced acute telomere shortening and FOS gene hyperexpression in human skin biopsies. Twelve volunteers (Fitzpatrick skin types I and II) were enrolled for this experimental study, and six circular areas (10 mm diameter) were marked out on the nonexposed lower back of each participant. One site was left untreated (site 1: negative control), whereas the remaining five sites (designated sites 2-6) were exposed to solar-simulated UVR at 3 times the MED on four consecutive days. Site 2 received UVR only (site 2: positive control), whereas the following products were applied to sites 3-6, respectively: vehicle (moisturizer base cream; applied both 30 minutes before and immediately after each irradiation; site 3); a traditional sunscreen (SS, SPF 50) 30 minutes before irradiation and a vehicle immediately after irradiation (site 4); a SS 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 5); a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 6). Skin biopsies were taken 24 h after the last irradiation. The degree of telomere shortening and c-FOS gene expression were measured in all specimens. Strikingly, the combined use of a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation completely abrogated telomere shortening and c-FOS gene hyperexpression induced by the experimental irradiations. We conclude that the topical application of preparations containing both photolyase from A. nidulans and endonuclease from M. luteus may be clinically useful to prevent skin aging and carcinogenesis by abrogating UVR-induced telomere shortening and c-FOS gene hyperexpression.

Drug treatment of metabolic syndrome.

The metabolic syndrome is a constellation of risk factors for cardiovascular diseases including: abdominal obesity, a decreased ability to metabolize glucose (increased blood glucose levels and/or presence of insulin resistance), dyslipidemia, and hypertension. Patients who have developed this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Genetic factors and the environment both are important in the development of the metabolic syndrome, influencing all single components of this syndrome. The goals of therapy are to treat the underlying cause of the syndrome, to reduce morbidity, and to prevent complications, including premature death. Lifestyle modification is the preferred first-step treatment of the metabolic syndrome. There is no single effective drug treatment affecting all components of the syndrome equally known yet. However, each component of metabolic syndrome has independent goals to be achieved, so miscellaneous types of drugs are used in the treatment of this syndrome, including weight losing drugs, antidiabetics, antihypertensives, antilipemic and anticlothing drugs etc. This article provides a brief insight into contemporary drug treatment of components the metabolic syndrome.

Metabolic syndrome influencing infarct size and heart failure in patients with acute coronary syndrome: does gender matter?

Metabolic syndrome (MetS) is the occurrence of diabetes mellitus/glucose intolerance, arterial hypertension, central obesity, dyslipidemia, and microalbuminuria in the same patient (definition by WHO). Presence of metabolic syndrome is associated with larger myocardial infarction size and complications following acute myocardial infarction. Two hundred and thirty patients with acute coronary syndromes were analyzed. Those with MetS (n=141) included patients with diabetes mellitus/glucose intolerance and at least two of the following criteria: hypertension, hypertriglyceridemia/low HDL cholesterol, android obesity/body mass index (BMI) ≥ 30, or microalbuminuria. Control group did not meet criteria for MetS. Presence of heart failure was assigned according to Killip classification. The MetS group had larger myocardial infarction size determined by peak creatine-kinase (CK) (1484±1354 vs. 981±890, p = 0.003) and CK MB (141±117 vs. 95±78, p = 0.002). While in non-MetS group males had larger myocardial infarction than females, in MetS group females had larger myocardial infarction than males. Cardiac failure occurred more in MetS group of patients, again was more prominent in females. Occurrence of metabolic syndrome in acute coronary syndrome patients predisposes to larger myocardial infarction size, more on the account of female patients having MetS. MetS, again particularly in females, predisposes to higher chance of having heart failure during acute coronary syndrome. Recognizing the female group with MetS as of higher risk for large myocardial infarction and heart failure leads us to pay special attention on this patient population.

Glucose metabolism disorders in patients with acute coronary syndromes.

Glucose metabolism disorders in acutely ill patients include oscillations in plasma glucose concentration outside the range of reference values. These disorders include both hyperglycemia and hypoglycemia, regardless of previous diagnosis of diabetes in a particular patient. Hyperglycemia is frequent in acute patients due to the increased release of stress hormones such as catecholamines and cortisol, but also as an effect of a cascade of proinflammatory cytokines in emergencies such as acute coronary syndrome, pulmonary edema, pulmonary embolism, injuries, severe infections and sepsis. Hyperglycemia occurs often even in patients in whom diabetes was not previously diagnosed, and in diabetic patients requirement for hypoglycemic medication may be temporarily increased. Hyperglycemia in cardiac emergencies is associated with more frequent adverse major cardiovascular events and worse prognosis. Hypoglycemia occurs seldom in these patients, its origin is almost always iatrogenic, and it worsens the patient's prognosis even more than moderate hyperglycemia. Good regulation of glycemia is necessary in the management of these patients; therefore plasma glucose determination and close monitoring are obligatory, and therapy with short acting insulin should be introduced if plasma glucose concentration exceeds 10 mmol/L, regardless of the risk of hypoglycemia. It is also useful to determine the acid-base status and blood or urine ketones.

Anti-inflammatory effects of a topical preparation containing nicotinamide, retinol, and 7-dehydrocholesterol in patients with acne: a gene expression study.

PURPOSE: Acne vulgaris is a skin disorder of the sebaceous follicles, involving hyperkeratinization and perifollicular inflammation. Aberrant extracellular matrix remodeling due to matrix metalloproteinases (MMPs) has been associated with the presence of acne conditions. Given the complex pathophysiology of acne, novel topical therapies should include combination products that target multiple pathogenetic mechanisms. In this pilot study we investigated the changes in gene expression of extracellular MMPs, the tissue inhibitors of metalloproteinases, and proinflammatory molecules after 45 days of topical application of a combination product containing nicotinamide, retinol, and 7-dehydrocholesterol in 16 patients with inflammatory acne on their back. MATERIALS AND METHODS: Skin biopsies were obtained before and after treatment for gene expression studies. RESULTS: Quantitative real-time polymerase chain reaction revealed a significant downregulation of MMP-1, MMP-2, MMP-9, MMP-14, interleukin-6, monocyte chemoattractant protein-1, and macrophage migration inhibitory factor. In contrast, the tissue inhibitors of metalloproteinases and transforming growth factor-ß1 were significantly upregulated. The gene expression findings correlated well with the clinical treatment response. CONCLUSIONS: The combination of nicotinamide, retinol, and 7-dehydrocholesterol appears to be effective for acne treatment from both clinical and molecular standpoints.

Reduced ultraviolet-induced DNA damage and apoptosis in human skin with topical application of a photolyase-containing DNA repair enzyme cream: clues to skin cancer prevention.

The exposure of human skin to ultraviolet radiation (UVR) results in the formation of DNA photolesions that give rise to photoaging, mutations, cell death and the onset of carcinogenic events. Photolyase (EC 4.1.99.3) is a DNA repair enzyme that reverses damage caused by exposure to UVR. We sought to investigate whether addition of photolyase enhances the protection provided by a traditional sunscreen (SS), by reducing the in vivo formation of cyclobutane-type pyrimidine dimers (CPDs) and UVR-induced apoptosis in human skin. Ten volunteers (Fitzpatrick skin type II) were exposed to solar-simulated (ss) UVR at a three times minimal erythema dose for 4 consecutive days. Thirty minutes prior to each exposure, the test materials [vehicle, SS (sun protection factor 50) alone, and SS plus photolyase from Anacystis nidulans] were applied topically to three different sites. One additional site was left untreated and one received ssUVR only. Biopsy specimens were taken 72 h after the last irradiation. The amount of CPDs and the extent of apoptosis were measured by ELISA. Photolyase plus SS was superior to SS alone in reducing both the formation of CPDs and apoptotic cell death (both P<0.001). In conclusion, the addition of photolyase to a traditional SS contributes significantly to the prevention of UVR-induced DNA damage and apoptosis when applied topically to human skin.

Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite.

BACKGROUND: Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. METHODS: A total of 15 lean (body mass index [BMI] < 25 kg/m(2) ) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. RESULTS: Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6 ± 3.1 AU versus 16.6 ± 4.1 AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3 ± 7.3 µg/ml) and without (19.3 ± 6.1 µg/ml) cellulite (P=0.69). CONCLUSIONS: Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue.