Clinical and Therapeutic Implications of Male Obesity.

The prevalence of obesity, a disorder linked to numerous comorbidities and metabolic complications, has recently increased dramatically worldwide and is highly prevalent in men, even at a young age. Compared to female patients, men with obesity more frequently have delayed diagnosis, higher severity of obesity, increased mortality rate, and only a minority of obese male patients are successfully treated, including with bariatric surgery. The aim of this review was to present the current state of knowledge about the clinical and therapeutic implications of obesity diagnosed in males.

Diagnosis and Non-Invasive Treatment of Obesity in Adults with Type 2 Diabetes Mellitus: A Review of Guidelines.

Obesity, a chronic disease with multifactorial etiopathogenesis, is characterized by excessive accumulation of adipose tissue. Obesity prevalence is growing globally at an alarming rate. The overwhelming majority of obesity cases are caused by inappropriate lifestyles, such as overconsumption of food and inadequate physical activity. Metabolic and biochemical changes due to increased adiposity resulted in numerous comorbidities, increased all-cause mortality, and reduced quality of life. T2DM (type 2 diabetes mellitus) and obesity have many common pathogenetic points and drive each other in a vicious cycle. The aim of this article is to review obesity management guidelines and highlight the most important points. Management of both obesity-related and T2DM complications incur enormous expenses on healthcare systems. It is, therefore, paramount to provide streamlined yet custom-tailored weight management in order to avoid the negative ramifications of both diseases. Efficient obesity treatment leads to better diabetes control since some antidiabetic medications support weight reduction. Obesity treatment should be overseen by a multi-disciplinary team providing indispensable information and individually tailored regimens to patients. Weight management should be multimodal and consist chiefly of MNT (medical nutrition therapy), physical activity, and lifestyle changes. A comprehensive approach to obesity treatment may give tangible results to quality of life and comorbidities.

Branched-chain amino acids as a novel biomarker of metabolic disturbances in women with polycystic ovary syndrome - literature review.

Polycystic ovary syndrome (PCOS) is a common, heterogeneous endocrine disorder which effects 5-10% of reproductive-age women. Recently, an association between PCOS and an increased risk of developing metabolic disturbances, such as insulin resistance, prediabetes, type 2 diabetes mellitus as well as obesity has been emphasised. Branched-chain amino acids (BCAAs), including valine (Val), leucine (Leu) and isoleucine (Ile), are a group of essential amino acids that cannot be synthesized in human body and need to be obtained from food. Several recent studies provide evidence that plasma BCAAs also serve as crucial nutrient signals and metabolic regulators. Interestingly, latest metabolomics analysis shows abnormalities in amino acid catabolism and biosynthesis in patients with PCOS, particularly in BCAAs. A growing body of evidence proves that elevated levels of BCAAs may have adverse effects on metabolic health leading to the development of insulin resistance, prediabetes, type 2 diabetes mellitus and obesity both in human and animal models. The aim of this review is to assess the current state of knowledge about the potential role of BCAAs as a novel biomarker of metabolic disturbances in women with polycystic ovary syndrome based on recent scientific literature published up to July 2021 and searches of the PubMed, Google Scholar, and Web of Science databases.

Subclinical hyperthyroidism in the course of autonomous nodules - clinical evaluation.

INTRODUCTION: Subclinical hyperthyroidism (SCH), also known as mildly symptomatic hyperthyroidism, has recently been diagnosed more frequently. One of the main endogenous causes of this disorder is autonomously functioning thyroid nodule (AFTN). Despite the fact that it is usually asymptomatic, SCH entails repercussions on the cardiovascular system and bone, and it carries a risk of progression to overt hyperthyroidism with a typical clinical picture. Treatment is still controversial, and its benefits are widely debated in literature. MATERIAL AND METHODS: From 459 patients authors selected a group of 49 patients (10.6% of all subjects with hyperthyroidism), 41 women (83.7%) with AFTN at the stage SCH treated in the Outpatient Endocrinological Clinic and the Department of Endocrinology of the Medical University of Lublin over a three-year period. The method applied in the study was a retrospective analysis of medical records with a particular account of medical history, physical examination, and additional tests obtained during the process of diagnostic and therapeutic procedures. RESULTS: Forty-one patients (83.7%) suffered from typical symptoms of hyperthyroidism; only eight patients (16.3%) were asymptomatic. The most frequently reported symptoms were tachycardia in women (51.2%) and anxiety in men (50%). The type of thyrostatic drugs and the length of therapy did not affect the outcome of iodine-131 therapy. In the vast majority of the patients (87.8%) radioidodine therapy was effective; 30 patients (61.2%) reached euthyreosis and 13 patients (22.5%) developed hypothyroidism. CONCLUSIONS: Most patients with SCH in the course of AFTN suffered from typical symptoms of overt hyperthyroidism; only every sixth patient was asymptomatic. The volume of autonomous adenomas did not affect the result of 131I therapy; however, the impact of AFTN volume as well as the thyroid volume on RIT efficacy requires futher investigation. In the vast majority of patients 131I therapy was an effective method of treatment, and an earlier therapeutic effect was observed more often in the patients with focal lesions located in the right lobe.

Fibroblast growth factor 21 - a key player in cardiovascular disorders?

Fibroblast growth factor 21 (FGF21) is a newly discovered adipokine, synthesized by several organs, mostly by the liver, which was introduced as a potent metabolic regulator and insulin-sensitizing factor. Numerous animal studies have demonstrated that FGF21 improves glucose and lipids metabolism and exerts anti-inflammatory effects. However, data obtained from human studies have shown contradictory results, in which circulating FGF21 levels were often elevated in obesity, dyslipidemia, type 2 diabetes (DM2) and other conditions connected with insulin resistance. This increase in basal FGF21 concentrations observed in patients with obesity and other conditions related to insulin resistance was being explained as a compensatory response to the underlying metabolic disturbances or tissue resistance to FGF21 action. Furthermore, the results of clinical trials have shown that increased FGF21 concentrations were associated with increased cardiovascular (CV) risk and had a prognostic value in CV outcomes. In recent years, it has been reported that FGF21 may exert cardioprotective effects. This mini-review aims to summarize the current state of knowledge about the role of FGF21 in CV disorders, and discuss the molecular mechanism underlying the anti-atherogenic properties of this compound.

The pharmacological and hormonal therapy of hot flushes in breast cancer survivors.

The side effects of oncological treatment, which appear during or after therapy, are sometimes very annoying for patients and are not adequately treated by physicians. Among the symptoms experienced by breast cancer patients are hot flushes, which result from a natural or cancer therapy-induced menopause. The intensity of hot flushes in breast cancer patients may be more severe than those experienced by women undergoing a natural menopause. Taking into account the incidence of breast cancer and long-lasting hormone-suppression therapies, the problem of hot flushes will affect many women. Hormonal replacement therapy, the most effective therapeutic means for alleviating hot flushes, is usually contraindicated for breast cancer patients. For intense and severe hot flushes, pharmacological treatment using agents from a group of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors such as venlafaxine or citalopram may be introduced. Other agents from different pharmacological groups, such as clonidine, gabapentin, or pregabalin, have also proved to be effective in treating hot flushes. The efficacy of phytoestrogens has not been proven in randomized clinical trials. The importance of the placebo effect in decreasing vasomotor symptoms has also been reported in many research papers. Educating breast cancer patients in lifestyle changes which decrease the frequency and intensity of vasomotor symptoms can offer significant help too. This paper reviews the current state of research in order to assess the options for the treatment of hot flushes in breast cancer survivors.

Clinical implications of vitamin D deficiency.

Vitamin D deficiency is a common medical problem worldwide and its prevalence rises along with latitude, obesity, sedentary lifestyle, limited sunlight exposure and aging. A great body of evidence has shown that patients with vitamin D deficiency have increased cardiovascular risks and total mortality. Conversely, the presence of comorbidities progressive with age such as abdominal obesity, insulin resistance, type 2 diabetes and hypertension places the patients at an increased risk of vitamin D deficiency. The multidirectional effect of vitamin D deficiency is present in different phases of the aging process. Based on the literature review, the risk factors for vitamin D insufficiency most often found in post-menopausal women include limited sun exposure and time spent outdoors, inadequate dietary vitamin D intake, winter season and increased age. Vitamin D supplementation in this group might offer prevention of falls and fractures and may be beneficial for cardiovascular health, what may be especially important in osteoporotic and elderly populations. Prevention and treatment processes involve education regarding sunlight exposure and pharmacological cholecalciferol supplementation according to the recommendations for Central Europe. This manuscript reviews the role of vitamin D and its deficiency and considers their clinical implications, with particular regard to peri- and postmenopausal women.

Postpartum adiponectin changes in women with gestational diabetes.

INTRODUCTION AND OBJECTIVE: Current literature provides contradictory information on the role of adiponectin (AdipoQ) in the course of gestational diabetes mellitus (GDM) and the changes after delivery. The aim of the study was to measure AdipoQ concentration in blood of women with GDM, and to conduct a comparative analysis of AdipoQ concentrations in gestation at 3 and 12 months after delivery. MATERIAL AND METHODS: The study group consisted of 50 women diagnosed with GDM between 24 and 28 weeks of gestation. Three months after delivery, 41 women underwent further tests, while 12 months after delivery 30 patients. All patients underwent clinical and laboratory evaluation at GDM diagnosis at 3 and 12 months after delivery. Laboratory evaluation included fasting glucose, fasting insulin, OGTT and lipid parameters in serum. Serum AdipoQ concentration was measured at GDM diagnosis as well as at 3 and 12 months after delivery. RESULTS: AdipoQ concentrations did not differ significantly between the groups during gestation (p=0.7054) and 3 months after delivery (p=0.9732), while a significant rise was observed 12 months after delivery, compared to the values during pregnancy (p=0.0006). AdipoQ in the GDM group 12 months after delivery inversely correlated with fasting glucose and 2-hour post-load plasma glucose after a 75-g oral glucose tolerance test (r=-0.37*; p<0.05 and r=-0.42, p<0.05, respectively). CONCLUSIONS: An increased level of AdipoQ after delivery in the comparison to women with GDM may be a marker for reversibility of carbohydrate metabolism disorders, while a negative correlation between AdipoQ and glucose levels suggests that this parameter may be a predictor In the future of disturbances in glucose tolerance in women with GDM.

Correlation between atherogenic risk and adiponectin in gestational diabetes mellitus.

INTRODUCTION AND OBJECTIVE: Gestational diabetes mellitus (GDM) is a pregnancy complication which increases the risk for maternal and foetal complications during pregnancy, and also significantly increases the cardiovascular risk for women's health in the postpartum. Current literature provides contradictory information on the role of adiponectin (AdipoQ) in the course of GDM. The aim of the study was to measure AdipoQ concentration in blood of women with GDM and to find correlations between this adipokine and clinical and biochemical parameters of the atherogenic risk. MATERIAL AND METHODS: The GDM group included 50 women diagnosed with GDM between 24 - 28 weeks of gestation who underwent routine prenatal tests for GDM in compliance with the guidelines of the Polish Diabetes Association. All patients underwent clinical and laboratory evaluation at GDM diagnosis. Laboratory tests included serum AdipoQ concentration, fasting glucose and insulin, OGTT, lipid parameters, C-reactive protein and fibrinogen in serum. RESULTS: The GDM group showed significantly elevated fasting glucose, insulin, HOMA-IR values, total cholesterol, LDLcholesterol and triglicerydes as compared with the control group (p<0.05). The atherogenic index, CRP, fibrinogen in women with GDM were significantly higher than in the control group (p<0.05). AdipoQ concentrations did not differ significantly between the groups during gestation (p=0.7054). No correlations, except with the neonatal weight (r= - 0.29, p<0.05), were found between AdipoQ and the studied parameters. CONCLUSIONS: Based on the conducted studies, it may be conclude that women with early diagnosed and promptly treated GDM have a normal adiponectin level, although insulin resistant changes and increased cardiovascular risk in basic metabolic parameters are observed. Moreover, adiponectin does not reflect the atherogenic risk in pregnant women with GDM.

Polycystic ovary syndrome: clinical implication in perimenopause.

Polycystic ovary syndrome (PCOS), a hyperandrogenic disorder, is the commonest endocrinopathy in premenopausal women. This syndrome is associated with fertility problems, clinical manifestations of hyperandrogenism and metabolic disturbances, particularly insulin resistance and obesity. There is a great body of evidence that patients with PCOS present multiple cardiovascular risk factors and cluster components of metabolic syndrome from early ages. The presence of comorbidities such as abdominal obesity, insulin resistance, type 2 diabetes, hypertension places these females at an increased risk of future cardiovascular events. However, the extent to which PCOS components are present in perimenopausal women and the degree to which PCOS increases various risk factors in addition to the known risk of the perimenopausal period have not been fully determined. The perimenopausal period per se is associated with weight gain and an increased cardiovascular risk, which may be additionally aggravated by the presence of metabolic disturbances connected with PCOS. The phenotype of PCOS may improve with aging and it is still uncertain whether the presence of PCOS significantly increases the cardiovascular risk later in women's life. Most recent data suggest that the prevalence of cardiovascular diseases and the related long-term consequences in females with PCOS seem to be lower than expected. This manuscript reviews long-term consequences of PCOS and considers their clinical implications in perimenopause.

Exenatide twice daily versus insulin glargine for the treatment of type 2 diabetes in Poland - subgroup data from a randomised multinational trial GWAA.

INTRODUCTION: We explored the safety and efficacy of exenatide BID v. insulin glargine in a subgroup of Polish patients with type 2 diabetes sub-optimally controlled with metformin plus a sulfonylurea, participating in a 26-week randomised, controlled open-label trial. MATERIAL AND METHODS: In Poland, 80 patients (HbA1c 7-10%, BMI 25-45 kg/m(2)) were randomised to exenatide 10 µg BID (n = 40) or insulin glargine once daily (n = 40). We present exploratory analyses on HbA1c, glucose profiles, body weight, hypoglycaemia and adverse events (AEs). RESULTS: Mean (SD) baseline HbA1c was 7.9% (0.86) for exenatide and 7.8% (1.02) for insulin glargine. At Week 26, LS mean (SEM) HbA1c decreased in both groups (exenatide -0.72% [0.12]; glargine -0.64% [0.12]), as did fasting glucose. Postprandial glucose excursions after breakfast and dinner were smaller in patients treated with exenatide. LS mean (SEM) body weight decreased by -1.9 (0.48) kg with exenatide and increased by 1.6 (0.48) kg with glargine (group difference [95%CI]: -3.5 kg [-4.9 to -2.2]). Hypoglycaemia was low in both groups; nocturnal hypoglycaemia was reported for three v. seven patients (three v. 24 episodes) in the exenatide and glargine groups, respectively. Adverse events were more common with exenatide (nausea n = 22 v. n = 1, vomiting n = 5 v. n = 0, headache n = 8 v. n = 2). CONCLUSION: This exploratory analysis confirms that findings from the global study apply to patients treated with exenatide BID and glargine in Poland, showing that exenatide BID was as effective as insulin glargine. Data suggested that changes in HbA1c were similar, with fasting glucose changes greater in the glargine group and postprandial changes greater in the exenatide BID group. Exenatide BID was associated with weight reduction, less nocturnal hypoglycaemia, but more gastrointestinal events compared to glargine.

Evaluation of concentrations of FGF-21 - a new adipocytokine in type 2 diabetes.

INTRODUCTION: Fibroblast growth factor 21 FGF-21 is a newly discovered adipocytokine which may play a vital role in improvement of insulin sensitivity and pathogenesis of type 2 diabetes. The aim of the study was to assess FGF-21 concentrations in the serum of patients with type 2 diabetes, in comparison to a control group, and evaluate the possible relationships between the studied cytokine and selected clinical and biochemical parameters MATERIAL AND METHODS: The study was conducted in 64 patients with type 2 diabetes, 28 women and 36 men aged 47-70 (median age 61.5), with a median duration of diabetes of 8.5 years. In fasting serum samples, concentrations of glucose, insulin, lipids profile parameters, creatinine, C-reactive protein (CRP), fibrinogen, HbA(1c), adiponectin, and FGF-21 were determined. The control group comprised 20 healthy persons matched for age to the study group, with no disturbances in carbohydrate metabolism: 14 women and 8 men. RESULTS: We found significant differences concerning the medians of body mass index (BMI) 32.4 kg/m(2) v. 24.1 kg/m(2), p < 0.001; waist circumference 114 cm v. 81 cm, p < 0.001; HDL cholesterol 42.5 mg/dl v. 62.5 mg/dl, p < 0.001; triglyceride (TG) 152 mg/dl v. 99 mg/dl, p < 0.01 in the studied group, in comparison with the control group, respectively. In patients with diabetes, median FGF-21 concentration was 239.9 pg/ml and was significantly greater in comparison to the control group: 112.6 pg/ml p < 0.01. Median adiponectin concentration in patients with type 2 diabetes was significantly lower in comparison to the control group, 7.5 ng/ml v. 9.95 ng/ml, p < 0.05. Significant correlations between FGF-21 concentrations and adiponectin (r = -0.24, p < 0.05), weight (r = 0.27, p < 0.05), glucose (r = 0.27, p < 0.05), HDL cholesterol (r = -0.26, p < 0.05), TG (r = 0.27, p < 005), and estimated glomerular filtration rate (eGFR) (r = -0.28, p < 0.05) were observed. No significant correlations between FGF-21 and parameters of metabolic control, markers of inflammatory status, and insulin resistance, or the presence of vascular complications of diabetes, were noticed. CONCLUSIONS: On the basis of the conducted studies it can be concluded that the greater FGF-21 concentration observed in the examined group of patients with type 2 diabetes may result from a compensatory reaction to metabolic disturbances or tissue resistance to this cytokine. The negative correlation between FGF-21 and eGFR suggests renal elimination of the examined compound. (Pol J Endocrinol 2010; 61 (1): 50-54).

[Incretin hormones in the treatment of type 2 diabetes. Part II. Incretins - new possibilities for pharmacotherapy of type 2 diabetes]. / Hormony inkretynowe w leczeniu cukrzycy typu 2. Czesc II. Inkretyny -- nowe mozliwosci farmakoterapii cukrzycy typu 2.

In the pathogenesis of diabetes type 2, increasing insulin resistance is accompanied by dysfunction of pancreatic islet b cells. It is hypothesized that at the basis of this pathology lies an incretin defect of insulinotropic gut-derived hormones, relying on decreased secretion of GLP-1 (glucagon-like peptide 1), with preserved insulinotropic effect, whereas GIP (glucose-dependent insulinotropic polypeptide) secretion remains within physiological limits, but its action is mostly impaired due to total loss of possibility for stimulation of the second phase insulin secretion. Possibilities for pharmacological correction of incretin defect create an opportunity of causative treatment of diabetes and provide basis for development of research on a new group of drugs which promote hypoglycemia. In the presence of these findings there are many ongoing clinical studies with the use of GLP-1 analogues or GLP-1 receptors activators (GLP-1 agonists), as well as the inhibitors of dipeptidyl peptidase IV (DPP-IV), the enzyme responsible for incretin proteolysis, in the treatment of type 2 diabetes. Multidirectional, glucoregulative mechanism of action of these drugs, aiming at the pathogenesis of the disease, restores the proper function of the intestinal-pancreatic axis in subjects with type 2 diabetes and ensures good metabolic control and improvement in quality of life in this group of patients.

[Incretin hormones in the treatment of type 2 diabetes. Part I: influence of insulinotropic gut-derived hormones (incretins) on glucose metabolism]. / Hormony inkretynowe w leczeniu cukrzycy typu 2 Czesc I: Wplyw insulinotropowych hormonów jelitowych (inkretyn) na metabolizm glukozy.

Insulinotropic gut-derived hormones (incretins) play a significant role in the regulation of glucose homeostasis in healthy subjects and are responsible for 50-70% of insulin response to a meal. The main mediators of the incretin effect are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). However, in patients with type 2 diabetes the effect of incretins action is to a large extent impaired, which seems to explain disturbed secretional activity of beta cells in pancreatic islets. Detailed analysis of incretin defect proved that GIP secretion remains within physiological limits, whereas GLP-1 secretion is significantly decreased. Nevertheless, GLP-1 insulinotropic effect is preserved and GIP effect is significantly impaired. In consequence, substitutional GLP-1 administration aiming at the reduction of its deficiency, seems to be logical therapeutic management, because despite a physiologically retained quantity response from GIP, resistance to this peptide is frequently found. Therefore, particularly promising are the results of clinical studies with the use of GLP-1 analogues , GLP-1 receptors activation, as well as the inhibitors of dipeptidyl peptidase-IV (DPP IV), the enzyme responsible for incretin proteolysis, which restores the proper function of the intestinal-pancreatic axis in subjects with type 2 diabetes and creates new possibilities of a glycaemia reducing therapy and improvement in quality of life in this group of patients.