Fibroblast Growth Factor 23 (FGF23) and Klotho Protein in Beta-Thalassemia.

Derangements in phosphate and calcium homeostasis are common in patients with beta-thalassemia. Fibroblast growth factor 23 (FGF23) is among the main hormones regulating phosphate levels, while several studies underline an interplay between iron (Fe) and FGF23. Herein, we investigated, for the first time, the serum intact molecule (iFGF23) and the carboxyl-terminal fragment (C-FGF23) and Klotho levels simultaneously in patients with beta-thalassemia major receiving iron chelation regimens in comparison to healthy control subjects. We also correlated them with the body iron burden. The observational case-control study included 81 subjects (40 thalassemic patients and 41 healthy controls). Serum iFGF23, C-FGF23 and Κlotho were measured by ELISA. Parathormone, 25-hydroxycholecalciferol, calcium, and phosphorus were measured in blood and/or urine. The degree of hemosiderosis was evaluated by assessing the serum ferritin levels and performing T2* MRI measurements. Serum C-FGF23 levels were significantly lower in patients compared to control subjects (p=0.04), while iFGF23 and Klotho levels did not differ. Serum C-FGF23 levels were negatively correlated with ferritin (r=-0,421, p=0.018), whereas there were no significant correlations of each of the three factors with the iron chelation therapy. Decreased serum C-FGF23 levels were found in ßTh patients which may be attributed to inhibition of proteolytic cleavage of iFGF23. Further studies in a greater number of patients will shed more light on the disturbances of the iFGF23, Klotho and C-FGF23 in thalassemia and their possible role in bone disease of such patients.

Menstrual Disorders and Androgen-Related Traits in Young Women with Type 1 Diabetes Mellitus: a Clinical Study.

OBJECTIVE: To investigate possible causes of menstrual disorders and androgen-related traits in young women with type 1 diabetes mellitus (T1DM). METHODS: Fifty-three women with T1DM (duration 8.0±5.6 years), 41 women with (polycystic ovary syndrome) PCOS, and 51 controls matched for age (19.4±4.3 years vs. 21.2±2.7 years vs. 20.8±3.1 years; P>.05) and body mass index (BMI) (22.2±2.7 kg/m2 vs. 21.9±2.0 kg/m2 vs. 21.4±1.9 kg/m2; P>.05) were prospectively recruited. RESULTS: Two women (3.8%) in the T1DM group had not experienced menarche (at 15.5 and 16.6 years); of the rest, 23.5% had oligomenorrhea, 32.1% hirsutism, and 45.3% had acne. The age at menarche was delayed in the T1DM group compared to controls (12.7±1.3 vs. 12.0±1.0 years; P = .004), while no difference was observed with the polycystic ovary syndrome (PCOS) group (12.4±1.2 years). There were no differences in total testosterone (0.43±0.14 ng/mL vs. 0.39±0.14 ng/mL; P>.05), dehydroepiandrosterone sulfate (DHEA-S) (269 ± 112 µg/dL vs. 238 ± 106 µg/dL; P>.05) or Δ4-androstenedione (2.4±1.3 ng/mL vs. 1.9±0.5 ng/mL; P>.05) concentrations between T1DM and controls. However, patients with T1DM had lower sex hormone binding globulin (SHBG) concentrations than controls (61 ± 17 nmol/L vs. 83 ± 18.1 nmol/L; P = .001), which were even lower in the PCOS group (39.5±12.9 nmol/L; P = .001 compared with T1DM). The free androgen index (FAI) was higher in the PCOS group compared with both other groups (T1DM vs. PCOS vs. controls: 2.53±0.54 vs. 7.88±1.21 vs. 1.6 ± 0.68; P<.001). FAI was higher in patients with T1DM compared to controls as well (P = .038). There was no difference in DHEA-S concentrations between T1DM and PCOS patients (269 ± 112 µg/dL vs. 297 ± 100 µg/dL; P>.05). CONCLUSION: Menstrual disorders and androgen-related traits in young women with T1DM may be attributed to an increase in androgen bioavailability due to decreased SHBG concentrations.

The effect of anti-TNF therapy on thyroid function in patients with inflammatory bowel disease.

The aim of this study was to investigate for first time the thyroid function in patients with inflammatory bowel disease (IBD) and the potential effect of anti-TNF (tumor necrosis factor) therapy. We evaluated 41 patients with IBD (25M/16F, 36.5 ± 11.3 y, 27 with Crohn's disease and 14 with ulcerative colitis), without any known thyroid disorder. Eighteen patients (9M/9F, 33.6 ± 8.8 y) were on anti-TNF therapy, while 23 patients (16M/7F, 38.7 ± 12.5 y) were treated with Azathioprine and Mesalazine (Aza/Mes) for more than 1 year. Twelve patients from the second group were then treated with anti-TNF and studied 6 months later. We assessed thyroid function by measuring thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3), thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TgAb) levels. One patient presented with overt and one with subclinical hyperthyroidism. Thyroid auto-antibodies were positive in 12.2%. Patients from the anti-TNF group had lower levels of FT4 (1.09 ± 0.15 vs. 1.38 ± 0.9 ng/dL, p = 0.042), while TSH and T3 were comparable. The percentage of patients with positive thyroid auto-antibodies was lower in the anti-TNF group (5.6% vs. 17.4%). In the subgroup of patients who changed to anti-TNF, we found statistically significant reduction in FT4 after 6 months (1.26 ± 0.24 vs. 1.08 ± 0.15 ng/dL, p = 0.044), without changes in TSH and T3 levels. There was no change regarding thyroid auto-antibodies. In conclusion, patients with IBD showed a quite high percentage of thyroid autoimmunity. After treatment with anti-TNF, FT4 levels were found to be reduced, while no changes in TSH, T3 levels and thyroid auto-antibodies were noted.

Current evidence on vitamin D deficiency and kidney transplant: What's new?

Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.

Diabetic cardiomyopathy: a clinical entity or a cluster of molecular heart changes?

BACKGROUND: Although the increasing rate of cardiovascular mortality in patients with diabetes is thought to be due to the coronary atherosclerosis caused mainly by compounding factors such as dyslipidaemia and hypertension, it is now well documented that diabetes alone can lead to a vast array of molecular changes in the heart. DESIGN: The aim of this article was to comprehensively review the pathophysiological and molecular changes leading to diabetic cardiomyopathy (DCM), as well as to critically analyse the literature that offers evidence in favour and against the existence of the overt clinical expression of this entity. RESULTS: We included in the discussion studies that have revealed the existence of diabetic cardiomyopathy with unique remodelling pattern when compared to other types of cardiomyopathies. On the other hand, several studies debate the existence of clinically discernible cardiomyopathy caused only by diabetes and were also presented and discussed in details. CONCLUSION: Clinicians should be aware of DCM when facing patients with diabetes in order both to recognize on time relevant symptoms and to intensively look for and treat other compounding factors, apart from optimal glucose control. Furthermore, the elucidation of the pathophysiological mechanisms leading to DCM could provide new therapeutic targets for heart disease, which will be wonderful for the good of our patients.

Early onset type 2 diabetes mellitus: an update.

The incidence and prevalence of type 2 diabetes mellitus (T2DM) in young individuals (aged <40 years) have significantly increased in recent years, approximating two to threefold increase in the respective rates. Numerous risk factors including severe obesity, family history, ethnicity, maternal diabetes or gestational diabetes, and female sex contribute to a younger age of onset. In terms of pathogenesis, impaired insulin secretion is the key operating mechanism, alongside with ectopic adiposity-related insulin resistance. T2DM diagnosis in a young adult requires the exclusion of type 1 diabetes mellitus (T1DM), latent autoimmune diabetes of adults (LADA) and maturity-onset diabetes of the young (MODY). The establishment of such diagnosis is critical for prognosis, because early-onset T2DM is associated with rapid deterioration in pancreatic ß-cell secretory function leading to earlier initiation of insulin therapy. Furthermore, mortality and lifetime risk of developing complications, especially microvascular, is increased in these patients compared to both later-onset T2DM and T1DM patients; also, the latter are often developed earlier in the course of disease. The management of early-onset T2DM follows the same guidelines as in later-onset T2DM; yet patients aged 18-39 years are underrepresented in the big clinical trials on which the development of guidelines is based. Finally, young people with T2DM face significant challenges associated with social determinants, which compromise their adherence to therapy and induce diabetes distress. Future research focusing on the pathogenesis of ß-cell decline and complications, as well as on specific treatment shall lead to better understanding and management of early-onset T2DM.

Cardiac disease in Cushing's syndrome. Emphasis on the role of cardiovascular magnetic resonance imaging.

BACKGROUND: Cushing's Syndrome (CS) is associated with increased cardiovascular morbidity and mortality. In endogenous CS, cardiovascular mortality remains increased for up to 15 years post remission of hypercortisolism. Similarly, patients with exogenous CS have 4-fold increased incidence of cardiovascular events, regardless of pre-existing cardiovascular disease (CVD). OBJECTIVE: To present the pathophysiology, prognosis, clinical and imaging phenotype of cardiac disease in CS. METHODS: A Pubmed search for cardiac disease in CS over the last 20 years was conducted using combinations of relevant terms. Preclinical and clinical studies, as well as review papers reporting on subclinical heart failure (HF), cardiomyopathy, coronary heart disease (CHD), and cardiovascular imaging were selected. RESULTS: Cardiac disease in CS is associated with direct mineralocorticoid and glucocorticoid receptor activation, increased responsiveness to angiotensin II, ectopic epicardial adiposity, arterial stiffness and endothelial dysfunction, as well as with diabetes mellitus, hypertension, hyperlipidemia, obesity and prothrombotic diathesis. Subclinical HF and cardiomyopathy are principally related to direct glucocorticoid (GC) effects and markedly improve or regress post hypercortisolism remission. In contrast, CHD is related to both direct GC effects and CS comorbidities and persists post cure. In patients without clinical evidence of CVD, echocardiography and cardiac magnetic resonance (CMR) imaging reveal left ventricular hypertrophy, fibrosis, diastolic and systolic dysfunction, with the latter being underestimated by echocardiography. Finally, coronary microvascular disease is encountered in one third of cases. CONCLUSION: Cardiovascular imaging is crucial in evaluation of cardiac involvement in CS. CMR superiority in terms of reproducibility, operator independency, unrestricted field of view and capability of tissue characterisation makes this modality ideal for future studies.

Female-specific risk factors for cardiovascular disease: an update.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. While it was previously believed that men have greater susceptibility to CVD, recent research suggests that women face an increased risk of CVD after the onset of menopause, primarily due to the loss of the protective effects of estrogens. Premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), and gestational factors, such as gestational diabetes mellitus (GDM), recurrent pregnancy loss, preterm delivery, and preeclampsia, are specific reproductive disorders that may contribute to an elevated risk of CVD at earlier ages, i.e., before the onset of menopause. This suggests that women with these conditions should be closely monitored for CVD risk factors even before reaching menopause. Such early intervention may help reduce the incidence of CVD and improve overall cardiovascular health in this population. The precise pathophysiological mechanism underlying the development of CVD in women with menopause, premature POI, PCOS, and gestational factors remains elusive. This review article seeks to elucidate the latest research on the relationship between these conditions and CVD in women, aiming to explore the underlying pathogenic mechanisms contributing to this association.

Food Cravings and Obesity in Women with Polycystic Ovary Syndrome: Pathophysiological and Therapeutic Considerations.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, constitutes a metabolic disorder frequently associated with obesity and insulin resistance (IR). Furthermore, women with PCOS often suffer from excessive anxiety and depression, elicited by low self-esteem due to obesity, acne, and hirsutism. These mood disorders are commonly associated with food cravings and binge eating. Hypothalamic signaling regulates appetite and satiety, deteriorating excessive food consumption. However, the hypothalamic function is incapable of compensating for surplus food in women with PCOS, leading to the aggravation of obesity and a vicious circle. Hyperandrogenism, IR, the reduced secretion of cholecystokinin postprandially, and leptin resistance defined by leptin receptors' knockout in the hypothalamus have been implicated in the pathogenesis of hypothalamic dysfunction and appetite dysregulation. Diet modifications, exercise, and psychological and medical interventions have been applied to alleviate food disorders, interrupting the vicious circle. Cognitive-behavioral intervention seems to be the mainstay of treatment, while the role of medical agents, such as GLP-1 analogs and naltrexone/bupropion, has emerged.

Secondary diabetes mellitus due to primary aldosteronism.

Primary aldosteronism (PA) and diabetes mellitus (DM) are clinical conditions that increase cardiovascular risk. Approximately one in five patients with PA have DM. Nevertheless, the pathophysiology linking these two entities is not entirely understood. In addition, the majority of patients with PA have glucocorticoid co-secretion, which is associated with increased risk of impaired glucose homeostasis. In the present review, we aim to comprehensively discuss all the available research data concerning the interplay between mineralocorticoid excess and glucose metabolism, with separate analysis of the sequalae in muscle, adipose tissue, liver and pancreas. Aldosterone binds both mineralocorticoid and glucocorticoid receptors and amplifies tissue glucocorticoid activity, via 11-ß-hydroxysteroid dehydrogenase type 1 stimulation. A clear classification of the molecular events as per specific receptor in insulin-sensitive tissues is impossible, while their synergistic interaction is plausible. Furthermore, aldosterone induces oxidative stress and inflammation, perturbs adipokine expression, thermogenesis and lipogenesis in adipose tissue, and increases hepatic steatosis. In pancreas, enhanced oxidative stress and inflammation of beta cells, predominantly upon glucocorticoid receptor activation, impair insulin secretion. No causality between hypokalemia and impaired insulin response is yet proven; in contrast, hypokalemia appears to be implicated with insulin resistance and hepatic steatosis. The superior efficacy of adrenalectomy in ameliorating glucose metabolism vs. mineralocorticoid receptor antagonists in clinical studies highlights the contribution of non-mineralocorticoid receptor-mediated mechanisms in the pathophysiologic process. The exact role of hypokalemia, the mechanisms linking mineralocorticoid excess with hepatic steatosis, and possible disease-modifying role of pioglitazone warrant further studies.

Biological therapies for premature ovarian insufficiency: what is the evidence?

Premature Ovarian Insufficiency (POI) is a multi-factorial disorder that affects women of reproductive age. The condition is characterized by the loss of ovarian function before the age of 40 years and several factors have been identified to be implicated in its pathogenesis. Remarkably though, at least 50% of women have remaining follicles in their ovaries after the development of ovarian insufficiency. Population data show that approximately up to 3.7% of women worldwide suffer from POI and subsequent infertility. Currently, the treatment of POI-related infertility involves oocyte donation. However, many women with POI desire to conceive with their own ova. Therefore, experimental biological therapies, such as Platelet-Rich Plasma (PRP), Exosomes (exos) therapy, In vitro Activation (IVA), Stem Cell therapy, MicroRNAs and Mitochondrial Targeting Therapies are experimental treatment strategies that focus on activating oogenesis and folliculogenesis, by upregulating natural biochemical pathways (neo-folliculogenesis) and improving ovarian microenvironment. This mini-review aims at identifying the main advantages of these approaches and exploring whether they can underpin existing assisted reproductive technologies.

Secondary diabetes mellitus in acromegaly.

Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly.

Secondary diabetes mellitus in pheochromocytomas and paragangliomas.

Secondary diabetes mellitus (DM) in secretory pheochromocytomas and paragangliomas (PPGLs) is encountered in up to 50% of cases, with its presentation ranging from mild, insulin resistant forms to profound insulin deficiency states, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state. PPGLs represent hypermetabolic states, in which adrenaline and noradrenaline induce insulin resistance in target tissues characterized by aerobic glycolysis, excessive lipolysis, altered adipokine expression, subclinical inflammation, as well as enhanced gluconeogenesis and glucogenolysis. These effects are mediated both directly, upon adrenergic receptor stimulation, and indirectly, via increased glucagon secretion. Impaired insulin secretion is the principal pathogenetic mechanism of secondary DM in this setting; yet, this is relevant for tumors with adrenergic phenotype, arising from direct inhibitory actions in beta pancreatic cells and incretin effect impairment. In contrast, insulin secretion might be enhanced in tumors with noradrenergic phenotype. This dimorphic effect might correspond to two distinct glycemic phenotypes, with predominant insulin resistance and insulin deficiency respectively. Secondary DM improves substantially post-surgery, with up to 80% remission rate. The fact that surgical treatment of PPGLs restores insulin sensitivity and secretion at greater extent compared to alpha and beta blockade, implies the existence of further, non-adrenergic mechanisms, possibly involving other hormonal co-secretion by these tumors. DM management in PPGLs is scarcely studied. The efficacy and safety of newer anti-diabetic medications, such as glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors (SGLT2is), as well as potential disease-modifying roles of metformin and SGLT2is warrant further investigation in future studies.

Patients with type 2 diabetes mellitus present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to healthy subjects: a prospective cohort study.

AIM: To compare the kinetics of neutralizing antibodies (NΑbs) against SARS-CoV-2 after vaccination with the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with T2DM and healthy controls. METHODS: NAb levels after the BNT162b2 mRNA vaccine were compared between 50 patients with non-insulin treated T2DM and 50 age-, gender-, and BMI-matched healthy controls up to 3 months after the second dose. The median age of both groups was 70 years. RESULTS: On day 1, mean NAbs of the control and T2DM groups were 14.64% (standard error, SE = 2.30) and 14.04% (SE = 2.14), respectively (p value = 0.926). Three weeks later, the mean NAb values were 39.98% (SE = 3.53) in the control group and 40.97% (SE = 3.99) in participants with T2DM (p value = 0.698). One month after the second vaccination, mean NAb values increased to 87.13% (SE = 2.94) in the control group and 89.00% (SE = 2.18) in the T2DM group. Three months after the second vaccine dose, the mean inhibitory titers decreased to 83.49% (SE = 3.82) (control group) and 76.36% (SE = 3.33) (T2DM group). On all occasions, no significant difference was found between the two groups (all p values > 0.05). CONCLUSIONS: Patients with T2DM present similar immunological response to COVID-19 BNT162b2 mRNA vaccine to that of healthy subjects.

Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Hellenic Endocrine Society.

PURPOSE: To investigate current practices of specialists in the use of thyroid hormone preparations in Greece as part of an ongoing international survey, namely THESIS-Treatment of Hypothyroidism in Europe by Specialists: an International Survey. METHODS: An electronic link leading to an anonymized questionnaire was sent to all (n = 837) members of the Hellenic Endocrine Society. RESULTS: In total, 501 respondents participated in the survey, though only part of the questionnaire was filled in by some participants. A total of 88.2% were endocrinologists and 57.9% worked in private practice. Levothyroxine (LT4) was the first-line choice (98.6%) for the treatment of hypothyroid patients. In total, 70.2% preferred LT4 soft-gel capsules for patients reporting intolerance to various foods. Soft-gel capsules were the preferred LT4 formulation for patients on generic LT4 and with unexplained poor biochemical control of hypothyroidism (66.3%) or inability to take LT4 fasted and separate from food/drink (68.3%). It was found that 48.4% would never use combined LT4 + LT3. However, 25% would use combination therapy for a short period in patients recovering from protracted hypothyroidism or in patients with normal serum TSH but persistent symptoms. Concerning euthyroid individuals, 31.9% considered treatment with thyroid hormones in infertile females with positive thyroid antibodies and 24.4% in patients with growing goiter. Selenium or iodine supplementation was used occasionally, mostly in patients with coexisting autoimmune thyroiditis. CONCLUSIONS: LT4 tablets are the treatment of choice for hypothyroidism in Greece. Several conditions may lead to various other practices, some of which deviate from current evidence-based guidelines and need more scrutiny.

Management of parathyroid disorders: recommendations of the working group of the Bone Section of the Hellenic Endocrine Society.

The Bone Section of the Hellenic Endocrine Society has issued the recommendations herein presented with the aim of providing guidance on optimal management of patients with parathyroid disorders in everyday clinical practice within the Greek health care setting. Although the methodology followed to formulate these recommendations was not strictly based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principles, they were drawn up after an extensive review of the literature and of the currently available guidelines for the management of parathyroid disorders worldwide. Specifically for primary hyperparathyroidism (PHPT), the 2011 guidelines of the Greek National Organization of Medicines were updated accordingly. In particular, definitions, etiologies, and recommended and optional laboratory and imaging examinations are provided both for PHPT and chronic hypoparathyroidism (HypoPT). Finally, treatment algorithms are provided for the management of both PHPT and HypoPT. Specifically for HypoPT, the treatment algorithm describes the recommended steps that should be followed to achieve optimal management of chronic hypocalcemia and the complications of HypoPT through the conventional treatment available in Greece and the use of recombinant human PTH(1-84).

Sudden 'cure' of type two diabetes due to pancreatic insulinoma: A case report.

Insulinomas are rare tumors of the islet cells of the pancreas and are the most common cause of endogenous hyperinsulinism. Although they usually present with symptoms of hypoglycemia, sometimes they can have vague symptoms. We present the case of a 62-year-old diabetic female who was diagnosed with a large insulinoma after being investigated for the 'cure' of her diabetes. We also review the literature regarding insulinomas in patients with diabetic. A 62-year-old, obese woman with type 2 diabetes mellitus was initially investigated for an unexplained normalization of her blood glucose levels after the cessation of antidiabetic medication due to an episode of severe hypoglycemia. She remained without antidiabetics for three months maintaining normoglycemia, and thereafter, she started experiencing frequent but less severe hypoglycemic episodes. She did not change her diet habits or level of activity and did not lose any weight. The patient underwent further investigation with a supervised 72 h fasting test, which resulted in the biochemical diagnosis of endogenous hyperinsulinism. Imaging studies revealed the presence of a large insulinoma in the head of the pancreas. Finally, the patient underwent a pylorus preserving Whipple procedure, which reversed the aforementioned 'normalization' of glucose levels and the underlying diabetes mellitus reappeared. Insulinomas are rare tumors causing hypoglycemia. Even more rarely are found in diabetic patients, making the diagnosis more challenging and probably delayed, as the symptoms are masked by the presence of diabetes, thereby leading to a more advanced disease diagnosis.

Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects 6-15% of women of reproductive age. Nonalcoholic fatty liver disease (NAFLD) affects 25-30% of the general population and its prevalence increases in parallel with the epidemics of obesity and type 2 diabetes mellitus. A growing body of evidence suggests that NAFLD and PCOS quite often co-exist. The aim of this article is to summarize and critically appraise the literature regarding: (1) the rates of co-existence of the two entities, (2) the possible pathophysiological links, (3) the proper diagnostic assessment and (4) the appropriate management of women with NAFLD and PCOS. Data from clinical studies and meta-analyses indicate a higher prevalence of NAFLD in women with PCOS ranging from 34% to 70% compared with 14% to 34% in healthy women. Inversely, women with NAFLD are more often diagnosed with PCOS. Insulin resistance (IR) and hyperandrogenism are two main potential pathophysiological links between the two entities. In this regard, IR seems to interplay with obesity and hyperandrogenism, thus affecting NAFLD and PCOS and being affected by them. Women with PCOS, particularly those with IR and/or hyperandrogenism, are suggested to be screened for NAFLD, while premenopausal women with NAFLD is suggested to be screened for PCOS. Lifestyle recommendations with a change in dietary habits, weight loss and exercise, constitute currently the cornerstone of the management of both NAFLD and PCOS. Insulin sensitizers maybe used for the treatment of these women, while there are limited promising data for the use of liraglutide.

The Effect of DPP-4i on Endothelial Function and Arterial Stiffness in Patients with Type 2 Diabetes: A Systematic Review of Randomized Placebo-controlled Trials.

We systematically reviewed the literature regarding the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on vascular function, including endothelial function and arterial stiffness, as predictors of atherosclerosis progression and cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). We searched PubMed in order to identify clinical trials that investigated the effect of DPP-4i on vascular function in patients with T2DM when compared with placebo. Although 168 articles were initially found, only 6 studies (total 324 patients) investigated the effect of DPP-4i in comparison with placebo, specifically linagliptin and sitagliptin, and satisfied the inclusion criteria. There are scarce data to indicate that linagliptin may enhance endothelial function and exert a slight beneficial effect on arterial wall properties. Sitagliptin seems to have a neutral effect on these variables. Further trials are needed to elucidate the topic. The standards of reporting were in accordance with the PRISMA guidelines.