Search

Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders.Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.

Purpose of Review In this review, we summarize current evidence on the association between antibiotics and the subsequent development of obesity through modulation of the gut microbiome. Particular emphasis is given on (i) animal and human studies and their limitations; (ii) the reservoir of antibiotics in animal feed, emerging antibiotic resistance, gut dysbiosis, and obesity; (iii) the role of infections, specifically viral infections, as a cause of obesity; and (iv) the potential therapeutic approaches other than antibiotics to modulate gut microbiome. Recent Findings Overall, the majority of animal studies and meta-analyses of human studies on the association between antibiotics and subsequent development of obesity are suggestive of a link between exposure to antibiotics, particularly early exposure in life, and the development of subsequent obesity as a result of alterations in the diversity of gut microbiota. The evidence is strong in animal models whereas evidence in humans is inconclusive requiring well-designed, long-term longitudinal studies to examine this association. Based on recent meta-analyses and epidemiologic studies in healthy children, factors, such as the administration of antibiotics during the first 6 months of life, repeated exposure to antibiotics for ≥ 3 courses, treatment with broad-spectrum antibiotics, and male gender have been associated with increased odds of overweight/obesity. Early antibiotic exposure in animal models has shown that reductions in the population size of specific microbiota, such as Lactobacillus, Allobaculum, Rikenellaceae, and Candidatus Arthromitus, are related to subsequent adiposity. These data suggest that the loss of diversity of the gut microbiome, especially early in life, may have potential long-term detrimental effects on the adult host gut microbiome and metabolic health. Genetic, environmental, and age-related factors influence the gut microbiome throughout the lifetime. More large-scale, longer-term, longitudinal studies are needed to determine whether changes that occur in the microbiome after exposure to antibiotics, particularly early exposure, are causal of subsequent weight gain or consequent of weight gain in humans. Summary Further well-designed, large-scale RCTs in humans are required to evaluate the effects of administration of antibiotics, particularly early administration, and the subsequent development of overweight/obesity. Therapeutic interventions, such as bacteriophage treatment or the use of probiotics, especially genetically engineered ones, need to be evaluated in terms of prevention and management of obesity.

We explored the association between circulating 25OHD and adherence to the Mediterranean Diet (MedDiet) in 402 Greek (21–65 years, 188 men and 214 women), normal weight, non-smoker, healthy volunteers in the Athens metropolitan area during summer and autumn, taking into account skin phototype, anthropometric, and lifestyle variables. Circulating 25OHD, parathormone, creatinine, calcium, and phosphate were determined. A vitamin D status of ≤25, ≤50, and ≤75 nmol/L was observed in 4.5, 37.3, and 74.1% of the subjects, respectively. The independent predictors of 25OHD deficiency were autumn, darker skin phototype, BMI, or waist circumference (WC), sunscreen use, less physical outdoor activity, and less adherence to the MedDiet. Higher intake of fish and olive oil was a positive independent predictor of elevated circulating 25OHD levels. In conclusion, higher adherence to the MedDiet, fish and olive oil consumption, were positively associated with circulating 25OHD independently from BMI or WC, skin phototype, season, and physical activity.

In this review, we summarize current evidence on gut microbiome and obesity; we discuss the role of probiotics, prebiotics, synbiotics, and postbiotics in obesity prevention and management; and we highlight and analyze main limitations, challenges, and controversies of their use. Overall, the majority of animal studies and meta-analyses of human studies examining the use of probiotics and synbiotics in obesity has shown their beneficial effects on weight reduction and other metabolic parameters via their involvement in gut microbiota modulation. Bifidobacterium and Lactobacillus strains are still the most widely used probiotics in functional foods and dietary supplements, but next generation probiotics, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, or Clostridia strains, have demonstrated promising results. On the contrary, meta-analyses of human studies on the use of prebiotics in obesity have yielded contradictory results. In animal studies, postbiotics, mainly short-chain fatty acids, may increase energy expenditure through induction of thermogenesis in brown adipose tissue as well as browning of the white adipose tissue. The main limitations of studies on biotics in obesity include the paucity of human studies; heterogeneity among the studied subgroups regarding age, gender, and lifestyle; and use of different agents with potential therapeutic effects in different formulations, doses, ratio and different pharmacodynamics/pharmacokinetics. In terms of safety, the supplementation with prebiotics, probiotics, and synbiotics has not been associated with serious adverse effects among immune-competent individuals, with the exception of the use of probiotics and synbiotics in immunocompromised patients. Further large-scale Randomized Controlled Trials (RCTs) in humans are required to evaluate the beneficial properties of probiotics, prebiotics, synbiotics, and postbiotics; their ideal dose; the duration of supplementation; and the durability of their beneficial effects as well as their safety profile in the prevention and management of obesity.

BACKGROUND AND AIMS Diabetes mellitus (DM) is tightly associated with the increased prevalence and rapid evolution of diabetic nephropathy (DN). Interestingly, deterioration of kidney function in diabetic patients is often nonetheless caused by other factors besides DM and frequently goes undiagnosed. Nondiabetic renal disease (non-DRD) could be suspected in case of rapid progression of renal function impairment and/or severe, nephrotic-range proteinuria. While biopsy of the kidneys is the ‘gold standard’ of the diagnostic approach in such cases, no real consensus exists regarding the profile of diabetic patients with renal disease and proteinuria, who should be submitted to kidney biopsy. Thus, this study intends to correlate the clinical and biochemical profile of diabetic patients with deteriorated kidney function to the histopathological data of a kidney biopsy and allows early differentiation between DN and non-DRD based on the results of kidney biopsy. METHOD A total of 32 patients, who were treated in our outpatient's diabetes clinic from a multidisciplinary team of endocrinologists and nephrologists at Evangelismos General Hospital, were retrospectively studied. All patients suffered from DM2 and presented with nephrotic-range levels of proteinuria. Biochemical data of glycemic control and renal function, clinical findings related to DN and histological findings of kidney biopsy were documented. All patients were submitted to kidney biopsy and depending on the histopathologic findings were categorized into three groups: (i) genuine diabetic nephropathy (GDN), (ii) renal disease due to cause other than diabetes mellitus (ODMRD) and (iii) mixed renal disease (MRD). RESULTS Among the 32 patients, 15 (46.9%) had findings of a GDN, while 17 patients (53.1%) suffered from ODMRD (13 patients) or MRD (4 patients). All patients were hypertensive. The patients with GDN were younger (54.1 versus 68.2 versus 70.5 years, P = 0.016) and had a higher HbA1C value (7.9 versus 6.5 versus 6.8%, P = 0.069) at the time of the kidney biopsy in comparison to the ODMRD and MRD patients. On the contrary, ODMRD patients had significantly smaller disease duration compared with the GDN and MRD groups (8.4 versus 11.6 versus 13.3 years, P = 0.04). Furthermore, the incidence of diabetic retinopathy was greater among patients with GDN and MRD in comparison to the ODMRD patients (60 versus 75 versus 7.6%, P 25%) of interstitial renal fibrosis [OR 5.71 (95% CI 1.16–28.1), P = 0.032] and longer DM2 duration (>10 years) [OR 5.04, (95% CI 1.1–22.96), P = 0.036] were recognized as factors, which were positively associated with GDN. CONCLUSIONS This study highlights emphatically the usefulness of the kidney biopsy and its histopathological findings in case of patients with diabetes mellitus and nephrotic-range levels of proteinuria. The value of a detailed and careful medical history seems to be critical for the early diagnosis of the type of kidney disease in diabetic patients. It is crucial to early differentiate the patients who suffer from nondiabetic nephropathy, from those with diabetic nephropathy and initiate the appropriate therapy, according to the underlying cause. Thus, the detection of nephrotic-range levels of proteinuria in diabetic patients should lead to kidney biopsy especially in case diabetic retinopathy is not present and longer disease duration is observed. Finally, the existing criteria/indications for a kidney biopsy in diabetic patients with nephrotic-range levels of proteinuria should be reconsidered or even revised.

Omentin-1, a newly discovered adipokine, is implicated in the modulation of the adipose phenotype, ameliorating systemic metabolism and exhibiting anti-atherogenic, anti-oxidative, cardioprotective, anti-inflammatory and insulin-sensitizing properties. Our goal was to explore circulating omentin-1 in subclinical hypothyroidism (SH) and determine its correlations with cardiometabolic risk factors.In a large case-control and interventional longitudinal study, serum omentin-1, metabolic and lipid parameters, inflammatory biomarkers, classic adipocytokines and cardiovascular risk factors were assessed in 120 consecutive patients with SH and 120 healthy controls matched on age, gender and date of blood draw. Sixteen patients with SH were administered L-T4 and, after six months, circulating omentin-1 and other biomarkers were determined.SH subjects presented significantly decreased circulating omentin-1 than control individuals (P0.001). In all study participants, omentin-1 was negatively correlated with TSH, anti-thyroid antibodies, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, adipokines and cardiovascular risk factors, including Framingham score and apolipoprotein B. Omentin-1 was positively associated with adiponectin and HDL-C. Circulating omentin-1 was independently associated with SH occurrence, above and beyond clinical and cardiometabolic factors (P=0.04). TSH was a negative independent predictor of serum omentin-1 levels (P0.001). L-T4 treatment did not alter considerably the lower omentin-1 levels in treated SH patients (P=0.07).Omentin-1 may be a useful non-invasive biomarker reflecting cardiometabolic risk as well as a promising therapeutic target. More mechanistic and larger prospective studies shedding light on the pathogenetic role of omentin-1 in SH are required to confirm these findings.

Εισαγωγή: Η ιρισίνη αποτελεί μία σχετικά πρόσφατα ανακαλυφθείσα λιπομυοκίνη που εκφράζεται κυρίως στον μυϊκό και στον λιπώδη ιστό. Αναπτύσσει πολύτροπη ενδοκρινική δράση εμπλεκόμενη σε σημαντικές μεταβολικές οδούς που κατευθύνουν τον οργανισμό στην απόκτηση ενός πιο ισορροπημένου μεταβολικού φαινοτύπου. Η ομεντίνη-1 είναι επίσης μία πρόσφατα ανακαλυφθείσα λιποκίνη με ενδοκρινική δράση, που εκφράζεται κυρίως στον σπλαγχνικό λιπώδη ιστό. Παρατηρήθηκε ότι ελαττώνεται σε δυσμεταβολικές καταστάσεις διαδραματίζοντας ενδεχομένως σημαντικό ρόλο στην παθογένεια της αγγειακής αθηρωμάτωσης ως αντιφλεγμονώδης λιποκίνη.Σκοπός: Ο σκοπός της παρούσας διδακτορικής διατριβής ήταν η διερεύνηση των κυκλοφορούντων προαναφερόμενων νεότερων λιποκινών, της ιρισίνης (λιπομυοκίνη) και της ομεντίνης-1, στον υποκλινικό υποθυρεοειδισμό και η μελέτη των πιθανών συσχετίσεών τους με γνωστούς παράγοντες καρδιομεταβολικού κινδύνου.Υλικό και μέθοδοι: Στο πλαίσιο μιας αναδρομικής συγκριτικής μελέτης τύπου ασθενών-μαρτύρων μελετήθηκαν 120 ασθενείς (48 άνδρες και 72 γυναίκες) με υποκλινικό υποθυρεοειδισμό και 120 υγιείς μάρτυρες εξομοιωμένοι ως προς το φύλο, την ηλικία (± 5 χρόνια) και τον μήνα διάγνωσης (± 1 μήνας). Έγινε πλήρης καταγραφή των κλινικών και εργαστηριακών δεδομένων των συμμετεχόντων και προσδιορίστηκαν με ανοσοενζυμικές τεχνικές οι κλασικές λιποκίνες λεπτίνη και αδιπονεκτίνη. Επίσης, προσδιορίστηκαν με ανοσοενζυμικές τεχνικές η κυκλοφορούσα ιρισίνη (ELISA, EK-067-29, Phoenix Pharmaceuticals, Burlingame, USA) και η κυκλοφορούσα ομεντίνη-1 (ELISA, RD191100200R, BioVendor, Brno, Τσεχία). Σε 16 ασθενείς χορηγήθηκε θεραπεία με L-T4 επί εξάμηνο και ακολούθησε κλινικοεργαστηριακή επανεκτίμησή τους. Η στατιστική επεξεργασία των αποτελεσμάτων πραγματοποιήθηκε με το πρόγραμμα IBM-SPSS®v.24.Αποτελέσματα: Οι ασθενείς εμφάνισαν σημαντικά υψηλότερες συγκεντρώσεις ιρισίνης και χαμηλότερες συγκεντρώσεις ομεντίνης -1 συγκριτικά με τους υγιείς μάρτυρες (p

BACKGROUND Leptin, the prototype adipokine, exerts immunomodulatory actions being implicated in inflammatory responses during sepsis. Clinical evidence regarding its role in sepsis has been contradictory, while free leptin has not been studied. The aim of this study was to jointly investigate circulating total leptin, its soluble receptor (sOB-R), and free leptin, as well as their kinetics in critically ill patients with sepsis regarding their diagnostic and prognostic value. METHODS In a prospective study, serum total leptin, sOB-R and free leptin index (FLI) were determined in 102 critically ill patients with sepsis within 48 hours from sepsis onset and one week after enrollment, and in 102 age and gender-matched healthy controls. RESULTS Upon enrolment, total leptin, sOB-R and FLI were significantly higher in septic patients compared to controls and they were positively correlated with sepsis severity scores, while they presented a significant decrease during the first week (P

Type 1 Diabetes Mellitus (T1DM) is characterized by progressive autoimmune-mediated destruction of the pancreatic beta-cells leading to insulin deficiency and hyperglycemia. It is associated with significant treatment burden and necessitates life-long insulin therapy. The role of immunotherapy in the prevention and management of T1DM is an evolving area of interest which has the potential to alter the natural history of this disease.In this review, we give insight into recent clinical trials related to the use of immunotherapeutic approaches for T1DM, such as proinflammatory cytokine inhibition, cell-depletion and cell-therapy approaches, autoantigen-specific treatments and stem cell therapies. We highlight the timing of intervention, aspects of therapy including adverse effects and the emergence of a novel lymphocyte crucial in T1DM autoimmunity. We also discuss the role of cardiac autoimmunity and its link to excess CVD risk in T1DM.We conclude that significant advances have been made in development of immunotherapeutic targets and agents for the treatment and prevention of T1DM. These immune-based therapies promise preservation of beta-cells and decreasing insulin dependency. In their current state, immunotherapeutic approaches cannot yet halt the progression from a preclinical state to overt T1DM nor can they replace standard insulin therapy in existing T1DM. It remains to be seen whether immunotherapy will ultimately play a key role in the prevention of progression to overt T1DM and whether it may find a place in our therapeutic armamentarium to improve clinical outcomes and quality of life in established T1DM.

Worldwide, diabetes mellitus (DM) represents a major public-health problem due to its increasing prevalence in tandem with the rising trend of obesity. However, climate change, with its associated negative health effects, also constitutes a worrisome problem. Patients with DM are experiencing more visits to emergency departments, hospitalizations, morbidity and mortality during heat waves at ever-increasing numbers. Such patients are particularly vulnerable to heat waves due to impaired thermoregulatory mechanisms in conjunction with impaired autonomous nervous system responses at high temperatures, electrolyte imbalances and rapid deterioration of kidney function, particularly among those aged > 80 years and with preexisting chronic kidney disease (CKD). Moreover, exposure to cold temperatures is associated with increased rates of acute myocardial infarction as well as poor glycaemic control, although results are conflicting regarding cold-related mortality among patients with DM. In addition to extremes of temperature, air pollution as a consequence of the climate crisis may also be implicated in the increased prevalence and incidence of DM, particularly gestational DM (GDM), and lead to deleterious effects in patients with DM. Thus, more large-scale studies are now required to elucidate the association between specific air pollutants and risk of DM. This review presents the currently available evidence for the detrimental effects of climate change, particularly those related to weather variables, on patients with DM (both type 1 and type 2) and GDM. Specifically, the effects of heat waves and extreme cold, and pharmaceutical and therapeutic issues and their implications, as well as the impact of air pollution on the risk for DM are synthesized and discussed here.

Patients admitted to the ICU present life-threatening conditions requiring support from multidisciplinary specialists and continuous monitoring of vital signs and other parameters by a state-of-the-art medical technology. Wireless monitoring through wearable devices could be useful for hospitalized patients, particularly those who are unstable or at higher risk for serious complications such as critically ill patients. This review aims at summarizing current evidence regarding the use of wireless monitoring in the ICU setting. Relevant studies address some practical issues regarding wireless vital signs monitoring, detection of emergencies and delirium and pressure ulcer prevention. In general, wearable devices may offer multiple applications in the ICU setting. However, there are important limitations in their applicability related to high clinical requirements and patient, staff and environment related factors. Given the fast evolving field of wireless technology, more healthcare applications regarding the ICU are anticipated in the near future.

Invasive blood pressure (IBP) is the gold standard method for BP monitoring in critically ill patients. However, due to practical difficulties and complications, noninvasive methods may offer an alternative. We aim to evaluate an automatic oscillometry-based wrist BP monitor in critically ill patients compared to IBP. Forty five adult patients were included, and systolic, diastolic and mean BP (SBP, DBP, MBP) were simultaneously measured by IBP in the radial artery and by non-invasive blood pressure (NIBP) monitoring using the OMRON RS7 automatic wrist monitor. NIBP and IBP (mean ± SD) were: SBP 114 ± 18 vs 130 ± 18; DBP 63 ± 13 vs 63 ± 13; MBP 80 ± 13 vs 86 ± 15 mmHg. Bland-Altman analysis of the differences (NIBP-IBP) mean bias was: SBP -16; DPB 0.5 and MBP -6. The OMRON wrist monitor may not be sufficiently accurate compared to IBP in critically ill patients.

The aim of our study is to propose a remote patient monitoring solution through a smart phone application (Smart Patient) collecting health data to support diagnosis, monitoring and predicting poor outcome in asymptomatic/mild cases of COVID-19, including signs and symptoms, risk factors, comorbidities, medications and vital signs such as body temperature, respiratory rate, heart rate and oxygen saturation. By continuous daily recording of suspected cases and patients, family doctors in the community will be able to follow up cases and intervene promptly when deterioration in vital signs and symptoms takes place referring the patient to the hospital.

Alterations in the diversity or structure of gut microbiota known as dysbiosis, may affect metabolic activities, resulting in metabolic disorders, such as obesity and diabetes. The development of more sophisticated methods, such as metagenomics sequencing, PCR-denaturing gradient gel electrophoresis, microarrays and fluorescence in situ hybridization, has expanded our knowledge on gut microbiome. Dysbiosis has been related to increased plasma concentrations of gut microbiota-derived lipopolysaccharide (LPS), which triggers the production of a variety of cytokines and the recruitment of inflammatory cells. Metabolomics have demonstrated that butyrate and propionate suppress weight gain in mice with high fat diet-induced obesity, and acetate has been proven to reduce food intake in healthy mice. The role of prebiotics, probiotics, genetically modified bacteria and fecal microbiota transplantation, as potential therapeutic challenges for type 2 diabetes will be discussed in this review.

Gestational Diabetes Mellitus (GDM) has been associated with a plethora of maternal and neonatal comorbidities as well as adverse pregnancy outcomes. Evidence supports that identifying women with GDM and tight controlling of blood glucose (BG) levels are the fundamental steps for an effective management and prevention of risks associated with GDM. Recent advances in mobile phone applications have shown that they may offer personalized health care services, improve patient's care, independence and self-management as well as enhance patient's compliance to BG monitoring and treatment. Our aim was to identify and appraise main mobile phone applications that were evaluated by published clinical studies. Therefore, mobile applications that were accepted and deployed by healthcare providers, mainly hospitals, such as MobiGuide (Spain), Pregnant+ (Norway) and GDm-Health (UK) were reviewed herein.

In this review, we summarize current evidence on the gut microbiome and microbial metabolites in relation to obesity and obesity-associated metabolic disorders. Special emphasis is given on mechanisms interconnecting gut microbiome and microbial metabolites with metabolic disorders as well as on potential preventive and therapeutic perspectives with a “bench to bedside” approach. Recent data have highlighted the role of gut dysbiosis in the etiology and pathogenesis of metabolic disorders, including obesity, metabolic syndrome, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Overall, most studies have demonstrated a reduction in gut microbiome diversity and richness in obese subjects, but there is still much debate on the exact microbial signature of a healthy or an obese gut microbiome. Despite the controversial role of an altered gut microbiome as a cause or consequence of obesity in human studies, numerous animal studies and certain human studies suggest beneficial metabolic effects of certain microbial intestinal metabolites, such as butyrate, that could be used in the prevention and treatment of obesity and its comorbidities. More randomized controlled trials and larger prospective studies including well-defined cohorts as well as a multi-omics approach are warranted to better identify the associations between the gut microbiome, microbial metabolites, and obesity and its metabolic complications.

Background The purpose of the present study was to determine whether patients with DM1 have shown improvement, stabilization or deterioration of their urine albumin excretion levels during a close follow-up. Patients and Methods A cohort of 84 patients, 18–76 years of age, a median duration of diabetes of 24 years (1–50 years) and a median follow-up duration of 12 years (1–37 years) were included in the study. Results Among the 84 patients for whom we had UAE levels at the beginning and by the end of the study, mean glycosylated hemoglobin was statistically significantly decreased during the follow-up period, from 8.02±2.04–7.06±1.05% (p=0.036). Normoalbuminuria was present in 66 patients and remained so in 56 patients while 9 patients progressed to microalbuminuria and one patient to macroalbuminuria by the end of the study. Microalbuminuria was present in 15 patients: regression was observed in 8 patients, and progression in one patient. Regression of macroalbuminuria to microalbuminuria was noted in one patient and to normoalbuminuria was noted in one participant, too. Conclusions Improvement of glycemic control with close monitoring of DM1 patients together with the appropriate use ACE or AT2 inhibitors and statins, seems to exert nephron-protective potential and to delay or even reverse the presence of micro/macroalbuminuria. This long term follow-up study has demonstrated a statistically significant increase in serum HDLcholesterol levels. The study also revealed that intensively treated diabetes patients may show reductions in serum ALP levels. Whether this finding is related to diabetic nephropathy, NAFLD, or diabetic hepatosclerosis remains to be assessed in future trials.

Background Diabetic ketoacidosis (DKA) has been related mainly to type 1 diabetes mellitus (T1DM). However, it is not solely related to T1DM. The purpose of this study was to assess the prevalence of DKA among type 1 and type 2 patients with diabetes mellitus, who were hospitalized in our Clinic due to DKA, as well as to determine the etiology beyond DKA. Patients and methods A cohort of 109 patients with DKA, 17–86 years of age, who were hospitalized in the Department of Endocrinology, Diabetes and Metabolism of our hospital between 2015 and 2017, were included in the study. Results Among the 109 patients, 50 (45.9%) had mild DKA, 48 (44.1%) had moderate DKA, whereas 11 patients (10%) had severe DKA. Sixty-five patients (60%) developed DKA as the first manifestation of T1DM, 30 patients (27%) developed DKA in the context of type 2 diabetes (T2DM), mainly due to the co-existence of serious infections, 11 patients (10%) had T1DM, but had omitted their insulin dosages, and 3 patients (3%) developed DKA due to unknown reasons. Conclusions Most patients with DKA presented with mild and moderate DKA and only a minority presented with the severe form of the disease. The etiology of DKA was mainly T1DM and less frequent uncontrolled T2DM, usually due to the co-existence of severe infections, while only in a tiny minority, the causes remained unidentifiable.

Background Subclinical hypothyroidism (SH) is more frequent in females than males, with a female to male ratio ranging from 1.5 to 5 in the general population. The aim of this study was to evaluate for the first time the association of reproductive factors, particularly age at menarche, with SH risk. Materials and methods In a cross-sectional study, reproductive factors such as age at menarche, at menopause and at first birth, lactation, parity, full-term pregnancies, reproductive years, use of oral contraceptives and hormonal replacement therapy, somatometric data and insulin resistance parameters were recorded in 72 consecutive female patients with SH and 72 healthy female controls matched on age (±5 years) and date of diagnosis (±1 month). Results SH cases exhibited significantly younger age at menarche than controls (12.6 ± 1.2 vs. 13.3 ± 0.8 years, respectively, p < 0.001). Cases presented later age at first pregnancy with a lower number of full-term pregnancies (p = 0.04). Early age at menarche was independently associated with SH risk, above and beyond thyroid autoimmunity, body mass index (BMI), hip circumference (HC), homeostatic model assessment of insulin resistance and alcohol consumption [odds ratio (OR): 0.22, 95% confidence interval (CI): 0.11–0.44; p < 0.001]. Conclusions It is possible that an interplay of early exposure to estrogens, as expressed by early menarche, and induction of thyroid autoimmunity may be associated with SH risk. More prospective studies shedding light on the role of estrogens in SH are required to confirm these findings.

The ratio of human to bacterial cells in the human body (microbiota) is around 1:1. As a result of co-evolution of the host mucosal immune system and the microbiota, both have developed multiple mechanisms to maintain homeostasis. However, dissociations between the composition of the gut microbiota and the human host may play a crucial role in the development of type 2 diabetes. Metformin, the most frequently administered medication to treat patients with type 2 diabetes, has only recently been suggested to alter gut microbiota composition through the increase in mucin-degrading Akkermansia muciniphila, as well as several SCFA-producing (short-chain fatty acid) microbiota. The gut microbiota of participants on metformin has exerted alterations in gut metabolomics with increased ability to produce butyrate and propionate, substances involved in glucose homeostasis. Thus, metformin appears to affect the microbiome, and an individual's metformin tolerance or intolerance may be influenced by their microbiome. In this review, we will focus on the effects of metformin in gut microbiota among patients with T2DM.

Background The purpose of this study was to evaluate the outcome of DM2 patients with nephropathy when they are under surveillance of a joined clinic run by endocrinologists & nephrologists. Patients and methods A cohort of 106 patients with DM2, 42–83 years of age, and eGFR Results Fifty percent of patients had no further progression, 25.9% improvement, while 24.1% had worsening of the UAE levels. During the follow-up in the joined clinic, there was a smaller than the expected from the medical literature decrease in median eGFR, i.e. 2,3 ml/min/m2 and a statistically significant improvement in glycosylated hemoglobin levels from 8.0% to 7.4% (p = 0.016). Time in years of follow-up in the joined clinic of our hospital appeared to be the most significant factor in the improvement or stabilization against deterioration of the UAE levels (p = 0.018). Conclusions Close follow-up of DM2 patients with eGFR

Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors. In a large case–control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed. SH cases exhibited significantly higher circulating irisin than controls (p

Objective To investigate the efficacy of medical treatment as an alternative option to bilateral adrenalectomy in patients with cortisol excess due to adrenocorticotropic hormone (ACTH) independent macronodular adrenal hyperplasia (AIMAH). Methods We focused on the efficacy of somatostatin analogues in a patient with food-dependent AIMAH and of leuprolide acetate in a patient with AIMAH due to aberrant LH/hCG receptor expression. Results Two female patients with bilateral macronodular adrenal hyperplasia and cortisol excess were evaluated for the presence of aberrant cortisol responses. One patient demonstrated an aberrant response to mixed meal and the other, a menopausal female, to luteinizing hormonereleasing hormone (LHRH) and human chorionic gonadotropin (hCG) administration. In the first patient, subcutaneous octreotide was administered prior to mixed meal and completely abolished food-induced cortisol secretion. Thus, the patient was treated with the long-acting somatostatin analogue octreotide long-acting release (LAR) for 3 months. There was no control of cortisol excess upon reevaluation and acute subcutaneous octreotide administration prior to meal was no longer effective in blocking food-induced cortisol secretion. The second patient successfully responded to leuprolide acetate and, for 40 months, her cortisol excess remains in long-term control. Conclusion A luteinizing hormone/human chorionic gonadotropin (LH/hCG) responsive patient with AIMAH sustained long-term control of cortisol excess on leuprolide acetate. In contrast, in a meal-responsive patient with apparent gastric inhibitory polypeptide (GIP) dependent AIMAH, did not achieve remission under somatostatin analogues. (Endocr Pract. 2013;19:e77-e82)

Aberrant receptors have been implicated in the pathogenesis of several types of adrenal tumours. So far the presence of aberrant receptors has been investigated in patients with massively enlarged adrenals due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) and unilateral adrenal adenomas associated with overt or subclinical Cushing’s syndrome. The likelihood of aberrant responses in patients presenting with bilateral adrenal incidentalomas (BI) presenting as discrete solitary bilateral adenomas has not been thoroughly addressed. This is an observational cross-sectional prospective study conducted in a secondary/tertiary care centre. We studied 33 patients; 28 with incidentally discovered bilateral discrete adrenal adenomas and five with massive bilateral adrenal macronodular hyperplasia. We probed responses to physiological stimuli, namely upright posture and meal; in a subgroup of menopausal women the presence of aberrant gonadotropin receptors was assessed by the LHRH test. Abnormal responses obtained in tests performed with no dexamethasone suppression were always repeated and confirmed under dexamethasone suppression. Aberrant cortisol responses were confirmed in 10 patients; 9 to posture, 1 to meal (along with a positive response to posture) and 1 to LHRH tests. Patients who responded to any test compared to those who tested negative had larger adenomas, higher post-LDDST and midnight cortisol and a trend for lower ACTH levels. Patients without subclinical hypercortisolism (SH) did not respond to any test while 50% of patients with SH had an aberrant response (P = 0.002). A greater prevalence of aberrant responses was noted in patients with bilateral macronodular hyperplasia compared to those with solitary bilateral adenomas (80 vs. 21.4%, P = 0.02). Aberrant cortisol responses, primarily to posture testing, are present in a substantial proportion of patients with bilateral adrenal incidentalomas. Such cortisol responses are observed only in patients with subclinical hypercortisolism and especially in those patients with larger adrenal lesions.

Brain natriuretic peptide (BNP) correlates well with left ventricular wall hypertrophy and the severity of left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to investigate the correlation of BNP levels with clinical status and left ventricular function in HCM patients.In 32 patients with HCM (age 58 +/- 14 years) we evaluated: (a) the severity of dyspnea and angina; (b) BNP plasma levels; (c) left ventricular wall thickness, sphericity index and mitral regurgitation; (d) LVOT obstruction; (e) ejection fraction; (f) left ventricular diastolic function, global and regional, by tissue Doppler imaging.BNP plasma levels correlated positively with dyspnea (r = 0.460, p0.001), angina (r = 0.460, p = 0.008), mitral regurgitation (r = 0.600, p0.001), thickness of interventricular septum (r = 0.526, p = 0.002), and LVOT obstruction (r = 0.551, p = 0.001 and r = 0.603, p0.001 for latent obstruction), while they were negatively correlated with left ventricular sphericity index (r = -0.368, p = 0.038). BNP plasma levels were strongly correlated with E/Vp and E/Eal (Vp: flow propagation velocity, Eal: E on the lateral side of the mitral annulus), representing the left ventricular filling pressures, and with some other parameters of regional diastolic function: Ams (A at the mid-segment of the interventricular septum) r = -0.518, p = 0.002; Aas (A on the septal side of the mitral annulus) r = -0.454, p = 0.009; Aal (A on the lateral side of the mitral annulus) r = -0.467, p = 0.007. From multiple regression analysis, angina and the ratio E/Eal were the strongest predictors of BNP plasma levels.BNP plasma levels in HCM patients can be used as an adjunctive objective method of evaluating cardiac dysfunction through their correlation with angina and left ventricular filling pressures.