Severe Hemophilia A and Moyamoya Syndrome in a 19-Year-Old Boy Caused by Xq28 Microdeletion.

Severe hemophilia A and moyamoya (SHAM) syndrome is a rare condition that combines hemophilia A and moyamoya disease (MMD) due to an Xq28 microdeletion encompassing the F8 and BRCC3 genes. Here, we report the case of a 19-year-old male patient with hemophilia A and hypogonadism that presented with right-sided hemiparesis and dysarthria. Brain magnetic resonance imaging and angiography revealed an ischemic lesion in the left lobe and stenosis of both middle cerebral arteries with a concomitant thick vascular network, compatible with moyamoya disease. Next-generation sequence revealed a large Xq28 deletion compatible with SHAM syndrome. The patient was treated with acetylsalicylic acid and neurosurgical intervention was scheduled. Our patient is one of the few cases reported in the literature with Xq28 microdeletion encompassing the F8, hemophilia A causative gene, and BRCC3, responsible for MMD, presenting with a compound phenotype that included neurological manifestations and hypogonadism. In conclusion, diagnosis of MMD should be considered in any male, young patient with symptoms of ischemic stroke with no obvious explanation, and especially in patients with known hemophilia, since a relationship between the two conditions has been documented.

Diabetes mellitus and multiple myeloma; common features of two distinct entities.

Diabetes mellitus (DM) has attained the status of a global pandemic. Cardiovascular disease (CV) was the leading cause of morbidity in people with type 2 DM, however, a transition from CV to cancer as the leading contributor to DM related death has been observed lately. Multiple myeloma (MM) is the second most common haematological malignancy. Obesity is a common risk factor for both DM and MM. Although data are limited, studies have shown that DM might be associated with increased risk for the development of MM. The presence of DM might affect the course of patients with MM, since hyperglycemia may have an impact on both the efficacy and the adverse effects of antimyeloma therapy. In parallel, DM and MM share common clinical presentations, such as nephropathy, neuropathy, and CV. In terms of antidiabetic medications, metformin might present a synergistic effect with antimyeloma drugs and also prevent some of the adverse effects of these drugs; pioglitazone might have favourable effects when given as add on treatment in people with relapsed or refractory MM. No clinically important interactions have been observed between antidiabetic agents and the most commonly used antimyeloma drugs. Further data are needed to examine the effect of all classes of antidiabetic medication on MM and its complications. A baseline assessment of risk factors for glucose intolerance and close monitoring of glucose levels during therapy is strongly suggested for patients with MM.

The Role of Diabetes and Hyperglycemia on COVID-19 Infection Course-A Narrative Review.

It was previously reported that subjects with diabetes mellitus (DM) are more vulnerable to several bacterial or viral infections. In the era of coronavirus disease 2019 (COVID-19) pandemic, it is reasonable to wonder whether DM is a risk factor for COVID-19 infection, too. It is not yet clear whether DM increases the risk for contracting COVID-19 infection or not. However, patients with DM when infected are more likely to develop severe or even fatal COVID-19 disease course than patients without DM. Certain characteristics of DM patients may also deteriorate prognosis. On the other hand, hyperglycemia per se is related to unfavorable outcomes, and the risk may be higher for COVID-19 subjects without pre-existing DM. In addition, individuals with DM may experience prolonged symptoms, need readmission, or develop complications such as mucormycosis long after recovery from COVID-19; close follow-up is hence necessary in some selected cases. We here present a narrative review of the literature in order to set light into the relationship between COVID-19 infection and DM/hyperglycemia.

The Role of Mitochondrial Adaptation and Metabolic Flexibility in the Pathophysiology of Obesity and Insulin Resistance: an Updated Overview.

PURPOSE OF REVIEW: The term "metabolic flexibility" denotes the dynamic responses of the cellular oxidative machinery in order to adapt to changes in energy substrate availability. A progressive loss of this adaptive capacity has been implicated in the development of obesity-related comorbidities. Mitochondria are dynamic intracellular organelles which play a fundamental role in energy metabolism, and the mitochondrial adaptation to environmental challenges may be viewed as the functional component of metabolic flexibility. Herein, we attempt to comprehensively review the available evidence regarding the role of mitochondrial adaptation and metabolic flexibility in the pathogenesis of obesity and related morbidities, namely insulin resistance states and non-alcoholic fatty liver disease (NAFLD). RECENT FINDINGS: Overall, there is a concrete body of evidence to support the presence of impaired mitochondrial adaptation as a principal component of systemic metabolic inflexibility in conditions related to obesity. There are still many unresolved questions regarding the relationship between the gradual loss of mitochondrial adaptability and the progression of obesity-related complications, such as causality issues, the timely appearance and reversibility of the described disturbances, and the generalizability of the findings to the mitochondrial content of every affected tissue or organ. The evidence regarding the causality between the observed associations remains inconclusive, although most of the available data points towards a bidirectional, potentially mutually amplifying relationship. The spectrum of NAFLD is of particular interest, since functional and pathological changes in the course of its development closely mirror the progression of dysmetabolism, if not constituting a dynamic component of the latter.

Comparison of Postprandial Serum Triglyceride and Apolipoprotein B Concentrations between the Two Phases of Menstrual Cycle in Healthy Women.

BACKGROUND: Sex hormones influence lipoprotein metabolism; whether the hormonal fluctuation during normal menstrual cycle has impact on non-fasting lipids remains unclear. OBJECTIVE: To examine the differences in postprandial triglyceride, apolipoprotein B (ApoB) and nonhigh density lipoprotein cholesterol (non-HDL-C) concentrations using a standardized fat tolerance test during the 2 menstrual cycle phases. METHODS: We enrolled 25 healthy, menstruating women. Each of them underwent a fat tolerance test during the 2 phases of the menstrual cycle. Blood samples were collected at baseline and up to 6 h postprandially. Differences in serum triglycerides, ApoB and non-HDL-C between the 2 phases were assessed. The incremental area under the curve (iAUC) was calculated. Reproducibility of the measurements was tested using the intraclass correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: Serum triglyceride concentrations increased postprandially in both phases and the values were higher during the follicular compared with the luteal phase; however, the overall triglyceride response expressed as iAUC [median value (interquartile range)] did not differ between the follicular and the luteal phase [54.0 (-26.5, 107.0) and 48.0 (6.0, 114.5) mg x h/dl, respectively, p=0.64]. Serum ApoB concentrations did not increase postprandially and the overall ApoB response was not different between the 2 phases. Non-HDL-C concentrations changed postprandially, but the overall response was not different between the 2 phases of the menstrual cycle. Reproducibility of the measurements was moderate: ICC 0.689-0.848 for triglycerides, 0.721-0.771 for ApoB, 0.457-0.867 for non-HDL-C, and %CV >8 for all parameters. CONCLUSION: Serum triglyceride levels were higher during the follicular compared with the luteal phase after standardized meal consumption, but the overall postprandial triglyceride response did not differ between the 2 phases. Postprandial ApoB and non-HDL-C serum concentrations were not affected by the menstrual cycle.

Adoption of and adherence to the Hellenic Diabetes Association guidelines for the management of subjects with type 2 diabetes mellitus by Greek physicians.

PURPOSE: The aim of this study was to evaluate the level of adoption of and adherence to the Hellenic Diabetes Association (HDA) guidelines for the management of individuals with type 2 diabetes mellitus (T2DM) by Greek physicians. METHODS: We used a constructed questionnaire distributed to physicians in Greece. The questionnaire assessed the adoption of and adherence to the general and treatment guidelines of the HDA, as well as factors affecting physicians' prescribing habits and demographic characteristics of the participating healthcare professionals. Factors affecting the preferred therapy or glycated hemoglobin target setting were evaluated using non-parametric tests. The likelihood of adherence was estimated by logistic regression models. RESULTS: Adoption of the HDA guidelines was reported by 92.2% of physicians. Adherence to the treatment algorithm was reported by 53.5% and to the general HDA guidelines by 42.0% of healthcare professionals; overall adherence to both general and treatment guidelines was 26.1%. Multivariate analysis demonstrated that the likelihood of adherence to treatment guidelines was higher among individuals attending over five in comparison with those attending under two diabetes seminars per year (p = 0.037); in contrast, years of work (professional experience ≥ 21 vs. ≤ 5 years) affected adherence negatively (p = 0.031). No significant association was found between other parameters and adherence to either general or overall guidelines. CONCLUSIONS: Adoption rates of the guidelines for the management of T2DM were high, while adherence rates to general and treatment guidelines were low. The rate of seminar attendance affected treatment adherence positively, while long professional practice affected treatment adherence negatively.

Eligibility and Awareness Regarding Metabolic Surgery in Patients With Type 2 Diabetes Mellitus in the Real-World Clinical Setting; Estimate of Possible Diabetes Remission.

Despite high-quality evidence highlighting metabolic surgery as an effective treatment option for type 2 diabetes mellitus (T2DM), the number of patients receiving bariatric surgery (BS) remains low. Since the introduction of the Diabetes Surgery Summit II (DSS-II) eligibility criteria, data on eligibility rates for BS in T2DM cohorts remain scarce. The aims of the present study were to examine in a real-world clinical setting: (i) what is the percentage of T2DM patients visiting diabetes outpatient clinics who meet the DSS-II eligibility criteria, (ii) how many of these have been informed about the option of BS, and (iii) what are the characteristics associated with eligibility and awareness of BS. Demographic, anthropometric, clinical and socioeconomic data were obtained for all patients with T2DM who were consecutively examined in the outpatient clinics of three large-volume university hospitals (n = 1167). A medical registry form was completed to screen for BS eligibility. Patients were considered eligible if the recommendation by DSS-II criteria was either to "consider" or "recommend" BS. Eligible patients were further inquired whether they had ever been informed about the option of BS by their physicians. The advanced DiaRem score (ADRS) was applied to eligible patients to assess their probability of achieving postoperative T2DM remission. A significant percentage of T2DM patients who are routinely assessed in outpatient clinics meet the DSS-II eligibility criteria (15.3%). Eligible patients are younger and more obese, have a shorter T2DM duration, worse glycaemic control and better renal function, compared to non-eligible ones. Among eligible patients, only 39.3% have been medically informed about the option of BS. Informed patients are younger and more severely obese than non-informed ones. A significant percentage of non-informed patients (35%) have an ADRS ≤10, indicating a considerable probability for T2DM remission after BS, and are thus deprived of this opportunity due to lack of appropriate medical counseling. Screening and awareness of BS remain an unmet need in current T2DM management. Future research should focus on intensifying screening for BS eligibility at every medical visit and promoting evidence-based clinical recommendations for patients expected to benefit the most.

Pre-Exercise Maltodextrin Ingestion and Transient Hypoglycemia in Cycling and Running.

This study examined the phenomenon of transient hypoglycemia and metabolic responses to pre-exercise carbohydrate (CHO) maltodextrin ingestion in cycling and running on the same individuals. Eleven active males cycled or ran for 30 min at 80% maximal heart rate (HRmax) after ingestion of either 1g/kg body mass maltodextrin (CHO-Cycle and CHO-Run respectively) or placebo (PL-Cycle and PL-Run) solutions. Fluids were ingested 30min before exercise in a double-blind and random manner. Blood glucose and serum insulin were higher before exercise in CHO (mean CHO-Cycle+CHO-Run) (Glucose: 7.4 ± 0.3 mmol·l-1; Insulin: 59 ± 10 mU·l-1) compared to placebo (mean PL-Cycle+PL-Run) (Glucose: 4.7 ± 0.1 mmol·l-1; Insulin: 8 ± 1 mU·l-1) (p<0.01), but no differences were observed during exercise among the 4 conditions. Mean blood glucose did not drop below 4.1 mmol·l-1 in any trial. However, six volunteers in CHO-Cycle and seven in CHO-Run experienced blood glucose concentration ≤ 3.5 mmol·l-1 at 20min of exercise and similar degree of transient hypoglycemia in both exercise modes. No association was found between insulin response to maltodextrin ingestion and drop in blood glucose during exercise. Blood lactate increased with exercise more in cycling compared to running, and plasma free fatty acids (FFA) concentrations were higher in placebo compared to CHO irrespective of exercise mode (p<0.01). The ingestion of maltodextrin 30min before exercise at about 80% HRmax produced similar glucose and insulin responses in cycling and running in active males. Lactate was higher in cycling, whereas maltodextrin reduced FFA concentrations independently of exercise mode.

Endothelium as a Therapeutic Target in Diabetes Mellitus: From Basic Mechanisms to Clinical Practice.

Endothelium plays an essential role in human homeostasis by regulating arterial blood pressure, distributing nutrients and hormones as well as providing a smooth surface that modulates coagulation, fibrinolysis and inflammation. Endothelial dysfunction is present in Diabetes Mellitus (DM) and contributes to the development and progression of macrovascular disease, while it is also associated with most of the microvascular complications such as diabetic retinopathy, nephropathy and neuropathy. Hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia are the main factors involved in the pathogenesis of endothelial dysfunction. Regarding antidiabetic medication, metformin, gliclazide, pioglitazone, exenatide and dapagliflozin exert a beneficial effect on Endothelial Function (EF); glimepiride and glibenclamide, dipeptidyl peptidase-4 inhibitors and liraglutide have a neutral effect, while studies examining the effect of insulin analogues, empagliflozin and canagliflozin on EF are limited. In terms of lipid-lowering medication, statins improve EF in subjects with DM, while data from short-term trials suggest that fenofibrate improves EF; ezetimibe also improves EF but further studies are required in people with DM. The effect of acetylsalicylic acid on EF is dose-dependent and lower doses improve EF while higher ones do not. Clopidogrel improves EF, but more studies in subjects with DM are required. Furthermore, angiotensin- converting-enzyme inhibitors /angiotensin II receptor blockers improve EF. Phosphodiesterase type 5 inhibitors improve EF locally in the corpus cavernosum. Finally, cilostazol exerts favorable effect on EF, nevertheless, more data in people with DM are required.

SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects.

Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the latest class of antidiabetic medication that inhibit the absorption of glucose from the proximal tubule of the kidney and hence cause glycosuria. Four SGLT2i are currently commercially available in many countries: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT2i reduce glycated hemoglobin by 0.5%-1.0% and have shown favorable effects on body weight, blood pressure, lipid profile, arterial stiffness and endothelial function. More importantly, SGLT2i have demonstrated impressive cardioprotective and renoprotective effects. The main mechanisms underlying their cardioprotective effects have been attributed to improvement in cardiac cell metabolism, improvement in ventricular loading conditions, inhibition of the Na+/H+ exchange in the myocardial cells, alteration in adipokines and cytokines production, as well as reduction of cardiac cells necrosis and cardiac fibrosis. The main adverse events of SGLT2i include urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Concerns have also been raised about the association of SGLT2i with lower limb amputations, Fournier gangrene, risk of bone fractures, female breast cancer, male bladder cancer, orthostatic hypotension, and acute kidney injury.

Management of diabetes mellitus and patients' attitude towards the disease: Data from a nationwide study in Greece.

AIM: To examine management of diabetes mellitus (DM) and patients' attitude towards DM in a random sample of the adult Greek population. METHODS: s: We selected a random sample of adults with self-reported DM (n = 1002) from a population-based nationwide study using the effective random sampling technique. Collection of data was performed through phone interviews. RESULTS: Prevalence of type 1 DM was 3.5% and of type 2 DM 96.5%. Prevalence of type 1 DM declined while of type 2 DM increased with age. No gender or residency differences were found between type 1 and type 2 DM. A total of 72.0% of subjects with type 2 DM were treated with oral antidiabetic drugs (OAD), 11.5% were treated with insulin and 7.1% were treated with both OAD and insulin. Internists specialized in DM were mainly doctors who started insulin treatment. Almost half of insulin naive subjects were skeptical towards insulin initiation and their main concern was the needle punch. CONCLUSIONS: In a random nationwide sample of the adult population in Greece the majority of subjects with self-reported DM had type 2 DM. Most patients with type 2 were treated with OAD. Almost half of insulin naive subjects were skeptical towards insulin initiation.

Advancements in improving health-related quality of life in patients living with diabetic foot ulcers.

INTRODUCTION: Diabetic foot ulcer (DFU) constitutes a burden to patients with diabetes deteriorating their quality of life. Health related quality of life (HRQoL) can now be quantified with the use of specific tools; some of them provide a holistic approach to patients' well-being, while others are disease specific or even region specific. Many of these tools are applicable to patients with DFU. This review will present current data about the impact different interventions in the management of DFU on quality of life related parameters. AREAS COVERED: We performed a search of literature using keywords 'diabetes mellitus', 'diabetic foot ulcer', 'diabetic foot', 'health related quality of life', 'quality of life' and 'SF-36' to identify studies that contained data about the relationship between different interventions and quality of life of patients with diabetic foot ulcers. EXPERT COMMENTARY: Available data are not sufficient to conclude on the impact of interventions aimed to heal DFU on HRQoL. There is need for more, better designed studies and meta-analysis to estimate the effect of treatments on HRQoL in patients with DFUs. The development of new, diabetic foot specific tools will help to improve our knowledge in this field.