Higher rate of hyperglycemia than hypoglycemia during Ramadan fasting in patients with uncontrolled type 1 diabetes: Insight from continuous glucose monitoring system.

BACKGROUND: Patients with uncontrolled type 1 diabetes mellitus (T1DM) are at a high risk for Ramadan fasting and are exempt from fasting; however, most still insist on fasting. The aim of this study was to examine glucose level fluctuations in those patients during Ramadan fasting using a real-time continuous glucose monitoring system (RT-CGMS). METHODS: This pilot study involved adult patients with uncontrolled T1DM (HbA1c > 7%) who insisted on fasting during Ramadan in 2014 from Maternity and Children's Hospital, Medina, Saudi Arabia. A Medtronic RT-CGMS was used to monitor the participants' glucose levels for 3 consecutive days during fasting. RESULTS: The study included 22 patients (mean age 22 ±â€¯6 years, duration of diabetes 10.9 ±â€¯7.2 years, HbA1c level 9.3 ±â€¯1.2). All participants were using the basal-bolus insulin regimen, except for one patient who was on an insulin pump. Sensor glucose (SG) profiles typically followed a pattern that was characterized by an exaggerated increase after iftar, which was sustained overnight, and a second rapid rise after suhoor, with a prolonged glucose decay over the daylight hours. The average SG was 199 ±â€¯104.1 mg/dl, which was lower during fasting 188.4 ±â€¯103.41 mg/dl than during the eating hours 212.5 ±â€¯103.51 mg/dl (P = 0.00). There was a higher rate of hyperglycemia (48%) than hypoglycemia (10%). CONCLUSIONS: Patients with uncontrolled T1DM who fasted during Ramadan experienced a wide fluctuation of glucose levels between fasting and eating hours, exhibiting a greater tendency toward hyperglycemia. The long-term effects for this finding are not known and warrant further investigation.

Unlocking the post-transplant microenvironment for successful islet function and survival.

Islet transplantation (IT) offers the potential to restore euglycemia for patients with type 1 diabetes mellitus (T1DM). Despite improvements in islet isolation techniques and immunosuppressive regimes, outcomes remain suboptimal with UK five-year graft survivals (5YGS) of 55% and most patients still requiring exogenous insulin after multiple islet infusions. Native islets have a significant non-endocrine component with dense extra-cellular matrix (ECM), important for islet development, cell survival and function. Collagenase isolation necessarily disrupts this complex islet microenvironment, leaving islets devoid of a supporting framework and increasing vulnerability of transplanted islets. Following portal venous transplantation, a liver injury response is potentially induced, which typically results in inflammation and ECM deposition from liver specific myofibroblasts. The impact of this response may have important impact on islet survival and function. A fibroblast response and ECM deposition at the kidney capsule and eye chamber alongside other implantation sites have been shown to be beneficial for survival and function. Investigating the implantation site microenvironment and the interactions of transplanted islets with ECM proteins may reveal therapeutic interventions to improve IT and stem-cell derived beta-cell therapy.

A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review.

Background: Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases. Methods: For the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis. Case presentation: An 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications. Results: Among the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death. Conclusion: Our findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes.

Development and validation of a machine learning model for classification of next glucose measurement in hospitalized patients.

BACKGROUND: Inpatient glucose management can be challenging due to evolving factors that influence a patient's blood glucose (BG) throughout hospital admission. The purpose of our study was to predict the category of a patient's next BG measurement based on electronic medical record (EMR) data. METHODS: EMR data from 184,361 admissions containing 4,538,418 BG measurements from five hospitals in the Johns Hopkins Health System were collected from patients who were discharged between January 1, 2015 and May 31, 2019. Index BGs used for prediction included the 5th to penultimate BG measurements (N = 2,740,539). The outcome was category of next BG measurement: hypoglycemic (BG  ≤  70 mg/dl), controlled (BG 71-180 mg/dl), or hyperglycemic (BG > 180 mg/dl). A random forest algorithm that included a broad range of clinical covariates predicted the outcome and was validated internally and externally. FINDINGS: In our internal validation test set, 72·8%, 25·7%, and 1·5% of BG measurements occurring after the index BG were controlled, hyperglycemic, and hypoglycemic respectively. The sensitivity/specificity for prediction of controlled, hyperglycemic, and hypoglycemic were 0·77/0·81, 0·77/0·89, and 0·73/0·91, respectively. On external validation in four hospitals, the ranges of sensitivity/specificity for prediction of controlled, hyperglycemic, and hypoglycemic were 0·64-0·70/0·80-0·87, 0·75-0·80/0·82-0·84, and 0·76-0·78/0·87-0·90, respectively. INTERPRETATION: A machine learning algorithm using EMR data can accurately predict the category of a hospitalized patient's next BG measurement. Further studies should determine the effectiveness of integration of this model into the EMR in reducing rates of hypoglycemia and hyperglycemia.

Non-Occlusive Mesenteric Ischemia in Children With Diabetic Ketoacidosis: Case Report and Review of Literature.

Introduction: Despite the use of technology, recurrent diabetic ketoacidosis (DKA) prevention remains an unmet need in children and adolescents with T1D and may be accompanied by life-threatening acute complications. We present a rare case of non-occlusive mesenteric ischemia (NOMI) with overt manifestation after DKA resolution and a discussion of recent literature addressing DKA-associated NOMI epidemiology and pathogenesis in children and adolescents. Case Presentation: A 13-year-old female with previously diagnosed T1D, was admitted at our emergency department with hypovolemic shock, DKA, hyperosmolar state and acute kidney injury (AKI). Mildly progressive abdominal pain persisted after DKA correction and after repeated ultrasound evaluations ultimately suspect for intestinal perforation, an intraoperative diagnosis of NOMI was made. Conclusion: The diagnosis of DKA-associated NOMI must be suspected in pediatric patients with DKA, persistent abdominal pain, and severe dehydration even after DKA resolution.

Cystic fibrosis-related diabetes: Prevalence, screening, and diagnosis.

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in patients with cystic fibrosis (CF). Prevalence of CFRD increases with age and is greater with severe mutations. Other risk factors associated with CFRD are female sex, pancreatic insufficiency, liver disease, need for gastrostomy tube feedings, history of bronchopulmonary aspergillosis, and poor pulmonary function. CFRD is related to worse clinical outcomes and increased mortality. Early diagnosis and treatment have been shown to improve clinical outcomes. Screening for CFRD is recommended with an annual oral glucose tolerance test (OGTT) starting at age 10 years. Diagnosis of CFRD is made by standard American Diabetes Association (ADA) criteria during baseline health. CFRD can also be diagnosed in individuals with CF during acute illness, while on enteral feeds, and after transplant. In this review we will discuss the epidemiology of CFRD and provide an overview of the advantages and pitfalls of current screening and diagnostic tests for CFRD.

Study on hypoglycemic effects of irradiated ginseng adventitious roots.

We aimed to explore the effects of the 60Co-γ irradiated ginseng adventitious root (GAR) with different radiation doses on the hypoglycemic effects of its extract (GARSE) through in vivo and in vitro experiments. The total saponin of GARSE was increased by 4.50% after 5 kGy irradiation, and the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability was enhanced by 5.10%. At 50 µg/mL, GARSE irradiated by 5 kGy displayed superior protective effects on human glomerular mesangial cells (HMCs) with high glucose damage. After feeding type 1 diabetes mellitus (T1DM) mice with GARSE irradiated by 5 kGy at 500 mg/kg·BW for 4 weeks, the glucose values was decreased by 16.0% compared with the unirradiated. The Keap1/Nrf2/HO-1 pathway was activated and the oxidative stress was attenuated, which further alleviated T1DM.

AD-MSCs and BM-MSCs Ameliorating Effects on The Metabolic and Hepato-renal Abnormalities in Type 1 Diabetic Rats.

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.

Navigating the cellular landscape in tissue: Recent advances in defining the pathogenesis of human disease.

Over the past decade, our understanding of human diseases has rapidly grown from the rise of single-cell spatial biology. While conventional tissue imaging has focused on visualizing morphological features, the development of multiplex tissue imaging from fluorescence-based methods to DNA- and mass cytometry-based methods has allowed visualization of over 60 markers on a single tissue section. The advancement of spatial biology with a single-cell resolution has enabled the visualization of cell-cell interactions and the tissue microenvironment, a crucial part to understanding the mechanisms underlying pathogenesis. Alongside the development of extensive marker panels which can distinguish distinct cell phenotypes, multiplex tissue imaging has facilitated the analysis of high dimensional data to identify novel biomarkers and therapeutic targets, while considering the spatial context of the cellular environment. This mini-review provides an overview of the recent advancements in multiplex imaging technologies and examines how these methods have been used in exploring pathogenesis and biomarker discovery in cancer, autoimmune and infectious diseases.

Efficacy of Hybrid Closed-Loop Insulin Delivery System in a Hospital Setting: A Case Series.

OBJECTIVE: We report a case series of 4 patients with type 1 diabetes who used hybrid closed-loop insulin pumps (Medtronic MiniMed 670 G) during hospitalization. METHODS: Clinical data and point-of-care glucose values are presented for each patient. Glucose values are shown graphically while in manual mode as well as in auto mode. RESULTS: The first case was a 30-year-old man admitted for pancreatitis. Mean point-of-care blood glucose was 165.7 mg/dL while in auto mode, without hypoglycemia, compared with 221 mg/dL while in manual mode. The second case was a 28-year-old woman who was admitted for a laparoscopic cholecystectomy. Mean point-of-care blood glucose in auto mode was 131.3 mg/dL, without hypoglycemia, compared with 117.6 mg/dL while in manual mode. The third case was a 46-year-old man admitted to the intensive care unit for influenzal pneumonia. Mean point-of-care blood glucose in auto mode was 159.1 mg/dL without hypoglycemia, compared with 218.5 mg/dL while in manual mode. The fourth case was a 60-year-old man who remained in auto mode throughout his hospitalization except for a period when he removed his pump for an endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. His mean point-of-care blood glucose while in auto mode was 156.8 mg/dL without hypoglycemia. CONCLUSION: These case reports support the use of hybrid closed-loop insulin-pump therapy in the inpatient setting to maintain inpatient glycemic targets and avoid hypoglycemia when part of an institution-sanctioned strategy for safe use of insulin pumps that includes point-of-care blood glucose monitoring.

Euglycemic Diabetic Ketoacidosis Caused by SGLT2 Inhibitors and a Ketogenic Diet: A Case Series and Review of Literature.

OBJECTIVE: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a relatively novel class of oral medications for the treatment of type 2 diabetes mellitus (T2DM). Their use has increased recently due to their beneficial renal and cardiovascular outcomes, but they come with the rare risk of diabetic ketoacidosis (DKA) at normal or slightly elevated glucose values, termed euglycemic DKA (euDKA). Recently, carbohydrate-deprived, ketogenic diets have gained popularity due to benefits of weight loss and improved control of T2DM. We describe 2 patients with T2DM who developed euDKA caused by SGLT2 inhibitor use while on a ketogenic diet and provide a review of the literature. METHODS: We describe the hospital course, laboratory data, and treatment of 2 patients and provide a literature review. RESULTS: Both of our patients were found to have normal or mildly elevated serum glucose levels, with an elevated anion gap and ketosis, representative of euDKA. The first patient developed euDKA after only 1 dose of empagliflozin, while the second patient developed euDKA after only 1 week of being on a ketogenic diet while on an SGLT2 inhibitor. CONCLUSION: While there have been a few reports of euDKA with SGLT2 inhibitors and ketogenic diets, many physicians prescribing these medications may not be aware of this association. Therefore, they must inform their patients to avoid a ketogenic diet if on an SGLT2 inhibitor. If a patient presents with symptoms of DKA and is eating a carbohydrate-free diet while taking an SGLT2 inhibitor, there should be a low threshold to screen for DKA.

Commercialized Hybrid Closed-Loop System (Minimed Medtronic 670G) Results During Pregnancy.

OBJECTIVE: Hybrid closed-loop (HCL) devices can achieve tight glycemic control but are rarely used in pregnancy, which remains an off-label indication. We present a case of a pregnant patient with type 1 diabetes mellitus (T1DM) who used the Medtronic MiniMed 670G HCL system. METHODS: MiniMed 670G includes an advanced automode option (HCL therapy), which our patient used from the first trimester to the end of the pregnancy. RESULTS: An unplanned pregnancy was detected in the T1DM patient, with a glycated hemoglobin level of 8.7 mmol/L (7.1%). The patient started sensor-augmented pump therapy at week 13. Subsequently, she entered automode (HCL) at week 16. The time in range (3.7-7.8 mmol/mol, 63-140 mg/dL) increased from 46.8% to 51.3% after HCL initiation. The glycated hemoglobin level remained close to 48 mmol/mol (6.5%) until the end of the pregnancy. Furthermore, the time under range (<3.7 mmol/mol, <63 mg/dL) remained below the optimal 4% level during the gestation. Finally, a healthy male baby was born at week 37. No safety events were recorded. CONCLUSION: This case represents the successful off-label use of HCL during pregnancy in a patient with T1DM.

Interleukin-1ß, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk.

Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1ß, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor 2 [RyR2]). Inhibiting IL-1ß and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM. Inhibiting SR Ca2+ leak by stabilizing the oxidized RyR2 channel reversed the diabetic arrhythmic risk. In conclusion, cardiac IL-1ß mediated the DM-associated arrhythmia through mitoROS generation that enhances SR Ca2+ leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.

COVID-19 Presenting With Diabetic Ketoacidosis: A Case Series.

OBJECTIVE: Diabetes mellitus has been recognized as one of the comorbidities that predict the severity of illness in patients infected with COVID-19. The characteristics of patients presenting with diabetic ketoacidosis (DKA) and COVID-19 infection have not been described. METHODS: We describe 5 patients with DKA and concomitant COVID-19 admitted to the intensive care unit of an academic medical center. Three patients had type 1 diabetes mellitus, and 2 patients had type 2 diabetes mellitus. RESULTS: While DKA with an infectious etiology is a common presentation, we observed that the patients with DKA precipitated by COVID-19 presented with atypical symptoms. COVID-19 infection was revealed during search for an etiology of DKA. CONCLUSION: It is prudent to have a low threshold to screen for COVID-19 infection in patients with DKA.

Development of a Novel Clinical Decision Support System for Exercise Prescription Among Patients With Multiple Cardiovascular Disease Risk Factors.

Cardiovascular disease (CVD) risk factors cluster in an individual. Exercise is universally recommended to prevent and treat CVD. Yet, clinicians lack guidance on how to design an exercise prescription (ExRx) for patients with multiple CVD risk factors. To address this unmet need, we developed a novel clinical decision support system to prescribe exercise (prioritize personalize prescribe exercise [P3-EX]) for patients with multiple CVD risk factors founded upon the evidenced-based recommendations of the American College of Sports Medicine (ACSM) and American Heart Association. To develop P3-EX, we integrated (1) the ACSM exercise preparticipation health screening recommendations; (2) an adapted American Heart Association Life's Simple 7 cardiovascular health scoring system; (3) adapted ACSM strategies for designing an ExRx for people with multiple CVD risk factors; and (4) the ACSM frequency, intensity, time, and time principle of ExRx. We have tested the clinical utility of P3-EX within a university-based online graduate program in ExRx among students that includes physicians, physical therapists, registered dietitians, exercise physiologists, kinesiologists, fitness industry professionals, and kinesiology educators in higher education. The support system P3-EX has proven to be an easy-to-use, guided, and time-efficient evidence-based approach to ExRx for patients with multiple CVD risk factors that has applicability to other chronic diseases and health conditions. Further evaluation is needed to better establish its feasibility, acceptability, and clinical utility as an ExRx tool.

Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy.

INTRODUCTION: Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs. METHODS: Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index. RESULTS: Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed. CONCLUSIONS: Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs.

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

The influence of the gut microbiota on the bioavailability of oral drugs.

Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.

An overview of Charcot's neuroarthropathy.

Charcot's neuroarthropathy is a destructive complication of the joints, which is often found in people with diabetes with peripheral neuropathy. Despite the fact that its description was published almost 130 years ago, its pathophysiology, diagnosis, and treatment remain areas that need to be described. Thanks to the use of bone remodelling, new therapeutic classes have emerged, we hope that this review will shed light on the pathology from its discovery through to the current state of knowledge on its classification, diagnosis and treatment methods.

Diabetes as a risk factor for Alzheimer's disease in the Middle East and its shared pathological mediators.

The incidence of Alzheimer's disease (AD) has risen exponentially worldwide over the past decade. A growing body of research indicates that AD is linked to diabetes mellitus (DM) and suggests that impaired insulin signaling acts as a crucial risk factor in determining the progression of this devastating disease. Many studies suggest people with diabetes, especially type 2 diabetes, are at higher risk of eventually developing Alzheimer's dementia or other dementias. Despite nationwide efforts to increase awareness, the prevalence of Diabetes Mellitus (DM) has risen significantly in the Middle East and North African (MENA) region which might be due to rapid urbanization, lifestyle changes, lack of physical activity and rise in obesity. Growing body of evidence indicates that DM and AD are linked because both conditions involve impaired glucose homeostasis and altered brain function. Current theories and hypothesis clearly implicate that defective insulin signaling in the brain contributes to synaptic dysfunction and cognitive deficits in AD. In the periphery, low-grade chronic inflammation leads to insulin resistance followed by tissue deterioration. Thus insulin resistance acts as a bridge between DM and AD. There is pressing need to understand on how DM increases the risk of AD as well as the underlying mechanisms, due to the projected increase in age related disorders. Here we aim to review the incidence of AD and DM in the Middle East and the possible link between insulin signaling and ApoE carrier status on Aß aggregation, tau hyperphosphorylation, inflammation, oxidative stress and mitochondrial dysfunction in AD. We also critically reviewed mutation studies in Arab population which might influence DM induced AD. In addition, recent clinical trials and animal studies conducted to evaluate the efficiency of anti-diabetic drugs have been reviewed.