Synthesis and Anti-Diabetic Activity of an 8-Purine Derivative as a Novel DPP-4 Inhibitor in Obese Diabetic Zücker Rats.

Type 2 diabetes mellitus (T2DM) is one of the world's principal metabolic diseases characterized by chronic hyperglycemia. The gut incretin hormones, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), which has been proposed as a new treatment for T2DM, are extensively metabolized by Dipeptidyl peptidase 4 (DPP-4). Inhibitors of DPP-4 block the degradation of GLP-1 and GIP and may increase their natural circulating levels, favoring glycemic control in T2DM. A novel and potent selective inhibitor of DPP-4 with an 8-purine derived structure (1) has been developed and tested in vitro and in vivo in Zücker obese diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome and T2DM to assess the inhibitory activity using vildagliptin as reference standard. ZDF rats were subdivided into three groups (n = 7/group), control (C-ZDF), and those treated with compound 1 (Compound1-ZDF) and with vildagliptin (V-ZDF), both at 10 mg/kg/d rat body weight, in their drinking water for 12 weeks, and a group of lean littermates (ZL) was used. ZDF rats developed DM (fasting hyperglycemia, 425 ± 14.8 mg/dL; chronic hyperglycemia, HbA1c 8.5 ± 0.4%), compared to ZL rats. Compound 1 and vildagliptin reduced sustained HbAl1c (14% and 10.6%, P < 0.05, respectively) and fasting hyperglycemia values (24% and 19%, P < 0.05, respectively) compared to C-ZDF group (P < 0.001). Compound 1 and vildagliptin have shown a potent activity with an IC50 value of 4.92 and 3.21 µM, respectively. These data demonstrate that oral compound 1 administration improves diabetes in ZDF rats by the inhibitory effect on DPP-4, and the potential to be a novel, efficient and tolerable approach for treating diabetes of obesity-related T2DM, in ZDF rats.

Relationship of Serum Vitamin D Levels With Diabetic Foot in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background and aims: Diabetic foot is one of the most severe complications in patients with diabetes mellitus and has been linked to 25-OH-vitamin D status. This study aims to determine the prevalence of 25-OH-vitamin D deficiency and its association with diabetic foot. Methods: Patients with type 2 diabetes mellitus were enrolled in this study. The patients were divided into the diabetic foot group (n = 95) and the non-diabetic foot group (n = 388). Weight, height, and waist circumference were measured. The 25-OH-vitamin D and the other biochemical tests were extracted from the electronic medical records. The difference in clinical parameters between the diabetic foot group and the non-diabetic foot group was analyzed, and the risk factors of the diabetic foot group were analyzed using logistic regression. Results: The prevalence of 25-OH-vitamin D deficiency was 44.6%, accounting for 57.9% of all the diabetic foot group patients and only 41.0% of the non-diabetic foot group patients. The mean serum 25-OH-vitamin D level was significantly different between the diabetic foot group and the non-diabetic foot group (19.8 ± 9.5 vs 24.1 ± 11.8; P = .011). Serum 25-OH-vitamin D and B12 were found to have a significant positive correlation (r = 0.410, P = <.01). The 25-OH-vitamin D level and body mass index were independently associated with diabetic foot (P = .043, OR = 1.21; P = .009, OR = 1.47), respectively. Conclusions: The 25-OH-vitamin D deficiency was higher in the diabetic foot group. More research is needed to understand the role of 25-OH-vitamin D in the development of diabetic foot.

Perceptions of primary healthcare physicians in Jordan of their role in the COVID-19 pandemic: A cross-sectional study.

BACKGROUND: Following the remarkable spread of coronavirus disease 2019 (COVID-19), worldwide, it quickly became apparent that many public health systems worldwide were not prepared to manage such a pandemic. We aimed to assess the perceptions of primary care physicians (PCPs) in Jordan towards their role during COVID-19. METHODS: A cross-sectional study using a self-administered questionnaire was performed. The study participants included PCPs from the Ministry of Health, academic institutions, and the private sector in Jordan. RESULTS: A total of 221 PCPs participated in the study. Most participants reported not having received any training on infection control (59.7%) or COVID-19 (81%). More than half PCPs (53.4%) felt positive about the way patients received and/or complied with their instructions. More than half PCPs (55.7%) educated their patients on protective measures against COVID-19 infection and considered this as part of their role and responsibility. Over 80% of the participants would apply social distancing, hand sanitation, facial masks, and patient education, but only half (51.1%) reported planning to order COVID-19 test kits. CONCLUSIONS: PCPs had a positive attitude towards controlling COVID-19 infection and showed a willingness to educate patients on how to protect themselves. However, PCPs should be provided special training on COVID-19.

Clinical, sinonasal, and long-term smell and taste outcomes in mildly symptomatic COVID-19 patients.

INTRODUCTION: Coronavirus 2019 disease (COVID-19) has variable clinical, sinonasal, and smell/taste outcomes. METHODS: Observational study was conducted at a tertiary hospital in Amman, Jordan. Demographic data, clinical presentation and smoking status were collected. Sinonasal symptoms, using Sino-Nasal Outcome Test (SNOT-22) Questionnaire, were evaluated. Smell/taste dysfunction was followed for three months. RESULTS: Ninety-Seven patients had satisfactory responses. Eighty-six patients were symptomatic (41 at presentation, and 45 during admission). Among those patients, 59.3% had cough, 52.3% sore throat and 48.8% fever. The most common initial symptom was sore throat. Shortness of breath and smell/taste dysfunction were significantly higher in females. Surprisingly, shortness of breath was more common in non-smokers. Smell/taste dysfunction affected 25.6% of patients, but was the first symptom in only one patient. Fourteen of 22 symptoms in SNOT-22 had significant increase. The overall average of symptoms scores increased from 0.472 to 1.034, with smell/taste dysfunction to have the most increment. The latter symptom recovered completely in 81% and dysgeusia developed in 9.5% at three months, and it recovered completely in all patients at six months. CONCLUSION: Although COVID-19 may produce severe lower airways disease, it has modest effect on nose and paranasal sinuses. Moreover, smell/taste dysfunction is a prominent symptom, but it usually recovers dramatically.

Attitudes and Awareness Towards Diabetic Retinopathy Among Patients with Diabetes in Amman, Jordan.

PURPOSE: This study aimed to investigate the attitudes and awareness about the development of retinopathy among the patients suffering from diabetes in Amman, Jordan. METHODS: A questionnaire was distributed among patients with diabetes visiting internal medicine and endocrinology clinics in a tertiary hospital, in addition to a primary health care center in Amman. The questionnaire inquired about retinopathy awareness, history of screening for retinopathy, and awareness about retinopathy treatment. The patients were also asked about risk factors and preventive measures for diabetic retinopathy management. RESULTS: A total of 303 patients were recruited in the study. Majority of the patients (77%) had their HbA1c levels tested at least once since diagnosis, and most of them (60%) do it regularly. However, 86% of patients reported an A1c >6.5%. Two thirds of patients are not aware about retinopathy being a recognized complication of diabetes. Lower level of education, female sex, younger age, and shorter duration of diabetes mellitus were associated with less awareness. CONCLUSION: The study concluded that majority of patients with diabetes were aware of diabetes management. However, the sample population indicated less awareness of diabetic retinopathy. Hence, more educational efforts are needed to further boost patients' awareness about diabetic retinopathy.

Iatrogenic occult infection causing hypoglycemia in a teenage female.

Hypoglycemia is a clinically significant disorder with a wide variety of underlying causes. We report an unusual case of hypoglycemic episodes caused by an iatrogenic infection in a 17-year-old white female who presented to our emergency department complaining of 2-3 episodes of syncope per week in the previous year, which started after an appendectomy in 2016. She was hypoglycemic and a vague painless abdominal mass was found upon palpation. An abdominal CT revealed a large, well-defined heterogeneous lesion. The excised mass was surrounded by pieces of gauze that had remained in her abdomen since the appendectomy. An asymptomatic infection was the cause of her hypoglycemic episodes. After antibiotic therapy, the abdominal symptoms resolved within the first week and at follow up at 6 months after surgery, her glucose level was back to normal. This is the first reported case of iatrogenic occult infection with episodic hypoglycemia as a cardinal feature. This case illustrates that infection should remain in the differential diagnosis although cardinal signs are absent. SIMILAR CASES PUBLISHED: 0.

Pilot study to build capacity for family medicine with abbreviated, low-cost training programme with minimal impact on patient care for a cohort of 84 general practitioners caring for Palestinian refugees in Jordan.

PURPOSE: Studies document that primary care improves health outcomes and controls costs. In regions of the world where primary care is underdeveloped, building capacity is essential. Most capacity building programmes are expensive and take physicians away from their clinical settings. We describe a programme created, delivered and evaluated from 2013 to 2014 in Jordan. DESIGN: Cohort study. SETTING: Physicians providing primary care in the United Nations Relief and Works Agency for Palestine Refugees clinics in Jordan. PARTICIPANTS: Eighty-four general practitioners (GPs) were invited to participate and completed the training and evaluation. GPs are physicians who have a license to practice medicine after completing medical school and a 1 year hospital-based rotating internship. Although GPs provide care in the ambulatory setting, their hospital-based education provides little preparation for delivering ambulatory primary care. INTERVENTION/PROGRAMME: This three-stage programme included needs assessment, didactics and on-the-job coaching. First, the learning needs and baseline knowledge of the trainees were assessed and the findings guided curriculum development. During the second stage, 48 hours of didactics covered topics such as communications skills and disease management. The third stage was delivered one on one in the trainee's clinical setting for a 4 to 6-hour block. The first, middle and final patient interactions were evaluated. PRIMARY AND SECONDARY OUTCOME MEASURES: Preknowledge and postknowledge assessments were compared. The clinical checklist, developed for the programme, assessed eight domains of clinical skills such as communication and history taking on a five-point Likert scale during the patient interaction. RESULTS: Preknowledge and postknowledge assessments demonstrated significantly improved scores, 46% to 81% (p<0.0001). Trainee's clinical checklist scores improved over the assessment intervals. Satisfaction with the training was high. CONCLUSION: This programme is a potential model for building primary care capacity at low cost and with little impact on patient care that addresses both knowledge and clinical skills on the job.

Are Risk Factors for Coronary Artery Disease Different in Persons With and Without Obesity?

BACKGROUND: Although obesity is an independent risk factor for coronary artery disease (CAD), observational studies have found that persons with obesity have a better prognosis in established CAD compared with those with a normal body weight, suggesting that the underlying risk factors might differ between the two groups. In this study, we studied risk factors for CAD in persons with and without obesity in a Middle Eastern setting where obesity is endemic. METHODS: Five hundred and fifty-six patients referred for elective coronary catheterization at Prince Hamza Hospital, Amman were included in a cross-sectional study. Patients with CAD (n = 353; 63.5%) were compared to patients with a normal coronary angiography (n = 203; 36.5%). Associations between CAD and baseline variables were assessed in multivariate logistic regression models. RESULTS: In persons with obesity, male sex [adjusted odds ratio (AOR) = 2.62, 95% confidence interval (CI): 1.37-4.99], increasing age (45-54 years: AOR = 5.00, 95% CI: 2.01-12.48; 55-64 years: AOR = 3.77, 95% CI: 1.39-10.23; ≥65 years: AOR = 13.87, 95% CI: 4.62-41.63), diabetes mellitus (AOR = 2.79, 95% CI: 1.49-5.22), and smoking (AOR = 2.25, 95% CI: 1.12-4.50) were strong and significant predictors of CAD. The same risk factors were identified in persons without obesity, but in addition, waist circumference (per 1 cm increment: AOR = 1.04, 95% CI: 1.01-1.07) was a significant predictor of CAD in this group. CONCLUSIONS: Sex, age, diabetes mellitus, and smoking predicted CAD in all patients. Waist circumference only predicted CAD in persons without obesity, suggesting that normal-weight central obesity might be an important risk factor in this setting.

Elevated fasting blood glucose, but not obesity, is associated with coronary artery disease in patients undergoing elective coronary angiography in a referral hospital in Jordan.

BACKGROUND: Obesity and its metabolic complications are endemic in the Middle East, but the cardiovascular consequences are not well defined in local studies. OBJECTIVE: To assess the association between fasting blood glucose (FBG), obesity and coronary artery disease (CAD) in Jordan. DESIGN: A cross-sectional, hospital-based study. SETTING: A referral hospital in Amman, Jordan. PATIENTS AND METHODS: Patients with complete anthropomorphic data who were referred for elective coronary angiography were included in the analysis. Associations between CAD, FBG and obesity were assessed in multivariate logistic regression models, adjusting for known risk factors. MAIN OUTCOME MEASURE: The presence of CAD. SAMPLE SIZE: 434 subjects. RESULTS: Only those who underwent coronary angiography and had complete anthropometric data were included in the study: 291 (67.1%) had CAD and 143 (32.9%) had a normal coronary angiogram.The mean body mass index, waist circumference and FBG of the study participants was 30.0 kg/m2, 106.0 cm and 8.8 mmol/L, respectively. The mean FBG was significantly higher in patients with CAD compared to those without CAD (9.5 vs. 7.3 mmol/L, P less than .001). Waist circumference was significantly higher in women with CAD compared to women without CAD (111.0 vs. 105.9 cm, P=.036), but no significant difference was observed in men. In a multivariate analysis, FBG was a strong and significant predictor of CAD; however, none of the measures of obesity were significantly associated with CAD. The findings were robust in a sensitivity analysis that excluded patients with known diabetes mellitus. CONCLUSIONS: Elevated FBG, but not obesity, predicted CAD in a Middle Eastern population. Improved prevention, detection and management of type 2 diabetes should be a priority in this setting. LIMITATIONS: The cross-sectional design cannot control for temporal changes in risk factors and/or reverse causation. CONFLICT OF INTEREST: None.

Risk factors for coronary artery disease in patients undergoing elective coronary angiography in Jordan.

BACKGROUND: Unhealthy lifestyle factors such as smoking, obesity, inactivity and type 2 diabetes are endemic in the Middle East. The public health consequences might be detrimental; however, local studies on risk factors for coronary artery disease (CAD) are scarce. METHODS: Patients referred for coronary angiography at a tertiary hospital in Amman, Jordan, between January and December 2015, were included in this study. Risk factors for CAD were assessed in a multivariate logistic regression model, and presented as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Among 557 participants, 356 (63.9%) had CAD and 201 (36.1%) had a normal cardiogram. The majority (n = 395, 70.9%) were male, and median age was 55 years (interquartile range 47-64). Two-hundred-and-fifteen (38.6%) individuals reported previous diabetes, and 287 (51.5%) were current or previous smokers. In multivariate analysis, male gender (OR 3.7, 95% CI 2.3-6.0), age (45-54 years: OR 4.8, 95% CI 2.7-8.5; 55-64 years: OR 6.0, 95% CI 3.2-11.4; ≥65 years: OR 15.7, 95% CI 7.8-31.3), previous diabetes (OR 2.6, 95% CI 1.7-4.1) and current/previous smoking (OR 2.1, 95% CI 1.3-3.4) were significant predictors of CAD. CONCLUSIONS: Age, gender, diabetes and smoking were strong and significant risk factors for CAD in Jordan. Public health interventions to reduce the prevalence of smoking and diabetes are urgently needed.

Diabetes Risk Score in a Young Student Population in Jordan: A Cross-Sectional Study.

Background. The Middle East is the home to the most obese population in the world, and type 2 diabetes mellitus is endemic in the region. However, little is known about risk factors for diabetes in the younger age groups. Methods. The Finnish Diabetes Risk Score (FINDRISC) is a simple, validated tool to identify persons at risk of diabetes. We investigated students at Hashemite University in Jordan with FINDRISC and measured fasting plasma glucose in those who were categorized in the high-risk group. Results. Overall, 1821 students (881 [48.4%] female) were included in the study. Risk factors for diabetes were common: 422 (23.2%) were overweight or obese and 497 (27.3%) had central obesity. Using the FINDRISC score, 94 (5.2%) students were at moderate risk and 32 (1.8%) at high risk of diabetes. The mean FINDRISC score was significantly higher in men than women (5.9 versus 5.4; p = 0.002). Twenty-eight students in the high-risk group had a subsequent plasma glucose measurement, and 8 (29%) of them fulfilled the diagnostic criteria for diabetes. Conclusions. Risk factors for diabetes were common in a young student population in Jordan, suggesting that preventive measures should be initiated early in adulthood to turn the diabetes epidemic in the region.