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Introduction The main objective of the current study was to perform a comparison of point-of-care testing for hemoglobin A1c (POCT-HbA1c) versus the standard laboratory method (Lab HbA1c) and their relationship to time-in-range (TIR) and glucose variability (GV) among patients with diabetes mellitus (DM) presented to the outpatient diabetes clinics. Methods This single-center cross-sectional study was carried out on diabetic patients (aged ≥14 years of both genders) who undergo routine follow-up at our institution and whose physicians ordered HbA1c analysis for routine care. The included patients were those using the intermittently scanned continuous glucose monitoring (isCGM) Abbott's FreeStyle Libre system for at least three months and regular CGM users with at least 70% use. Results We included 97 diabetic patients (41 female and 56 male), with a median age of 25 years (Interquartile range= 18) and a mean DM duration of 10.33±5.48 years. The mean values of Lab-HbA1c and POCT HbA1c were 8.82%±0.85% and 8.53%±0.89%, respectively. The TIR, time below range, and time above range were 33.47±14.38 minutes (47.78%±14.32%), 5.44±2.58 minutes (8.41%±4.42%), and 28.8±8.27 minutes (43.81%±13.22%), respectively. According to the Bland-Altman plot analysis, the POCT-HbA1c values are consistent with the standard Lab-HbA1c values (SD of bias= 0.55, and 95% CI= -0.78 to 1.4). The univariate linear regression analysis showed a statistically significant relationship between laboratory HbA1c and POCT HbA1c (R2= 0.637,  p  <0.001), TIR (R2= 0.406,  p  <0.001), and GV (R2= 0.048,  p = 0.032). After adjusting for age, gender, disease duration, diabetes type, and percentage of sensor data in a multivariable linear regression model, the linear associations remained significant (all   p < 0.05). Conclusion The current findings show that TIR and GV can be used as endpoints and valuable parameters for the therapy of DM., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Al Hayek et al.)

Diabetes prevalence is on the rise in the Middle East. In countries of the Gulf region-Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates-prevalence rates are among the highest in the world. Further, Egypt now ranks as one of the top 10 countries in the world for high number of people with diabetes. Medical nutrition therapy is key to optimal management of diabetes. Patient adherence to nutritional guidance depends on advice that is tailored to regional foods and cultural practices. In 2012, international experts created a transcultural Diabetes Nutrition Algorithm (tDNA) for broad applicability. The objective of this current project was to adapt the algorithm and supportive materials to the Middle East region. A Task Force of regional and global experts in the fields of diabetes, obesity, and metabolic disorders met to achieve consensus on Middle East-specific adaptations to the tDNA. Recommendations, position statements, figures, and tables are presented here, representing conclusions of the tDNA-Middle Eastern (tDNA-ME) Task Force. Educational materials can be used to help healthcare professionals optimize nutritional care for patients with type 2 diabetes. The tDNA-ME version provides evidence-based guidance on how to meet patients' nutritional needs while following customs of people living in the Middle Eastern region., Competing Interests: AA and RH were employees of Abbott Laboratories, the material presented in this article is based on the best-known clinical evidence and is not affected by this financial relationship. JM has received honoraria from Abbott Nutrition, and he serves on Advisory Boards of Aveta, Life, L-Nutra, and Twin Health. OH has received research support from Novo-Nordisk, Eli-Lilly, Gilead, and National Dairy Council, he is on advisory board of Numera, Twin Health, L-Neutra, he is a share-holder of Healthimation, and he has received consultation honoraria from Abbott Nutrition, Sanofi, and Merck Serono. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hamdy, Al Sifri, Hassanein, Al Dawish, Al-Dahash, Alawadi, Jarrah, Ballout, Hegazi, Amin and Mechanick.)

Introduction Because of the difficulties in interpreting the level of blood glucose using the traditional numeric glucometers, the blood glucose meters featuring color-coded range indicators (CRI) offered a simple way to understand and interpret blood glucose readings. Therefore, this study aimed to assess glucose monitoring satisfaction (GMS) and clinical efficacy of blood glucose meters featuring color-coded in patients with Type 1 Diabetes (T1DM) in Saudi Arabia. Methods T1DM patients who switched to color-coded Medisafe Fit Smile glucometer were included in this study. Demographic data, clinical characteristics, glycemic parameters were collected. A trained interviewer collected the GMS survey at baseline and 12 weeks. At the end of the study, patient-reported satisfaction with the Medisafe Fit Smile color-coded features (MSCF) survey was collected.  Results This study included 62 T1DM patients with a mean age of 17.8 (±3.1), and the majority had three or more confirmed hypoglycemic episodes per month. Compared to baseline data, we showed a significant improvement in the mean hemoglobin A1C level (8.43 [±1.2] versus 8.36 [±1.1], p<0.001), with a significantly lower frequency of hypoglycemic episodes (2.74 [±1.1] versus 2.0 [±0.78], p<0.001) after 12 weeks of using glucometer featuring CRI. Most importantly, significant improvements in the GMS survey subdomains of openness (p<0.001), emotional burden (p<0.001), behavioral burden (p<0.001), but not trust (p=0.71) were detected at the end of the study with a significantly higher total GMS survey of 4.33 (±0.13) after using blood glucose meters featuring CRI compared to the lower score of 2.84 (±0.22) at baseline (p<0.001). Furthermore, patient satisfaction with the MSCF survey revealed evidence of satisfaction among the TIDM patients at the end of the study. Conclusion The current study confirmed that individuals with T1DM may benefit from blood glucose meters featuring CRI device exposure. Also, using a glucometer featuring CRI was associated with a high level of satisfaction with blood glucose measures and significant improvement in the glycemic parameters. However, definitely, further studies are needed to confirm whether the long-term use of the CRI-based blood glucose meters will produce improved results in the GMS survey., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Al Hayek et al.)

Introduction: The effect of flash glucose monitoring on glycaemic control and patient satisfaction in insulin-treated type 2 diabetes (T2D) from Saudi Arabia is uncertain. The aim of this prospective observational study was to evaluate the change in HbA1c (Hemoglobin A1c) and satisfaction with treatment following the initiation of flash glucose monitoring., Methods: This single-arm, single-centre prospective observational study included flash glucose monitoring-naive adult patients with T2D managed with multiple daily injections of insulin therapy (MDI) and HbA1c ≥7%. HbA1c was measured, and the Diabetes Treatment Satisfaction Questionnaire (DTSQ, Arabic version) and Glucose Monitoring Satisfaction Survey (GMSS) were completed at baseline and 12 weeks., Results: For participants (n=54) from one diabetes centre, HbA1c significantly improved by 0.44% from 8.22%±0.69 (mean±SD) at baseline to 7.78%±0.71 at 12 weeks, p<0.001. Confirmed hypoglycaemic episodes reduced from 4.43±1.51 episodes/month to 1.24±1.15 (-3.19, p<0.001). Glucose monitoring frequency improved, indicated by the number of scans per day, with a mean increase of 5.13 (p <0.001) tests/day. GMSS scores improved across all four categories, as did overall treatment satisfaction (p<0.001 for all categories). Patients perceived clear improvements across all questions relating to satisfaction and frequency of hypo- or hyperglycaemic episodes., Conclusion: Following initiation of flash glucose monitoring in patients with T2D and MDI insulin therapy, HbA1c improved with reduced hypoglycaemic events and increased patient-reported satisfaction. This study contributes valuable data on the use of flash glucose monitoring in this population, and a larger multicentre study is warranted to inform future health policy for T2D in Saudi Arabia., Competing Interests: Ayman A. Al Hayek, Mohamed A. Al Dawish have nothing to disclose. Manal El Jammal is an employee of Abbott, Diabetes Care, United Arab Emirates., (Copyright © 2021, Al Hayek et al.)

Background and Aims: This study aimed to estimate the prevalence of bone fractures and analyze their associated risk factors in people with and without type 2 diabetes (T2D) in Saudi Arabia., Methods: This study was conducted among 1188 people (581 type 2 diabetes) in Prince Sultan Military Medical City, Riyadh, Saudi Arabia. In addition to the demographic variables, glycated hemoglobin (HbA1c), creatinine, estimated glomerular filtration rate (eGFR), use of teriparatide, presence of rheumatoid arthritis, presence of chronic obstructive pulmonary disease (COPD), Bone mineral density (BMD), Trabecular Bone Score (TBS) and Fracture Risk using the Fracture Risk Assessment Tool (FRAX) were also collected., Results: There were 1188 people (mean age 66.5 ± 8.7yrs) included in this study, of which 1068 (89.9%) were female, and 120 (10.1%) were male. A total of 112 (9.4%) individuals had a fracture history. Female, use of teriparatide, TBS (partially degraded and degraded), FRAX with TBS (MOF), and FRAX with TBS (Hip fx) were identified as independent risk factors for fracture in the whole study population. Teriparatide use and FRAX with TBS (MOF) were observed as independent risk factors for fracture in the non-diabetic population, whereas age, creatinine, eGFR, teriparatide, osteopenia, osteoporosis, TBS (partially degraded, degraded), FRAX with TBS (MOF), FRAX with TBS (Hip fx) were determined as independent risk factors for fracture among patients with diabetes., Conclusion: Patients with T2D were observed to have a higher risk for fractures. The findings of the study highlight the requirement for fracture prevention strategies in patients with diabetes., Competing Interests: Declaration of competing interest Authors have no conflict of interest and the work was not supported or funded by any drug company., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose Current evidence indicates that diabetic patients' preference and medication adherence can be affected by the type of insulin pen needles. We aimed to assess the impact of insulin pen devices with safety needles (SPN) on the usability, behavioral, lifestyle, and emotional aspects of type 1 diabetes mellitus (T1DM) in adolescents and young adults. Patients and methods We conducted a prospective single-center study on adolescent T1DM patients treated with multiple insulin doses using basal-bolus therapy for at least one year. Patients were followed for 12 weeks to compare the changes in the baseline usability and insulin fear of self-injection scales between SPN and conventional needles. Results In this 12-week study, we included 72 participants with a mean age of 15.5 ± 1.3 years. The mean disease duration was 5.1 ± 2.2 years. At 12 weeks, substantial improvement was evident in the SPN group, compared to the conventional group, in terms of the overall satisfaction score with a mean difference (MD) of 4.1 ± 1.9 (p < 0.01). Participants in the SPN group reported significant reduction in all aspect of fear from self-injection, such as being restless (MD = -1.4 ± 0.9), tense (MD = -1.8 ± 0.9), afraid (MD = -1.9 ± 0.9), worried (MD = -1.9 ± 0.9), nervous (MD = -1.7 ± 0.9), and brood using the SPN needles (MD = -1.6 ± 0.9), as compared to the conventional needles group. The glycemic control parameters, as determined by HbA1c and fasting blood glucose, exhibited significant improvements in the SPN group compared to the conventional group (p < 0.05). Conclusion SPN significantly improved usability, glycemic parameters, and reduced the fear of insulin self-injections amongst T1DM patients compared to conventional pen therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Al Hayek et al.)

Background and Aims: To examine the efficacy of FreeStyle Libre Flash Glucose Monitoring System (FGMS) on Diabetes Self-Management Practices (DSMP) and glycemic control among patients with type 2 diabetes (T2D)., Methods: This prospective study was conducted among 105 patients with T2D (aged 30-70 years), who self-tested their glucose levels by conventional finger-prick method using blood glucose meters (BGM). At baseline visit, FGMS sensors were fixed by a diabetes educator to all patients. At the baseline and at 12 weeks of the study, an interviewer collected the responses of Diabetes Self-Management (DSM) from all the study population using a questionnaire., Results: At 12 weeks, significant improvements in the DSM subscales were observed, which includes glucose management (P = 0.042), dietary control (P = 0.048), physical activity (P = 0.043), health care use (P = 0.001) and self-care (P = 0.001), compared to the values at baseline. At baseline, when the HbA1c level was 8.2%, at 12 weeks, it dropped to 7.9%. Also, at baseline, when the hypoglycemia frequency was 3.1, it declined to 1.2 episodes/month at 12 weeks. While comparing the blood glucose monitoring through BGM at the baseline (1.92/day), a higher degree of frequency of blood glucose monitoring was evident at 12 weeks (6.84/day), after the patients employed the FreeStyle Libre., Conclusion: After 12 weeks of using the FreeStyle Libre, the frequency of hypoglycemic episodes and the HbA1c levels were dropped, while the practice of DSM and frequency of blood glucose monitoring were improved., Competing Interests: Declaration of competing interest Authors have no conflict of interests., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: To determine and analyze the factors related to anxiety and depression in patients having diabetic foot ulcer (DFU)., Methods: This two-center, cross-sectional study was conducted among 250 patients with DFU, who were receiving treatment in the outpatient diabetes foot care clinic at Prince Sultan Military Medical City, Saudi Arabia and National Center for Diabetes, Endocrinology and Genetics, Jordan. Employing the Hospital Anxiety and Depression Scale (HADS), the anxiety and depression levels of the study population were measured. The demographic variables were also recorded., Results: Females displayed significantly higher anxiety (p = 0.032) and depression levels (p = 0.043); and those who were unmarried showed higher anxiety (p = 0.042). School educated patients showed reduced degrees of anxiety (p = 0.023) and depression (p = 0.003) and college educated showed reduced anxiety (p = 0.047) compared to uneducated. Compared to patients on treatment with diet, a significant decline was found in depression (p = 0.034) levels among orally treated patients. Compared to patients on oral medication, patients with oral and insulin treatments revealed higher depression (p = 0.026). Higher-income patients showed a significant decline for anxiety (p = 0.004). Patients who were past smokers had higher anxiety (p = 0.046) than current and never had been smokers. Higher anxiety (p = 0.017) was observed in patients having higher HbA1c levels, similarly, patients with three diabetes-related complications showed higher levels of anxiety (p = 0.001) and depression (p = 0.001)., Conclusion: Female gender, lower education levels, patients on oral and insulin treatments, low income, high HbA1c levels and patients experiencing a higher number of diabetes-related complications showed either higher anxiety or depression levels., Competing Interests: Declaration of competing interest Authors have no conflict of interests., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: To elucidate the clinical features of COVID-19 patients with type 1 diabetes (T1D) under hospitalization and home isolation conditions., Method: This retrospective study was conducted among 32 patients with COVID-19 and T1D, who sought treatment at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia between May 01, 2020 and July 30, 2020. Patients data were extracted from electronic medical records., Results: Of the total of 32 COVID-19 patients with T1D, 21.9% required hospitalization, while 78.1% underwent home isolation. Among the study population, 9.4% (3/32) were reported to have hypertension, 21.9% (7/32) had chronic pulmonary disease (CPD), 18.8% (6/32) had thyroid disorders, and 18.8% (6/32) had the celiac disease. Of the 32 studied patients, 68.8% (22/32) of them were reported as normal, while 28.1% (9/32) had chronic kidney disease (CKD) II and 3.1% (1/32) had end-stage renal failure. The most common symptoms observed among the hospitalized patients were nausea and vomiting (71.4%; 5/7), followed by fever (57.1%; 4/7), cough (42.8%; 3/7), sore throat (42.8%; 3/7), abdominal pain (42.8%; 3/7) and dyspnea (42.%; 3/7). The most common reasons for hospitalization were diabetic ketoacidosis (71.4%; 5/7) followed by bacterial pneumonia (14.3%; 1/7), fever (14.3%; 1/7), sore throat (14.3%; 1/7), severe hyperglycemia (14.3%; 1/7) and COVID-19 pneumonia (14.3%; 1/7). Except the severity of COVID-19 (p = 0.0001), none of the demographic and clinical parameters indicated statistically significant differences between patients requiring hospitalization and home isolation., Conclusion: Majority of the COVID-19 patients with T1D recovered with conservative treatment at home. Diabetic ketoacidosis was the most common reason for hospitalization., Competing Interests: Declaration of competing interest Authors have no conflict of interests., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: To Investigate the factors associated with Diabetic Ketoacidosis (DKA) among patients with type 1 diabetes (T1D)., Methods: This was a descriptive, retrospective study conducted among 1118 patients with T1D, at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia. After, exclusion process, 336 patients were selected for analysis. Among these, 105 patients with T1D were hospitalized for DKA, whereas 231 patients without DKA were outpatients who visited the hospital for T1D follow-up treatment., Results: Bivariate analysis between patients with DKA and those without DKA revealed significant relationships in terms of gender (p = 0.014), age (p = 0.0001), body mass index (BMI) (p = 0.017), hemoglobin A1c (HbA1c) (p = 0.0001), duration of diabetes (p = 0.001) and clinic appointments (p = 0.001). From the logistic regression analysis, it was clear that females (OR 1.88; p = 0.038) had a higher risk for DKA. As compared to the age group of ≥30 years, those in the age category of 20-29 years (OR 1.35; p = 0.001) and teenagers (OR 3.64; p = 0.001) faced a higher risk of having DKA episodes. Compared with patients having HbA1c levels <8%, those showing HbA1c levels 8-9.9% (OR 1.77; p = 0.224) and ≥10% (OR 4.06; p = 0.003) revealed higher risk for DKA. Likewise, in comparison with the patients who were compliant to clinic appointments, those who were non-compliant to clinic appointments exhibited higher than six times the risk (OR 6.38; p = 0.0001) of being more prone to experiencing the DKA episodes., Conclusion: Patients with higher risk for DKA comprise, those having high HbA1c levels, longer period of diabetes duration, teenagers, female gender and non-compliant to clinic appointments., Competing Interests: Declaration of competing interest Authors have no conflict of interests., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Introduction Self-monitoring of blood glucose (SMBG) plays an important role in diabetes management. The Contour ® Next One glucometer is a recent glucometer that delivers blood glucose results by an immediate color indicator to aware users when blood glucose is at a critical high or low. The main purpose of the study was to assess the impact of an application of a blood glucose meter (BGM) having a color range indicator on clinical characteristics and glucose monitoring satisfaction (GMS) among patients having type 2 diabetes (T2D). Methods A total of 85 (male 42 and female 43) patients with T2D were switched to a BGM having smartLIGHT™ target range indicator (blood glucose meters featuring color range indicator) using Contour ® Next One glucometer. Demographic data, as well as glycemic control, were collected at baseline and 12 weeks. At the time of the baseline and 12 weeks of the study, a trained interviewer gave the GMS survey questionnaire to every patient in order to collect the glucose monitoring satisfaction. In addition to GMS, a patient's perceptions of smartLIGHT™ feature satisfaction survey responses were also collected from the patients at the end of the study (12 weeks). Results Compared to baseline, a significant improvement was observed in the subdomains of glucose monitoring satisfaction survey (GMSS) score on openness (p=0.0001), emotional burden (p=0.0001), behavioral burden (p=0.0001), and trust (p=0.0001) at the end of the study. Overall, the total GMS score at baseline was 2.61 ± 0.51, which improved up to 3.16 ± 0.63 (p=0.0001) during the period of 12 weeks. The patient satisfaction with smartLIGHT™ survey outcomes exposed evidence of satisfaction among the study population at the end of the study. There were statistically insignificant reductions observed in glycosylated hemoglobin (HbA1c) (p=0.063) and the frequency of hypoglycemia (p=0.057) at the end of the study. Conclusions The study demonstrates a significant improvement in the subdomains of GMSS - openness, emotional burden, behavioral burden, and trust - at 12 weeks than at the baseline, with the increased total GMSS score. Similarly, high satisfaction with the color-based smartLIGHT™ feature was also observed at the end of the study., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Al Hayek et al.)

Objectives: To elucidate the risk factors for hospital admission among COVID-19 patients with type 2 diabetes mellitus (T2DM)., Methods: This retrospective study was conducted at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia between May 2020 and July 2020. Out of 7,260 COVID-19 patients, 920 were identified as T2DM. After the exclusion process, 806 patients with T2DM were included in this analysis. Patients' data were extracted from electronic medical records. A logistic regression model was performed to estimate the risk factors of hospital admission. Results: Of the total of 806 COVID-19 patients with T2DM, 48% were admitted in the hospital, 52% were placed under home isolation. Older age between 70-79 years (OR [odd ratio] 2.56; p=0.017), ≥80 years (OR 6.48; p=0.001) were significantly more likely to be hospitalized compared to less than 40 years. Similarly, patients with higher HbA1c level of ≥9% compared to less than 7%; (OR 1.58; p=0.047); patients with comorbidities such as, hypertension (OR 1.43; p=0.048), cardiovascular disease (OR 1.56; p=0.033), cerebrovascular disease (OR 2.38; p=0.016), chronic pulmonary disease (OR 1.51; p=0.018), malignancy (OR 2.45; p=0.025), chronic kidney disease (CKD) IIIa, IIIb, IV (OR 2.37; p=0.008), CKD V (OR 5.07; p=0.007) were significantly more likely to be hospitalized. Likewise, insulin-treated (OR 1.46; p=0.03) were more likely to require hospital admission compared to non-insulin treated patients., Conclusion: Among COVID-19 patients with diabetes, higher age, high HbA1c level, and presence of other comorbidities were found to be significant risk factors for the hospital admission.

Background and objective Diabetic foot ulcers (DFU) have been shown to have a high impact on the patients' perceived health-related quality of life (HRQOL). The aim of this study was to estimate the HRQOL and its related risk factors in patients with foot ulcers associated with type 2 diabetes mellitus (T2DM). Methods This cross-sectional study was performed on 81 patients with DFU, from January 2019 to July 2019 at the Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia. The study population was purposively and conveniently chosen based on patients' availability during their regular and customary outpatient clinic visits. Using the Arabic version of the Short-Form 36-Item Survey (SF-36), these patients were interviewed and their HRQOL scores were was assessed. The SF-36 covered eight aspects of health such as physical functioning, body pain, limitations in the roles induced by physical health problems, limitations in the roles caused by personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Results It was evident that age, gender, education, occupation, smoking, duration of diabetes, hypertension, dyslipidemia, body mass index (BMI), and the number of diabetes-associated complications, hypertension, and dyslipidemia significantly affected the patients' physical functions. The physical health of the patient was strongly influenced by gender, education, occupation, income, BMI, and the number of complications. The emotional health of the patient was affected by dyslipidemia, deformity, prior amputations, as well as BMI and glycosylated hemoglobin (HbA1c). The social standing of the patient was influenced by age, income, education, and occupation. The degree of pain experienced by the patient varied with age and the number of complications, as well as notable differences in their general health. The factors of age, education, occupation, income, and the number of diabetic complications induced several health changes in varying degrees. The patients with DFU revealed overall lower HRQOL relating to all the eight aspects of the SF-36. Conclusion The patients with DFU in Saudi Arabia generally revealed lower HRQOL. However, prospective and large-scale studies are required in the future to support these findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Al Ayed et al.)

Background Selecting the appropriate insulin pen needle is important to reduce pain and injection-related adverse events like insulin leakage. It also helps to improve medication adherence and glycemic control in patients with type 1 diabetes mellitus (T1DM). Objective This study aimed to compare the 6-mm and 8-mm 32.5-gauge insulin pen needles in terms of glycemic control, pain score, user preference, medication adherence, and injection adverse events in patients with T1DM. Methods We conducted a prospective cohort study of 62 patients with T1DM. All patients constituted an experimental group initially and then changed the length of the needle to be part of a self-control group. The glycemic control, visual analog scale (VAS) pain score, Morisky Medication Adherence Scale (MMAS) score, needle attribute score, and injection-related adverse events were measured for all patients with both lengths of needles. Patients were assessed at the baseline visit and followed up for three months. Statistical comparisons were done by the chi-squared test, paired t-test, and paired Wilcoxon test when appropriate with a two-tailed alpha level below 0.05 indicating statistical significance. Results With the NanoPass® 32.5-gauge, 6-mm needle (Terumo Corp., Tokyo, Japan), patients had significantly lower glycated hemoglobin (HbA1c) compared to 8-mm needles (7.9% vs. 8.3%; p<0.001). The proportions of patients who reported no hypoglycemic episodes were 22/62 and 9/62, with the 6-mm and 8-mm needles, respectively. The 6-mm needles were better in terms of the following parameters compared to 8-mm needles: mean needle attribute scores (36.7 vs. 24.2; p<0.001), median VAS pain scores (20 vs. 55; p<0.001), insulin leakage (6/62 vs. 20/62; p=0.002), and the MMAS score (4.9 vs. 3.4; p<0.001). Conclusion This study provided an overview of the safety, adherence, pain score, and glycemic control relating to the 6-mm and 8-mm insulin needle lengths. Insulin injections using the NanoPass 32.5-gauge, 6-mm needle were associated with lower pain score, higher patient adherence, fewer adverse events, and better glycemic control compared to the 8-mm needle. Therefore, we recommend the use of the NanoPass 6-mm needle for patients with T1DM. Further studies are needed to confirm these findings in patients with type 2 diabetes mellitus (T2DM)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Al Hayek et al.)

Background The Bethesda System for Reporting Thyroid Cytolopathology (TBSRTC) is the standardized category-based reporting system for thyroid nodule (TN) aspirations; however, atypia of undetermined significance/follicular lesion of undetermined significance (Bethesda category III, AUS/FLUS) is the most controversial category. The aim of this study was to identify the degree of malignancy risk and the related risk factors in the surgical pathology of the Bethesda Category III thyroid nodules.  Methods A total of 4074 patients (15-90 years, 81.5% of females) were subjected to retrospective analysis, and a total of 463 nodules were classified as Bethesda Class III and included in the analysis. Once all the thyroid cytopathological slides and ultrasound (US) reports were reviewed, they were classified according to the Bethesda System for Reporting Thyroid Cytology, the American College of Radiology (ACR) and the Thyroid Imaging Reporting and Data System (TI-RADS). Results Among the 463 Bethesda class III nodules, 167 nodules were surgically excised, showing an overall malignancy of 27.6% (n = 46/167). Patients having thyroid-stimulating hormone (TSH) levels of >4.5 mIU/L (35%), TN <2 cm (34.6%), solid or nearly solid (28.7%), highly hypoechoic (58.3%), longer than wide (50%), lobulated (45.5%), punctate echogenic (48.6%), ACR TI-RAD 5 (55.2%) and falling under the ATA category of high suspicion (50%), displayed a higher risk of malignancy (ROM). The chi-square test revealed a strong association between the echogenicity, echogenic foci, ACR TI-RAD and American Thyroid Association (ATA) category between the malignant and benign nodules. The papillary thyroid carcinoma (PTC) follicular variant (39%) and PTC classical (27%) were identified, in this study population, as the commonest forms of thyroid cancer. Conclusion The nodules with AUS/FLUS cytology malignancy rate are comparable with the earlier estimations of other countries. The ACR TI-RAD displayed more accurate diagnostic performances in predicting malignancy in the Bethesda III nodules. However, to confirm the accuracy of the molecular marker tests in specific cytological scenarios, more extensive studies are required in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Al Dawish et al.)

Background: Thyroid cancer is the second most common cancer affecting Saudi women after breast cancer, with papillary thyroid carcinoma (PTC) accounting for 80-90% of thyroid cancers. DNA methyltransferases affect DNA methylation, and it is thought that they play an important role in the malignant transformation of various cancers., Methods: We sought to evaluate the frequency of DNA methyltransferase 3A (DNMT3A) alterations in a large cohort of >1000 PTC cases using exome sequencing, capture sequencing, immunohistochemistry and methylation-specific polymerase chain reaction. We also performed in vitro analysis to investigate the role of DNMT3A methylation in PTC cell lines., Results: DNMT3A pathogenic mutations were noted in 1.2% (12/1013) of PTC cases. Reduced/loss of DNMT3A expression was seen in 59.8% (579/968) of PTC cases and was significantly associated with the DNMT3A mutation (p = 0.0120). DNMT3A alterations (mutation and/or loss of expression) were associated with aggressive clinical parameters and a poor outcome. The promoter region of the DNMT3A gene was methylated in 57.1% of PTC cases tested and was significantly associated with reduced DNMT3A protein expression (p = 0.0253). Treatment of the methylated PTC cell line with 5-aza-2'-deoxycytidine resulted in demethylation of the DNMT3A gene, leading to restoration of its expression. Demethylation significantly potentiated the TRAIL-mediated apoptosis in PTC cells. Interestingly, silencing of DNMT3A using siRNA suppressed TRAIL-mediated apoptosis., Conclusion: These findings suggest that DNMT3A alterations play an important role in PTC pathogenesis and demethylation agents can be used to restore the function of DNMT3A in a subset of patients with PTC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Tumor recurrence occurs in ∼20% of PTCs and some reach advanced stages. Promoter mutation in the telomerase reverse transcriptase (TERT) gene is identified to be a prognostic marker in PTC. However, the contribution of TERT promoter mutation to cancer progression in PTC patients is still not fully understood. In this study, we investigated the incidence of TERT promoter mutations and TERT protein expression and their association with clinicopathological outcomes in a large cohort of PTC samples using direct sequencing technology and immunohistochemistry. Furthermore, two PTC cell lines were utilized to investigate role of TERT mutations in mediating metastasis. Two promoter hotspot mutations C228T and C250T were identified in 18.0% (167/927) of our cohort and were significantly associated with poor 5 years disease-free survival and distant metastasis of PTC. TERT protein overexpression was noted in 20.1% of our PTC cohort and was significantly associated with poor prognostic markers such as older age, extrathyroidal extension and Stage IV tumors. A significant association was also found between TERT overexpression and epithelial-mesenchymal transition (EMT) markers. Functional analysis showed that TERT inhibition reduced cell growth, invasion, migration and angiogenesis in PTC via suppression of EMT in PTC cells. Our results suggest that TERT promoter mutation is an independent predictor of disease-free survival and might drive the metastasis, and downregulation of TERT could potentiate antitumor and antimetastatic activities in PTC., (© 2017 UICC.)

Context and Objective: S-phase kinase protein 2 (SKP2) is an F-box protein with proteasomal properties and has been found to be overexpressed in a variety of cancers. However, its role in papillary thyroid cancer (PTC) has not been fully elucidated., Experimental Design: SKP2 expression was assessed by immunohistochemistry in a tissue microarray format on a cohort of >1000 PTC samples. In vitro and in vivo studies were performed using proteasome inhibitor bortezomib and proapoptopic death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) either alone or in combination on PTC cell lines., Results: SKP2 was overexpressed in 45.5% of PTC cases and was significantly associated with extrathyroidal extension (P = 0.0451), distant metastasis (P = 0.0435), and tall cell variant (P = 0.0271). SKP2 overexpression was also directly associated with X-linked inhibitor of apoptosis protein overexpression (P < 0.0001) and Bcl-xL overexpression (P = 0.0005) and inversely associated with death receptor 5 (P < 0.0001). The cotreatment of bortezomib and TRAIL synergistically induced apoptosis via mitochondrial apoptotic pathway in PTC cell lines. Furthermore, bortezomib and TRAIL synergistically induced reactive oxygen species (ROS) generation and caused death receptor 5 upregulation through activation of the extracellular signal-regulated kinase-C/EBP homologous protein signaling cascade. Finally, bortezomib treatment augmented the TRAIL-mediated anticancer effect on PTC xenograft tumor growth in nude mice., Conclusion: These data suggest that SKP2 is a potential therapeutic target in PTC and that a combination of bortezomib and TRAIL might be a viable therapeutic option for the treatment of patients with aggressive PTC.

Our ability to identify germline variants in hereditary cancer cases remains challenged by the incomplete cataloging of relevant genes and lack of consensus on who should be tested. We designed a panel [hereditary oncogenesis predisposition evaluation (HOPE)] that encompasses most of the genes known to be associated with cancer development and tested its yield on more than 1300 samples of cancer patients. Pathogenic or likely pathogenic variants in high and intermediate risk genes were identified in 16, 23.9, 9.7 and 2.7%, respectively, of peripheral blood or normal tissue samples taken from patients with breast, ovarian, colorectal and thyroid cancer. To confirm specificity of these findings, we tested an ethnically matched cohort of 816 individuals and only identified pathogenic or likely pathogenic variants in 1.59% (0.98% in high risk and 0.61% in intermediate risk). Remarkably, pathogenic or likely pathogenic alleles in DNA repair/genomic instability genes (other than BRCA2, ATM and PALB2) accounted for at least 16.8, 11.1, 50 and 45.5% of mutation-positive breast, ovarian, thyroid and colorectal cancer patients, respectively. Family history was noticeably lacking in a substantial fraction of mutation-positive cases (63.7, 81.5, 42.4 and 87.5% in breast, ovarian, colorectal and thyroid, respectively). Our results show high contribution of germline mutations to cancer predisposition that extends beyond "classical" hereditary cancer genes. Family history was lacking in 63.5% mutation-positive cases, shows that hereditary cancer need not appear familial and suggests that relaxed selection of cancer patients for hereditary cancer panels should be considered.

Papillary thyroid carcinoma (PTC) has a wide geographic variation in incidence; it is most common in Saudi Arabia, where it is only second to breast cancer as the most common cancer among females. Genomic profiling of PTC from Saudi Arabia has not been attempted previously. We performed whole-exome sequencing of 101 PTC samples and the corresponding genomic DNA to identify genes with recurrent somatic mutations, then sequenced these genes by using a next-generation gene-panel approach in an additional 785 samples. In addition to BRAF, N-RAS, and H-RAS, which have previously been shown to be recurrently mutated in PTC, our analysis highlights additional genes, including thyroglobulin (TG), which harbored somatic mutations in 3% of the entire cohort. Surprisingly, although TG mutations were not exclusive to mutations in the RAS-MAP kinase pathway, their presence was associated with a significantly worse clinical outcome, which suggests a pathogenic role beyond driving initial oncogenesis. Analysis of metastatic PTC tissue revealed significant enrichment for TG mutations (p < 0.001), including events of apparent clonal expansion. Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution., (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to find out the evolving role of professional continuous glucose monitoring (PCGM) on hemoglobin A1c (HbA1c) and the frequency of hypoglycemia., Methods: This was a 3-month, prospective study conducted among patients (aged 15-24 years) with type 1 diabetes mellitus who attended a diabetes clinic [Diabetes Treatment Center, Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia] due to recurrent unexplained hypoglycemia unawareness episodes between July 2014 and December 2014. The respondents were purposively and conveniently selected and they were asked to wear the PCGM device (iPro(®)2; Medtronic MiniMed, Inc., Northridge, CA, USA) for 5 days. The PCGM results were collected by the diabetic educator and reviewed by the treating physician on the same day as removal of the device. Clinical and demographic data were also collected., Results: Overall, 56 patients were included in the study. The mean (±SD) age of the study cohort was 18.1 ± 1.82 years and 27 (48.2%) patients were male. Compared with baseline, non-significant but positive differences were observed in HbA1c levels in both male and female patients and in those who were older (aged 20-24 years). Similar results were observed in the frequency of hypoglycemia and a significant change was observed for female patients (P < 0.05). Compared with baseline, a significant positive difference was observed in patients' overall frequency of hypoglycemia by the end of the study (P < 0.001)., Conclusions: Professional continuous glucose monitoring is a valuable tool for detecting episodes of hypoglycemia and may help to decrease HbA1c levels and reduce the frequency of hypoglycemia.