Severe vitamin D deficiency is not related to SARS-CoV-2 infection but may increase mortality risk in hospitalized adults: a retrospective case-control study in an Arab Gulf country.

PURPOSE: As the world continues to cautiously navigate its way through the coronavirus disease 2019 (COVID-19) pandemic, several breakthroughs in therapies and vaccines are currently being developed and scrutinized. Consequently, alternative therapies for severe acute respiratory coronavirus 2 (SARS-CoV-2) prevention, such as vitamin D supplementation, while hypothetically promising, require substantial evidence from countries affected by COVID-19. The present retrospective case-control study aims to identify differences in vitamin D status and clinical characteristics of hospitalized patients screened for SARS-CoV-2, and determine associations of vitamin D levels with increased COVID-19 risk and mortality. METHODS: A total of 222 [SARS-CoV-2 (+) N = 150 (97 males; 53 females); SARS-CoV-2 (-) N = 72 (38 males, 34 females)] out of 550 hospitalized adult patients screened for SARS-CoV-2 and admitted at King Saud University Medical City-King Khalid University Hospital (KSUMC-KKUH) in Riyadh, Saudi Arabia from May-July 2020 were included. Clinical, radiologic and serologic data, including 25(OH)D levels were analyzed. RESULTS: Vitamin D deficiency (25(OH)D < 50 nmol/l) was present in 75% of all patients. Serum 25(OH)D levels were significantly lower among SARS-CoV-2 (+) than SARS-CoV-2 (-) patients after adjusting for age, sex and body mass index (BMI) (35.8 ± 1.5 nmol/l vs. 42.5 ± 3.0 nmol/l; p = 0.037). Multivariate regression analysis revealed that significant predictors for SARS-CoV-2 include age > 60 years and pre-existing conditions (p < 0.05). Statistically significant predictors for mortality adjusted for covariates include male sex [Odds ratio, OR 3.3 (95% confidence interval, CI 1.2-9.2); p = 0.02], chronic kidney disease [OR 3.5 (95% CI 1.4-8.7); p = 0.008] and severe 25(OH)D deficiency (< 12.5 nmol/l), but at borderline significance [OR 4.9 (95% CI (0.9-25.8); p = 0.06]. CONCLUSION: In hospital settings, 25(OH)D deficiency is not associated with SARS-CoV-2 infection, but may increase risk for mortality in severely deficient cases. Clinical trials are warranted to determine whether vitamin D status correction provides protective effects against worse COVID-19 outcomes.

Diabetes and Covid-19 among hospitalized patients in Saudi Arabia: a single-centre retrospective study.

BACKGROUND: Information on the clinical characteristics and outcomes of hospitalized Covid-19 patients with or without diabetes mellitus (DM) is limited in the Arab region. This study aims to fill this gap. METHODS: In this single-center retrospective study, medical records of hospitalized adults with confirmed Covid-19 [RT-PCR positive for SARS-CoV2] at King Saud University Medical City (KSUMC)-King Khaled University Hospital (KKUH), Riyadh, Saudi Arabia from May to July 2020 were analyzed. Clinical, radiological and serological information, as well as outcomes were recorded and analyzed. RESULTS: A total of 439 patients were included (median age 55 years; 68.3% men). The most prevalent comorbidities were vitamin D deficiency (74.7%), DM (68.3%), hypertension (42.6%) and obesity (42.2%). During hospitalization, 77 out of the 439 patients (17.5%) died. DM patients have a significantly higher death rate (20.5% versus 12.3%; p = 0.04) and lower survival time (p = 0.016) than non-DM. Multivariate cox proportional hazards regression model revealed that age [Hazards ratio, HR 3.0 (95% confidence interval, CI 1.7-5.3); p < 0.001], congestive heart failure [adjusted HR 3.5 (CI 1.4-8.3); p = 0.006], smoking [adjusted HR 5.8 (CI 2.0-17.2); p < 0.001], ß-blocker use [adjusted HR 1.7 (CI 1.0-2.9); p = 0.04], bilateral lung infiltrates [adjusted HR 1.9 (CI 1.1-3.3); p = 0.02], creatinine > 90 µmol/l [adjusted HR 2.1 (CI 1.3-3.5); p = 0.004] and 25(OH)D < 12.5 nmol/l [adjusted HR 7.0 (CI 1.7-28.2); p = 0.007] were significant predictors of mortality among hospitalized Covid-19 patients. Random blood glucose ≥ 11.1 mmol/l was significantly associated with intensive care admission [adjusted HR 1.5 (CI 1.0-2.2); p = 0.04], as well as smoking, ß-blocker use, neutrophil > 7.5, creatinine > 90 µmol/l and alanine aminotransferase > 65U/l. CONCLUSION: The prevalence of DM is high among hospitalized Covid-19 patients in Riyadh, Saudi Arabia. While DM patients have a higher mortality rate than their non-DM counterparts, other factors such as old age, congestive heart failure, smoking, ß-blocker use, presence of bilateral lung infiltrates, elevated creatinine and severe vitamin D deficiency, appear to be more significant predictors of fatal outcome. Patients with acute metabolic dysfunctions, including hyperglycemia on admission are more likely to receive intensive care.

Hypofibrinolysis in type 2 diabetes: the role of the inflammatory pathway and complement C3.

AIMS/HYPOTHESIS: Plasminogen activator inhibitor-1 (PAI-1) has been regarded as the main antifibrinolytic protein in diabetes, but recent work indicates that complement C3 (C3), an inflammatory protein, directly compromises fibrinolysis in type 1 diabetes. The aim of the current project was to investigate associations between C3 and fibrinolysis in a large cohort of individuals with type 2 diabetes. METHODS: Plasma levels of C3, C-reactive protein (CRP), PAI-1 and fibrinogen were analysed by ELISA in 837 patients enrolled in the Edinburgh Type 2 Diabetes Study. Fibrin clot lysis was analysed using a validated turbidimetric assay. RESULTS: Clot lysis time correlated with C3 and PAI-1 plasma levels (r = 0.24, p < 0.001 and r = 0.22, p < 0.001, respectively). In a multivariable regression model involving age, sex, BMI, C3, PAI-1, CRP and fibrinogen, and using log-transformed data as appropriate, C3 was associated with clot lysis time (regression coefficient 0.227 [95% CI 0.161, 0.292], p < 0.001), as was PAI-1 (regression coefficient 0.033 [95% CI 0.020, 0.064], p < 0.05) but not fibrinogen (regression coefficient 0.003 [95% CI -0.046, 0.051], p = 0.92) or CRP (regression coefficient 0.024 [95% CI -0.008, 0.056], p = 0.14). No correlation was demonstrated between plasma levels of C3 and PAI-1 (r = -0.03, p = 0.44), consistent with previous observations that the two proteins affect different pathways in the fibrinolytic system. CONCLUSIONS/INTERPRETATION: Similarly to PAI-1, C3 plasma levels are independently associated with fibrin clot lysis in individuals with type 2 diabetes. Therefore, future studies should analyse C3 plasma levels as a surrogate marker of fibrinolysis potential in this population.

The Relationship Between Hemoglobin A1c, Time in Range, and Glycemic Management Indicator in Patients With Type 1 and Type 2 Diabetes in a Tertiary Care Hospital in Saudi Arabia.

OBJECTIVES: This study aimed to assess the correlation between glycated hemoglobin A1 (HbA1c), time in range (TIR), and glycemic management indicator (GMI) in patients with both type 1 diabetes (T1D) and type 2 diabetes (T2D) who were using a flash glucose monitoring (FGM) device (FreeStyle Libre; Abbott Diabetic Care, Witney, UK). METHODS: This was a retrospective study that looked at T1D and T2D FreeStyle Libre users' LibreView database in the period between January 2020 to June 2022. The study was conducted at the diabetes department at the King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia, following Institutional Review Board (IRB) approval. Data were collected from the LibreView website, as well as from the electronic privacy information center (EPIC) hospital records. RESULTS: Data were available for 327 patients, mean age of 33.08(±17.1) years old, and 55.7% were females. HbA1c had a statistically significant correlation with both TIR and GMI with coefficient of correlation (r) values of 0.78 (p<0.001) and 0.82 (p<0.001), respectively. A linear regression model between TIR and Hb1Ac was also developed and found to be statistically significant (p<0.001) with an acceptable R2 value (0.60). CONCLUSION: Study findings revealed that the %TIR could be a reliable predictor of Hb1Ac. Thus, Freestyle Libre was able to determine Hb1Ac as close to the lab results as possible. Therefore, it is necessary to encourage diabetes patients to achieve at least 70% TIR in order to keep Hb1Ac within the desired range.

Manual and Application-Based Carbohydrate Counting and Glycemic Control in Type 1 Diabetes Subjects: A Narrative Review.

Type 1 diabetes (T1DM) is the most common chronic disease in young adults and children, which is treated with insulin, usually given as basal and boluses. Carbohydrate counting (CHOC) helps patients to determine the correct meal doses. The aim of this review is to study the effect of CHOC on glucose control, body weight, insulin dose and quality of life (QoL). The literature search was conducted using PubMed from January 2010 to October 2022. Studies included in this review are limited to randomized controlled studies involving an intervention group undergoing CHOC and a control group following the usual practice, measuring glycosylated hemoglobin (HbA1c) as a parameter of glucose control and involving only T1DM subjects. A total of ten articles were found to fulfill the criteria involving 1034 patients. Most of the studies showed a positive impact of CHOC on glucose control, especially in adults, where five out of six studies were statistically positive. However, in pediatrics, only two out of four showed a positive outcome. In all four studies using mobile applications, CHOC was better at controlling glucose. No difference was seen between the CHOC group and the control regarding the risk of severe hypoglycemia. In fact, two studies have shown lower hypoglycemia rates. No change in weight was observed in most of the studies (six out of eight). In subjects with T1DM, CHOC might provide better glucose control than traditional care without a significant increment in severe hypoglycemia or weight gain. Mobile application-based models showed promising results in glucose control.

Consanguinity and Diabetes in Saudi Population: A Case-Control Study.

BACKGROUND AND AIM: Diabetes mellitus (DM) of both types is a genetically determined disorder and is prevalent in the Saudi population. Furthermore, the rate of consanguineous marriages is also high among Saudis. Therefore, we aimed to determine the prevalence of consanguinity among people with DM and investigate the effect of consanguinity on the occurrence of diabetes at different levels. METHODS: A descriptive cross-sectional study was carried out at the Obesity, Metabolism and Endocrine Center of King Fahad Medical City in Riyadh, Saudi Arabia in January 2021. Information on patients' demographics (age, gender), family history of DM, and presence of consanguinity, and degree of consanguineous marriage were collected. RESULTS: We included 324 people with DM, 143 (44.1%) with type 1 diabetes (T1DM), and 181 (55.9%) with type 2 diabetes (T2DM). We included 201 people without DM for T1DM control and 300 people for T2DM control. The mean age was 26.6 ± 11.1 years for the T1DM group and 57.8 ± 11.6 years for the T2DM group. Consanguinity was noted among 73 (51.4%) T1DM patients, but T1DM was not significantly related to consanguinity. T2DM was significantly correlated with consanguinity (r=0.132, p=0.004) particularly among patients with a degree of consanguinity as first-cousins for both paternal and maternal sides (odds ratio [OR]=1.151 and 1.476). Gender and positive family history for DM and consanguineous marriage between cousins were significant factors for T2DM. After controlling for gender and a positive family history of DM, consanguineous marriage between cousins from both the paternal and maternal sides remained significant. CONCLUSION: T2DM occurrence increases in presence of consanguinity in the Saudi population. This relationship might contribute to the higher risk of DM prevalence. Further studies are needed to elucidate this relationship deeply. It's unclear whether lowering consanguineous marriages would decrease the prevalence of diabetes or not. However, a clear message about this correlation has to be delivered to the public.

Glycemic control and pregnancy outcomes in patients with diabetes in pregnancy: A retrospective study.

CONTEXT: Diabetes in pregnancy (DIP) is either pregestational or gestational. AIMS: To determine the relationship between glycemic control and pregnancy outcomes in a cohort of DIP patients. SETTINGS AND DESIGN: In this 12-month retrospective study, a total of 325 Saudi women with DIP who attended the outpatient clinics at a tertiary center Riyadh, Saudi Arabia, were included. SUBJECTS AND METHODS: The patients were divided into two groups, those with glycated hemoglobin (HbA1c) ≤6.5% (48 mmol/mol) and those with glycated hemoglobin (HbA1c) above 6.5%. The two groups were compared for differences in maternal and fetal outcomes. STATISTICAL ANALYSIS USED: Independent Student's t-test and analysis of variance were performed for comparison of continuous variables and Chi-square test for frequencies. Odds ratio and 95% confidence intervals were calculated using logistic regression. RESULTS: Patients with higher HbA1c were older (P = 0.0077), had significantly higher blood pressure, proteinuria (P < 0.0001), and were multiparous (P = 0.0269). They had significantly shorter gestational periods (P = 0.0002), more preterm labor (P < 0.0001), more perineal tears (P = 0.0406), more miscarriages (P < 0.0001), and more operative deliveries (P < 0.0001). Their babies were significantly of greater weight, had more Neonatal Intensive Care Unit (NICU) admissions, hypoglycemia, and macrosomia. CONCLUSIONS: Poor glycemic control during pregnancy is associated with adverse maternal and fetal outcomes (shortened gestational period, greater risk of miscarriage, increased likelihood of operative delivery, hypoglycemia, macrosomia, and increased NICU admission). Especially at risk are those with preexisting diabetes, who would benefit from earlier diabetes consultation and tighter glycemic control before conception.

The Saudi clinical practice guideline for the management of overweight and obesity in adults.

OBJECTIVE: To assist healthcare providers in evidence-based clinical decision-making for the management of overweight and obese adults in Saudi Arabia. METHODS: The Ministry of Health, Riyadh, Kingdom of Saudi Arabia assembled an expert Saudi panel to produce this clinical practice guideline in 2015. In collaboration with the methodological working group from McMaster University, Hamilton, Canada, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which describes both the strength of recommendation and the quality of evidence  RESULTS: After identifying 11 questions, corresponding recommendations were agreed upon as guidance for the management of overweight and obese adults. These included strong recommendations in support of lifestyle interventions rather than usual care alone, individualized counseling interventions rather than generic educational pamphlets, physical activity rather than no physical activity, and physical activity in addition to diet rather than diet alone. Metformin and orlistat were suggested as conditional recommendations for the management of overweight and obesity in adults. Bariatric surgery was recommended, conditionally, for the management of obese adults (body mass index of ≥40 or ≥35 kg/m2 with comorbidities).  CONCLUSIONS: The current guideline includes recommendation for the non-pharmacological, pharmacological, and surgical management of overweight and obese adults. In addition, the panel recommends conducting research priorities regarding lifestyle interventions and economic analysis of drug therapy within the Saudi context, as well as long term benefits and harms of bariatric surgery.

Characterization of thyroid function and antithyroid antibody tests among Saudis.

OBJECTIVE: To determine the reference intervals for thyroid function tests and the prevalence of thyroid autoimmunity in the Saudi population.   METHODS: A cross-sectional prospective study was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies were measured using enzyme-linked immunosorbent-assay. Subjects with previous or a family history of thyroid disorders, those taking medications affecting thyroid function, pregnant or lactating women, and those with goiter were excluded. Individuals with positive antibodies were excluded from the final analysis of the TSH reference range, but were used to determine the prevalence of thyroid autoimmunity.   RESULTS: Out of 337 Saudi subjects initially screened, 132 (aged 13-60 years) were candidates for reference calculation, the mean±standard deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96±0.9 (0.59-4.37), for FT4 (pmol/L) was 15.47±1.83 (12.04-19.13), and for FT3 (pmol/L) was 5.22±0.7 (4.07-6.76). The TSH was higher in the antibodies positive group (2.5±1.17 mIU/L) compared with the negative one (1.96±0.9 mIU/L) (p less than 0.05). Finally, 26% of subjects were tested positive for antithyroid antibodies.   CONCLUSION: The TSH reference range was similar to laboratory references. Thyroid antibodies were prevalent in Saudis, necessitating further work in larger scale studies.

Gender-specific alterations in fibrin structure function in type 2 diabetes: associations with cardiometabolic and vascular markers.

CONTEXT: Diabetes is associated with increased incidence of atherothrombotic disease. The fibrin network forms the backbone of the arterial thrombus, and fibrin clot structure determines predisposition to cardiovascular events. OBJECTIVES: The aim of the study was to investigate fibrin clot structure/fibrinolysis in the largest type 2 diabetes cohort and analyze associations with cardiometabolic risk factors and vascular pathology. DESIGN: Clot structure/fibrinolysis was assessed in 875 participants of the Edinburgh Type 2 Diabetes Study [age, 68 (range, 60-75) yr; 450 males] by turbidimetric assays, and clots were visualized by confocal microscopy. Four parameters of clot structure/fibrinolysis were analyzed, and plasma levels of fibrinogen and plasminogen activator inhibitor-1 were studied by Clauss assay and ELISA, respectively. RESULTS: Clot maximum absorbance was increased in females compared with males (0.37 ± 0.005 and 0.34 ± 0.005 arbitrary unit, respectively; P < 0.001), and took longer to lyse (803 ± 20 and 665 ± 12 sec, respectively; P < 0.001). These gender differences in clot structure and fibrinolysis were still evident after correcting for fibrinogen and plasminogen activator inhibitor-1 plasma levels. A prothrombotic fibrin structure profile was associated with increased body mass index and low levels of high-density lipoprotein in women and with inadequate diabetes control in men. Clot formation time was related to previous cardiac ischemic events in both men and women after adjusting for traditional risk factors [odds ratio, 1.22 (95% confidence interval, 1.07, 1.38); and 1.33 (1.15, 1.50), respectively], and prothrombotic clots were associated with low ankle brachial index, renal impairment, and smoking, regardless of gender. CONCLUSIONS: Women with type 2 diabetes have compact clots with compromised fibrinolysis compared with men. There are gender-specific associations between clotting parameters and cardiometabolic risk factors in this population, whereas vascular abnormalities, impaired renal function, and smoking are associated with prothrombotic clot structure profile regardless of gender.