Association between vitamin D and cardiovascular health: Myth or Fact? A narrative review of the evidence.

Vitamin D deficiency is prevalent worldwide. Since the discovery of the expression of vitamin D receptor in ventricular cardiomyocytes, fibroblasts, and blood vessels, there has been a growing body of literature assessing the link between vitamin D status and cardiovascular health from one side, and the effect of vitamin D supplementation on prevention of cardiovascular diseases from the other side. In this review, we summarized studies highlighting the role of vitamin D on cardiovascular health, namely atherosclerosis, hypertension, heart failure, and metabolic syndrome, a recognized significant risk factor for cardiovascular diseases. Studies showed discrepancies between findings from cross-sectional and longitudinal cohorts and those from interventional trials, but also between one outcome and another. Cross-sectional studies found a strong association between low 25 hydroxyvitamin D (25(OH)D3) and acute coronary syndrome, and heart failure. These findings encouraged the promotion for vitamin D supplementation as a preventive measure for cardiovascular diseases in the elderly, namely in women. This fact, however, turned out into a myth with the results of large interventional trials that did not show any benefit from vitamin D supplementation in reducing ischemic events, heart failure or its outcomes, or hypertension. Although some clinical studies showed beneficial effect of vitamin D supplementation on insulin sensitivity and metabolic syndrome, this effect was not consistent across all studies.

Prevalence of menopausal hot flashes in Lebanon: A cross-sectional study.

BACKGROUND: Menopausal hot flashes or vasomotor symptoms are prevalent and could be debilitating in postmenopausal women. There is controversy regarding the risk factors for hot flashes, some of which may vary from one country or culture to another. OBJECTIVE: To shed light on this matter by assessing the prevalence of hot flashes, their effect on quality of life, and their association with certain factors such as physical exercise, caffeine, spicy food consumption, dietary intake, smoking, alcohol, etc. MATERIALS AND METHODS: A large cross-sectional study was conducted among 627 Lebanese women, aged 45-67 yr using a well-developed and comprehensive questionnaire, in order to better assess the prevalence of hot flashes, focusing on their characteristics, association with various factors, severity, and effect on the women's quality of life. RESULTS: 62.5% of participants experienced hot flashes. A statistically significant difference was noted between women who experience hot flashes and their counterparts with respect to smoking, body mass index, spicy food consumption, education level, age, menstrual status, and parity. An association was not found with physical activity or other dietary factors. CONCLUSION: As an alternative for hormone therapy, clinicians should consider lifestyle changes to help manage hot flashes, which impose a tremendous physical and social toll on the women experiencing them.

Minimally invasive parathyroidectomy guided by intraoperative parathyroid hormone monitoring (IOPTH) and preoperative imaging versus bilateral neck exploration for primary hyperparathyroidism in adults.

BACKGROUND: Bilateral neck exploration (BNE) is the traditional approach to sporadic primary hyperparathyroidism. With the availability of the preoperative imaging techniques and intraoperative parathyroid hormone assays, minimally invasive parathyroidectomy (MIP) is fast becoming the favoured surgical approach. OBJECTIVES: To assess the effects of minimally invasive parathyroidectomy (MIP) guided by preoperative imaging and intraoperative parathyroid hormone monitoring versus bilateral neck exploration (BNE) for the surgical management of primary hyperparathyroidism. SEARCH METHODS: We searched CENTRAL, MEDLINE, WHO ICTRP and ClinicalTrials.gov. The date of the last search of all databases was 21 October 2019. There were no language restrictions applied. SELECTION CRITERIA: We included randomised controlled trials comparing MIP to BNE for the treatment of sporadic primary hyperparathyroidism in persons undergoing surgery for the first time. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance. Two review authors independently screened for inclusion, extracted data and carried out risk of bias assessment. The content expert senior author resolved conflicts. We assessed studies for overall certainty of the evidence using the GRADE instrument. We conducted meta-analyses using a random-effects model and performed statistical analyses according to the guidelines in the latest version of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We identified five eligible studies, all conducted in European university hospitals. They included 266 adults, 136 participants were randomised to MIP and 130 participants to BNE. Data were available for all participants post-surgery up to one year, with the exception of missing data for two participants in the MIP group and for one participant in the BNE group at one year. Nine participants in the MIP group and 11 participants in the BNE group had missing data at five years. No study had a low risk of bias in all risk of bias domains. The risk ratio (RR) for success rate (eucalcaemia) at six months in the MIP group compared to the BNE group was 0.98 (95% confidence interval (CI) 0.94 to 1.03; P = 0.43; 5 studies, 266 participants; very low-certainty evidence). A total of 132/136 (97.1%) participants in the MIP group compared with 129/130 (99.2%) participants in the BNE group were judged as operative success. At five years, the RR was 0.94 (95% CI 0.83 to 1.08; P = 0.38; 1 study, 77 participants; very low-certainty evidence). A total of 34/38 (89.5%) participants in the MIP group compared with 37/39 (94.9%) participants in the BNE group were judged as operative success. The RR for the total incidence of perioperative adverse events was 0.50, in favour of MIP (95% CI 0.33 to 0.76; P = 0.001; 5 studies, 236 participants; low-certainty evidence). Perioperative adverse events occurred in 23/136 (16.9%) participants in the MIP group compared with 44/130 (33.9%) participants in the BNE group. The 95% prediction interval ranged between 0.25 and 0.99. These adverse events included symptomatic hypocalcaemia, vocal cord palsy, bleeding, fever and infection. Fifteen of 104 (14.4%) participants experienced symptomatic hypocalcaemia in the MIP group compared with 26/98 (26.5%) participants in the BNE group. The RR for this event comparing MIP with BNE at two days was 0.54 (95% CI 0.32 to 0.92; P = 0.02; 4 studies, 202 participants). Statistical significance was lost in sensitivity analyses, with a 95% prediction interval ranging between 0.17 and 1.74. Five out of 133 (3.8%) participants in the MIP group experienced vocal cord paralysis compared with 2/128 (1.6%) participants in the BNE group. The RR for this event was 1.87 (95% CI 0.47 to 7.51; P = 0.38; 5 studies, 261 participants). The 95% prediction interval ranged between 0.20 and 17.87. The effect on all-cause mortality was not explicitly reported and could not be adequately assessed (very low-certainty evidence). There was no clear difference for health-related quality of life between the treatment groups in two studies, but studies did not report numerical data (very low-certainty evidence). There was a possible treatment benefit for MIP compared to BNE in terms of cosmetic satisfaction (very low-certainty evidence). The mean difference (MD) for duration of surgery comparing BNE with MIP was in favour of the MIP group (-18 minutes, 95% CI -31 to -6; P = 0.004; 3 studies, 171 participants; very low-certainty evidence). The 95% prediction interval ranged between -162 minutes and 126 minutes. The studies did not report length of hospital stay. Four studies reported intraoperative conversion rate from MIP to open procedure information. Out of 115 included participants, there were 24 incidences of conversion, amounting to a conversion rate of 20.8%. AUTHORS' CONCLUSIONS: The success rates of MIP and BNE at six months were comparable. There were similar results at five years, but these were only based on one study. The incidence of perioperative symptomatic hypocalcaemia was lower in the MIP compared to the BNE group, whereas the incidence of vocal cord paralysis tended to be higher. Our systematic review did not provide clear evidence for the superiority of MIP over BNE. However, it was limited by low-certainty to very low-certainty evidence.

Management and control of type 2 diabetes mellitus in Lebanon: Results from the International Diabetes Management Practices Study Wave 6.

BACKGROUND: Diabetes mellitus is a worldwide public health problem associated with significant complications. There is lack of data on the quality of care of patients with diabetes, specifically among the non-Western countries. Efforts have been made in Lebanon to better study the characteristics of patients with diabetes mellitus in order to improve glycemic control and prevent late-term complications. AIM: To investigate control and therapeutic management of patients with diabetes mellitus in the current medical practice in Lebanon. METHODS: Wave 6 of the International Diabetes Management Practice Study in Lebanon is an international and multicenter study involving selected countries. RESULTS: Only 1 patient with type 1 diabetes and 595 patients with type 2 diabetes were included in Wave 6. Average age was around 60 years, with a mean body mass index of 30. The mean fasting serum glucose was 159.42 mg/dL, and the mean glycosylated hemoglobin (HbA1c) level was 7.98 with around 30% achieving an HbA1c target of < 7%. More patients were on oral anti-diabetic medications. Screening of diabetic complications has improved over the years. A large percentage is diagnosed with hypertension and dyslipidemia, the majority of whom were treated but only a small percentage were controlled. CONCLUSION: Diabetes, with its associated dyslipidemia and hypertension, is still not very well controlled. Screening for diabetes complications has improved over the years. Patients need to have more proper care, and physicians need to follow diabetes guidelines, and to have a larger number of patients who have appropriate treatment of diabetes, hypertension and lipids.

Diabetes and depression in Lebanon and association with glycemic control: a cross-sectional study.

BACKGROUND: Diabetes mellitus is a chronic noncommunicable disease characterized by hyperglycemia and is associated with chronic complications affecting the overall quality of life. As of 2017, the prevalence of diabetes in Lebanon is estimated to be 14.6%. Depression is noted to be common among Lebanese citizens, present in around 17.3%. This study aims to investigate the prevalence of depression among the diabetic Lebanese citizens and to study its relationship with poor glycemic control and diabetes complications. METHODS: In total, 436 diabetic patients participated in this cross-sectional study. Patients with diabetes mellitus attending several private clinics and health care centers were asked to fill out a well-structured questionnaire developed by an expert. Depression was assessed using Beck Depression Inventory (BDI). The study collected demographic information about the participants including their lifestyles, their last reported glycosylated hemoglobin values, and their reported microvascular and macrovascular complications. Data were collected, entered, and analyzed on SPSS software version 23.1. A descriptive analysis is carried out by calculating the mean and standard deviation for continuous variables and number and percentage for categorical ones. Association between categorical variables is evaluated using a chi-squared test. A P-value of <0.05 is considered to be significant. RESULTS: Depression was prevalent among 28.8% of the patients with diabetes mellitus. The average age of participants was 64.08 years. In total, 280 (64.2%) of the participants were females and the average diabetes duration was 8.89 years. There was no significant relationship found between depression and glycemic control. By contrast, a significant association between retinopathy, nephropathy, and stroke and depression was found. CONCLUSION: Depression was found to be present among 28.8% of the patients with diabetes mellitus in Lebanon; however, no association was established between depression and glycemic control.

Perception of peri-menopausal and postmenopausal Lebanese women on osteoporosis: A cross-sectional study.

INTRODUCTION: Osteoporosis is a generalized skeletal disorder characterized by decreased bone mineral density and microarchitectural deterioration, resulting in increased susceptibility to fractures. The prevalence of osteoporosis in Lebanon, defined as T-score <-2.5 at the total hip using NHANES gender-specific database was estimated to be 31% among postmenopausal women. PURPOSE: To assess the general perception of osteoporosis among women in Lebanon as well as their general knowledge of its lifestyle, risk factors, diagnostic, preventive and therapeutic measures. METHODS: A cross-sectional study was conducted in Lebanon between January and December 2017. Women above the age of 50 were invited to participate. A standardized questionnaire regarding the perception of personal risk of osteoporosis and fractures was used. Risk factors for osteoporosis, previous fractures or falls, family history of fracture, smoking, alcohol consumption, and secondary causes of osteoporosis were evaluated. Data were recorded on excel and analyzed on SPSS using variety of descriptive analysis, ANOVA tests, and others. P value <0.05 was considered to be statistically significant. RESULTS: From 396 interviewed women, 85% were in menopause and were more likely to be diagnosed with osteoporosis. 45% knew the true definition of osteoporosis and their most frequent source of information was doctors. Around 60% had heard of BMD screening but only 54.5% of those women actually did it. CONCLUSION: This study reveals that osteoporosis knowledge and perception is low among the Lebanese woman aged 50 years and older.

Effects of Sodium Glucose Cotransporter-2 Inhibitors on Serum Uric Acid in Type 2 Diabetes Mellitus.

Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter-related, type 2 diabetes mellitus was more at risk of having a higher serum uric acid level, and also individuals with higher serum uric acid had higher risk of developing type 2 diabetes in the future. Insulin resistance seems to play an important role in the causal relationship between metabolic syndrome, type 2 diabetes, and hyperuricemia. Oral diabetic drugs that would have additional beneficial effects on reducing serum uric acid levels are of importance. Selective SGLT2 inhibitors were extensively studied in type 2 diabetes mellitus and were found to have improvement of glycemic control, in addition to their proven metabolic effects on weight and blood pressure. Additional beneficial effect of SGLT2 inhibitors on serum uric acid level reduction is investigated. Recently, data have been accumulating showing that they have additional beneficial effects on serum uric acid reduction. As for the postulated mechanism, serum uric acid decreased in SGLT2 inhibitor users as a result of the increase in the urinary excretion rate of uric acid, due to the inhibition of uric acid reabsorption mediated by the effect of the drug on the GLUT9 isoform 2, located at the collecting duct of the renal tubule.

Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus.

The burden of diabetes mellitus (DM) in general has been extensively increasing over the past few years. Selective sodium glucose cotransporter-2 (SGLT2) inhibitors were extensively studied in type 2 DM and found to have sustained urinary glucose loss, improvement of glycemic control, in addition to their proven metabolic effects on weight, blood pressure, and cardiovascular benefits. Type 1 DM (T1D) patients clearly depend on insulin therapy, which till today fails to achieve the optimal glycemic control and metabolic targets that are needed to prevent risk of complications. New therapies are obviously needed as an adjunct to insulin therapy in order to try to achieve optimal control in T1D. Many oral diabetic medications have been tried in T1D patients as an adjunct to insulin treatment and have shown conflicting results. Adjunctive use of SGLT2 inhibitors in addition to insulin therapies in T1D was found to have the potential to improve glycemic control along with decrease in the insulin doses, as has been shown in certain animal and short-term human studies. Furthermore, larger well-randomized studies are needed to better evaluate their efficacy and safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were found to be increased among users of SGLT2 inhibitors, although the incidence remains very low. Recent beneficial effects of ketone body production and this shift in fuel energetics have been suggested based on the findings of protective cardiovascular benefits associated with one of the SGLT2 inhibitors.

The role of incretin-based therapies in prediabetes: a review.

Prediabetes, a high-risk state for future development of diabetes, is prevalent globally. Abnormalities in the incretin axis are important in the progression of B-cell failure in type 2 diabetes. Incretin based therapy was found to improve B cell mass and glycaemic control in addition to having multiple beneficial effects on the systolic and diastolic blood pressure, weight loss in addition to their other beneficial effects on the liver and cardiovascular system. In prediabetes, several well-designed preventive trials have shown that lifestyle and pharmacologic interventions such as metformin, thiazolidinediones (TZD), acarbose and, nateglinide and orlistat, are effective in reducing diabetes development. In recent small studies, incretin based therapy (DPP IV inhibitors and GLP-1 agonists) have also been extended to patients with prediabetes since it was shown to better preserve B-cell function and mass in animal studies and in clinical trials and it was also shown to help maintain good long term metabolic control. Because of the limited studies and clinical experience, their side effects and costs currently guidelines do not recommend incretin-based therapies as an option for treatment in patients with prediabetes. With future clinical trials and studies they may be recommended for patients with impaired fasting glucose or impaired glucose tolerance.

Liver disease and diabetes: association, pathophysiology, and management.

Diabetes is associated with a spectrum of liver diseases including nonalcoholic liver disease, steatohepatitis, and liver cirrhosis with their increased complications and mortality. Hepatitis C virus (HCV) and its associated liver cirrhosis has been associated with diabetes through insulin resistance. Cryptogenic diabetes occurs as a consequence of liver cirrhosis with the pathophysiology being complex, but mostly attributed to the increased insulin resistance in muscle, liver, and adipose tissue. As for the management of diabetes in patients with liver disease, lifestyle modification plays an important role. Oral diabetic medications are contraindicated in patients with advanced liver diseases with associated cirrhosis, ascites, or encephalopathy. As for stable liver disease, metformin and thiazolenediones have shown mixed results, with some showing them to be effective in improving liver transaminases in addition to histological improvement in steatosis and inflammation. α-glucosidase inhibitors may be helpful in decreasing hepatic encephalopathy. Upregulation of Dipeptidyl peptidase-4 (DPP-4) has been suggested as a possible pathogenetic mechanism for HCV-related insulin resistance, and treatment with DPP-4 inhibitors could improve insulin sensitivity in diabetic patients with liver disease. Patients with impaired liver function with associated insulin resistance may need increased insulin requirements. On the other hand patients with altered liver metabolism might need decreased insulin requirements.

Editorial on the original article entitled "Changes in diabetes-related complications in the United States, 1990-2010" published in the New England Journal of Medicine on April 17, 2014.

The paper entitled "Changes in diabetes-related complications in the United States, 1990-2010" published recently in the New England Journal of Medicine examined the spectrum of diabetes complications over the past 20 years based on a unique, nationally representative database in the Unites States. It was noted that although adults with diagnosis of diabetes have more than tripled between the years 1990 and 2010, the rates of all five major complications of diabetes have declined significantly with the greatest absolute declines being noted for acute myocardial infarction followed by stroke, lower-extremity amputation, end-stage renal disease and finally the death from hyperglycemic crisis. The greatest declines in most of the diabetes-related complications were observed among elderly persons who are above the age of 75 years with the exception of end stage renal disease which declined only in younger people but not among elderly. These findings could be due to the fact that over the past years there have been great advancements with regards to creating diabetes education programs especially after the publication of many trials that looked at the importance of intensive versus conventional glucose control, along with the enhanced management of other associated risk factors such as blood pressure, lipid levels, and smoking cessation.

Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment.

Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multitargeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. Since their introduction as adjunct treatment for renal cell carcinoma and gastrointestinal stromal tumors (GIST), a number of reports have demonstrated that TKI can induce thyroid dysfunction which was especially more common with sunitinib maleate. Many mechanisms with respect to this adverse effect of tyrosine kinase inhibitors have been proposed including their induction of thyroiditis, capillary regression in the thyroid gland, antithyroid peroxidase antibody production, and their ability to decrease iodine uptake by the thyroid gland. Of interest is the observation that TKI-induced thyroid dysfunction may actually be protective as it was shown to improve overall survival, and it was suggested that it may have a prognostic value. Followup on thyroid function tests while patients are maintained on tyrosine kinase inhibitor is strongly recommended. When thyroid dysfunction occurs, appropriate treatment should be individualized depending on patients symptoms and thyroid stimulating hormone level.

Hypovitaminosis d in patients with type 2 diabetes mellitus: a relation to disease control and complications.

Aims. This study aims at assessing the relationship between 25 (OH) vitamin D (25-OHD) levels and microvascular complications in patients with type 2 diabetes mellitus (DM2). Methods. 136 patients (59 ± 11 years) with DM2 (disease duration 8.6 ± 7 years) participated in this cross-sectional study. Anthropometric data, HbA1c, 25-OHD levels, serum creatinine, and urine microalbumin/creatinine ratio were collected. Dilated retinal exam was performed, and diabetic neuropathy was assessed using the United Kingdom Screening Score. Results. Serum 25-OHD correlated negatively with HbA1c (r = -0.20, P = 0.049). Mean 25-OHD levels were lower in subjects with diabetic retinopathy compared to those without retinopathy (12.3 ± 5.5 versus 21.8 ± 13.7, P < 0.001) and lower in subjects with diabetic neuropathy compared to those without neuropathy (16.4 ± 10.4 versus 23.5 ± 14.5, P = 0.004). After adjustment for BMI, diabetes duration, and smoking, 25-OHD was an independent predictor of HbA1c ( ß -0.14; P = 0.03). After adjustment for HbA1c, age, smoking, BMI and disease duration, 25-OHD were independent predictors for diabetic retinopathy: OR 2.8 [95% CI 2.1-8.0] and neuropathy: OR 4.5 [95% CI 1.6-12] for vitamin D < 20 versus vitamin D ≥ 20 ng/mL. Conclusion. Low serum 25-OHD level was an independent predictor of HbA1c, diabetic neuropathy, and diabetic retinopathy in patients with DM2.

Type 2 diabetes mellitus, oral diabetic medications, insulin therapy, and overall breast cancer risk.

Breast cancer is among the most common cancers worldwide. Diabetes is an important chronic health problem associated with insulin resistance, increased insulin level, changes in growth hormones and factors, and activation of mitogen-activating protein kinase (MAPK) pathways, leading to an increased breast cancer risk. This paper looked at the epidemiologic studies of the association between type 2 diabetes and risk of breast cancer and its effect on overall cancer-specific survival. The combined evidence overall supported a modest association between type 2 diabetes and the risk of breast cancer, which was found to be more prevalent among postmenopausal women. Effect of oral diabetics and insulin therapy on breast cancer risk was also evaluated. It was found that metformin and thiazolidinones tended to have a protective role. Metformin therapy trials for its use as an adjuvant for breast cancer treatment are still ongoing. Sulfonylurea and insulin therapy were found to be mildly associated with increased overall cancers. No evidence or studies evaluated the association of DPPIV inhibitors and GLP 1 agonists with breast cancer risk because of their recent introduction into the management of diabetes.

Controversies in the management and followup of differentiated thyroid cancer: beyond the guidelines.

Thyroid cancer is among the most common endocrine malignancies. Genetic and environmental factors play an important role in the pathogenesis of differentiated thyroid cancer. Both have good prognosis but with frequent recurrences. Cancer staging is an essential prognostic part of cancer management. There are multiple controversies in the management and followup of differentiated thyroid cancer. Debate still exists with regard to the optimal surgical approach but trends toward a more conservative approach, such as lobectomy, are being more favored, especially in papillary thyroid cancer, of tumor sizes less than 4 cm, in the absence of other high-risk suggestive features. Survival of patients with well-differentiated thyroid cancer was adversely affected by lymph node metastases. Prophylactic central LN dissection did improve accuracy in staging and decrease postop TG level, but it had no effect on small-sized tumors. Conservative approach was more applied with regard to the need and dose of radioiodine given postoperatively. There have been several advancements in the management of radioiodine resistant advanced differentiated thyroid cancers. Appropriate followup is required based on risk stratification of patients postoperatively. Many studies are still ongoing in order to reach the optimal management and followup of differentiated thyroid cancer.

Vitamins and bone health: beyond calcium and vitamin D.

Osteoporosis is a major health disorder associated with an increased risk of fracture. Nutrition is among the modifiable factors that influence the risk of osteoporosis and fracture. Calcium and vitamin D play important roles in improving bone mineral density and reducing the risk of fracture. Other vitamins appear to play a role in bone health as well. In this review, the findings of studies that related the intake and/or the status of vitamins other than vitamin D to bone health in animals and humans are summarized. Studies of vitamin A showed inconsistent results. Excessive, as well as insufficient, levels of retinol intake may be associated with compromised bone health. Deficiencies in vitamin B, along with the consequent elevated homocysteine level, are associated with bone loss, decreased bone strength, and increased risk of fracture. Deficiencies in vitamins C, E, and K are also associated with compromised bone health; this effect may be modified by smoking, estrogen use or hormonal therapy after menopause, calcium intake, and vitamin D. These findings highlight the importance of adequate nutrition in preserving bone mass and reducing the risk of osteoporosis and fractures.