Mona Nasrallah

Endocrine and musculoskeletal abnormalities in patients with Down syndrome

Down syndrome has a prevalence of one in 500 to one in 1,000 live births and is the most common cause of mental retardation. Most patients are treated in childhood and adolescence for mental or growth retardation. Studies that evaluate bone mass in Down syndrome are limited, and many are small case series in pediatric and adult populations who live either in the community or in residential institutions. Several environmental and hormonal factors contribute to low bone mineral density in such patients. Muscle hypotonia, low amounts of physical activity, poor calcium and vitamin D intakes, hypogonadism, growth retardation and thyroid dysfunction contribute to substantial impairments in skeletal maturation and bone-mass accrual that predispose these patients to fragility fractures. Here, we review indications and limitations of bone-mass measurements in children, summarize the endocrine and skeletal abnormalities in patients presenting with Down syndrome, and review studies that investigate therapeutic strategies for such patients.

Overview of the Physiology and Pathophysiology of Leptin With Special Emphasis on its Role in the Kidney

The adipocyte product leptin is a pleiotropic adipokine and hormone, with a role extending beyond appetite suppression and increased energy expenditure. This review summarizes the biology of the leptin system and the roles of its different receptors in a multitude of cellular functions in different organs, with special emphasis on the kidney. Leptins physiological functions as well as deleterious effects in states of leptin deficiency or hyperleptinemia are emphasized. Chronic hyperleptinemia can increase blood pressure through the sympathetic nervous system and renal salt retention. The concept of selective leptin resistance in obesity is emerging, whereby leptins effect on appetite and energy expenditure is blunted, with a concomitant increase in leptins other effects as a result of the accompanying hyperleptinemia. The divergence in response likely is explained by different receptors and post-receptor activating mechanisms. Chronic kidney disease is a known cause of hyperleptinemia. There is an emerging view that the effect of hyperleptinemia on the kidney can contribute to the development and/or progression of chronic kidney disease in selective resistance states such as in obesity or type 2 diabetes mellitus. The mechanisms of renal injury are likely the result of exaggerated and undesirable hemodynamic influences as well as profibrotic effects.

Taurine Intestinal Absorption and Renal Excretion Test in Diabetic Patients: A pilot study

There is evidence that diabetes is characterized by taurine deficiency (1–4), which has been linked to diabetic retinopathy, neuropathy, and nephropathy (5–7). Taurine is involved in neuronal modulation, osmoregulation (8), and protection against oxidative stress (9). Its plasma levels are maintained within a normal range through protein intake, and de novo synthesis is limited by the activity of hepatic cysteinesulphinic acid decarboxylase, which is low in humans. Taurine depletion can occur rapidly (10), possibly leading to retinal, cardiac, neural, immune, and hemostatic dysfunction (4,11–14). The reasons for taurine deficiency in diabetes remain unclear. A decrease in the overall body pool (1,2) and/or internal redistribution between the intra- and extracellular compartments are possibilities. The former can be secondary to decreased oral intake, poor intestinal absorption, renal wasting, or a combination of factors. In diabetic rats, intestinal absorption of taurine is reduced (K.B., Camille Nassar, unpublished data), while urinary taurine excretion is enhanced (15). Kidney loss in uncontrolled diabetes is aggravated by severe hyperglycemia and ketoacidosis (4). Data are lacking, however, on urinary excretion and pharmacokinetics of taurine absorption in human diabetes with mild-to-moderate hyperglycemia. This pilot study was therefore conducted in patients with moderately impaired glucose control and in matched nondiabetic subjects to evaluate the pharmacokinetics of taurine absorption following an oral load and to elucidate the mechanism of taurine deficiency in diabetes. A total of 16 subjects were enrolled in the study: 6 patients with type 2 diabetes, 2 with type 1 diabetes, and 8 healthy subjects; subjects were pair-matched for age, sex, and BMI. …

Role of Gut-Related Peptides and Other Hormones in the Amelioration of Type 2 Diabetes after Roux-en-Y Gastric Bypass Surgery

Bariatric surgery is currently the most effective and durable therapy for obesity. Roux-en-Y gastric bypass surgery, the most commonly performed procedure worldwide, causes substantial weight loss and improvement in several comorbidities associated with obesity, especially type 2 diabetes. Several mechanisms are proposed to explain the improvement in glucose metabolism after RYGB surgery: the caloric restriction and weight loss per se, the improvement in insulin resistance and beta cell function, and finally the alterations in the various gastrointestinal hormones and adipokines that have been shown to play an important role in glucose homeostasis. However, the timing, exact changes of these hormones, and the relative importance of these changes in the metabolic improvement postbariatric surgery remain to be further clarified. This paper reviews the various changes post-RYGB in adipokines and gut peptides in subjects with T2D.

Prevalence and determinants of retinopathy in a cohort of Lebanese type II diabetic patients

OBJECTIVE Our aim was to determine the prevalence and the risk factors for diabetic retinopathy (DR) in a cohort of type II diabetic patients in Lebanon. DESIGN Prospective observational cohort study. PARTICIPANTS Five hundred consecutive patients with type II diabetes mellitus followed at the American University of Beirut Medical Center diabetes clinic were enrolled in the study. METHODS All patients 18 years or older with diabetes mellitus who did not have gestational diabetes and who were able to complete the laboratory data and the retinal examination were invited to participate in the study; they were followed up for a period of 3 years. RESULTS DR was present in 175 patients (35%), 130 (26%), and 45 (9%) having nonproliferative and proliferative DR, respectively. Clinically significant macular edema was present in 42 patients (8%). Microvascular and macrovascular diabetic complications, duration of disease, glycemic control, presence of hypertension (p < 0.003), systolic blood pressure (p = 0.04), and insulin use (p < 0.001) were individually significantly associated with a higher prevalence of DR on bivariate analysis. However, on multivariate regression analysis, only glycosylated hemoglobin >7% (odds ratio [OR] 2.81, 95% CI 1.06-7.43, p = 0.038), duration of diabetes (per 10 years, OR 9.0, 95% CI 4.0-20.0, p < 0.001), macroalbuminuria (OR 2.6, 95% CI 1.14-5.96 p = 0.023), and systolic blood pressure (per 10 mm Hg, OR 1.27, 95% CI 1.0-1.56, p = 0.037) were independent risk factors for DR. CONCLUSIONS The elevated prevalence of DR in type II diabetic patients with high risk profiles calls for early medical intervention and education about DR and its identified controllable risk factors.

Vascular complications of diabetes in Lebanon: Experience at the American University of Beirut

Aim To examine the metabolic control and presence ofcomplications, among a cohort of diabetic patients in Lebanon. Method A total of 313 diabetic patients presenting for their usual care were screened in a cross-sectional manner for metabolic control and presence of complications at the American University of Beirut.Results Only 235 subjects completed their data of whom 220 (93%) had type 2 diabetes with mean duration of disease of 8.2 (±6.6) years. Only 30% had haemoglobin A1C < 7%, and 35.5% had low-density lipoprotein Cholesterol < 2.6 mmol/L. About 50.5% were obese, 34.9% current smokers, and 40.7% had blood pressure ≥ 140/90 mmHg. Microvascular complications were present as 46.3, 39.9 and 33% for albuminuria, neuropathy, 33% for albuminuria, neuropathy, and retinopathy, respectively. Macrovascular complications were as follows: 19.3, 18.3 and 4.1% for coronary artery disease, peripheral vascular disease and cerebrovascular disease, respectively.Conclusions This study highlights the poor control and h...

Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon.

BACKGROUND AND OBJECTIVES Few data are available on the extent of albuminuria in diabetic populations in the Middle East generally and in Lebanon specifically. We conducted this study to determine the prevalence of albuminuria and its major risk factors in a cohort of diabetic patients in Lebanon. PATIENTS AND METHODS Diabetic patients followed in the outpatient department at the American University of Beirut Medical Center (AUBMC) were included in a prospective observational study. AUBMC is a tertiary referral center and the outpatient department typically handles patients of low socioeconomic status with advanced disease. Patients were classified according to their urinary albumin-to-creatinine ratio (ACR) as having normoalbuminuria (ACR<30 mg/g creatinine), microalbuminuria (ACR=30 to <300 mg/g creatinine), or macroalbuminuria (ACR ≥300 mg/g creatinine). The three groups were compared to analyze the association between albuminuria and its risk factors. In addition, independent predictors of albuminuria were determined using multivariate logistic regression and presented as an odds ratio. RESULTS Microalbuminuria and macroalbuminuria were present in 33.3% and 12.7% of 222 patients (mean age 56.4 years, mean deviation of diabetes 8.6 years, 58.7% women, 43.8% obese), respectively. Factors significantly associated with microalbuminuria included glycemic control, insulin use, and total and LDL cholesterol. Those associated with macroalbuminuria included in addition to glycemic control and insulin use, duration of diabetes, hypertension, elevated mean arterial pressure (MAP), and presence of neuropathy, retinopathy and peripheral vascular disease by bivariate analysis. Only glycemic control was an independent risk factor for both in addition to MAP and retinopathy for macroalbuminuria by multivariate analysis. CONCLUSION Albuminuria is highly prevalent among this cohort of diabetic patients in Lebanon. Both glycemic control and blood pressure need to be better targeted in its management.

A minimally processed dietary pattern is associated with lower odds of metabolic syndrome among Lebanese adults

Objective To (i) estimate the consumption of minimally processed, processed and ultra-processed foods in a sample of Lebanese adults; (ii) explore patterns of intakes of these food groups; and (iii) investigate the association of the derived patterns with cardiometabolic risk. Design Cross-sectional survey. Data collection included dietary assessment using an FFQ and biochemical, anthropometric and blood pressure measurements. Food items were categorized into twenty-five groups based on the NOVA food classification. The contribution of each food group to total energy intake (TEI) was estimated. Patterns of intakes of these food groups were examined using exploratory factor analysis. Multivariate logistic regression analysis was used to evaluate the associations of derived patterns with cardiometabolic risk factors. Setting Greater Beirut area, Lebanon. Subjects Adults ≥18 years (n 302) with no prior history of chronic diseases. Results Of TEI, 36·53 and 27·10 % were contributed by ultra-processed and minimally processed foods, respectively. Two dietary patterns were identified: the ‘ultra-processed’ and the ‘minimally processed/processed’. The ‘ultra-processed’ consisted mainly of fast foods, snacks, meat, nuts, sweets and liquor, while the ‘minimally processed/processed’ consisted mostly of fruits, vegetables, legumes, breads, cheeses, sugar and fats. Participants in the highest quartile of the ‘minimally processed/processed’ pattern had significantly lower odds for metabolic syndrome (OR=0·18, 95 % CI 0·04, 0·77), hyperglycaemia (OR=0·25, 95 % CI 0·07, 0·98) and low HDL cholesterol (OR=0·17, 95 % CI 0·05, 0·60). Conclusions The study findings may be used for the development of evidence-based interventions aimed at encouraging the consumption of minimally processed foods.

Enhancing Nonmydriatic Color Photographs of the Retina with Monochromatic Views and a Stereo Pair to Detect Diabetic Retinopathy

BACKGROUND AND OBJECTIVE Nonmydriatic digital color imaging is rapidly gaining an important role in screening for diabetic retinopathy. However, it has yet to equal a dilated fundus examination or seven Early Treatment Diabetic Retinopathy Study field 35-mm photography. The authors therefore attempted to enhance efficacy and validity by adding two low-cost steps to the nonmydriatic digital image evaluation. PATIENTS AND METHODS The fundi of 145 consecutive patients with diabetes mellitus were evaluated for diabetic retinopathy using two different nonmydriatic reading techniques: creating a red-free view (using digital filters) and looking at a stereo pair of each field taken. These methods were each compared to a mydriatic fundus examination. RESULTS Although the first technique yielded views with sensitivities and specificities similar to what exists in the literature using this same technique, enhancing these photographs (second technique) yielded a statistically significant increase in sensitivity and specificity (P < .005). CONCLUSION The authors recommend using both low-cost steps when screening for diabetic retinopathy through nonmydriatic digital color imaging.

Activating BRAF Mutations Detected in Mixed Hürthle Cell Carcinoma and Multifocal Papillary Carcinoma of the Thyroid Gland: Report of an Unusual Case and Review of the Literature.

Despite the increase in the incidence of thyroid carcinomas, the occurrence of collision tumors in the thyroid remains a rare event. We present the case of a 69-year-old female who presented to the emergency department with a chief complaint of painful neck swelling. Imaging revealed a large right hemithyroid mass and a left hemithyroid nodule. Fine needle aspiration of the lesions and subsequent total thyroidectomy revealed a Hürthle cell carcinoma in the right lobe and bilateral multicentric papillary carcinoma foci, including 2 foci with a classical pattern and 1 encapsulated follicular variant in the isthmus. BRAF gene mutation analysis revealed V600E gene mutation in the classical variants of papillary carcinoma and in the Hürthle cell carcinoma. The focus of follicular variant of papillary carcinoma in the isthmus and a sample from normal thyroid tissue did not harbor BRAF mutations. This case is remarkable in being an unusual report of a follicular Hürthle cell carcinoma harboring the BRAF V600E mutation and occurring in collision with multifocal papillary carcinoma. Documentation of such cases is important as it helps better understand the pathogenesis, clinical behavior, and radiologic findings of such rare lesions and to determine the optimal treatment modalities.