Publications

This 12-month, randomized, controlled lifestyle intervention study was aimed at assessing the effectiveness of a lifestyle intervention in terms of (1) the reduction of at least 5% of body weight compared to baseline and (2) the percentage of participants in which fasting blood glucose (FBG) normalizes (<5.6 mmol/L) post-intervention, in predominantly overweight/obese Saudi adults with impaired fasting glucose. A total of 300 Saudi adults with prediabetes at baseline (FBG 5.6–6.9 mmol/L) were enrolled to receive either general advice (GA) or a rigorous, self-monitored, lifestyle modification program (intervention group, IG) for 12 months, focused on food choices, physical activity, and weight loss. Anthropometric and biochemical estimations were analyzed at baseline, 6, and 12 months. At baseline, 136/150 in the GA group (90.7%) and 127/150 in the IG group (84.7%) were either overweight or obese. A total of 14% (n = 21) of the subjects in the IG arm discontinued, compared to 8% (n = 12) in the GA arm. Data from completers (92% (n = 138) and 86% (n= 129) participants in GA and IG arms, respectively) were considered for the final analysis. Post-intervention, 37.2% (n = 48) of participants in the IG group had ≥5% weight reduction, as compared to 12.3% (n = 17) in the GA group (p < 0.01). Similarly, the percentage of participants who normalized their FBG post-intervention was 46.5% (n = 60) in the IG group compared to 21.7% (n = 30) in the GA group (p < 0.01). A 12-month Diabetes Prevention Program (DPP)-styled intensive lifestyle program translated effectively in decreasing weight and improving fasting glucose compared to the GA group in predominantly overweight/obese Saudi adults with prediabetes, suggesting that in the case of guided intervention programs, people are willing to participate and possibly change a sedentary lifestyle.

Abstract If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p <0.05). Circulating androstenedione levels did not differ between PA-PP and PCOS women (0.11±0.05 vs. 0.12±0.03), but was higher than that of controls (0.02±0.0 nmol/l, p <0,05). Ovarian volume was increased in PA-PP and PCOS (11.14±3.3 vs. 10.99±4.61) compared to controls (6.74±1.83 cm3). PA-PP women had a higher score of state/trait anxiety and depressive and eating disorder symptoms than controls, with a pattern that matched that of PCOS women. Only 14% of the PA-PP group fulfilled the Rotterdam PCOS criteria. Some women with a history of PA-PP displayed hormonal and psychologic profile similar to PCOS, and accordingly a regular monitoring of these girls during adulthood is advised.

Frailty is a natural state of physical, cognitive and mental decline that is expected in the elderly. The role of inflammation in the pathogenesis of frailty has been hypothesized, and so far many studies have been performed in order to understand the mechanism of action underlying this association. Recent studies support this hypothesis and show a clear association between inflammation, frailty, and age-related disease. Chronic inflammation is key pathophysiologic process that contributes to the frailty directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and other age-related specific diseases. Herein, we investigate the link between chronic inflammation and frailty of the older people. In particular, we present an up-to-date review of the role of cytokines, interleukins, cardiovascular abnormalities, chronic high blood pressure, hyperlipidemia and diabetes in relation to the severity of frailty in the elderly.

A bstract : Cortic otropin‐releasing hormone (CRH) is a major regulator of the hypothalamic‐pituitary‐adrenal axis (HPA) and principal coordinator of the stress response. As in stress, intracerebroventricular administration of CRH suppresses the immune system indirectly, via glucocorticoid and/or sympathetic system‐mediated mechanisms. Also, during inflammatory stress, the cytokines TNFα, IL‐1, and IL‐6 stimulate hypothalamic CRH and/or vasopressin secretion as a way of preventing the inflammatory reaction from overreacting. Recently, CRH receptors were described in peripheral sites of the immune system, and CRH was found to promote several immune functions in vitro . We demonstrated a direct role of CRH in the inflammatory immune process in vivo , by first studying the effect of systemic CRH immunoneutralization in an experimental model of carrageenin‐induced aseptic inflammation in Spague‐Dawley rats. We extended these observations to other forms of experimental inflammation, including streptococcal cell wall polysaccharide‐ and adjuvant‐induced arthritides and peptide R16 (epitope of the interphotoreceptor retinoid‐binding protein)‐induced uveitis in Lewis rats. We also studied human disease states, including rheumatoid arthritis, Hashimoto thyroiditis, and ulcerative colitis. Inflamed tissues contained large amounts of IR CRH, reaching levels similar to those observed in the hypophyseal portal system. We also demonstrated the presence of CRH mRNA and CRH receptors in inflammatory cells and identified the mast cells as a major immune target for CRH. In addition to production by immune cells, the peripheral nervous system, including the postganglionic sympathetic neurons and the sensory fibers type C, appears to contribute to IR CRH production in inflammatory sites. The production of CRH from the post‐ganglionic sympathetic neurons may be responsible for the stress‐induced activation of allergic/autoimmune phenomena, such as asthma and eczema, via mast cell degranulation. Antalarmin, a novel nonpeptide CRH receptor antagonist, displaced 125 I‐labeled ovine CRH binding in rat pituitary, frontal cortex, and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor. In vivo antalarmin significantly inhibited CRH‐stimulated ACTH release and carrageenin‐induced subcutaneous inflammation in rats. Thus, antalarmin and other related compounds that antagonize CRH at the level of its own receptor have therapeutic potential in some forms of inflammation directly mediated by type 1 CRH receptors and promise to enhance our understanding of the many roles of CRH in immune/inflammatory reactions.

Understanding the interplay between sleep duration and quality, diet and hormones of obesity may help design effective lifestyle intervention strategies. Here we studied such associations in lean and obese teen-aged Saudi girls. In this cross-sectional observational study, 126 girls (62 lean and 64 obese) aged 14 -18 years (16.5 ± 1.5) were evaluated. A general questionnaire, which included sleep and diet questions, was obtained and anthropometric measurements and overnight fasting blood samples for determination of glucose, lipid profile and serum levels of leptin, adiponectin, resistin and ghrelin were collected. Subjects that slept < 5 hours/day had a higher percent of carbohydrate intake (p = 0.04) than those who slept > 7 hours/day. Adiponectin levels were higher in the lean than the obese group and increased in proportion to hours of sleep. Ghrelin had an inverse association with subjective sleep duration (p = 0.04), while resistin levels were directly proportional to it. Thus, the duration and quality of sleep influenced diet composition and the circulating levels of adipocytokines and ghrelin in adolescent girls. Long and uninterrupted sleep was associated with a better diet and a more favorable hormonal profile.

Background. Lipodystrophy characterized by adipose tissue redistribution and lipid and glucose metabolism abnormalities, is common among HIV-infected adults and children on highly-active-antiretroviral-therapy (HAART). In a previous study of HIV-infected children, we did not detect insulin resistance, despite a high percentage of body fat redistribution abnormalities. Aim of the study. To investigate the non-traditional adipokines Retinol-binding-Protein-4 (RBP4), neutrophil-gelatinase-associated-lipocalin (NGAL), a-Fatty-Acid-Binding-Protein (a-FABP) and YKL-40 in HIV-infected children on highly-active-antiretroviral-therapy and evaluate their possible association to lipodystrophic changes or insulin resistance. Methods. Seventeen vertically HIV-infected children (mean age: 12.5 years, mean duration of HAART: 5.2 years) and 20 age- and BMI-matched controls were recruited. The HIV-children were re-evaluated after 12 months. RBP4, NGAL, a-FABP and YKL-40 were assessed at study entry and 12 months later and were correlated to body fat content and insulin resistance. Results. RBP4 values were similar at study entry and 12 months later in HIV-children and controls and showed no correlation to body fat or insulin resistance. NGAL was lower in HIV children at study entry but normalized after 12 months with no positive correlation to insulin resistance. a-FABP was positively correlated to body fat content, especially to trunk fat, both at initial evaluation and at follow-up in HIV children and, after prolonged highly-active-antiretroviral-therapy, it was also positively correlated to insulin resistance. Conclusions. This study is the first one to demonstrate that a-FABP could be a useful marker in unraveling central fat accumulation in HIV-infected children on highly-active-antiretroviral-therapy. Large prospective studies are needed to confirm these results.