The role of first trimester maternal body mass index (BMI) and adipocytokines in cord blood c-pep... more The role of first trimester maternal body mass index (BMI) and adipocytokines in cord blood c-peptide and birth weight in pregnancy was investigated. Seventy non-diabetic pregnant Caucasian women were recruited. Anthropometry and measurements of fasting adipocytokines (visfatin, leptin, adiponectin), insulin and glucose were performed in each of the three trimesters. At birth, birth weight and cord blood c-peptide, glucose, insulin, visfatin, leptin, adiponectin and IL6 in each neonate were measured. First trimester maternal BMI correlated positively with cord blood c-peptide (p=0.035, r=0.74) and negatively with cord blood visfatin (p=0.049, r=-0.67). First trimester HOMAR was negatively correlated with cord blood visfatin (p=0.037, r=-0.90) and negatively with cord blood leptin (p=0.031, r=0.90). First trimester maternal BMI was a positive predictor of cord blood c-peptide (p=0.007). First trimester maternal visfatin levels were negative predictors of birth weight (p=0.017). We co...
Background: The dietary supply of methyl donors such as folate, vitamin B 12 , betaine, methionin... more Background: The dietary supply of methyl donors such as folate, vitamin B 12 , betaine, methionine, and choline is essential for normal growth, development, and physiological functions through the life course. Both human and animal studies have shown that vitamin B 12 deficiency is associated with altered lipid profile and play an important role in the prediction of metabolic risk, however, as of yet, no direct mechanism has been investigated to confirm this. Results: Three independent clinical studies of women (i) non-pregnant at child-bearing age, (ii) in early pregnancy, and (iii) at delivery showed that low vitamin B 12 status was associated with higher total cholesterol, LDL cholesterol, and cholesterol-to-HDL ratio. These results guided the investigation into the cellular mechanisms of induced cholesterol biosynthesis due to vitamin B 12 deficiency, using human adipocytes as a model system. Adipocytes cultured in low or no vitamin B 12 conditions had increased cholesterol and homocysteine levels compared to control. The induction of cholesterol biosynthesis was associated with reduced s-adenosylmethionine (AdoMet)-to-s-adenosylhomocysteine (AdoHcy) ratio, also known as methylation potential (MP). We therefore studied whether reduced MP could lead to hypomethylation of genes involved in the regulation of cholesterol biosynthesis. Genome-wide and targeted DNA methylation analysis identified that the promoter regions of SREBF1 and LDLR, two key regulators of cholesterol biosynthesis, were hypomethylated under vitamin B 12 -deficient conditions, and as a result, their expressions and cholesterol biosynthesis were also significantly increased. This finding was further confirmed by the addition of the methylation inhibitor, 5-aza-2′-deoxycytidine, which resulted in increased SREBF1 and LDLR expressions and cholesterol accumulation in vitamin B 12 -sufficient conditions. Finally, we observed that the expression of SREBF1, LDLR, and cholesterol biosynthesis genes were increased in adipose tissue of vitamin B 12 deficient mothers compared to control group. Conclusions: Clinical data suggests that vitamin B 12 deficiency is an important metabolic risk factor. Regulation of AdoMet-to-AdoHcy levels by vitamin B 12 could be an important mechanism by which it can influence cholesterol biosynthesis pathway in human adipocytes.
Objectives: South-Asians have lower adiponectin levels compared to Caucasians. It was not clear h... more Objectives: South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels.
Introduction: Inflammation contributes to cardiovascular disease and is exacerbated with increase... more Introduction: Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood.
Self-reported disability in performing daily life activities was assessed in adults with severe o... more Self-reported disability in performing daily life activities was assessed in adults with severe obesity (BMI ≥ 35 kg/m 2 ) using the Health Assessment Questionnaire (HAQ). 262 participants were recruited into three BMI groups: Group I: 35-39.99 kg/m 2 ; Group II: 40-44.99 kg/m 2 ; Group III: ≥45.0 kg/m 2 . Progressively increasing HAQ scores were documented with higher BMI; Group I HAQ score: 0.125 (median) (range: 0-1.75); Group II HAQ score: 0.375 (0-2.5); Group III HAQ score: 0.75 (0-2.65) (Group III versus II P < 0.001; Group III versus I P < 0.001; Group II versus I P = 0.004). HAQ score strongly correlated with BMI and age. Nearly three-fourths of the study participants reported some degree of disability (HAQ score > 0). The prevalence of this degree of disability increased with increasing BMI and age. It also correlated to type 2 diabetes, metabolic syndrome, and clinical depression, but not to gender. Our data suggest that severe obesity is associated with self-reported disability in performing common daily life activities, with increasing degree of disability as BMI increases over 35 kg/m 2 . Functional assessment is crucial in obesity management, and establishing the disability profiles of obese patients is integral to both meet the specific healthcare needs of individuals and develop evidence-based public health programs, interventions, and priorities.
Adipose tissue is an active endocrine organ, and our knowledge of this secretory tissue, in recen... more Adipose tissue is an active endocrine organ, and our knowledge of this secretory tissue, in recent years, has led us to completely rethink how our body functions and becomes dysregulated with weight gain. Human adipose tissue appears to act as a multifunctional secretory organ with the capacity to control energy homoeostasis through peripheral and central regulation of energy homoeostasis. It also plays an important role in innate immunity. However, the capability to more than double its original mass to cope with positive energy balance in obesity leads to many pathogenic changes. These changes arise within the adipose tissue as well as inducing secondary detrimental effects on other organs like muscle and liver, including chronic low-grade inflammation mediated by adipocytokines (adipokine inflammation). This inflammation is modulated by dietary factors and nutrients including glucose and lipids, as well as gut bacteria in the form of endotoxin or LPS. The aim of this current review is to consider the impact of nutrients such as glucose and lipids on inflammatory pathways, specifically within adipose tissue. Furthermore, how nutrients such as these can influence adipokine inflammation and consequently insulin resistance directly through their effects on secretion of adipocytokines (TNFα, IL6 and resistin) as well as indirectly through increases in endotoxin is discussed.
In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energ... more In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energy intake for the mother and for the fetus. The role of maternal appetite-related peptides and their possible association with neonatal energy stores and glucose metabolism have not been investigated as yet. The aim was to investigate, during pregnancy, the association of fasting maternal appetite-related hormones levels [ghrelin (active), GLP1 (active), total PYY and leptin] with neonatal waist, percent total body fat and insulin levels at birth. Forty-two normal and thirty eight overweight women (mean±SD; age: 26.9±2.5years; pre-pregnancy BMI 26±2.2kg/m(2)) were seen during each of the three trimesters, had blood sampling and a 75g oral glucose tolerance test. At birth, neonates underwent anthropometry and cord blood sampling for c-peptide, glucose, insulin. During all three trimesters maternal weight correlated positively with percent total neonatal body fat while during the second and third trimesters it correlated positively with birth weight. The second trimester maternal active ghrelin levels correlated positively with neonatal waist and were its best positive predictor. The third trimester maternal active ghrelin levels correlated positively with neonatal waist and negatively with percent total neonatal body fat, fetal cord blood insulin levels and were the best negative predictor of the latter. The third trimester maternal leptin levels correlated negatively with neonatal waist. During pregnancy circulating maternal active ghrelin, a pro-appetite hormone, is associated with neonatal visceral energy storage (as expressed by neonatal waist). By inhibiting glucose-driven maternal insulin secretion, ghrelin might ensure adequate fasting glucose and nutrient supplies to the fetus while limiting overall fetal adipose tissue deposition.
Psychosocial profiles were examined in 255 morbidly obese patients attending a hospital service o... more Psychosocial profiles were examined in 255 morbidly obese patients attending a hospital service offering access to standard weight loss therapies. 129 patients were reassessed after at least 6-month follow-up. At baseline, 51.8% and 32.7% of patients, respectively, had evidence of anxiety and depressive disorders, 24% had severe impairments in self esteem, and 29.7% had an increased risk of eating disorders. At follow-up, weight loss from baseline was significant in all 3 therapies: diet only is 0.74 ± 1.8 kg; pharmacotherapy is 6.7 ± 4.2 kg; and surgery is 20.1 ± 13.6 kg. Anxiety scores improved in all three groups (P < .05). Patients having pharmacotherapy or surgery had significant improvements in physical and work function and public distress compared to those having dietary treatment only (P < .05). Our observational data suggest that weight management services can lead to psychosocial benefit in morbidly obese patients. Well-designed studies are necessary to examine the link between weight loss and emotional health.
Meal duration may influence cardiometabolic health. The aim of this study was to explore postpran... more Meal duration may influence cardiometabolic health. The aim of this study was to explore postprandial effects of meal duration on human metabolism and appetite. Postprandial comparisons following a standard meal eaten slowly over 40 min ('D40') and the same meal eaten quickly over 10 min ('D10') on a different day. Each participant therefore acted as their own control, thereby limiting confounding factors. Obese premenopausal Caucasian women (n = 10) with confirmed normoglycaemia were recruited from an obesity clinic at UHCW, Coventry UK. Subjects underwent whole-body calorimetry (8-h) on two separate days. Following standard lunch (D40 vs D10), 4-h postprandial analysis included thermic effect of food (TEF) and bloods taken at predefined times (including baseline fasting). Analytes included lipid profile, adiponectin, insulin, glucose, ghrelin, leptin, endotoxin, gut and pancreatic hormones. Appetite was measured using visual-analogue scales and ad libitum food inta...
Background: Metformin, a standard therapy in type 2 diabetes, reduces vitamin B12 levels. Studies... more Background: Metformin, a standard therapy in type 2 diabetes, reduces vitamin B12 levels. Studies linking low vitamin B12 levels and cardiovascular disease are equivocal and suggest improving B12 levels may help in primary prevention. The role of vitamin B12 deficiency on cardiovascular risk factors, especially in type 2 diabetes has not been explored. The aim of this study is to investigate whether vitamin B12 deficiency in type 2 diabetes patients is associated with cardiovascular risk factors in two different ethnic groups in UK and India. Methods: Type 2 diabetes patients from two secondary care diabetic centres (Europeans -UK and Indians -India) were studied. Serum vitamin B12, folate and biochemical parameters were measured.
Non-high-density lipoprotein cholesterol (non-HDL-C) has been identified as a significant predict... more Non-high-density lipoprotein cholesterol (non-HDL-C) has been identified as a significant predictor of various cardiovascular events in adults. Limited studies have been conducted in the pediatric population with diverse results, depending on ethnic origin. None has been conducted in the Arabic adolescent population so far; this study aims to fill this gap. In this cross-sectional study, 1690 Saudi school adolescents (968 boys [mean age 14.8 ± 1.7] and 722 girls [mean age 14.6 ± 1.7]) were recruited. Anthropometrics were obtained. Fasting blood glucose and lipid profiles were quantified routinely. Non-HDL-C was calculated and screening was done for dyslipidemia using cutoffs obtained from the cohort and elevated fasting glucose. Using the 90th percentile cutoff obtained, the overall prevalence of high non-HDL-C (≥4.26 mmol/L) was 10.1%. Prevalence was slightly higher in girls (10.5%) than boys (9.9%). Non-HDL-C was similar to other lipids in terms of significant associations with anthropometric measures and glucose in both boys and girls. Elevated triglycerides was most predictive of elevated glucose in both girls (odds ratio 2.41; confidence interval 1.43-4.08; P = .001) and boys (odds ratio 2.61; confidence interval 1.70-4.0); P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Non-HDL-C appears to be gender-specific and is cardiometabolically more associated with Saudi boys, despite higher levels in girls. It is inferior compared with triglycerides in assessing elevated glucose risk. Further investigations may provide a more definite value for non-HDL-C use as a biomarker in assessing cardiometabolic risk in the Arab adolescent population.
Background: The over-all age-adjusted prevalence of diabetes mellitus type 2 (DMT2) in Saudi Arab... more Background: The over-all age-adjusted prevalence of diabetes mellitus type 2 (DMT2) in Saudi Arabia is unprecedented at 31%. Aggressive measures should be done to curb down increasing incidence. In this prospective 6-month study we aim to determine whether a self-monitoring, life-style modification program that includes increased sunlight exposure confer improvement in vitamin D status and health benefits among adult Saudi overweight and obese patients with varying glycemic status.
Background: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the U... more Background: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design: This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD -a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA 1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients.
Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with s... more Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes.
Background: Configuring high quality care for the rapidly increasing number of people with type 2... more Background: Configuring high quality care for the rapidly increasing number of people with type 2 diabetes (T2D) is a major challenge worldwide for both providers and commissioners. In the UK, about two thirds of people with T2D are managed entirely in primary care, with wide variation in management strategies and achievement of targets. Pay for performance, introduced in 2004, initially resulted in improvements but disparities exist in ethnic minorities and the improvements are levelling off. Community based, intermediate care clinics for diabetes (ICCDs) were considered one solution and are functioning across the UK. However, there is no randomised trial evidence for the effectiveness of such clinics.
Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and... more Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and pathology of human metabolism relevant to diabetes and cardiovascular disease. We determined the relationship of the pattern of these circulating hormones with obesity-related phenotypes and whether such pattern is transmitted from parent to offspring. A combined total of 403 individuals from 156 consenting Saudi families divided into initial (119 families with 123 adults and 131 children) and replication (37 families with 58 adults and 91 children) cohorts were randomly selected from the RIYADH Cohort study. Anthropometrics were evaluated and metabolic measures such as fasting serum glucose, lipid profiles, insulin, leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFa), activated plasminogen activator inhibitor 1 (aPAI1), high sensitivity C-reactive protein (hsCRP) and angiotensin II were also assessed. Parent-offspring regressions revealed that with the exception of hsCRP, all hormones measured showed evidence for significant inheritance. Principal component (PC) analysis of standardized hormone levels demonstrated surprising heritability of the three most common axes of variation. PC1, which explained 21% of the variation, was most strongly loaded on levels of leptin, TNFa, insulin, and aPAI1, and inversely with adiponectin. It was significantly associated with body mass index (BMI) and phenotypically stronger in children, and showed a heritability of ,50%, after adjustment for age, gender and generational effects. We conclude that adipocytokines are highly heritable and their pattern of co-variation significantly influences BMI as early as the pre-teen years. Investigation at the genomic scale is required to determine the variants affecting the regulation of the hormones studied.
There is uncertainty regarding preoperative predictors of a successful outcome for bariatric surg... more There is uncertainty regarding preoperative predictors of a successful outcome for bariatric surgery (BarSurg), on which to determine appropriateness for such a procedure. Our aims were to identify preoperative clinical and psychosocial predictors of success following BarSurg and to explore the influence of body mass index (BMI) on these parameters. Preoperative data, including Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scores transformed to Health-Related Quality of Life (HRQOL) scores, were accrued from 76 morbidly obese adults awaiting BarSurg. Pre- and postoperative data were also accrued for 26 patients who had completed 1-year follow-up post-bariatric surgery (laparoscopic adjustable gastric banding-LAGB). Statistical analysis was performed to assess the relationships between preoperative HRQOL scores, preoperative BMI and excess weight loss 1 year following BarSurg (EWL-1 year). Preoperative BMI showed a significant independent, negative linear correlation with the public distress domain of preoperative quality of life (QOL) (r = -0.368, p = 0.001; β = -0.245, p = 0.009). Preoperative BMI had a significant, positive and independent association with EWL-1 year (r = 0.499, p = 0.009; β = 0.679, p = 0.015). Preoperative QOL scores had no association with EWL-1 year. Preoperative BMI appears to predict EWL-1 year following restrictive bariatric surgery (LAGB). Preoperatively, patients with higher BMI appear to manifest greater public distress. Preoperative QOL scores, however, do not appear to have any predictive value for EWL-1 year post-LAGB. Preoperative BMI should therefore be employed as a predictor of EWL-1 year post-LAGB. Other measures of successful outcomes of bariatric surgeries (such as effects on QOL scores at 1 year) should be explored in future, larger and longer term studies.
Laparoscopic greater curvature plication (LGCP) is an emerging bariatric procedure that reduces t... more Laparoscopic greater curvature plication (LGCP) is an emerging bariatric procedure that reduces the gastric volume without implantable devices or gastrectomy. The aim of this study was to explore changes in glucose homeostasis, postprandial triglyceridemia, and meal-stimulated secretion of selected gut hormones [glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, and obestatin] in patients with type 2 diabetes mellitus (T2DM) at 1 and 6 months after the procedure. Thirteen morbidly obese T2DM women (mean age, 53.2 ± 8.76 years; body mass index, 40.1 ± 4.59 kg/m2) were prospectively investigated before the LGCP and at 1- and 6-month follow-up. At these time points, all study patients underwent a standardized liquid mixed-meal test, and blood was sampled for assessment of plasma levels of glucose, insulin, C-peptide, triglycerides, GIP, GLP-1, ghrelin, and obestatin. All patients had significant weight loss both at 1 and 6 months after the LGCP (p ≤ 0.002), with mean percent excess weight loss (%EWL) reaching 29.7 ± 2.9% at the 6-month follow-up. Fasting hyperglycemia and hyperinsulinemia improved significantly at 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), with parallel improvement in insulin sensitivity and HbA1c levels (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Meal-induced glucose plasma levels were significantly lower at 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and postprandial triglyceridemia was also ameliorated at the 6-month follow-up (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Postprandial GIP plasma levels were significantly increased both at 1 and 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), whereas the overall meal-induced GLP-1 response was not significantly changed after the procedure (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). Postprandial ghrelin plasma levels decreased at 1 and 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) with no significant changes in circulating obestatin levels. During the initial 6-month postoperative period, LGCP induces significant weight loss and improves the metabolic profile of morbidly obese T2DM patients, while it also decreases circulating postprandial ghrelin levels and increases the meal-induced GIP response.
The role of first trimester maternal body mass index (BMI) and adipocytokines in cord blood c-pep... more The role of first trimester maternal body mass index (BMI) and adipocytokines in cord blood c-peptide and birth weight in pregnancy was investigated. Seventy non-diabetic pregnant Caucasian women were recruited. Anthropometry and measurements of fasting adipocytokines (visfatin, leptin, adiponectin), insulin and glucose were performed in each of the three trimesters. At birth, birth weight and cord blood c-peptide, glucose, insulin, visfatin, leptin, adiponectin and IL6 in each neonate were measured. First trimester maternal BMI correlated positively with cord blood c-peptide (p=0.035, r=0.74) and negatively with cord blood visfatin (p=0.049, r=-0.67). First trimester HOMAR was negatively correlated with cord blood visfatin (p=0.037, r=-0.90) and negatively with cord blood leptin (p=0.031, r=0.90). First trimester maternal BMI was a positive predictor of cord blood c-peptide (p=0.007). First trimester maternal visfatin levels were negative predictors of birth weight (p=0.017). We co...
Background: The dietary supply of methyl donors such as folate, vitamin B 12 , betaine, methionin... more Background: The dietary supply of methyl donors such as folate, vitamin B 12 , betaine, methionine, and choline is essential for normal growth, development, and physiological functions through the life course. Both human and animal studies have shown that vitamin B 12 deficiency is associated with altered lipid profile and play an important role in the prediction of metabolic risk, however, as of yet, no direct mechanism has been investigated to confirm this. Results: Three independent clinical studies of women (i) non-pregnant at child-bearing age, (ii) in early pregnancy, and (iii) at delivery showed that low vitamin B 12 status was associated with higher total cholesterol, LDL cholesterol, and cholesterol-to-HDL ratio. These results guided the investigation into the cellular mechanisms of induced cholesterol biosynthesis due to vitamin B 12 deficiency, using human adipocytes as a model system. Adipocytes cultured in low or no vitamin B 12 conditions had increased cholesterol and homocysteine levels compared to control. The induction of cholesterol biosynthesis was associated with reduced s-adenosylmethionine (AdoMet)-to-s-adenosylhomocysteine (AdoHcy) ratio, also known as methylation potential (MP). We therefore studied whether reduced MP could lead to hypomethylation of genes involved in the regulation of cholesterol biosynthesis. Genome-wide and targeted DNA methylation analysis identified that the promoter regions of SREBF1 and LDLR, two key regulators of cholesterol biosynthesis, were hypomethylated under vitamin B 12 -deficient conditions, and as a result, their expressions and cholesterol biosynthesis were also significantly increased. This finding was further confirmed by the addition of the methylation inhibitor, 5-aza-2′-deoxycytidine, which resulted in increased SREBF1 and LDLR expressions and cholesterol accumulation in vitamin B 12 -sufficient conditions. Finally, we observed that the expression of SREBF1, LDLR, and cholesterol biosynthesis genes were increased in adipose tissue of vitamin B 12 deficient mothers compared to control group. Conclusions: Clinical data suggests that vitamin B 12 deficiency is an important metabolic risk factor. Regulation of AdoMet-to-AdoHcy levels by vitamin B 12 could be an important mechanism by which it can influence cholesterol biosynthesis pathway in human adipocytes.
Objectives: South-Asians have lower adiponectin levels compared to Caucasians. It was not clear h... more Objectives: South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels.
Introduction: Inflammation contributes to cardiovascular disease and is exacerbated with increase... more Introduction: Inflammation contributes to cardiovascular disease and is exacerbated with increased adiposity, particularly omental adiposity; however, the role of epicardial fat is poorly understood.
Self-reported disability in performing daily life activities was assessed in adults with severe o... more Self-reported disability in performing daily life activities was assessed in adults with severe obesity (BMI ≥ 35 kg/m 2 ) using the Health Assessment Questionnaire (HAQ). 262 participants were recruited into three BMI groups: Group I: 35-39.99 kg/m 2 ; Group II: 40-44.99 kg/m 2 ; Group III: ≥45.0 kg/m 2 . Progressively increasing HAQ scores were documented with higher BMI; Group I HAQ score: 0.125 (median) (range: 0-1.75); Group II HAQ score: 0.375 (0-2.5); Group III HAQ score: 0.75 (0-2.65) (Group III versus II P < 0.001; Group III versus I P < 0.001; Group II versus I P = 0.004). HAQ score strongly correlated with BMI and age. Nearly three-fourths of the study participants reported some degree of disability (HAQ score > 0). The prevalence of this degree of disability increased with increasing BMI and age. It also correlated to type 2 diabetes, metabolic syndrome, and clinical depression, but not to gender. Our data suggest that severe obesity is associated with self-reported disability in performing common daily life activities, with increasing degree of disability as BMI increases over 35 kg/m 2 . Functional assessment is crucial in obesity management, and establishing the disability profiles of obese patients is integral to both meet the specific healthcare needs of individuals and develop evidence-based public health programs, interventions, and priorities.
Adipose tissue is an active endocrine organ, and our knowledge of this secretory tissue, in recen... more Adipose tissue is an active endocrine organ, and our knowledge of this secretory tissue, in recent years, has led us to completely rethink how our body functions and becomes dysregulated with weight gain. Human adipose tissue appears to act as a multifunctional secretory organ with the capacity to control energy homoeostasis through peripheral and central regulation of energy homoeostasis. It also plays an important role in innate immunity. However, the capability to more than double its original mass to cope with positive energy balance in obesity leads to many pathogenic changes. These changes arise within the adipose tissue as well as inducing secondary detrimental effects on other organs like muscle and liver, including chronic low-grade inflammation mediated by adipocytokines (adipokine inflammation). This inflammation is modulated by dietary factors and nutrients including glucose and lipids, as well as gut bacteria in the form of endotoxin or LPS. The aim of this current review is to consider the impact of nutrients such as glucose and lipids on inflammatory pathways, specifically within adipose tissue. Furthermore, how nutrients such as these can influence adipokine inflammation and consequently insulin resistance directly through their effects on secretion of adipocytokines (TNFα, IL6 and resistin) as well as indirectly through increases in endotoxin is discussed.
In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energ... more In pregnancy physiological mechanisms activated by maternal appetite contribute to adequate energy intake for the mother and for the fetus. The role of maternal appetite-related peptides and their possible association with neonatal energy stores and glucose metabolism have not been investigated as yet. The aim was to investigate, during pregnancy, the association of fasting maternal appetite-related hormones levels [ghrelin (active), GLP1 (active), total PYY and leptin] with neonatal waist, percent total body fat and insulin levels at birth. Forty-two normal and thirty eight overweight women (mean±SD; age: 26.9±2.5years; pre-pregnancy BMI 26±2.2kg/m(2)) were seen during each of the three trimesters, had blood sampling and a 75g oral glucose tolerance test. At birth, neonates underwent anthropometry and cord blood sampling for c-peptide, glucose, insulin. During all three trimesters maternal weight correlated positively with percent total neonatal body fat while during the second and third trimesters it correlated positively with birth weight. The second trimester maternal active ghrelin levels correlated positively with neonatal waist and were its best positive predictor. The third trimester maternal active ghrelin levels correlated positively with neonatal waist and negatively with percent total neonatal body fat, fetal cord blood insulin levels and were the best negative predictor of the latter. The third trimester maternal leptin levels correlated negatively with neonatal waist. During pregnancy circulating maternal active ghrelin, a pro-appetite hormone, is associated with neonatal visceral energy storage (as expressed by neonatal waist). By inhibiting glucose-driven maternal insulin secretion, ghrelin might ensure adequate fasting glucose and nutrient supplies to the fetus while limiting overall fetal adipose tissue deposition.
Psychosocial profiles were examined in 255 morbidly obese patients attending a hospital service o... more Psychosocial profiles were examined in 255 morbidly obese patients attending a hospital service offering access to standard weight loss therapies. 129 patients were reassessed after at least 6-month follow-up. At baseline, 51.8% and 32.7% of patients, respectively, had evidence of anxiety and depressive disorders, 24% had severe impairments in self esteem, and 29.7% had an increased risk of eating disorders. At follow-up, weight loss from baseline was significant in all 3 therapies: diet only is 0.74 ± 1.8 kg; pharmacotherapy is 6.7 ± 4.2 kg; and surgery is 20.1 ± 13.6 kg. Anxiety scores improved in all three groups (P < .05). Patients having pharmacotherapy or surgery had significant improvements in physical and work function and public distress compared to those having dietary treatment only (P < .05). Our observational data suggest that weight management services can lead to psychosocial benefit in morbidly obese patients. Well-designed studies are necessary to examine the link between weight loss and emotional health.
Meal duration may influence cardiometabolic health. The aim of this study was to explore postpran... more Meal duration may influence cardiometabolic health. The aim of this study was to explore postprandial effects of meal duration on human metabolism and appetite. Postprandial comparisons following a standard meal eaten slowly over 40 min ('D40') and the same meal eaten quickly over 10 min ('D10') on a different day. Each participant therefore acted as their own control, thereby limiting confounding factors. Obese premenopausal Caucasian women (n = 10) with confirmed normoglycaemia were recruited from an obesity clinic at UHCW, Coventry UK. Subjects underwent whole-body calorimetry (8-h) on two separate days. Following standard lunch (D40 vs D10), 4-h postprandial analysis included thermic effect of food (TEF) and bloods taken at predefined times (including baseline fasting). Analytes included lipid profile, adiponectin, insulin, glucose, ghrelin, leptin, endotoxin, gut and pancreatic hormones. Appetite was measured using visual-analogue scales and ad libitum food inta...
Background: Metformin, a standard therapy in type 2 diabetes, reduces vitamin B12 levels. Studies... more Background: Metformin, a standard therapy in type 2 diabetes, reduces vitamin B12 levels. Studies linking low vitamin B12 levels and cardiovascular disease are equivocal and suggest improving B12 levels may help in primary prevention. The role of vitamin B12 deficiency on cardiovascular risk factors, especially in type 2 diabetes has not been explored. The aim of this study is to investigate whether vitamin B12 deficiency in type 2 diabetes patients is associated with cardiovascular risk factors in two different ethnic groups in UK and India. Methods: Type 2 diabetes patients from two secondary care diabetic centres (Europeans -UK and Indians -India) were studied. Serum vitamin B12, folate and biochemical parameters were measured.
Non-high-density lipoprotein cholesterol (non-HDL-C) has been identified as a significant predict... more Non-high-density lipoprotein cholesterol (non-HDL-C) has been identified as a significant predictor of various cardiovascular events in adults. Limited studies have been conducted in the pediatric population with diverse results, depending on ethnic origin. None has been conducted in the Arabic adolescent population so far; this study aims to fill this gap. In this cross-sectional study, 1690 Saudi school adolescents (968 boys [mean age 14.8 ± 1.7] and 722 girls [mean age 14.6 ± 1.7]) were recruited. Anthropometrics were obtained. Fasting blood glucose and lipid profiles were quantified routinely. Non-HDL-C was calculated and screening was done for dyslipidemia using cutoffs obtained from the cohort and elevated fasting glucose. Using the 90th percentile cutoff obtained, the overall prevalence of high non-HDL-C (≥4.26 mmol/L) was 10.1%. Prevalence was slightly higher in girls (10.5%) than boys (9.9%). Non-HDL-C was similar to other lipids in terms of significant associations with anthropometric measures and glucose in both boys and girls. Elevated triglycerides was most predictive of elevated glucose in both girls (odds ratio 2.41; confidence interval 1.43-4.08; P = .001) and boys (odds ratio 2.61; confidence interval 1.70-4.0); P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Non-HDL-C appears to be gender-specific and is cardiometabolically more associated with Saudi boys, despite higher levels in girls. It is inferior compared with triglycerides in assessing elevated glucose risk. Further investigations may provide a more definite value for non-HDL-C use as a biomarker in assessing cardiometabolic risk in the Arab adolescent population.
Background: The over-all age-adjusted prevalence of diabetes mellitus type 2 (DMT2) in Saudi Arab... more Background: The over-all age-adjusted prevalence of diabetes mellitus type 2 (DMT2) in Saudi Arabia is unprecedented at 31%. Aggressive measures should be done to curb down increasing incidence. In this prospective 6-month study we aim to determine whether a self-monitoring, life-style modification program that includes increased sunlight exposure confer improvement in vitamin D status and health benefits among adult Saudi overweight and obese patients with varying glycemic status.
Background: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the U... more Background: World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design: This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD -a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA 1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients.
Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with s... more Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes.
Background: Configuring high quality care for the rapidly increasing number of people with type 2... more Background: Configuring high quality care for the rapidly increasing number of people with type 2 diabetes (T2D) is a major challenge worldwide for both providers and commissioners. In the UK, about two thirds of people with T2D are managed entirely in primary care, with wide variation in management strategies and achievement of targets. Pay for performance, introduced in 2004, initially resulted in improvements but disparities exist in ethnic minorities and the improvements are levelling off. Community based, intermediate care clinics for diabetes (ICCDs) were considered one solution and are functioning across the UK. However, there is no randomised trial evidence for the effectiveness of such clinics.
Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and... more Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and pathology of human metabolism relevant to diabetes and cardiovascular disease. We determined the relationship of the pattern of these circulating hormones with obesity-related phenotypes and whether such pattern is transmitted from parent to offspring. A combined total of 403 individuals from 156 consenting Saudi families divided into initial (119 families with 123 adults and 131 children) and replication (37 families with 58 adults and 91 children) cohorts were randomly selected from the RIYADH Cohort study. Anthropometrics were evaluated and metabolic measures such as fasting serum glucose, lipid profiles, insulin, leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFa), activated plasminogen activator inhibitor 1 (aPAI1), high sensitivity C-reactive protein (hsCRP) and angiotensin II were also assessed. Parent-offspring regressions revealed that with the exception of hsCRP, all hormones measured showed evidence for significant inheritance. Principal component (PC) analysis of standardized hormone levels demonstrated surprising heritability of the three most common axes of variation. PC1, which explained 21% of the variation, was most strongly loaded on levels of leptin, TNFa, insulin, and aPAI1, and inversely with adiponectin. It was significantly associated with body mass index (BMI) and phenotypically stronger in children, and showed a heritability of ,50%, after adjustment for age, gender and generational effects. We conclude that adipocytokines are highly heritable and their pattern of co-variation significantly influences BMI as early as the pre-teen years. Investigation at the genomic scale is required to determine the variants affecting the regulation of the hormones studied.
There is uncertainty regarding preoperative predictors of a successful outcome for bariatric surg... more There is uncertainty regarding preoperative predictors of a successful outcome for bariatric surgery (BarSurg), on which to determine appropriateness for such a procedure. Our aims were to identify preoperative clinical and psychosocial predictors of success following BarSurg and to explore the influence of body mass index (BMI) on these parameters. Preoperative data, including Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scores transformed to Health-Related Quality of Life (HRQOL) scores, were accrued from 76 morbidly obese adults awaiting BarSurg. Pre- and postoperative data were also accrued for 26 patients who had completed 1-year follow-up post-bariatric surgery (laparoscopic adjustable gastric banding-LAGB). Statistical analysis was performed to assess the relationships between preoperative HRQOL scores, preoperative BMI and excess weight loss 1 year following BarSurg (EWL-1 year). Preoperative BMI showed a significant independent, negative linear correlation with the public distress domain of preoperative quality of life (QOL) (r = -0.368, p = 0.001; β = -0.245, p = 0.009). Preoperative BMI had a significant, positive and independent association with EWL-1 year (r = 0.499, p = 0.009; β = 0.679, p = 0.015). Preoperative QOL scores had no association with EWL-1 year. Preoperative BMI appears to predict EWL-1 year following restrictive bariatric surgery (LAGB). Preoperatively, patients with higher BMI appear to manifest greater public distress. Preoperative QOL scores, however, do not appear to have any predictive value for EWL-1 year post-LAGB. Preoperative BMI should therefore be employed as a predictor of EWL-1 year post-LAGB. Other measures of successful outcomes of bariatric surgeries (such as effects on QOL scores at 1 year) should be explored in future, larger and longer term studies.
Laparoscopic greater curvature plication (LGCP) is an emerging bariatric procedure that reduces t... more Laparoscopic greater curvature plication (LGCP) is an emerging bariatric procedure that reduces the gastric volume without implantable devices or gastrectomy. The aim of this study was to explore changes in glucose homeostasis, postprandial triglyceridemia, and meal-stimulated secretion of selected gut hormones [glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, and obestatin] in patients with type 2 diabetes mellitus (T2DM) at 1 and 6 months after the procedure. Thirteen morbidly obese T2DM women (mean age, 53.2 ± 8.76 years; body mass index, 40.1 ± 4.59 kg/m2) were prospectively investigated before the LGCP and at 1- and 6-month follow-up. At these time points, all study patients underwent a standardized liquid mixed-meal test, and blood was sampled for assessment of plasma levels of glucose, insulin, C-peptide, triglycerides, GIP, GLP-1, ghrelin, and obestatin. All patients had significant weight loss both at 1 and 6 months after the LGCP (p ≤ 0.002), with mean percent excess weight loss (%EWL) reaching 29.7 ± 2.9% at the 6-month follow-up. Fasting hyperglycemia and hyperinsulinemia improved significantly at 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), with parallel improvement in insulin sensitivity and HbA1c levels (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Meal-induced glucose plasma levels were significantly lower at 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and postprandial triglyceridemia was also ameliorated at the 6-month follow-up (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Postprandial GIP plasma levels were significantly increased both at 1 and 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), whereas the overall meal-induced GLP-1 response was not significantly changed after the procedure (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). Postprandial ghrelin plasma levels decreased at 1 and 6 months after the LGCP (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) with no significant changes in circulating obestatin levels. During the initial 6-month postoperative period, LGCP induces significant weight loss and improves the metabolic profile of morbidly obese T2DM patients, while it also decreases circulating postprandial ghrelin levels and increases the meal-induced GIP response.
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