Akheel A. Syed

Association of glucocorticoid receptor polymorphism A3669G in exon 9β with reduced central adiposity in women

The glucocorticoid receptor (GR) may be a common link between human obesity/metabolic syndrome and Cushings syndrome. The effects of glucocorticoids are mediated through the functional isoform, GRα. An alternative isoform, GRβ, behaves as a dominant negative inhibitor of GRα and has been implicated as a contributing factor to glucocorticoid resistance. A naturally occurring ATTTA to GTTTA single nucleotide polymorphism (A3669G) located in the 3′ end of exon 9β results in increased stability of GRβ mRNA and increased GRβ protein expression. Enhanced GRβ expression may result in greater inhibition of GRα transcriptional activity, resulting in glucocorticoid insensitivity. To test the hypothesis that the 3669G allele would result in a phenotype less likely to express features of glucocorticoid excess, we studied the prevalence of this polymorphism and its relationship with obesity and features of the metabolic syndrome in 322 Europid and 262 South‐Asian subjects in northeast England. We report evidence that 3669G allele is associated with reduced central obesity in Europid women and a more favorable lipid profile in Europid men. These data suggest that the 3669G allele may attenuate the undesirable effects of glucocorticoids on fat distribution and lipid metabolism, although its penetrance may vary in different ethnic groups.

A common intron 2 polymorphism of the glucocorticoid receptor gene is associated with insulin resistance in men

Objective  Clinical similarities between the metabolic syndrome and Cushings syndrome have led to speculation of genetic association between them. The Bcl1 polymorphism in intron 2 of the glucocorticoid receptor (GR) gene has been associated with insulin resistance/hyperinsulinaemia. Our objective was to test the association of rs2918419, a T→C single nucleotide change in intron 2 downstream of the Bcl1 locus, with components of the metabolic syndrome and its interaction with the Bcl1 locus.

Bariatric surgery in women of childbearing age

BACKGROUND Although bariatric surgery in women of childbearing age reduces the risks of pregnancy complications associated with maternal obesity, little is known of the effect of gestation on weight loss outcomes. AIM To study weight loss and pregnancy outcomes after bariatric surgery in women of childbearing age. DESIGN AND METHODS We performed a retrospective, observational cohort analysis of women aged 18-45 years in a university teaching hospital. The results shown represent mean ± standard deviation where appropriate. RESULTS A total of 232 women aged 34.0 ± 5.9 years with pre-operative weight 137.7 ± 21.3 kg and body mass index (BMI) 50.6 ± 7.2 kg/m(2) underwent bariatric surgery that included 197 (84.9%) gastric bypass, 19 (8.2%) gastric banding, 8 (3.4%) sleeve gastrectomy and 8 other procedures. Twenty-one women had 28 pregnancies following bariatric surgery, of which 24 (85.7%) resulted in live births, 3 (10.7%) terminations of pregnancy and 1 (3.6%) spontaneous miscarriage. The pregnancy group was younger compared with the non-pregnancy group (28.0 ± 5.4 vs. 34.6 ± 5.6 years; P < 0.001) but well matched for pre-operative weight (136.5 ± 18.5 vs. 137.8 ± 21.6 kg), BMI (49.2 ± 7.4 vs. 50.7 ± 7.2 kg/m(2)) and bariatric procedure. The interval between bariatric surgery and first pregnancy was a median 11 months. The pregnancy group lost 70.4% of excess weight compared with 70.0% in the non-pregnancy group at median 30 months of follow-up. CONCLUSION Pregnancy after bariatric surgery is safe and does not adversely affect weight loss outcomes.

Weight loss and metabolic outcomes of bariatric surgery in men versus women — A matched comparative observational cohort study

BACKGROUND Despite the high prevalence of morbid obesity, the global frequency of bariatric surgery in men is significantly lower than in women. It is unclear if this is due to the perception of poorer outcomes in men. OBJECTIVES Compare weight loss and metabolic outcomes in men vs. women after bariatric surgery. SETTING University teaching hospital in North West England. METHODS We performed an observational cohort analysis of 79 men matched to 79 women for baseline age (± 5 years), body mass index (BMI; ± 2 kg/m(2)), bariatric procedure (69 gastric bypass and 10 sleeve gastrectomy each), type 2 diabetes (33 each), and continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA; 40 each). RESULTS Overall mean (95% confidence interval) reduction in BMI was 17.5 (15.7-19.4) kg/m(2) (P<0.001) at 24 months. There was no significant difference between men and women in mean percentage excess BMI loss (65.8% vs. 72.9%) at 24 months. Likewise, there were significant reductions in blood pressure, glycosylated haemoglobin and total cholesterol-to-high density lipoprotein cholesterol overall but no significant gender differences. Postoperatively, 77.5% of men and 90.0% of women with OSA discontinued CPAP therapy (non-significant). CONCLUSIONS Weight loss and metabolic outcomes after bariatric surgery are of similar magnitude in men compared to women. The use of bariatric surgery in eligible men should be encouraged.

Effect of weight loss after gastric bypass surgery on thyroid function in euthyroid people with morbid obesity

Obesity is positively associated with serum thyrotropin (TSH) concentrations at the high end of the normal range. The relationship between weight loss and thyroid function is less clear and studies to date have yielded inconsistent results. Our aim was to describe changes in thyroid function in obese people in relation to durable and significant weight loss after Roux‐en‐Y gastric bypass (RYGB) surgery. We recorded percentage of excess weight loss (% EWL), serum TSH and free thyroxine (fT4) before and median 4.5, 15 and 24 months after RYGB in 55 euthyroid patients with morbid obesity ranging in age from 18 to 64 years in a retrospective cohort analysis in a university hospital in Greater Manchester. Mean ± standard error preoperative weight was 135.13 ± 4.23 kg and BMI 48.08 ± 1.58 kg m−2. Patients attained nadir %EWL of 68% by median 15 months after RYGB. TSH was 2.00 ± 0.14 mU L−1 at baseline and 2.02 ± 0.22 mU L−1 at 24 months after RYGB (non‐significant). Baseline fT4 was 13.46 ± 0.28 pmol L−1, and increased significantly to 15.14 ± 0.55 pmol L−1 at 24 months (P < 0.004). In conclusion, we report that weight loss after RYGB was accompanied by significant increase in serum fT4 but no change in TSH concentrations. Further study to elucidate the effect of significant weight loss on the thyroid axis is required.

Metabolic Outcomes 1 Year after Gastric Bypass Surgery in Obese People with Type 2 Diabetes.

Objective: To assess metabolic outcomes in obese people with type 2 diabetes (T2D) in the first year following gastric bypass surgery. Subjects and Methods: Forty-nine obese patients with T2D who had undergone gastric bypass surgery 12 or more months previously were identified. Body weight and glycosylated haemoglobin (HbA1c) pre-operatively and 3, 6 and 12 months postoperatively, changes to glucose-lowering therapies, and blood pressure (BP) and total and high-density lipoprotein (HDL) cholesterol pre-operatively and 12 months postoperatively were recorded. The primary outcome measure was change in HbA1c; secondary outcomes included changes in BP and lipid profile. Results: The mean pre-operative body weight was 141.4 kg, the body mass index 49.4 and HbA1c 8.1%. The mean postoperative percentage of excess body weight loss at 3, 6 and 12 months was 39.0, 53.9 and 71.1 with reduction in HbA1c to 6.6, 6.2 and 5.8%, respectively (p < 0.0001). Remission of diabetes (HbA1c <6.5%) occurred in 12 of 18 patients (67%) at 3 months, 20 of 27 (74%) at 6 months and 21 of 25 (84%) at 12 months; of 41 patients under glucose-lowering treatment, 26 (63%) achieved complete withdrawal of treatment and 7 (17%) had their doses reduced. The mean of differences between baseline and 12-month measurements of systolic BP was 10.5 mm Hg (p = 0.021) and the total-to-HDL cholesterol ratio 0.9 (p < 0.002). Conclusion: Our study confirmed the finding of previous studies that gastric bypass surgery in obese people with T2D results in significant weight loss, and improved glycaemic, BP and lipid profiles. Bariatric surgery should be regarded as an effective therapeutic intervention in this patient population.

Pregnancy after bariatric surgery: screening for gestational diabetes

Safer alternatives are needed to traditional test

Impairment of high-density lipoprotein resistance to lipid peroxidation and adipose tissue inflammation in obesity complicated by obstructive sleep apnea.

CONTEXT Obstructive sleep apnea (OSA) complicates morbid obesity and is associated with increased cardiovascular disease incidence. An increase in the circulating markers of chronic inflammation and dysfunctional high-density lipoprotein (HDL) occur in severe obesity. OBJECTIVE The objective of the study was to establish whether the effects of obesity on inflammation and HDL dysfunction are more marked when complicated by OSA. DESIGN AND PATIENTS Morbidly obese patients (n = 41) were divided into those whose apnea-hypoapnea index (AHI) was more or less than the median value and on the presence of OSA [OSA and no OSA (nOSA) groups]. We studied the antioxidant function of HDL and measured serum paraoxonase 1 (PON1) activity, TNFα, and intercellular adhesion molecule 1 (ICAM-1) levels in these patients. In a subset of 19 patients, we immunostained gluteal sc adipose tissue (SAT) for TNFα, macrophages, and measured adipocyte size. RESULTS HDL lipid peroxide levels were higher and serum PON1 activity was lower in the high AHI group vs the low AHI group (P < .05 and P < .0001, respectively) and in the OSA group vs the nOSA group (P = .005 and P < .05, respectively). Serum TNFα and ICAM-1 levels and TNFα immunostaining in SAT increased with the severity of OSA. Serum PON1 activity was inversely correlated with AHI (r = -0.41, P < .03) in the OSA group. TNFα expression in SAT directly correlated with AHI (r = 0.53, P < .03) in the subset of 19 patients from whom a biopsy was obtained. CONCLUSION Increased serum TNFα, ICAM-1, and TNFα expression in SAT provide a mechanistic basis for enhanced inflammation in patients with OSA. Decreased serum PON1 activity, impaired HDL antioxidant function, and increased adipose tissue inflammation in these patients could be a mechanism for HDL and endothelial dysfunction.

Iodinated contrast–induced thyrotoxicosis

A 72-year-old man presented to the emergency department with shortness of breath. He had a history of left ventricular failure, hypertension, treated esophageal carcinoma and recurrent deep vein thromboses. His medications included warfarin, bumetanide, spironolactone, ramipril, bisoprolol,

Benign thyroid disease in pregnancy: A state of the art review

Highlights • Overt hypothyroidism needs to be treated with levothyroxine.• Subclinical hypothyroidism treated with thyroxine has not been proven to improve maternal outcomes.• Overt hyperthyroidism usually needs to be treated with thioamides.• Subclinical hyperthyroidism does not require treatment.• Evidence linking TPO antibodies with miscarriages and preterm labour is unequivocal.