Dietary Intakes of Folate, Vitamin D and Iodine during the First Trimester of Pregnancy and the Association between Supplement Use and Demographic Characteristics amongst White Caucasian Women Living with Obesity in the UK.

Folate, vitamin D and iodine are key micronutrients in pregnancy, with deficiency associated with poor maternal and infant outcomes. For folate and vitamin D especially, deficiency is more common amongst women with obesity and recommended intakes and guidance on supplementation varies worldwide. The present study aims to investigate dietary and supplementary intakes of these micronutrients amongst a population of pregnant women with obesity in the United Kingdom, alongside key maternal demographic characteristics. Expectant women (n = 75) with a body mass index ≥ 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Participants were asked about their supplement use preconception and during trimester one in a baseline questionnaire which also asked about demographic characteristics. Women also completed a four day diet diary from which dietary and supplemental intakes of micronutrients intakes were estimated. Folic acid was taken by 96% of women at any point in trimester 1, whilst only 26% of women took the higher 5 mg dose recommended for women with obesity in the UK. For vitamin D and iodine, 56% and 44% of women met the UK RNI, respectively. Maternal age was positively associated with taking supplements of any kind and the 5 mg folic acid supplement, whilst parity was inversely associated with both outcomes. This study strengthens the rationale for further work to be done raising awareness of the need for women with obesity to supplement both with a higher dose of folic acid and vitamin D and to be aware of the role of iodine during pregnancy.

The relationship between gestational weight gain, maternal upper-body subcutaneous fat changes and infant birth size: A pilot observational study amongst women with obesity.

BACKGROUND: It is widely acknowledged that maternal obesity and excessive gestational weight gain (GWG) are associated with increased risk of fetal macrosomia and recent studies have suggested a role for the timing and composition of GWG. AIMS: To examine the effect of the rate of change in GWG and maternal upper-body subcutaneous fat on neonatal anthropometric outcomes in a pilot observational study amongst women with obesity. STUDY DESIGN: Expectant women with a body mass index (BMI) > 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Maternal height, weight and skinfold thickness (SFT) measurements were collected at baseline and repeated at 28 and 36 weeks gestation. Following delivery, World Health Organisation (WHO)-UK infant birthweight z-scores were calculated, and infant anthropometric measurements were obtained. RESULTS: The sum of upper body SFT measurements increased in mid-pregnancy (0.08 ± 0.71 mm/week) and decreased in late pregnancy (-0.04 ± 1.17 mm/week). After adjustment for maternal age, BMI and parity, mid- but not late- pregnancy GWG was positively associated with infant birthweight z-score (p<0.05), while mid- but not late-pregnancy changes in the sum of SFT were inversely associated with infant birthweight z-score (p<0.01). CONCLUSIONS: The present study suggests that mid- rather than late-pregnancy changes in weight and upper-body subcutaneous fat are associated with infant birthweight. Further research is required in larger, more diverse populations to explore whether pregnancy interventions aiming to improve maternal and offspring health can be personalised beyond BMI and GWG.

Objectively measured sleep duration and plasma glucose values following an oral glucose tolerance test amongst pregnant women with obesity in the UK.

BACKGROUND/OBJECTIVES: Short sleep duration has been linked to maternal hyperglycaemia following a 1-h 50 g oral glucose tolerance test (OGTT) in observational studies conducted primarily in the USA. Our objective was to examine the relationship between objectively measured sleep duration and plasma glucose values following the 2-h 75 g OGTT routinely used in the UK amongst women with obesity. METHODS: Sleep and OGTT data were available for 49 pregnant women who wore wrist actigraphs for at least two nights, and took a 2-h 75 g OGTT at the end of their second trimester. Multivariable regression was used to evaluate associations between sleep duration and OGTT results. RESULTS: Higher 2-h plasma glucose values were significantly associated with shorter sleep duration and higher maternal age and BMI, with no association observed between wake after sleep onset (WASO) and 2-h plasma glucose values. No associations were observed between fasting plasma glucose values and any sleep parameters. CONCLUSIONS: We found that shorter sleep duration, as measured using actigraphy, is associated with higher 2-h plasma glucose values following a 2-h 75 g OGTT in the UK. These findings are in keeping with those observed elsewhere in the world, employing alternative OGTT protocols. Future studies should investigate sleep extension as a potential candidate for inclusion in future RCTs aiming to improve glucose tolerance and prevent GDM amongst those at risk.

Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes.

AIMS: To investigate the association between circulating non-transferrin-bound iron [NTBI], and markers of oxidative stress, endothelial function and inflammation in subjects with type 2 diabetes and non-diabetic subjects with varying degrees of obesity. METHODS: Plasma NTBI was measured by HPLC, together with total iron, iron-binding capacity, transferrin saturation and soluble transferrin receptor, together with total and reduced ascorbate, malondialdehyde [MDA], E-selectin and high-sensitivity c-reactive protein [hs-CRP] in groups of 28 subjects with type 2 diabetes, 28 non-obese controls and 17 obese non-diabetic subjects. RESULTS: Levels of NTBI were higher than controls in the diabetes group, but the total serum iron levels were lower. MDA levels were higher than controls in both the diabetes and obese groups, and this was associated with higher levels of oxidised ascorbate. hs-CRP levels were higher in both the diabetes and obese groups, and E-selectin was significantly higher in the diabetes group. There were strong positive correlations between HbA1c levels and NTBI [P<0.01], HbA1c and E-selectin [P<0.001] and NTBI and E-selectin [P<0.02] in the diabetes group. CONCLUSION: These results support the hypothesis that iron-mediated oxidative stress may be a mechanism linking poor glycaemic control with vascular dysfunction in type 2 diabetes.

Acute peripheral administration of synthetic human GLP-1 (7-36 amide) decreases circulating IL-6 in obese patients with type 2 diabetes mellitus: a potential role for GLP-1 in modulation of the diabetic pro-inflammatory state?

BACKGROUND: To explore the effects of acute administration of GLP-1 and GIP on circulating levels of key adipocyte-derived hormones and gut-brain peptides with established roles in energy and appetite regulation, modulation of insulin sensitivity and inflammation. METHODS: Six obese male patients with diet-treated type 2 diabetes (T2DM) and 6 healthy lean subjects were studied. The protocol included 4 experiments for each participant that were carried out in randomised order and comprised: GLP-1 infusion at a rate of 1 pmol/kg/min for 4h, GIP at a rate of 2 pmol/kg/min, GLP-1+GIP and placebo infusion. Plasma leptin, adiponectin, IL-6, insulin, ghrelin and obestatin were measured at baseline, 15, 60, 120, 180 and 240 min following the start of infusion. RESULTS: Patients with T2DM had higher baseline IL-6 compared with healthy [day of placebo infusion: T2DM IL-6 mean (SEM) 1.3 (0.3) pg/ml vs 0.3 (0.1)pg/ml, p=0.003]. GLP-1 infusion in T2DM was associated with a significant reduction in circulating IL-6 [baseline IL-6 1.2 pg/ml vs IL-6=0.7 at 120 min, p=0.0001; vs IL-6=0.8 at 180 min, p=0.001]. There was no significant change in leptin, adiponectin, ghrelin or obestatin compared to baseline on all 4 experimental days in both groups. CONCLUSION: Short-term infusion of supraphysiological concentrations of GLP-1 in T2DM results in suppression of IL-6, a key inflammatory mediator strongly linked to development of obesity and T2DM-related insulin resistance. It remains to be confirmed whether GLP-1-based diabetes therapies can impact favourably on cardiovascular outcomes.

Human RBP4 adipose tissue expression is gender specific and influenced by leptin.

OBJECTIVE: The role of retinol-binding protein-4 (RBP4) in human insulin resistance remains controversial, which may in part be explained by a gender-specific secretion of RBP4 in adipose tissue (AT). The aim of the study was to determine gender-specific depot expression of RBP4 and to identify metabolic parameters and cytokines/adipokines associated with RBP4. RESEARCH DESIGN AND METHODS: The study is an ex-vivo prospective analysis of paired AT-samples from 22 men and 26 women of similar age [men: 43·4 ± 13 (mean ± SD)years, women: 44·1 ± 12 years], BMI (men: 41·9 ± 18kg/m(2) , women: 38·4 ± 11kg/m(2) ) and homeostasis model assessment of insulin resistance taken during elective surgery and ex-vivo culture using visceral-AT (VAT)-explants (n = 10). Plasma RBP4 and cytokines were measured by ELISA and mRNA expression in AT by real-time PCR. VAT-explants were cultured with recombinant leptin and insulin and RBP4 determined by western blot analyses. RESULTS: Overall subcutaneous AT (SCAT)-RBP4 mRNA expression was higher than VAT-expression [3·1 ± 0·26 signal units (SU; mean ± SE) vs 1·79 ± 0·18SU, n = 48, P < 0·0001], but neither correlated with circulating RBP4. SCAT-RBP4 expression was higher in women and correlated with BMI (r =-0·5, P = 0·009) and fat mass (r= -0·5, P = 0·002). VAT-RBP4 correlated positively with GLUT-4 expression and adiponectin in men only (r= 0·54, P = 0·03 and r = 0·64, P < 0·002, respectively) when correcting for age and fat mass. Multiple regression determined leptin AT-expression as a positive predictor of AT-RBP4 in women (SCAT: ß = 0·50, P = 0·002; VAT: ß = 0·58, P = 0·003) and adiponectin for VAT-RBP4 in men (ß = 0·69; P=0·001). AT-RBP4 mRNA expression showed no relation with insulin resistance. Leptin stimulated RBP-4 secretion ex-vivo, whilst insulin did not affect RBP4. CONCLUSION: AT-derived RBP4-mRNA expression is gender specific and regulated by leptin. Circulating RBP4 levels appear to be independent of AT-RBP4 secretion.

Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose.

OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ (450 kcal)/day for 16 weeks and serial subcutaneous-abdominal-adipose tissue (SCAT) biopsies (weight loss: 28 +/- 3.7 kg). Another six lean subjects underwent fast-food-based hyperalimentation for 4 weeks (weight gain: 7.2 +/- 1.6 kg). Finally, visceral adipose tissue explants were cultured with recombinant leptin, insulin, and glucose, and SPARC mRNA and protein expression determined by Western blot analyses. RESULTS: SPARC expression in human adipose tissue correlated with fat mass and was higher in SCAT. Weight loss induced by very-low-calorie diet lowered SPARC expression by 33% and increased by 30% in adipose tissue of subjects gaining weight after a fast-food diet. SPARC expression was correlated with leptin independent of fat mass and correlated with homeostasis model assessment-insulin resistance. In vitro experiments showed that leptin and insulin potently increased SPARC production dose dependently in visceral adipose tissue explants, while glucose decreased SPARC protein. CONCLUSIONS: Our data suggest that SPARC expression is predominant in subcutaneous fat and its expression and secretion in adipose tissue are influenced by fat mass, leptin, insulin, and glucose. The profibrotic effects of SPARC may contribute to metabolic dysregulation in obesity.

Is there a role for ghrelin and peptide-YY in the pathogenesis of obesity in adults with acquired structural hypothalamic damage?

CONTEXT: Obesity is a common sequel to hypothalamic tumors and their treatment, but the underlying mechanisms are not fully established. OBJECTIVE: Our objective was to evaluate the role of ghrelin and peptide-YY (PYY) in human hypothalamic obesity. SETTING: The study took place at a University Medical Center. PARTICIPANTS: Subjects included 14 adult patients (six male, eight female) with tumors of the hypothalamic region and 15 healthy controls (six male and nine female) matched for age, body mass index, and percentage of body fat. INTERVENTIONS: Plasma ghrelin and total PYY were measured using RIAs after an overnight fast and 15, 30, 60, 120, and 180 min after a mixed meal. MAIN OUTCOME MEASURES: We assessed ghrelin, PYY, and appetite ratings. RESULTS: The fall in ghrelin levels after the test meal was similar in the two groups. There was no statistically significant change postprandially in circulating PYY in the patients with hypothalamic damage. Fasting leptin levels and postprandial insulin responses were also similar in the two groups. Patients with hypothalamic damage reported higher hunger ratings at 3 h after the meal (P = 0.01) and a stronger desire to eat at 2 h (P = 0.01) and 3 h (P = 0.02) compared with the control group. CONCLUSIONS: Adult patients with structural hypothalamic damage show impaired satiety, but the changes observed in circulating ghrelin and PYY concentrations in response to a test meal do not indicate a central role for these gut hormones in the control of appetite and the pathogenesis of obesity in these patients.

Endocrine and neuroanatomic features associated with weight gain and obesity in adult patients with hypothalamic damage.

PURPOSE: Obesity is a common consequence in patients with tumors of the hypothalamic region and of related treatment in children. Much less information is available on adult patients and long-term survivors. The aims of this study were to estimate the prevalence of obesity in adult patients with acquired structural hypothalamic damage and to define the characteristics of patients at greatest risk of obesity. METHODS: A retrospective study was conducted of 52 patients (25 women; median age at diagnosis, 44 years; range, 17 to 78 years) with tumors involving the hypothalamic region. These included 22 craniopharyngiomas, 24 pituitary adenomas, and six other hypothalamic tumors. Changes in body mass index were determined, magnetic resonance imaging scans were scored by a radiologist for tumor size and the extent of involvement of the hypothalamus, and current hormone replacement therapy was recorded, to identify possible features associated with new or worsened obesity (defined as a body mass index > or =30 kg/m(2) at the latest follow-up, which had increased by at least 2 kg/m(2) since diagnosis of the tumor). RESULTS: Serial body mass index data from diagnosis to the latest follow-up were available for 42 patients. After a median of 5 years (range, 1 to 19 years) of follow-up, most patients with hypothalamic damage were obese (52% [n = 22] vs. 24% [n = 10] at the time of diagnosis, P < 0.0001). In a multivariate model, use of desmopressin (odds ratio [OR] = 13; 95% confidence interval [CI]: 2.0 to 86; P = 0.007) and growth hormone replacement (OR = 7.6; 95% CI: 1.1 to 51; P = 0.04) were associated with new or worsened obesity during follow-up. No correlation was found between the initial size or location of the tumor and subsequent weight gain. CONCLUSION: Obesity is highly prevalent in adult survivors of hypothalamic tumors. Use of desmopressin and growth hormone therapy, but not size or location of the tumor, were associated with weight gain and obesity following diagnosis. These findings may be helpful in identifying patients at increased risk of obesity, to whom earlier intervention could be offered.