Beta and alpha cell function in metabolically healthy but obese subjects: Relationship with entero‐insular axis

Objective:

Obesity is widely acknowledged as a critical risk factor for metabolic complications. Among obese subjects, there is a phenotype of metabolically healthy but obese (MHO) individuals that shows a favorable cardiometabolic risk profile. We aimed to evaluate the potential mechanisms underlying the metabolic profile of this subset, including alpha and beta cell function and entero‐insular axis.

Design and Methods:

One hundred twenty‐nine obese and 24 nonobese subjects were studied. Obese participants were defined as MHO or at‐risk obese, according to the homeostasis model of assessment‐insulin resistance (HOMA‐IR) index (MHO: lower tertile of HOMA‐IR, n = 43; at‐risk: upper tertile of HOMA‐IR index, n = 41). Insulin, glucagon, and incretin responses after a 120′ oral glucose tolerance test (75‐g OGTT) were investigated.

Results:

During OGTT, MHO individuals showed in comparison with at‐risk subjects: lower fasting and afterloads plasma levels of glucose, insulin, and C‐peptide; higher disposition index; lower fasting (P = 0.004) and at 30′ (P = 0.01) plasma glucose‐dependent insulinotropic polypeptide (GIP) levels; lower area under the curve (AUC) (0‐30) for GIP (P = 0.008); higher glucagon‐like peptide‐1 (GLP‐1) plasma levels at 90′ (P = 0.02) and 120′ (P = 0.02); lower glucagon plasma levels at baseline (P = 0.04) and at 30′ (P = 0.03); and appropriate glucagon suppression after the oral glucose load.

Conclusions:

MHO subjects show, as well as normal‐weight individuals, a lower diabetogenic profile by virtue of higher disposition index and unaffected entero‐insular axis. At‐risk obese individuals present increased GIP levels that might play a role in determining increased glucagon secretion and inappropriate glucagon responses after glucose load, thus contributing to impaired glucose homeostasis.     

Sympathetic support of energy expenditure and sympathetic nervous system activity after gastric bypass surgery

Objective:

This study was designed to determine how gastric bypass affects the sympathetically‐mediated component of resting energy expenditure (REE) and muscle sympathetic nerve activity (MSNA).

Design and Methods:

We measured REE before and after beta‐blockade in seventeen female subjects approximately three years post‐gastric bypass surgery and in nineteen female obese individuals for comparison. We also measured MSNA in a subset of these subjects.

Results:

The gastric bypass subjects had no change in REE after systemic beta‐blockade, reflecting a lack of sympathetic support of REE, in contrast to obese subjects where REE was reduced by beta‐blockade by approximately 5% (P < 0.05). The gastric bypass subjects, while still overweight (BMI = 29.3 vs 38.0 kg·m^?2 for obese subjects, P < 0.05), also had significantly lower MSNA compared to obese subjects (10.9 ± 2.3 vs. 21.9 ± 4.1 bursts·min^?1, P < 0.05). The reasons for low MSNA and a lack of sympathetically mediated support of REE after gastric bypass are likely multifactorial and may be related to changes in insulin sensitivity, body composition, and leptin, among other factors.

Conclusions:

These findings may have important consequences for the maintenance of weight loss after gastric bypass. Longitudinal studies are needed to further explore the changes in sympathetic support of REE and if changes in MSNA or tissue responsiveness are related to the sympathetic support of REE.

     

Serum adiponectin levels are associated with hepatitis B viral load in overweight to obese hepatitis B virus carriers

Objective:

This study aimed to investigate the association between serum adiponectin and chronic hepatitis B virus (HBV) infection.

Design and Methods:

We conducted a campus‐based cross‐sectional study in Northern Taiwan, an HBV‐endemic country. A total of 506 participants, including 147 chronic HBV‐infected individuals and 359 healthy controls, were assessed for anthropometric indices, serum adiponectin levels, serum HBV viral load and markers, serum alanine aminotransferase levels and metabolic factors.

Results:

Older age, male gender, higher alanine aminotransferase, higher body mass index, greater waist circumference, lower fasting glucose, higher triglycerides, and higher adiponectin were associated with chronic HBV infection in univariate analyses. In multivariate analysis, the presence of chronic HBV infection was positively associated with serum adiponectin levels (P < 0.0001) and high adiponectin levels over the 75th percentile (odds ratio, 4.25; 95% confidence interval, 2.36‐7.66; P < 0.0001) after adjusting for age, gender, body mass index, and insulin resistance index. Furthermore, serum adiponectin levels were positively associated with HBV viral load in overweight to obese HBV‐infected subjects (P = 0.018).

Conclusion:

Although chronic HBV‐infected individuals were heavier than healthy controls, they had significantly higher serum adiponectin levels than healthy counterparts. Additionally, adiponectin levels were positively associated with HBV viral load in overweight to obese HBV‐infected subjects. Future research should focus on elucidating adiponectin pathways, which may contribute to the development of adjuvant treatments for chronic HBV infection.     

Liver steatosis in obese prepubertal children: a possible role of insulin resistance

Objective: To determine whether in obese prepubertal children insulin resistance (IR) is associated with the development of liver steatosis. Methods and Procedures: Cross‐sectional study evaluating the prevalence of liver steatosis in 100 severely obese prepubertal children and comparing IR indexes between children with (group 1) and without steatosis (group 2). Furthermore, IR indexes were compared to values of 50 normal weight children. Fasting blood samples were collected for the evaluation of liver function tests, lipid profile, plasma glucose, and insulin levels. All children underwent an oral glucose tolerance test and anthropometric measurements. Hepatic ultrasound was performed according to international criteria and by one single operator. Analysis was performed by Mann–Whitney U‐test, Pearson correlation, and logistic regression. Results: Liver steatosis was found in 52% obese children and was equally distributed between the two sexes. Obese children were more insulin resistant when compared to controls (homeostasis model assessment of IR (HOMA‐IR): P = 0.0001; whole body insulin sensitivity index (WBISI): P = 0.0005; fasting glucose/fasting insulin ratio (G/I): P = 0.0001), and group 1 presented an even higher degree of IR when compared to group 2 (HOMA‐IR P = 0.0001; WBISI P = 0.0004; G/I P = 0.0001). The area under the curve (AUC) for insulin was significantly higher in group 1 when compared to group 2, while no difference was found in the AUC for glucose. There was no association between IR and adiposity indexes (P >0.05). The role of IR as a predictor for the development of steatosis was analyzed by multiple logistic regression, which documented that IR indexes were significantly related to steatosis independently of BMI‐SDS. Discussion: Liver steatosis is an emerging problem in prepubertal severely obese children, and it appears to be an association between liver steatosis and IR in these subjects.     

Association between body mass index and suicide,and suicide attempt among british adults: The health improvement network database

Objective:

To examine the associations between body mass index (BMI) and incidence rate (IR) of suicide attempt and suicide.

Design and Methods:

849,434 British adults were identified from The Health Improvement Network (THIN) database between January 2000 and October 2007. BMI was categorized into six levels: <18.5 (underweight), 18.5‐24.9 (normal weight), 25.0‐29.9 (overweight), 30.0‐34.9, 35.0‐39.9, and ≥40 (obese levels I‐III).

Results:

We identified 3,111 suicide attempts by Read codes and 75 suicides with medical records. The overall IR of suicide attempt was 82.2 cases per 100,000 person‐years. The IR decreased with BMI in men with depression (471.3‐166.0 cases per 100,000 person‐years, P for trend = 0.02) and in men without depression (241.5‐58.0 cases per 100,000 person‐years, P for trend < 0.0001). In women with depression, an L‐shaped relationship was observed, that is, a higher rate in underweight group when compared with reference group (503.2 vs. 282.7 per 100,000 person‐years) and no significant differences in others (231.8‐195.5 cases per 100,000 person‐years). In women without depression, the IR was U‐shaped with BMI (125.2 in underweight, 68.6 in reference, and 48.5‐79.9 cases in overweight and obese I‐III groups per 100,000 person‐years, P for trend < 0.0001). The above trends remained after adjustment for the covariates. Regarding suicide, the overall IR was 2.0 cases per 100,000 person‐years, which tended to decrease with BMI (P = 0.14).

Conclusions:

We concluded an inverse linear association between BMI and suicide attempt among men, an L‐shaped association in nondepressive women, and a U‐shaped association in depressive women were observed. The study also suggested an inverse linear tendency between BMI and suicide.     

Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects

Background:

Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).

Methods:

In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.

Results:

Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.

Conclusions:

Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.     

Cortisol,obesity, and the metabolic syndrome: A cross‐sectional study of obese subjects and review of the literature

Objective:

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome (MS). To evaluate these relationships, a cross‐sectional study of 369 overweight and obese subjects and 60 healthy volunteers was performed and reviewed the previous literature.

Design and Methods:

Overweight and obese subjects had at least two other features of Cushing's syndrome. They underwent measurements representing cortisol dynamics (24 h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol, and weight from 60 healthy volunteers were analyzed.

Results:

No subject had Cushing's syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P < 0.0001), and correlated with waist circumference (WC) in men (r_s = 0.28, P = 0.02) and systolic BP in women (r_s = 0.24, P = 0.0008). Post‐dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (r_s = ?0.31, P = 0.01) and HOMA‐IR (r_s = ?0.31, P = 0.01) in men and systolic (r_s = 0.18, P = 0.02) and diastolic BP (r_s = 0.20, P = 0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA‐IR, and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters.

Conclusion:

Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or MS.

     

Health Outcomes of Gastric Bypass Patients Compared to Nonsurgical,Nonintervened Severely Obese

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight‐loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m²) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population‐based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes‐related variables, resting metabolic rate (RMR), sleep apnea, and health‐related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF‐36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux‐en‐Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight‐loss intervention was highly effective for weight loss, improved health‐related quality of life, and resolution of major obesity‐associated complications measured at 2 years.     

Serum hemorphin‐7 levels are decreased in obesity

Objective:

Hemorphin peptides exhibit biological activities that interfere with the endorphin system, the inflammatory response, and blood‐pressure control. VV‐hemorphin‐7 and LVV‐hemorphin‐7 peptides exert a hypotensive effect, in particular, by inhibiting the renin–angiotensin system. Furthermore, levels of circulating hemorphin‐7 peptides have been found to be decreased in diseases such as type 1 and type 2 diabetes.

Design and Methods:

Because type 2 diabetes and obesity share common features, such as insulin resistance, microinflammation, high glomerular‐filtration rate (GFR), and cardiovascular risk, we evaluated serum VV‐hemorphin‐7 like immunoreactivity (VVH7‐i.r.) levels, using an enzyme‐linked immunosorbent assay method, on a group of 54 obese subjects without diabetes or hypertension, compared with a group of 33 healthy normal‐weight subjects.

Results:

Circulating VVH7‐i.r. levels were significantly decreased in the obese group compared with the control group (1.98 ± 0.19 vs. 4.86 ± 0.54 µmol/l, respectively, P < 0.01), and a significant negative correlation between VVH7‐i.r. and diastolic blood pressure (DBP) was found in obese patients (r = ?0.35, P = 0.011). There was no significant correlation between VVH7‐i.r. level and insulin resistance, metabolic syndrome, or GFR.

Conclusions:

The decreased serum hemorphin‐7 found in obese subjects, as in diabetes, may contribute to the development of hypertension and to the cardiovascular risk associated with these metabolic diseases.

     

Adipocyte Fatty Acid‐binding Protein as a Determinant of Insulin Sensitivity in Morbid‐obese Women

The aim of the study was to evaluate human plasma circulating levels of adipocyte fatty acid‐binding protein (A‐FABP) and its relationship with proinflammatory adipocytokines and insulin resistance in a severely obese cohort, before and 1 year after a surgical gastric bypass. Plasmatic levels of A‐FABP were measured in 77 morbid‐obese women before and 1 year after bariatric surgery. Anthropometrical parameters and body composition by bioelectrical impedance analysis were determined. Circulating levels of soluble tumor necrosis factor receptor 2 (sTNFR2), Interleukin 18 (IL‐18), adiponectin, and high‐sensitive C‐reactive protein (hsCRP) were also analyzed. Insulin resistance by homeostasis model assessment of insulin resistance (HOMA‐IR) index was calculated. After massive weight loss, A‐FABP plasmatic levels decreased significantly [7.6 (8.9) vs. 4.3 (5.1); P < 0,001] but no association with circulating adipokines or proinflammatory cytokines, both at the beginning and at the end of follow‐up, was observed. A decrease in sTNFR2, IL‐18, hsCRP, and an increase in adiponectin levels (P < 0.001 in all cases) were observed after the gastric bypass. HOMA‐IR index improved 1 year after surgery and after multiple regression analysis remained associated with A‐FABP after controlling for confounding variables (β = 0.322, P = 0.014; R² for the model 0.281). In morbid‐obese women, plasma A‐FABP concentrations were dramatically reduced after gastric bypass surgery. After weight loss this protein contributed to HOMA‐IR index independently of proinflammatory/antinflammatory cytokine profile. Further studies are warranted to elucidate the role of A‐FABP in the pathogenesis of insulin resistance in morbid obesity.     

Obesity and body fat classification in the metabolic syndrome: Impact on cardiometabolic risk metabotype

Objective:

Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study).

Design and Methods:

Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n‐3 polyunsaturated fatty acids (LC n‐3 PUFAs)).

Results:

About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (≥30 kg/m²) and BF% (≥25% (men) and ≥35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor‐1 (PAI‐1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA‐IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor‐α (TNF‐α) concentrations were lower post‐intervention in NOO individuals compared with OO subjects (P < 0.001).

Conclusions:

In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone.     

Serum amyloid A is found on ApoB‐containing lipoproteins in obese humans with diabetes

Objective:

In murine models of obesity/diabetes, there is an increase in plasma serum amyloid A (SAA) levels along with redistribution of SAA from high‐density lipoprotein (HDL) to apolipoprotein B (apoB)‐containing lipoprotein particles, namely, low‐density lipoprotein and very low‐density lipoprotein. The goal of this study was to determine if obesity is associated with similar SAA lipoprotein redistribution in humans.

Design and Methods:

Three groups of obese individuals were recruited from a weight loss clinic: healthy obese (n = 14), metabolic syndrome (MetS) obese (n = 8), and obese with type 2 diabetes (n = 6). Plasma was separated into lipoprotein fractions by fast protein liquid chromatography, and SAA was measured in lipid fractions using enzyme‐linked immunosorbent assay and Western blotting.

Results:

Only the obese diabetic group had SAA detectable in apoB‐containing lipoproteins, and SAA reverted back to HDL with active weight loss.

Conclusions:

In human subjects, SAA is found in apoB‐containing lipoprotein particles only in obese subjects with type 2 diabetes, but not in healthy obese or obese subjects with MetS.     

Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk

Objective:

Reduced numbers of regulatory T (T_reg) cells have been observed in visceral adipose tissue of obese mice and humans. However, it is unknown whether human obesity affects circulating Treg cells and whether their number is associated with markers of systemic inflammation or glucose intolerance.

Design and Methods:

Peripheral blood mononuclear cells were isolated from venous blood of obese (BMI ≥ 27 kg/m²; n = 30) and nonobese (BMI ≥ 27 kg/m²; n = 13) individuals and analyzed using flow cytometry for the expression of CD4, CD25, and Foxp3.

Results:

Reduced circulating T_reg‐cell numbers were detected in obese compared with nonobese study participants (P = 0.038). Circulating CD4⁺CD25⁺CD127^?Foxp3 T_reg cells inversely correlated with body weight (P = 0.009), BMI (P = 0.004) and plasma leptin levels (P = 0.004) and were reduced in subjects with hsCRP ≥ 3.0 mg/L (P = 0.034) or HbA1c ≥ 5.5% (P < 0.005). Receiver operating characteristic curve analysis revealed a cutoff of circulating Treg cells < 1.06% to be predictive for hsCRP levels ≥ 3.0 mg/L, and logistic regression showed that the risk of having hsCRP levels ≥ 3.0 mg/L was increased 9.6‐fold (P = 0.008), if T_reg cells were below this threshold. The T_reg cutoff for HbA1c levels ≥ 5.5% was 0.73%, and this cutoff also predicted an increased risk of having elevated levels of both hsCRP and HbA1c, if only obese subjects were examined.

Conclusion:

Our findings thus reveal an association between circulating T_reg cells and measures of adiposity, inflammation, and glucose intolerance. Although further prospective studies are needed, we present data suggesting that the determination of T_reg cells might be useful to identify obese subjects at increased risk of developing cardiovascular and/or metabolic complications.

     

The inverse relation of HDL anti‐oxidative functionality with serum amyloid a is lost in metabolic syndrome subjects

Objective:

Anti‐oxidative properties of high density lipoproteins (HDL) are relevant for atheroprotection. HDL carry serum amyloid A (SAA), which may impair HDL functionality. We questioned whether HDL anti‐oxidative capacity is determined by SAA.

Design and Methods:

Relationships of HDL anti‐oxidative capacity (% inhibition of low density lipoprotein oxidation in vitro) with SAA were determined in 54 non‐diabetic subjects without metabolic syndrome (MetS) and 68 subjects with MetS (including 51 subjects with Type 2 diabetes mellitus).

Results:

SAA levels were higher in MetS subjects, coinciding higher high sensitive C‐reactive protein (hs‐CRP) and lower HDL cholesterol and apolipoprotein (apo) A‐I levels (P<0.001 for all). HDL anti‐oxidative capacity was not different between subjects with and without MetS (P=0.76), but the HDL anti‐oxidation index (HDL anti‐oxidative capacity multiplied by individual HDL cholesterol concentrations), as a measure of global anti‐oxidative functionality of HDL, was lower in Mets subjects (P<0.001). HDL anti‐oxidative capacity was correlated inversely with SAA levels in subjects without MetS (r=‐0.286, P=0.036). Notably, this relationship was independent of HDL cholesterol or apoA‐I (P<0.05 for both). In contrast, no relation of HDL anti‐oxidative capacity with SAA was observed in MetS subjects (r=0.032, P=0.80). The relationship of SAA with HDL anti‐oxidative capacity was different in subjects with MetS compared to subjects without MetS (P=0.039 for the interaction between the presence of MetS and SAA on HDL anti‐oxidative capacity) taking age and diabetes status into account.

Conclusion:

Higher SAA levels may impair HDL anti‐oxidative functionality. The relationship of this physiologically relevant HDL functionality measure with circulating SAA levels is apparently disturbed in metabolic syndrome.     

Restoration of acute insulin response in T2DM subjects 1 month after biliopancreatic diversion

Objective: Biliopancreatic diversion (BPD) restores normal glucose tolerance in a few weeks in morbid obese subjects with type 2 diabetes, improving insulin sensitivity. However, there is less known about the effects of BPD on insulin secretion. We tested the early effects of BPD on insulin secretion in obese subjects with and without type 2 diabetes. Methods and Procedures: Twenty‐one consecutive morbid obese subjects, 9 with type 2 diabetes (T2DM) and 12 with normal fasting glucose (NFG) were evaluated, just before and 1 month after BPD, by measuring body weight (BW), glucose, adipocitokines, homeostasis model assessment of insulin resistance (HOMA‐IR), acute insulin response (AIR) to e.v. glucose and the insulinogenic index adjusted for insulin resistance ([ΔI5/ΔG5]/HOMA‐IR). Results: Preoperatively, those with T2DM differed from those with NFG in showing higher levels of fasting glucose, reduced AIR (57.9 ± 29.5 vs. 644.9 ± 143.1 pmol/l, P < 0.01) and reduced adjusted insulinogenic index (1.0 ± 0.5 vs. 17.6 ± 3.9 1/mmol², P < 0.001). One month following BPD, in both groups BW was reduced (by ～11%), but all subjects were still severely obese; HOMA‐IR and leptin decreased significanlty, while high‐molecular weight (HMW) adiponectin and adjusted insulinogenic index increased. In the T2DM group, fasting glucose returned to non‐diabetic values. AIR did not change in the NFG group, while in the T2DM group it showed a significant increase (from 58.0 ± 29.5 to 273.8 ± 47.2 pmol/l, P < 0.01). In the T2DM group, the AIR percentage variation from baseline was significantly related to changes in fasting glucose (r = 0.70, P = 0.02), suggesting an important relationship exists between impaired AIR and hyperglycaemia. Discussion: BPD is able to restore AIR in T2DM even just 1 month after surgery. AIR restoration is associated with normalization of fasting glucose concentrations.     

Plasma MR‐proADM Correlates to BMI and Decreases in Relation to Leptin After Gastric Bypass Surgery

Adrenomedullin (ADM) is a vasoactive peptide found to be related to obesity and its comorbidities: type 2 diabetes, hypertension, atherosclerosis, and coronary heart disease. ADM is increased both in plasma and in adipose tissue of obese individuals when compared to lean subjects and is considered as a member of the adipokine family. We determined plasma midregional proadrenomedullin (MR‐proADM) concentrations in a cohort of 357 subjects with BMI ranging from 17.5 to 42.3 kg/m² and no additional medical history. In parallel, 28 severely obese patients scheduled to undergo laparoscopic Roux‐en‐Y gastric bypass (RYGB) surgery were studied at two time points: before and 1 year after surgery. Outcome measurements were: MR‐proADM, cortisol, leptin, C‐reactive protein (CRP) thyroid‐stimulating hormone (TSH), creatinine and metabolic parameters. BMI correlated significantly to plasma MR‐proADM levels (r = 0.714, P < 0.001), also after adjustment for age and gender (r = 0.767, P < 0.001). In obese subjects, there was a positive relationship between MR‐proADM and leptin (r = 0.511, P = 0.006). Following RYGB, plasma MR‐proADM decreased from 0.76 ± 0.03 to 0.62 ± 0.02 pg/ml (P < 0.0001). RYGB‐induced changes in MR‐proADM correlated significantly to changes in leptin (r = 0.533, P = 0.004) and in CRP (r = 0.429, P = 0.023). We conclude that BMI is an independent predictor of circulating MR‐proADM levels. Weight loss after RYGB is associated with a significant decrease in plasma MR‐proADM, which is related to surgery‐induced changes in both circulating leptin and systemic inflammation.     

Gastric bypass does not normalize obesity‐related changes in ghrelin profile and leads to higher acylated ghrelin fraction

Objective:

Gastric bypass (GBP) lowers food intake, body weight, and insulin resistance in severe obesity (SO). Ghrelin is a gastric orexigenic and adipogenic hormone contributing to modulate energy balance and insulin action. Total plasma ghrelin (T‐Ghr) level is low and inversely related to body weight and insulin resistance in moderately obese patients, but these observations may not extend to the orexigenic acylated form (A‐Ghr) whose plasma concentration increase in moderate obesity.

Design and Methods:

We investigated the impact of GBP on plasma T‐, A‐, and A/T‐Ghr in SO patients (n = 28, 20 women), with measurements at baseline and 1, 3, 6, and 12 months after surgery. Additional cross‐sectional comparison was performed between nonobese, moderately obese, and SO individuals before GBP and at the end of the follow‐up period.

Results:

Before GBP, SO had lowest T‐Ghr and highest A/T‐Ghr profile compared with both nonobese and moderately obese individuals. Lack of early (0‐3 months from GBP) T‐Ghr changes masked a sharp increase in A‐Ghr and A/T‐Ghr profile (P < 0.05) that remained elevated following later increments (6‐12 months) of both T‐ and A‐Ghr (P < 0.05). Levels of A‐Ghr and A/T‐Ghr at 12 months of follow‐up remained higher than in matched moderately obese individuals not treated with surgery (P < 0.05).

Conclusions:

The data show that following GBP, early T‐Ghr stability masks elevation of A/T‐Ghr, that is stabilized after later increments of both T‐ and A‐hormones. GBP does not normalize the obesity‐associated elevated A/T‐Ghr ratio, instead resulting in enhanced A‐Ghr excess. Excess A‐Ghr is unlikely to contribute to, and might limit, the common GBP‐induced declines of appetite, body weight, and insulin resistance.     

Objectively measured sedentary behavior,physical activity,and plasma lipids in overweight and obese children

Objective:

This study examines the associations between objectively measured sedentary behavior, light physical activity (LPA), and moderate‐to‐vigorous physical activity (MVPA), and plasma lipids in overweight and obese children.

Design and Methods:

Cross‐sectional analyses were conducted among 126 children aged 5.5‐9.9 years. Sedentary behavior, LPA, and MVPA were assessed using accelerometry. Fasting blood samples were analyzed for plasma lipids (high‐density lipoprotein cholesterol [HDL‐C], low‐density lipoprotein cholesterol [LDL‐C], total cholesterol [TC], and triglycerides [TG]).

Results:

MVPA was not related to plasma lipids (P > 0.05). Independent of age, sex, energy intake, and waist circumference z‐score, sedentary behavior and LPA were associated with HDL‐C (β = ?0.23, 95% CI ?0.42 to ?0.04, P = 0.020; β = 0.20, 95% CI 0.14 to 0.39, P = 0.036, respectively). The strength of the associations remained after additionally adjusting for MVPA (sedentary behavior: β = ?0.22, 95% CI ?0.44 to 0.006, P = 0.056; LPA: β = 0.19, 95% CI ?0.005 to 0.38, P = 0.056, respectively).

Conclusion:

Substituting at least LPA for sedentary time may contribute to the development of healthy HDL‐C levels among overweight and obese children, independent of their adiposity. Comprehensive prevention and treatment strategies to improve plasma HDL‐C among overweight and obese children should target reductions in total sedentary time and promote the benefits of LPA, in addition to promoting healthy levels of adiposity, healthy dietary behaviors, and MVPA.

     

The relationship of C‐reactive protein to obesity‐related depressive symptoms: A longitudinal study

Objective:

Obesity has been shown to produce a state of systematic low‐grade inflammation that may have detrimental neuropsychiatric effects.

Design and Methods:

Longitudinal associations between obesity, inflammation, and depressive symptoms amongst a cohort of older English adults over 4 years of follow‐up were examined. Participants were 3,891 obese and nonobese people drawn from the English longitudinal study of ageing (ELSA) [aged 64.9 (SD = 8.8) years, 44.6% men]. Depressive symptoms were assessed at baseline and after 4 years of follow‐up using the eight‐item center for epidemiological studies—depression scale (CES‐D).

Results:

Approximately 26.3% (N = 1,025) of the sample were categorized as obese at baseline. Obesity at baseline was associated with elevated levels of depressive symptoms at follow‐up (P < 0.001), in analyses that adjusted for depression levels at baseline and sociodemographic and background variables including the prevalence of permanent illness/disability, alcohol consumption, sedentary behavior, and smoking. In addition, C‐reactive protein (CRP) concentrations at baseline were independently associated with CES‐D depression scores at follow‐up (P = 0.008) in fully adjusted analyses. Subsequent mediation analyses revealed that CRP levels explained ～20% of the obesity‐related longitudinal change in depression scores.

Conclusion:

These data suggest that chronic inflammation may be a key determinant of depressive symptoms in obesity.