Low 25‐Hydroxyvitamin D Does Not Affect Insulin Sensitivity in Obesity after Bariatric Surgery

Objective: A positive correlation between levels of 25‐hydroxyvitamin D [25(OH)D] and insulin sensitivity has been shown in healthy subjects. We aimed to test the hypothesis that concentration of 25(OH)D influences insulin sensitivity in obesity before and after weight loss. Research Methods and Procedures: We investigated the relation between serum 25(OH)D and insulin sensitivity (estimated by euglycemic‐hyperinsulinemic clamp) in 116 obese women (BMI ≥ 40 kg/m²) evaluated before and 5 and 10 years after biliopancreatic diversion (BPD). Body composition was estimated by the isotope dilution method. Results: Prevalence of hypovitaminosis D was 76% in the obese status and 91% and 89% at 5 and 10 years after BPD, respectively, despite ergocalciferol supplementation. 25(OH)D concentration decreased from 39.2 ± 22.3 in obesity (p = 0.0001) to 27.4 ± 16.4 and 25.1 ± 13.9 nM 5 and 10 years after BPD, respectively. Whole‐body glucose uptake increased from 24.27 ± 4.44 at the baseline to 57.29 ± 11.56 and 57.71 ± 8.41 μmol/kg_{fat free mass} per minute 5 and 10 years after BPD, respectively (p = 0.0001). Predictor of 25(OH)D was fat mass (R² = 0.26, p = 0.0001 in obesity; R² = 0.20, p = 0.02 after BPD). Parathormone correlated with fat mass (R² = 0.19; p = 0.0001) and BMI (R² = 0.053; p = 0.01) and inversely with M value (R² = 0.16; p = 0.0001), but only in obese subjects. Discussion: A high prevalence of hypovitaminosis D was observed in morbid obesity both before and after BPD. Low 25(OH)D did not necessarily imply increased insulin resistance after BPD, a condition where, probably, more powerful determinants of insulin sensitivity overcome the low circulating 25(OH)D levels. However, the present data cannot exclude some kind of influence of vitamin D status on glucose and insulin metabolism.     

Insulin‐ and Exercise‐Stimulated Skeletal Muscle Blood Flow and Glucose Uptake in Obese Men

Objective: Insulin resistance in obese subjects results in the impaired use of glucose by insulin‐sensitive tissues, e.g., skeletal muscle. In the present study, we determined whether insulin resistance in obesity is associated with an impaired ability of exercise to stimulate muscle blood flow, oxygen delivery, or glucose uptake. Research Methods and Procedures: Nine obese (body mass index = 36 ± 2 kg/m²) and 11 age‐matched nonobese men (body mass index = 22 ± 1 kg/m²) performed one‐legged isometric exercise during hyperinsulinemia. Rates of femoral muscle blood flow, oxygen consumption, and glucose uptake were measured simultaneously in both legs using [¹⁵O]H₂O, [¹⁵O]O₂, [¹⁸F]fluoro‐deoxy‐glucose, and positron emission tomography. Results: The obese subjects exhibited resistance to insulin stimulation of glucose uptake in resting muscle, regardless of whether glucose uptake was expressed per kilogram of femoral muscle mass (p = 0.001) or per the total mass of quadriceps femoris muscle. At similar workloads, oxygen consumption, blood flow, and glucose uptake were lower in the obese than the nonobese subjects when expressed per kilogram of muscle, but similar when expressed per quadriceps femoris muscle mass. Discussion: We conclude that obesity is characterized by insulin resistance of glucose uptake in resting skeletal muscle regardless of how glucose uptake is expressed. When compared with nonobese individuals at similar absolute workloads and under identical hyperinsulinemic conditions, the ability of exercise to increase muscle oxygen uptake, blood flow, and glucose uptake per muscle mass is blunted in obese insulin‐resistant subjects. However, these defects are compensated for by an increase in muscle mass.     

Relationship of adiponectin with insulin sensitivity in humans, independent of lipid availability

Objective: To test in humans the hypothesis that part of the association of adiponectin with insulin sensitivity is independent of lipid availability. Research Methods and Procedures: We studied relationships among plasma adiponectin, insulin sensitivity (by hyperinsulinemic‐euglycemic clamp), total adiposity (by DXA), visceral adiposity (VAT; by magnetic resonance imaging), and indices of lipid available to muscle, including circulating and intramyocellular lipid (IMCL; by ¹H‐magnetic resonance spectroscopy). Our cohort included normal weight to obese men (n = 36). Results: Plasma adiponectin was directly associated with insulin sensitivity and high‐density lipoprotein‐cholesterol and inversely with plasma triglycerides but not IMCL. These findings are consistent with adiponectin promoting lipid uptake and subsequent oxidation in muscle and inhibiting TG synthesis in the liver. In multiple regression models that also included visceral and total fat, free fatty acids, TGs, and IMCL, either alone or in combination, adiponectin independently predicted insulin sensitivity, consistent with some of its insulin‐sensitizing effects being mediated through mechanisms other than modulation of lipid metabolism. Because VAT directly correlated with total fat and all three indices of local lipid availability, free fatty acids, and IMCL, an efficient regression model of insulin sensitivity (R² = 0.69, p < 0.0001) contained only VAT (part R² = 0.12, p < 0.002) and adiponectin (part R² = 0.41, p < 0.0001) as independent variables. Discussion: Given the broad range of total adiposity and body fat distribution in our cohort, we suggest that insulin sensitivity is robustly associated with adiponectin and VAT.     

Skeletal muscle fat oxidation is increased in African-American and white women after 10 days of endurance exercise training

Objective: Obesity is associated with lower rates of skeletal muscle fatty acid oxidation (FAO), which is linked to insulin resistance. FAO is reduced further in obese African‐American (AAW) vs. white women (CW) and may also be lower in lean AAW vs. CW. In lean CW, endurance exercise training (EET) elevates the oxidative capacity of skeletal muscle. Therefore, we determined whether EET would elevate skeletal muscle FAO similarly in AAW and CW with a lower lipid oxidative capacity. Research Methods and Procedures: In vitro rates of FAO were assessed in rectus abdominus muscle strips using [1‐¹⁴C] palmitate (Pal) from lean AAW [BMI = 24.2 ± 0.9 (standard error) kg/m²] and CW (23.6 ± 0.8 kg/m²) undergoing voluntary abdominal surgery. Lean AAW (22 ± 0.9 kg/m²) and CW (24 ± 0.8 kg/m²) and obese AAW (36 ± 1.2 kg/m²) and CW (40 ± 1.3 kg/m²) underwent 10 consecutive days of EET on a cycle ergometer (60 min/d, 75% peak oxygen uptake). FAO was measured in vastus lateralis homogenates as captured ¹⁴CO₂ using [1‐¹⁴C] Pal, palmitoyl‐CoA (Pal‐CoA), and palmityl‐carnitine (Pal‐Car). Results: Muscle strip experiments showed suppressed rates of FAO (p = 0.03) in lean AAW vs. CW. EET increased the rates of skeletal muscle Pal oxidation (p = 0.05) in both lean AAW and CW. In obese subjects, Pre‐EET Pal (but not Pal‐CoA or Pal‐Car) oxidation was lower (p = 0.05) in AAW vs. CW. EET increased Pal oxidation 100% in obese AAW (p < 0.05) and 59% (p < 0.05) in obese CW. Similar increases (p < 0.05) in post‐EET FAO were observed for Pal‐CoA and Pal‐Car in both groups. Discussion: Both lean and obese AAW possess a lower capacity for skeletal muscle FAO, but EET increases FAO similarly in both AAW and CW. These data suggest the use of EET for treatment against obesity and diabetes for both AAW and CW.     

Independent Influences of Central Fat and Skeletal Muscle Lipids on Insulin Sensitivity

Objective: Insulin resistance is closely associated with two disparate aspects of lipid storage: the intracellular lipid content of skeletal muscle and the magnitude of central adipose beds. Our aim was to determine their relative contribution to impaired insulin action. Research Methods and Procedures: Eighteen older (56 to 75 years of age) men were studied before elective knee surgery. Insulin sensitivity (M/ΔI) was determined by hyperinsulinemic–euglycemic clamp. Central abdominal fat (CF) was assessed by DXA. Skeletal muscle was excised at surgery and assayed for content of metabolically active long‐chain acyl‐CoA esters (LCAC). Results: Significant inverse relationships were observed between LCAC and M/ΔI (R² = 0.34, p = 0.01) and between CF and M/ΔI (R² = 0.38, p = 0.006), but not between CF and LCAC (R² = 0.0005, p = 0.93). In a multiple regression model (R² = 0.71, p < 0.0001), both CF (p = 0.0006) and LCAC (p = 0.0009) were independent statistical predictors of M/ΔI. Leptin levels correlated inversely with M/ΔI (R² = 0.60, p = 0.0002) and positively with central (R² = 0.41, p = 0.006) and total body fat (R² = 0.63, p = 0.0001). Discussion: The mechanisms by which altered lipid metabolism in skeletal muscle influences insulin action may not be related directly to those linking central fat and insulin sensitivity. In particular, it is unlikely that muscle accumulation of lipids directly derived from labile central fat depots is a principal contributor to peripheral insulin resistance. Instead, our results imply that circulating factors, other than nonesterified fatty acids or triglyceride, mediate between central fat depots and skeletal muscle tissue. Leptin was not exclusively associated with central fat, but other factors, secreted specifically from central fat cells, could modulate muscle insulin sensitivity.     

The Association between Plasma Adiponectin and Insulin Sensitivity in Humans Depends on Obesity

Objective: In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity. Research Methods and Procedures: We investigated the cross‐sectional association between plasma adiponectin levels and insulin sensitivity in different ranges of body fat content [expressed as percentage of body fat (PFAT)] in a large cohort of normal glucose‐tolerant subjects (n = 900). All individuals underwent an oral glucose tolerance test (OGTT), and 299 subjects additionally a euglycemic hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin at baseline with change in insulin sensitivity was investigated in a subgroup of 108 subjects. Results: In cross‐sectional analyses, the association between plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT, depended on whether subjects were lean or obese [p for interaction adiponectin × PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R² = 0.10, p = 0.13, OGTT; and R² = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R² = 0.36, p < 0.0001, OGTT; and R² = 0.48, p = 0.003, clamp). In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals. Discussion: These data suggest that adiponectin is especially critical in sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce insulin resistance by increasing adiponectin concentrations may be effective particularly in obese, insulin‐resistant individuals.     

Effect of sarcopenia on cardiovascular disease risk factors in obese postmenopausal women

Objective: To compare sarcopenic‐obese and obese postmenopausal women for risk factors predisposing to cardiovascular disease (CVD) and determine whether there may be a relationship between muscle mass and metabolic risk in obese postmenopausal women. Research Methods and Procedures: In this cross‐sectional study, 22 healthy obese postmenopausal women (mean age, 66 ± 5 years; mean BMI, 27 ± 3 kg/m²) were divided into two groups matched for age (±2 years) and fat mass (FM) (±2%). Sarcopenia was defined as a muscle mass index of <14.30 kg fat‐free mass (FFM)/m² (which corresponds to 1 standard deviation below the values of a young reference population), and obesity was defined as an FM of >35% (which corresponds to the World Health Organization guidelines). FM, FFM (measured by DXA), daily energy expenditure (accelerometry), dietary intake (3‐day dietary record), and blood biochemical analyses (lipid profile, insulin, glucose, and C‐reactive protein) were obtained. Visceral fat mass (VFM) was calculated by the equation of Bertin, which estimates VFM from DXA measurements. Results: Obese women had more FFM (p = 0.006), abdominal FM (p = 0.047), and VFM (p = 0.041) and a worse lipid profile [p = 0.040 for triglycerides; p = 0.004 for high‐density lipoprotein (HDL); p = 0.026 for total cholesterol/HDL] than sarcopenic‐obese postmenopausal women. Obese women also ingested significantly more animal (p = 0.001) and less vegetal proteins (p = 0.013), although both groups had a similar total protein intake (p = 0.967). Discussion: Sarcopenia seems to be associated with lower risk factors predisposing to CVD in obese postmenopausal women. With the increase in the number of aging people, the health implications of being sarcopenic‐obese merit more attention.     

Adipocyte Differentiation‐related Protein in Human Skeletal Muscle: Relationship to Insulin Sensitivity

Objective: To determine whether adipocyte differentiation‐related protein (ADRP), a lipid droplet—associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non‐diabetic (OND) and obese diabetic (OD) subjects. Research Methods and Procedures: Ten OND subjects and 15 OD subjects underwent a weight loss or pharmacological intervention program to improve insulin sensitivity. Anthropometric data, hemoglobin A_1C, fasting glucose, lipids, and glucose disposal rate were determined at baseline and at completion of studies. Biopsies of the vastus lateralis muscle (SkM) were obtained in the fasting state from OND and OD subjects. Protein expression was determined by Western blotting. Results: ADRP was highly expressed in SkM from OND (4.4 ± 1.54 AU/10 μg, protein, n = 10) and OD (5.02 ± 1.33 AU/10 μg, n = 12) subjects. OND subjects undergoing weight loss had decreased triglyceride levels and improved insulin action. SkM ADRP content increased with weight loss from 5.14 ± 2.15 AU/10 μg to 9.92 ± 1.57 AU/10 μg (p < 0.025). OD subjects were treated with either troglitazone or metformin, together with glyburide, for 3 to 4 months. Both treatments attained similar levels of glycemic control. OD subjects with lower baseline ADRP content (2.85 ± 1.07 AU/10 μg, n = 6) displayed up‐regulation of ADRP expression (to 9.27 ± 2.76 AU/10 μg, p < 0.025). Discussion: ADRP is the predominant lipid droplet—associated protein in SkM, and low ADRP expression is up‐regulated in circumstances of improved glucose tolerance. Up‐regulation of ADRP may act to sequester fatty acids as triglycerides in discrete lipid droplets that could protect muscle from the detrimental effects of fatty acids on insulin action and glucose tolerance.     

Relationship of Insulin Sensitivity and Left Ventricular Mass in Uncomplicated Obesity

Objective: We studied uncomplicated obesity as a model to evaluate the influence of insulin sensitivity per se on left ventricular mass (LVM) and geometry. Research Methods and Procedures: We selected 50 obese subjects (BMI > 30 kg/m²; 38 women and 12 men; mean age, 38.4 ± 10 years; BMI, 36.4 ± 10.5 kg/m²) with normal blood pressure, glucose tolerance, and plasmatic lipid levels. Thirty lean subjects formed the control group. Each subject underwent euglycemic insulin clamp (7 pmol/min per kg) to evaluate whole body glucose use (M index) and echocardiogram to calculate LVM and indexed LVM. Results: Insulin‐resistant obese subjects had higher LVM, LVM/h^2.7, LVM/body surface area, and LVM/fat‐free mass_kg (p = 0.001; p = <0.001 p = 0.001, and p = 0.04, respectively) than obese subjects with normal insulin sensitivity. Multivariate regression analysis showed that M index was the strongest independent correlate of LVM (r² = 0.34; p = 0.03). Discussion: Our findings showed that insulin resistance, in uncomplicated obesity, is associated with an increased LVM and precocious changes of left ventricular geometry, whereas preserved insulin sensitivity is not associated with increased LVM.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Effects of Weight Loss and Physical Activity on Muscle Lipid Content and Droplet Size

Objectives : To address the potential effects of weight loss and physical activity (WL + Ex) on intramyocellular lipid (IMCL) and lipid droplet size in overweight and obese previously sedentary individuals. Research Methods and Procedures : IMCL and lipid droplet size was determined in vastus lateralis, obtained by percutaneous biopsy, from 21 obese volunteers (9 men/12 women), using Oil Red O staining, along with succinate dehydrogenase histochemistry and mitochondrial immunohistochemistry as measures of skeletal muscle oxidative capacity. Insulin sensitivity (IS) was determined by glucose clamp. Results : A 4‐month WL + Ex intervention resulted in ～10% WL and ～15% increase in maximal oxygen uptake, leading to a 46% increase in IS (all p < 0.01). IMCL did not significantly change (p = 0.36). However, the size of lipid droplets decreased after WL + Ex (p < 0.01), and this decrease in lipid droplet size correlated with increased IS (p < 0.01) and the amount of physical activity (p < 0.05). Succinate dehydrogenase activity and mitochondrial labeling increased significantly (p < 0.01), without a significant shift in fiber type distribution. Discussion : In summary, IMCL does not decrease in response to WL + Ex in obese, previously sedentary individuals, yet the lipid within muscle is dispersed into smaller droplets. This change in the size of lipid droplets, likely coupled with a concomitant increase in oxidative enzyme capacity, is correlated to improved IS.     

Increased extravasation of macromolecules in skeletal muscles of the Zucker rat model

Objective: Assess whether changes in permeability of the muscle regional microcirculation occur in the obese Zucker rat model. Research Methods and Procedures: Capillary permeability to albumin was assessed in vivo in Zucker rats (n = 15) and lean controls (n = 15) by quantifying the extravasation of albumin‐bound Evans Blue (EB) in different organs. Unanaesthetized animals were injected with EB 20 mg/kg in the caudal vein, and EB was extracted by formamide from selected organs collected after exsanguination. Results: Relative to control animals, Zucker rats had higher body weight (Δ = +33%; p < 0.001), plasma triglycerides (Δ = +244%; p < 0.001), and insulin (Δ = +240%; p < 0.001) concentrations. Plasma glucose concentrations were not different between the two groups (p = not significant). Using the EB technique, we showed a 30% to 50% (p < 0.01) increase in the extravasation of EB in the obese rats, regardless of the skeletal muscle group studied. This increase in skeletal muscle vasopermeability was not paralleled by any increase in the expression of the muscle endothelium—nitric oxide (NO) system because the total NO synthase (NOS) activity in skeletal muscle of the obese Zucker rat was significantly lower (p < 0.001), as was the endothelial NOS immunoreactive mass (p < 0.001), compared with lean controls. Discussion: In conclusion, there seems to be dissociation between capillary permeability and local regulation of microcirculation in skeletal muscles of the obese Zucker rat. It is suggested that the increase in skeletal muscle vasopermeability (extravasation of macromolecules) is a compensation for the loss of NO‐dependent vasodilation and capillary recruitment noted in this model of obesity and insulin resistance.     

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.     

Biliopancreatic diversion reduces QT interval and dispersion in severely obese patients

Objectives: The objectives were to evaluate QT interval (QTc) and QT‐interval dispersion (QTd) in severely obese individuals and to determine the effects of biliopancreatic diversion (BPD) and weight loss after BPD on ventricular repolarization parameters. Background: People with severe obesity (SO) have a 50% to 100% increased risk of death associated with a 1.6‐fold increased risk of sudden death. BPD surgery induces rapid and considerable weight loss through severe lipid malabsorption, thus achieving long‐term weight control. Research Methods and Procedures: A total of 85 subjects with SO (age, 42 ± 12 years; 66 females; mean body weight, 120 ± 29 kg; BMI, 45 ± 11 kg/m²) of 330 who had a bariatric surgical consultation between January 2001 and July 2002 were enrolled. Inclusion criteria were sinus rhythm, unremarkable 12 leads surface electrocardiogram, no atrioventricular blocks and/or bundle branch blocks, normal serum electrolyte profile, and no medical therapies exerting known effects on QTc. Exclusion criteria were previous diagnosis of coronary artery disease, known cardiovascular disease, atrial fibrillation or any other known cardiac arrhythmias, cancer, or renal dysfunction. Results: A total of 86% of patients had QTc >440 ms and/or QTd >60 ms. Subjects with SO showed a mean maximum QTc of 446 ± 28 ms and a mean QTd of 52 ± 20 ms. A close correlation was found between QTc and QTd (p < 0.0001; R² = 0.33). One month after BPD, mean QTc was 420 ms and remained stable at follow‐up; QTd was 32 ms at 1 and 6 months and became 35 ms at 1 year. Conclusions: Ventricular repolarization abnormalities are significantly increased in subjects with SO. Reduction of QT abnormalities after BPD is independent of weight loss and is caused by the 100% reduction of glucose plasma shortly after surgery. This effect may be related to surgical interruption of the entero‐insular axis.     

Change in Vascular Adhesion Protein‐1 and Metabolic Phenotypes after Vertical Banded Gastroplasty for Morbid Obesity

Objective: The association between circulating vascular adhesion protein‐1 (VAP‐1) and metabolic phenotypes has been shown to be inconsistent. The current study explored whether the changes in serum VAP‐1 levels correlate with the changes in metabolic phenotypes after weight reduction surgery. Research Methods and Procedures: Clinical characteristics and serum VAP‐1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m²) were measured before and after vertical banded gastroplasty. Results: Before surgery, serum VAP‐1 levels correlated positively with fasting plasma glucose (γ = 0.56, p = 0.01) and negatively with insulin levels (γ = ?0.51, p = 0.021). After surgery, the changes in serum VAP‐1 levels were negatively correlated with the changes in waist circumference (γ = ?0.57, p = 0.011), diastolic blood pressure (DBP) (γ = ?0.56, p = 0.015), and mean arterial pressure (γ = ?0.46, p = 0.055). In multivariate regression, serum VAP‐1 levels were negatively correlated with waist circumference (β = ?2.36, p = 0.014) and DBP (β = ?3.02, p = 0.017) after adjusting for age and gender. The change in DBP was negatively correlated with the change in VAP‐1 levels after adjusting for age, gender, and steady‐state plasma glucose. Discussion: The results suggest that VAP‐1 levels are correlated with fasting glucose and insulin levels in morbidly obese subjects. After surgery, the changes in VAP‐1 levels were associated with changes in visceral adiposity and DBP. Serum VAP‐1 might modulate DBP independently from the changes in insulin resistance in morbidly obese people.     

Differential regulation of adiponectin receptor gene expression by adiponectin and leptin in myotubes derived from obese and diabetic individuals

Objective: This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin. Research Methods and Procedures: Four distinct primary cell culture groups were established [Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 μg/mL) or leptin (2.5 μg/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real‐time polymerase chain reaction analysis. Results: AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8‐fold and 2.5‐fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups. Discussion: Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy individuals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese‐prone individuals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic individuals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene.     

Body Weight Modulates Cholesterol Metabolism in Non‐Insulin Dependent Type 2 Diabetics

Objective: Cholesterol metabolism was studied in 64 subjects with type 2 diabetes who had body weight ranging from normal to obese, to find out whether weight interferes with cholesterol metabolism in diabetes. Research Methods and Procedures: Cholesterol absorption was measured with peroral isotopes and by assaying serum plant sterol and cholestanol to cholesterol ratios, cholesterol synthesis with sterol balance, and measuring serum cholesterol precursor ratios. Results: The study population was divided into normal‐weight (body mass index, 24.1 ± 0.4 kg/m²; mean ± SEM; n = 20) and obese (31.0 ± 0.5 kg/m²; n = 44) groups. Despite similar serum cholesterol and blood glucose values, fecal neutral sterol excretion, cholesterol and bile acid synthesis, cholesterol turnover (1649 ± 78 vs. 1077 ± 52 mg/d; p < 0.001), and serum cholesterol precursors were higher, and cholesterol absorption % (32 ± 1 vs. 40 ± 2%; p < 0.05), serum cholestanol, and plant sterols were lower in the obese vs. the non‐obese groups. Serum sex hormone‐binding globulin was positively associated with variables of cholesterol absorption, whereas blood glucose, serum insulin, and body mass index were associated with variables of cholesterol synthesis. In multiple stepwise regression analysis, cholesterol absorption percentage (R² = 24%) and body mass index (R² = 15%) were the only variables explaining the variability of cholesterol synthesis. Discussion: Body weight, through its entire range, regulates cholesterol metabolism in type 2 diabetes such that with increasing insulin resistance, cholesterol absorption is lowered and cholesterol synthesis increased.