Browsing by Author "Lin, Edward"

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Abnormal Primary Tissue Collagen Composition in the Skin of Recurrent Incisional Hernia Patients
(American Surgeon, 2007-12) Gletsu-Miller, Nana; White, Brent; Jeansonne, Louis; Baghai, Mercedeh; Sherman, Melanie; C. Daniel, Smith; Ramshaw, Bruce; Lin, Edward
Recurrence of incisional hernia may be as high as 50 per cent. Abnormal collagen I/III ratios have been observed within scar tissue of patients with recurrent incisional hernias. We sought to determine whether collagen composition in primary, nonscarred tissue was similarly affected in these patients. In this prospective, case–control study, nonscarred, primary abdominal wall skin and fascia biopsies were obtained in 12 patients with a history of recurrent incisional hernias and 11 control subjects without any history of hernia while undergoing abdominal laparoscopic surgery. Tissue protein expression of collagen I and III was assessed by immunohistochemistry followed by densitometry analysis. The collagen I/III ratio in skin biopsies from the recurrent hernia group was significantly less compared with control subjects (0.88 ± 0.01 versus 0.98 ± 0.04, respectively, P < 0.05). Fascia biopsies from patients with recurrent hernias was not significantly decreased in collagen I/III ratio compared with control subjects (0.90 ± 0.04 versus 0.94 ± 0.03, respectively, P = 0.17). Decreased collagen I/III ratios within the skin of patients with recurrent hernias not involved with scar or healing tissue suggest an underlying collagen composition defect. Such a primary collagen defect, in addition to abnormal scar formation, likely plays a significant role in the pathogenesis of recurrent incisional hernias.
Contribution of Adipose Tissue to Plasma 25-Hydroxy vitamin D Concentrations During Weight Loss Following Gastric Bypass Surgery
(Obesity, 2011-03) Gletsu-Miller, Nana; Lin, Edward; Armstrong-Moore, Dereka; Liang, Zhe; Sweeney, John F.; Torres, William E.; Ziegler, Thomas R.; Tangpricha, Vin
Roux‐en‐y gastric bypass (RYGB) surgery is associated with dramatic improvements in obesity‐related comorbidity, but also with nutritional deficiencies. Vitamin D concentrations are depressed in the severely obese, but the impact of weight loss via RYGB is unknown. We determined associations between adiposity and systemic 25‐hydroxyvitamin D (25(OH)D) during weight loss and the immediate and longer‐term effects of RYGB. Plasma 25(OH)D concentrations and fat mass (FAT) were determined by immunoassay and air displacement plethysmography, respectively, at 0 (before RYGB surgery), and at 1, 6, and 24 months in severely obese white and African American (AA) women (n = 20). Decreases in adiposity were observed at 1, 6, and 24 months following RYGB (P < 0.05). Plasma 25(OH)D concentrations increased at 1 month (P = 0.004); a decreasing trend occurred over the remainder months after surgery (P = 0.02). Despite temporary improvement in vitamin D status, a high prevalence of vitamin D insufficiency was observed (76, 71, 67, and 82%, at baseline, 1, 6, and 24 months, respectively), and plasma 25(OH)D concentrations were lower in AA compared to white patients (P < 0.05). Strong positive baseline and 1 month cross‐sectional correlations between FAT and plasma 25(OH)D were observed, which remained after adjustment for age and race subgroup (β = 0.76 and 0.61, respectively, P = 0.02). In conclusion, 25(OH)D concentrations increased temporarily and then decreased during the 24 months following RYGB. The acute increase and the positive associations observed between adipose tissue mass and systemic 25(OH)D concentrations suggest storage in adipose tissue and release during weight loss.
Dual mechanism for type-2 diabetes resolution after Roux-en-Y gastric bypass
(American Surgeon, 2009-06) Gletsu-Miller, Nana; Lin, Edward; Davis, S. Scott; Srinivasan, Jahnavi; Sweeney, John F.; Ziegler, Thomas R.; Phillips, Lawrence
Resolution of Type-2 diabetes mellitus (DM) after weight loss surgery is well documented, but the mechanism is elusive. We evaluated the glucose‐insulin metabolism of patients undergoing a Roux-en-Y gastric bypass (RYGB) using the intravenous glucose tolerance test (IVGTT) and compared it with patients who underwent laparoscopic adjustable gastric band (AB) placement. Thirty-one female patients (age range, 20 to 50 years; body mass index, 47.2 kg/m2) underwent RYGB. Nine female patients underwent AB placement and served as control subjects. All patients underwent IVGTT at baseline and 1 month and 6 months after surgery. Thirteen patients undergoing RYGB and one patient undergoing AB exhibited impaired glucose tolerance or DM defined by the American Diabetes Association. By 6 months post surgery, diabetes was resolved in all but one patient undergoing RYGB but not in the patient undergoing AB. Patients with diabetes undergoing RYGB demonstrated increased insulin secretion and β-cell responsiveness 1 month after surgery and continued this trend up to 6 months, whereas none of the patients undergoing AB had changes in β-cell function. Both patients undergoing RYGB and those undergoing AB demonstrated significant weight loss (34.6 and 35.0 kg/m2, respectively) and improved insulin sensitivity at 6 months. RYGB ameliorates DM resolution in two phases: 1) early augmentation of beta cell function at 1 month; and 2) attenuation of peripheral insulin resistance at 6 months. Patients undergoing AB only exhibited reduction in peripheral insulin resistance at 6 months but no changes in insulin secretion.
Loss of Total and Visceral Adipose Tissue Mass Predicts Decreases in Oxidative Stress After Weight Loss Surgery
(Obesity, 2009-03) Gletsu-Miller, Nana; Hansen, Jason M.; Jones, Dean P.; Go, Young-Mi; Torres, William E.; Ziegler, Thomas R.; Lin, Edward
It is not known whether there are mechanisms linking adipose tissue mass and increased oxidative stress in obesity. This study investigated associations between decreasing general and abdominal fat depots and oxidative stress during weight loss. Subjects were severely obese women who were measured serially at baseline and at 1, 6 (n = 30), and 24 months (n = 18) after bariatric surgery. Total fat mass (FAT) and volumes of visceral (VAT) and subcutaneous abdominal adipose tissue (SAT) were related to plasma concentrations of derivatives of reactive oxidative metabolites (dROMS), a measure of lipid peroxides and oxidative stress. After intervention, BMI significantly decreased, from 47.7 ± 0.8 kg/m2 to 43.3 ± 0.8 kg/m2 (1 month), 35.2 ± 0.8 kg/m2 (6 months), and 30.2 ± 1.2 kg/m2 (24 months). Plasma dROMS also significantly deceased over time. At baseline, VAT (r = 0.46), FAT (r = 0.42), and BMI (r = 0.37) correlated with 6‐month decreases in dROMS. Similarly, at 1 month, VAT (r = 0.43) and FAT (r = 0.41) correlated with 6‐month decreases in dROMS. Multiple regression analysis showed that relationships between VAT and dROMS were significant after adjusting for FAT mass. Increased plasma dROMS at baseline were correlated with decreased concentrations of high‐density lipoprotein (HDL) at 1 and 6 months after surgery (r = −0.38 and −0.42). This study found longitudinal associations between general, and more specifically intra‐abdominal adiposity, and systemic lipid peroxides, suggesting that adipose tissue mass contributes to oxidative stress.
Sagittal Abdominal Diameter and Visceral Adiposity: Correlates of Beta-Cell Function and Dysglycemia in Severely Obese Women
(Obesity Surgery, 2013-07) Gletsu-Miller, Nana; Kahn, Henry S.; Gasevic, Danijela; Liang, Zhe; Frediani, Jennifer K.; Torres, William E.; Ziegler, Thomas R.; Phillips, Lawrence S.; Lin, Edward
Background: In the context of increasing obesity prevalence, the relationship between large visceral adipose tissue (VAT) volumes and type 2 diabetes mellitus (T2DM) is unclear. In a clinical sample of severely obese women (mean body mass index [BMI], 46 kg/m2) with fasting normoglycemia (n = 40) or dysglycemia (impaired fasting glucose + diabetes; n = 20), we sought to determine the usefulness of anthropometric correlates of VAT and associations with dysglycemia. Methods: VAT volume was estimated using multi-slice computer tomography; anthropometric surrogates included sagittal abdominal diameter (SAD), waist circumference (WC) and BMI. Insulin sensitivity (Si), and beta-cell dysfunction, measured by insulin secretion (AIRg) and the disposition index (DI), were determined by frequently sampled intravenous glucose tolerance test. Results: Compared to fasting normoglycemic women, individuals with dysglycemia had greater VAT (P < 0.001) and SAD (P = 0.04), but BMI, total adiposity and Si were similar. VAT was inversely associated with AIRg and DI after controlling for ancestry, Si, and total adiposity (standardized beta, −0.32 and −0.34, both P < 0.05). In addition, SAD (beta = 0.41, P = 0.02) was found to be a better estimate of VAT volume than WC (beta = 0.32, P = 0.08) after controlling for covariates. Receiver operating characteristic analysis showed that VAT volume, followed by SAD, outperformed WC and BMI in identifying dysglycemic participants. Conclusions: Increasing VAT is associated with beta-cell dysfunction and dysglycemia in very obese women. In the presence of severe obesity, SAD is a simple surrogate of VAT, and an indicator of glucose dysregulation.
Surgical Stress Induces an Amplified Inflammatory Response in Patients with Type 2 Diabetes
(ISRN Obesity, 2013) Gletsu-Miller, Nana; Lin, Edward
Background. Morbid obesity is believed to be an extreme of the metabolic spectrum. Moreover, diabetes is hypothesized to be associated with a chronic inflammatory state that is not observed in nondiabetic healthy individuals. We investigated the differences in expression of inflammatory cytokines induced by surgical stress between diabetic and nondiabetic individuals. Method. 39 morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass (9 with type 2 diabetes mellitus) were compared with 8 nonobese euglycemic patients undergoing laparoscopic antireflux surgery. Cytokine levels for IL-6, IL-10, and IL-18 were measured 15 minutes before surgery and immediately after surgery. Results. IL-6 and IL-10 levels were elevated from baseline following surgery, but morbidly obese patients exhibited a much higher elevation than lean patients. Individuals with type 2 diabetes had the most pronounced IL-6 and IL-10 elevations. Baseline IL-18 levels were significantly higher in diabetic patients compared with nondiabetic or lean patients. However, IL-18 levels were not changed in response to surgery. Conclusions. Diabetes and morbid obesity are associated with augmented cytokine expression in response to surgical trauma that is several folds higher than in nonobese euglycemic patients. Diabetic patients exhibit a chronic elevation in IL-18 that is not changed by surgical stress.
The Effects of Gastric Surgery on Systemic Ghrelin Levels in the Morbidly Obese
(Archives of Surgery, 2004-07) Gletsu-Miller, Nana; Lin, Edward; Fugate, Kim; McClusky, David; Gu, Li H.; Ramshaw, Bruce J.; Papanicolaou, Dimitris A.; Ziegler, Thomas R.; Smith, C. Daniel; Zhu, Juan-Li
Hypothesis: Circulating ghrelin, produced primarily in the stomach, is a powerful orexigen. Ghrelin levels are elevated in states of hunger, but rapidly decline postprandially. Early alterations in ghrelin levels in morbidly obese patients undergoing weight reduction surgery may be attributed to gastric partitioning. Design and Patients: Thirty-four patients underwent Roux-en-Y gastric bypass with a completely divided gastroplasty to create a 15-mL vertically oriented gastric pouch. Eight other patients underwent other gastric procedures that did not involve complete division of the stomach, including 4 vertical banded gastroplasties and 4 antireflux surgical procedures. Six additional patients undergoing antireflux surgery served as lean control subjects. Plasma samples were obtained before surgery and immediately after surgery. In a substudy, plasma was collected after Roux-en-Y limb formation and after dividing the stomach to identify any changes in plasma ghrelin levels. Setting: Tertiary university medical center. Main Outcome Measures: Ghrelin levels at different stages of surgical intervention. Results: Mean ± SEM preoperative and postoperative ghrelin levels in the gastric bypass group were 355 ± 20 and 246 ± 13 pg/mL, respectively (P<.001). In the vertical banded gastroplasty group and in all patients undergoing antireflux surgery, ghrelin levels were not significantly changed. Conclusions: Compared with morbidly obese humans, lean controls had significantly higher plasma ghrelin levels at baseline. A divided gastroplasty creating a small proximal gastric pouch results in significant early declines in circulating ghrelin levels that are not observed with other gastric procedures. This may explain, in part, the loss of hunger sensation and rapid weight loss observed following gastric bypass surgery.