Kareem Jabbour

Hepatic and Peripheral Insulin Sensitivity and Diabetes Remission at 1 Month After Roux-en-Y Gastric Bypass Surgery in Patients Randomized to Omentectomy

OBJECTIVE Early after Roux-en-Y gastric bypass (RYGB), there is improvement in type 2 diabetes, which is characterized by insulin resistance. We determined the acute effects of RYGB, with and without omentectomy, on hepatic and peripheral insulin sensitivity. We also investigated whether preoperative diabetes or postoperative diabetes remission influenced tissue-specific insulin sensitivity after RYGB. RESEARCH DESIGN AND METHODS We studied 40 obese (BMI 48 ± 8 kg/m2) participants, 17 with diabetes. Participants were randomized to RYGB alone or in conjunction with omentectomy. Hyperinsulinemic-euglycemic clamps with isotopic-tracer infusion were completed at baseline and at 1 month postoperatively to assess insulin sensitivity. RESULTS Participants lost 11 ± 4% of body weight at 1 month after RYGB, without an improvement in peripheral insulin sensitivity; these outcomes were not affected by omentectomy, preoperative diabetes, or remission of diabetes. Hepatic glucose production (HGP) and the hepatic insulin sensitivity index improved in all subjects, irrespective of omentectomy (P ≤ 0.001). Participants with diabetes had higher baseline HGP values (P = 0.003) that improved to a greater extent after RYGB (P = 0.006). Of the 17 participants with diabetes, 10 (59%) had remission at 1 month. Diabetes remission had a group × time effect (P = 0.041) on HGP; those with diabetes remission had lower preoperative and postoperative HGP. CONCLUSIONS Peripheral insulin sensitivity did not improve 1 month after RYGB, irrespective of omentectomy, diabetes, or diabetes remission. Hepatic insulin sensitivity improved at 1 month after RYGB and was more pronounced in patients with diabetes. Improvement in HGP may influence diabetes remission early after RYGB.

Parenteral glutamine infusion alters insulin-mediated glucose metabolism.

BACKGROUND Glutamine is a conditionally essential amino acid that is critical for many basic cellular processes. Its supplementation has been found to be beneficial during several critical illnesses. This study examines the effects of increased glutamine availability on insulin-mediated glucose homeostasis in vivo in multicatheterized conscious canines (n = 5). METHODS Two weeks before the study, catheters were placed in the femoral artery and the portal, hepatic, femoral, and renal veins for blood sampling and in the splenic vein for intraportal infusion of insulin and glucagon. Doppler probes were placed to measure blood flow. The metabolic study consisted of equilibration, basal, and experimental periods during which [3-3H]glucose was infused to measure glucose kinetics. During the 5-hour experimental period, a hyperinsulinemic-euglycemic clamp was performed by infusing somatostatin, basal glucagon, fivefold basal insulin, and glucose to maintain euglycemia. The experimental period was divided evenly into two subperiods performed in random order: (1) i.v. glutamine infusion (0.72 mmol kg(-1) h(-1)) and (2) i.v. saline infusion. RESULTS With glutamine, the glucose required to maintain euglycemia was increased 46% over saline (6.8 +/- 1.0 to 9.9 +/- 1.7 mg kg(-1) min(-1). In addition, whole-body glucose production and utilization were increased by 1.4 and 4.6 mg kg(-1) min(-1), respectively. Finally, the increase in whole-body glucose utilization was manifested by increased hepatic and hindlimb glucose utilization. CONCLUSIONS Increased glutamine availability blunted insulins action on glucose production and enhanced insulin-mediated glucose utilization with the changes in utilization being threefold greater than the changes in production. Thus parenteral glutamine has potential benefit as a nutrient adjuvant during clinical situations associated with insulin resistance.

Zonation of acetate labeling across the liver: Implications for studies of lipogenesis by MIDA

Measurement of fractional lipogenesis by mass isotopomer distribution analysis (MIDA) of fatty acids or cholesterol labeled from [(13)C]acetate assumes constant enrichment of lipogenic acetyl-CoA in all hepatocytes. This would not be the case if uptake and release of acetate by the liver resulted in transhepatic gradients of acetyl-CoA enrichment. Conscious dogs, prefitted with transhepatic catheters, were infused with glucose and [1, 2-(13)C(2)]acetate. Stable concentrations and enrichments of acetate were measured in artery (17 microM, 36%), portal vein (61 microM, 5. 4%), and hepatic vein (17 microM, 1.0%) and were computed for mixed blood entering the liver (53 microM, 7.4%). We also measured balances of propionate and butyrate across gut and liver. All gut release of propionate and butyrate is taken up by the liver. The threefold decrease in acetate concentration and the sevenfold decrease in acetate enrichment across the liver strongly suggest that the enrichment of lipogenic acetyl-CoA decreases across the liver. Thus fractional hepatic lipogenesis measured in vivo by MIDA may be underestimated.

Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with elevated ghrelin

We sought to determine: (1) if early weight regain between 1 and 2 years after Roux‐en‐Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB.

Effects of Proximal Gut Bypass on Glucose Tolerance and Insulin Sensitivity in Humans

Roux-en-Y gastric bypass (RYGB) surgery produces a significant improvement in glucose metabolism prior to substantial weight loss; this is proposed to result from an enhanced incretin effect secondary to bypass of the duodenum and proximal jejunum. However, the caloric restriction that occurs early after surgery also has beneficial metabolic effects. To dissect the contribution of nutrient bypass of the proximal gut to improved glucose tolerance after RYGB surgery from caloric restriction, we induced a “non-surgical, proximal gut bypass” by directly administering a glucose load to the jejunum via a nasally inserted feeding tube. We studied 10 obese participants (BMI = 41.3 ± 7.4 kg/m2; 36 ± 9 years; 60% female; HbA1c = 5.5 ± 0.5%) on two occasions. At each visit, a 50-g glucose load was administered to either the stomach or proximal jejunum in random order. Blood was sampled −10, 0, 2, 4, 6, 8, …

Reduction of 8-iso-prostaglandin F2α in the first week after Roux-en-Y gastric bypass surgery.

Obesity is associated with increased markers of oxidative stress. We examined whether oxidative stress is reduced within the first week after Roux‐en‐Y gastric bypass (RYGB) surgery and could be related to changes in adipose tissue depots. The reactive oxygen species (ROS) marker 8‐iso‐prostaglandin F2α (8‐iso‐PGF2α) and activity of antioxidant glutathione peroxidases (GPX) in plasma were compared before and ∼1 week after RYGB. The effects of RYGB on subcutaneous adipose tissue and interstitial fluid 8‐iso‐PGF2α levels and subcutaneous adipose tissue expression of GPX‐3 were also assessed. Levels of 8‐iso‐PGF2α in subcutaneous and visceral adipose tissue were determined. Plasma 8‐iso‐PGF2α levels decreased (122 ± 75 to 56 ± 15 pg/ml, P = 0.001) and GPX activity increased (84 ± 18 to 108 ± 25 nmol/min/ml, P = 0.003) in the first week post‐RYGB. RYGB also resulted in reductions of 8‐iso‐PGF2α in subcutaneous adipose tissue (1,742 ± 931 to 1,132 ± 420 pg/g fat, P = 0.046) and interstitial fluid (348 ± 118 to 221 ± 83 pg/ml, P = 0.046) that were comparable to plasma (26–33%, P = 0.74). Adipose GPX‐3 expression was increased (6.7 ± 4.7‐fold, P = 0.004) in the first postoperative week. The improvements in oxidative stress occurred with minimal weight loss (2.4 ± 3.4%, P = 0.031) and elevations in plasma interleukin‐6 (18.0 ± 46.8 to 28.0 ± 58.9 pg/ml, P = 0.004). Subcutaneous and visceral adipose tissues express comparable 8‐iso‐PGF2α levels (1,204 ± 470 and 1,331 ± 264 pg/g fat, respectively; P = 0.34). These data suggest that RYGB affects adipose tissue leading to the restoration of adipose redox balance within the first postoperative week and that plasma 8‐iso‐PGF2α is primarily derived from subcutaneous adipose tissue.

Chronic Hypocaloric Parenteral Nutrition Containing Glutamine Promotes Hepatic Rather Than Skeletal Muscle or Gut Uptake of Glutamine After Fasting

Background : The effect of chronic parenteral infusions of either saline (S), dextrose (D), amino acids without glutamine (AA), or amino acids including glutamine dipeptides (AA+GLN) on interorgan movement of glutamine (GLN) and glutamate (GLU) after fasting was examined. Methods : Multicatheterized mongrel dogs were stressed by fasting for 4 days followed by a 4-day IV infusion of either S (30 mL/h, n = 8), D (8.6 kcal/h, n = 8), isocaloric AA (8.3 g N/d, n = 7), or isocaloric AA+GLN (8.3 g N/d, 6.8 g GLN/d, n = 6). Hepatic and hindlimb blood flows were estimated, and net arterio-venous balance measurements (μmol/kg per minute) were made during the last 2 hours of infusion. Results : Arterial blood concentrations of GLU were 47 ± 6, 52 ± 3, 47 ± 5, and 62 ± 8 and of GLN were 587 ± 25, 548 ± 20, 423 ± 22 (p ≤.05 vs S), and 512 ± 59 μmol/L for S, D, AA, and AA+GLN, respectively. Slight GLU uptake and GLN release by the hindlimb were observed in all groups. Gut GLU production was -0.31 ± 0.06, -0.04 ± 0.07 (p ≤.05 vs S), -0.15 ± 0.05, and -0.14 ± 0.02 (p ≤.05 vs S), and gut GLN uptake was 0.64 ± 0.38, 1.54 ± 0.25, 0.80 ± 0.16, and 0.85 ± 0.11. Hepatic GLU uptake was 0.16 ± 0.06, 0.09 ± 0.05, 0.23 ± 0.06, and 0.43 ± 0.10 (p ≤.05 vs S). Net hepatic GLN balance was - 0.06 ± 0.54, - 0.77 ± 0.17, -0.21 ± 0.13, and 1.92 ± 0.39 (p ≤.05 vs S). Conclusions : Neither hindlimb GLU uptake nor GLN release were influenced by nutrient infusion. Parenteral D blunted gut GLU release with no effect on gut GLN uptake. AA did not alter GLN or GLU balances in the organs measured. However, although AA+GLN infusion did not enhance gut GLN uptake, it did alter hepatic metabolism with a threefold increase in GLU uptake and a shift from net GLN equilibrium to GLN utilization. Thus, GLN administered parenterally after fasting was not directed preferentially for use by skeletal muscle or by gut tissues but rather was used extensively by the liver.

Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with elevated ghrelin: Early Weight Regain After RYGB

We sought to determine: (1) if early weight regain between 1 and 2 years after Roux‐en‐Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB.

Early weight regain after gastric bypass does not affect insulin sensitivity but is associated with higher ghrelin levels

We sought to determine: (1) if early weight regain between 1 and 2 years after Roux‐en‐Y gastric bypass (RYGB) is associated with worsened hepatic and peripheral insulin sensitivity, and (2) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB.