Metabolic Surgery Comparing Sleeve Gastrectomy with Jejunal Bypass and Roux-en-Y Gastric Bypass in Type 2 Diabetic Patients After 3 Years.

INTRODUCTION: Sleeve gastrectomy with jejunal bypass (SGJB) and Roux-en-Y gastric bypass (RYGB) has shown good results with respect to type 2 diabetes mellitus (T2D) remission in our institution. In this study, we compared the efficacy and safety of SGJB versus RYGB in terms of T2D remission up to 3 years postoperatively. MATERIALS AND METHODS: A retrospective cohort study of two groups of patients with T2D who underwent SGJB or RYGB. All patients were matched by age, presurgical body mass index (BMI), glycated hemoglobin (HbA1c), and diabetes duration. Complete remission was defined as HbA1c of < 6%, fasting plasma glucose (FPG) of < 100 mg/dL, and no antidiabetic drugs. RESULTS: In total, 57 and 55 patients in the SGJB and RYGB groups, respectively, met the inclusion criteria. The diabetes remission rate was similar between the SGJB and RYGB groups at 1 year postoperatively (69.2 vs. 64.7%) and 3 years postoperatively (56.1 vs. 58.8%). There were no significant differences in HbA1c or FPG at 1 or 3 years between the two groups. Additionally, weight loss and other metabolic parameters were similar between the groups. Clinical chemistry values were similar at 12 months except for hematocrit and calcium, which were significantly lower in the RYGB group. There were no differences in surgical complications. CONCLUSIONS: Both procedures showed similar results in terms of T2D remission and other metabolic markers at 3 years. Hematocrit and calcium were significantly higher in the SGJB than RYGB group. SGJB is as effective and safe as RYGB in obese patients with T2D.

BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes.

Type 2 diabetes (T2D) can go undiagnosed for years, leading to a stage where chronic high blood sugar produces complications such as delayed wound healing. Reports have shown that BLT2 activation improves keratinocyte migration and wound healing, as well as protecting the epidermal barrier through the promotion of actin polymerization. The goal of this study was to elucidate the role of BLT2 expression in skin epithelial integrity in T2D. For this purpose, we used both wild type (WT) and BLT2 knockout mice in a model, in which a T2D-like phenotype was induced by keeping the animals on a high fat (HF) diet over 5 weeks. In a parallel in vitro approach, we cultured BLT2-transfected HaCaT cells at both low and high glucose concentrations for 48 h. Structure, transepithelial resistance (TEER), IL-1ß, IL-8 or CXCL2, MMP9, Filaggrin, Loricrin and Keratin 10 (K10) were evaluated ex vivo and in vitro. Additionally, wound healing (WH) was studied in vitro. The skin from T2D and BLT2 knockout mice showed a reduction in TEER and the expression of IL-1ß, and in increase in CXCL2, MMP9, Filaggrin, Loricrin and K10 expression. The structure suggested an atrophic epidermis; however, the skin was dramatically affected in the BLT2 knockout mice kept on a HF diet. HaCaT-BLT2 cells presented as an organized monolayer and showed higher TEER and wound healing compared with vector only-transfected HaCaT-Mock cells. Likewise, alterations in the expression of skin inflammatory, matrix degradation and differentiation markers under low and high glucose conditions were less severe than in HaCaT-Mock cells. Our results suggest that BLT2 improves epithelial integrity and function by regulating differentiation markers, cytokines and MMP9. Furthermore, BLT2 attenuates the damaging effects of high glucose levels, thereby accelerating wound healing.

Platelet tissue factor activity and membrane cholesterol are increased in hypercholesterolemia and normalized by rosuvastatin, but not by atorvastatin.

BACKGROUND AND AIMS: High plasma LDL-cholesterol (LDL-C) and platelet responses have major pathogenic roles in atherothrombosis. Thus, statins and anti-platelet drugs constitute mainstays in cardiovascular prevention/treatment. However, the role of platelet tissue factor-dependent procoagulant activity (TF-PCA) has remained unexplored in hypercholesterolemia. We aimed to study platelet TF-PCA and its relationship with membrane cholesterol in vitro and in 45 hypercholesterolemic patients (HC-patients) (LDL-C >3.37 mmol/L, 130 mg/dL) and 37 control subjects (LDL-C <3.37 mmol/L). The effect of 1-month administration of 80 mg/day atorvastatin (n = 21) and 20 mg/day rosuvastatin (n = 24) was compared. METHODS: Platelet TF-PCA was induced by GPIbα activation with VWF-ristocetin. RESULTS: Cholesterol-enriched platelets in vitro had augmented aggregation/secretion and platelet FXa generation (1.65-fold increase, p = 0.01). HC-patients had 1.5-, 2.3- and 2.5-fold increases in platelet cholesterol, TF protein and activity, respectively; their platelets had neither hyper-aggregation nor endogenous thrombin generation (ETP). Rosuvastatin, but not atorvastatin, normalized platelet cholesterol, TF protein and FXa generation. It also increased slightly the plasma HDL-C levels, which correlated negatively with TF-PCA. CONCLUSIONS: Platelets from HC-patients were not hyper-responsive to low concentrations of classical agonists and had normal PRP-ETP, before and after statin administration. However, washed platelets from HC-patients had increased membrane cholesterol, TF protein and TF-PCA. The platelet TF-dependent PCA was specifically expressed after VWF-induced GPIbα activation. Rosuvastatin, but not atorvastatin treatment, normalized the membrane cholesterol, TF protein and TF-PCA in HC-patients, possibly unveiling a new pleiotropic effect of rosuvastatin. Modulation of platelet TF-PCA may become a novel target to prevent/treat atherothrombosis without increasing bleeding risks.

High prevalence of undiagnosed liver cirrhosis and advanced fibrosis in type 2 diabetic patients.

UNLABELLED:  Background. Patients with type 2 diabetes mellitus (T2DM) are at risk for developing end-stage liver disease due to nonalcoholic steatohepatitis (NASH), the aggressive form of non-alcoholic fatty liver disease (NAFLD). Data on prevalence of advanced fibrosis among T2DM patients is scarce. AIM: To evaluate prevalence of steatosis, advanced fibrosis and cirrhosis using non-invasive methods in T2DM patients. MATERIAL AND METHODS: 145 consecutive T2DM patients (> 55 years-old) were prospectively recruited. Presence of cirrhosis and advanced fibrosis was evaluated by magnetic resonance imaging (MRI) and NAFLD fibrosis score (NFS) respectively. Exclusion criteria included significant alcohol consumption, markers of viral hepatitis infection or other liver diseases. Results are expressed in percentage or median (interquartile range). RESULTS: 52.6% of patients were women, the median age was 60 years old (57-64), mean BMI was 29.6 ± 4.7 kg/m2 and diabetes duration was 7.6 ± 6.9 years. A high prevalence of liver steatosis (63.9%), advanced fibrosis assessed by NFS (12.8%) and evidence of liver cirrhosis in MRI (6.0%) was observed. In a multivariate analysis GGT > 82 IU/L (P = 0.004) and no alcohol intake (P = 0.032) were independently associated to advanced fibrosis. CONCLUSION: A high frequency of undiagnosed advanced fibrosis and cirrhosis was observed in non-selected T2DM patients. Screening of these conditions may be warranted in this patient population.

Increased RhoA/Rho-Kinase Activity and Markers of Endothelial Dysfunction in Young Adult Subjects with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, is increasingly prevalent in young adults. Dyslipidemia, proinflammatory cytokines, endothelial dysfunction signs, and RhoA/Rho-kinase (ROCK) activation are considered risk factors of cardiovascular diseases. The occurrence of these factors in young patients with metabolic syndrome but without type 2 diabetes or hypertension has not been fully studied. The objective of this study was to evaluate young subjects with enlarged waist circumference and dyslipidemia but without type 2 diabetes or hypertension,for markers associated with a higher risk of cardiovascular diseases. METHODS: Thirty-two male patients aged 31 ± 1.3 years diagnosed with metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guide for enlarged waist circumference, elevated triglycerides, and low HDL levels, but with blood pressure and fasting glucose within normal ranges, were evaluated for RhoA/ROCK activity in leukocytes, serum fatty acid methyl esters profile, proinflammatory cytokines, and oxidative stress markers in addition to thrombin generation and biochemical analysis. Age- and gender-matched healthy subjects were equivalently evaluated. RESULTS: Patients showed higher RhoA/ROCK activity, elevated levels of interleukin-6, soluble CD40L, monocyte chemoattractant protein, and high-sensitivity C-reactive protein (P < 0.001) as well as parameters of endogenous thrombin generation potential (P < 0.05) compared with healthy subjects. Increased thiobarbituric acid reactive substances, advanced oxidation protein product, and insulin levels and low nitric oxide biodisponibility (P < 0.001) were also found in patients as compared with controls. Palmitic acid was one of the saturated fatty acids found to be significantly elevated in patients compared with control subjects (P = 0.0087). CONCLUSIONS: Increased markers of cardiovascular risk are already present in young adults with metabolic syndrome but without type 2 diabetes or hypertension.

[Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance]. / Evaluación de la insulinemia post carga oral de glucosa como método diagnóstico de resistencia a la insulina.

BACKGROUND: In our country, the assessment of insulin resistance (IR) measuring serum insulin levels at 60 and 120 minutes after a 75 g oral glucose tolerance test (OGTT), is usual. However, there is no information about the distribution of serum insulin levels in the Chilean population. AIM: To assess the distribution of serum insulin levels at 60 and 120 minutes during OGTTs and suggest a statistical cut-off point to estimate the degree of IR. MATERIAL AND METHODS: Retrospective analysis of 1815 OGTTs performed in non-diabetic subjects aged between 18 and 75 years, at a university medical center. HOMA-IR (Homeostasis Model Assessment), insulin sensitivity index of Matsuda (ISI-Composite), and their correlation with serum insulin levels at 60 and 120 minutes were calculated. RESULTS: The 75th percentiles for serum insulin levels at 60 and 120 minutes were 127 and 81 µU/mL, respectively. There was a high correlation between HOMA-IR and ISI-Composite (r = -089, p < 0.001). There was a weaker although significant correlation between HOMA-IR and ISI-Composite and insulin levels at 60 (r = 0.56 and -0.79 respectively, p < 0,001) and 120 minutes (r = 0.54 and -0.75 respectively, p < 0,001). CONCLUSIONS: We propose 60 and 120 min serum insulin levels of 130 and 80 µU/mL respectively, as cut-off values for normality during OGTT in Chilean normoglycemic individuals.

Evaluación de la insulinemia post carga oral de glucosa como método diagnóstico de resistencia a la insulina / Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance

Background: In our country, the assessment of insulin resistance (IR) measuring serum insulin levels at 60 and 120 minutes after a 75 g oral glucose tolerance test (OGTT), is usual. However, there is no information about the distribution of serum insulin levels in the Chilean population. Aim: To assess the distribution of serum insulin levels at 60 and 120 minutes during OGTTs and suggest a statistical cut-off point to estimate the degree of IR. Material and Methods: Retrospective analysis of 1815 OGTTs performed in non-diabetic subjects aged between 18 and 75 years, at a university medical center. HOMA-IR (Homeostasis Model Assessment), insulin sensitivity index of Matsuda (ISI-Composite), and their correlation with serum insulin levels at 60 and 120 minutes were calculated. Results: The 75th percentiles for serum insulin levels at 60 and 120 minutes were 127 and 81 µU/mL, respectively. There was a high correlation between HOMA-IR and ISI-Composite (r = -089, p < 0.001). There was a weaker although significant correlation between HOMA-IR and ISI-Composite and insulin levels at 60 (r = 0.56 and -0.79 respectively, p < 0,001) and 120 minutes (r = 0.54 and -0.75 respectively, p < 0,001). Conclusions: We propose 60 and 120 min serum insulin levels of 130 and 80 µU/mL respectively, as cut-off values for normality during OGTT in Chilean normoglycemic individuals.

Feeding and bone turnover in gastric bypass.

CONTEXT: Roux-en-Y gastric bypass (RYGB) is associated with high bone turnover. In healthy subjects, feeding causes acute reduction of bone resorption, which is regulated by several intestinal and pancreatic peptides. OBJECTIVE: Our objective was to assess bone turnover after feeding in patients with RYGB. DESIGN AND SETTING: This was a cross-sectional case-control study at a university hospital. PARTICIPANTS: Fifteen postmenopausal women who underwent RYGB 7.4 ± 4.1 years previously were matched by age and body mass index with 15 nonoperated women (controls). MAIN OUTCOMES: Serum PTH, calcium, phosphorus, insulin, carboxy telopeptide (CTX), procollagen type I N-terminal propeptide (P1NP), and glucagon-like peptide 2 (GLP-2) were measured while fasting and after a standard meal (SM). RESULTS: The fasting calcium, phosphorus, and PTH were similar in both groups and exhibited similar decreases after an SM. The fasting CTX level was higher in the RYGB than in the control group (0.589 ± 0.18 vs 0.382 ± 0.11 ng/mL; P < .05) and fell to a nadir of 42.2% of the basal value in the RYGB and 53.9% in controls (P < .05). The fasting and postprandial P1NP levels were similar in both groups and fell to a nadir of 85.8% in the RYGB and 89.3% in controls. Insulin and GLP-2 levels were similar during fasting in both groups. RYGB patients had exaggerated postprandial insulin and GLP-2 response compared with the controls with the insulin and GLP-2 area under the curve being significantly higher in the RYGB group. There was a significant negative correlation between the peak of insulin levels and the CTX changes. CONCLUSION: The acute reduction in bone resorption after feeding is preserved in RYGB and is even higher than in nonoperated subjects. This phenomenon is related to the increase of postprandial levels of insulin. These findings suggest a bone-protecting mechanism in RYGB that may counteract the elevated bone resorption that occurs during fasting.

Medical and surgical treatments for obesity have opposite effects on peptide YY and appetite: a prospective study controlled for weight loss.

CONTEXT: The effects of medical and surgical treatments for obesity on peptide YY (PYY) levels, in patients with similar weight loss, remain unclear. OBJECTIVE: The objective of the study was to assess PYY and appetite before and after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and medical treatment (MED). DESIGN: This was a prospective, controlled, nonrandomized study. SETTING: The study was conducted at the Departments of Nutrition and Digestive Surgery at a university hospital. PARTICIPANTS: PARTICIPANTS included three groups of eight patients with similar body mass indexes (RYGB 37.8 +/- 0.8, SG 35.3 +/- 0.7, and MED 39.1 +/- 1.7 kg/m(2), P = NS) and eight lean controls (body mass index 21.7 +/- 0.7 kg/m(2)). MAIN OUTCOME MEASURES: Total plasma PYY, hunger, and satiety visual analog scales in fasting and after ingestion of a standard test meal were measured. RESULTS: At baseline there were no differences in the area under the curve (AUC) of PYY, hunger, or satiety in obese groups. Two months after the interventions, RYGB, SG, and MED groups achieved similar weight loss (17.7 +/- 3, 14.9 +/- 2.4, 16.6 +/- 4%, respectively, P = NS). PYY AUC increased in RYGB (P < 0.001) and SG (P < 0.05) and did not change in MED. PYY levels decreased at fasting, 30 min, and 180 min after a standard test meal in MED (P < 0.05). Hunger AUC decreased in RYGB (P < 0.05). Satiety AUC increased in RYGB (P < 0.05) and SG (P < 0.05). Appetite did not change in MED. PYY AUC correlated with satiety AUC (r = 0.35, P < 0.05). CONCLUSION: RYGB and SG increased PYY and reduced appetite. MED failed to produce changes. Different effects occur despite similar weight loss. This suggests that the weight-loss effects of these procedures are enhanced by an increase in PYY and satiety.

Increase of bone resorption and the parathyroid hormone in postmenopausal women in the long-term after Roux-en-Y gastric bypass.

BACKGROUND: The effects of Roux-en-Y Gastric Bypass (RYGB) on bone in the long-term remains unclear. We assessed bone metabolism and bone mineral density (BMD) 1 to 5 years after RYGB. METHODS: We designed a retrospective cohort study in 26 postmenopausal women (58.0+/-3.9 years old) with RYGB 3.5+/-1.1 years before (body mass index (BMI) 29.5+/-3.8 kg/m2, presurgery 43.6+/-5.5 kg/m2) and 26 nonoperated women (57.5+/-4.7 years old, BMI 29.2+/-4.1 kg/m2) matched by age and BMI. The main measures were BMD, serum carboxy telopeptide (CTx), total alkaline phosphatases (ALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ghrelin. RESULTS: RYGB group, compared to nonoperated women, had higher CTx (0.71+/-0.21 vs. 0.43+/-0.15 ng/ml; P<0.01) and PTH (68.3+/-35 vs. 49.4+/-16 pg/ml; P=0.02). There were no differences between RYGB and nonoperated women in: calcium and vitamin D intake (759+/-457 vs. 705+/-460 mg/day; 176+/-160 vs. 111+/-86 UI/day), ghrelin (763+/-336 vs. 621+/-274 pg/ml), ALP (101+/-22 vs. 94+/-25 UI/l), 25OHD (18.8+/-7.6 vs. 17.4 +/- 5.9 ng/ml), lumbar spine BMD (1.059+/-0.32 vs. 1.071+/-0.207 g/cm2), or femoral neck BMD (0.892+/-0.109 vs. 0.934+/-1.1 g/cm2). CONCLUSIONS: RYGB is associated to high bone resorption and hyperparathyroidism prevalence in postmenopausal women in the long-term. This occurs independently of the intake of calcium, vitamin D status, or ghrelin and does not seem to affect BMD after RYGB.