Metabolic Parameters, Weight Loss, and Comorbidities 4 Years After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

BACKGROUND: Sleeve gastrectomy (LSG) is now the predominant bariatric surgery performed, yet there is limited long-term data comparing important outcomes between LSG and Roux-en-Y gastric bypass (RYGB). This study compares weight loss and impact on comorbidities of the two procedures. METHODS: We retrospectively evaluated weight, blood pressure, hemoglobin A1c, cholesterol, and medication use for hypertension, diabetes, and hyperlipidemia at 1-4 years post-operatively in 380 patients who underwent RYGB and 334 patients who underwent LSG at the University of Michigan from January 2008 to November 2013. Follow-up rates from 714 patients initially were 657 (92%), 556 (78%), 507 (71%), and 498 (70%) at 1-4 years post-operatively. RESULTS: Baseline characteristics were similar except for higher weight and BMI in LSG. There was greater weight loss with RYGB vs. LSG at all points. Hemoglobin A1c and total cholesterol improved more in RYGB vs. LSG at 4 years. There was greater remission of hypertension and discontinuation of all medications for hypertension and diabetes with RYGB at 4 years. CONCLUSIONS: Weight loss, reduction in medications for hypertension and diabetes, improvements in markers of diabetes and hyperlipidemia, and remission rates of hypertension were superior with RYGB vs. LSG 4 years post-operatively. Choice of bariatric procedures should be tailored to surgical risk, comorbidities, and weight loss goals.

Fatty Liver Disease, Women, and Aldosterone: Finding a Link in the Jackson Heart Study.

CONTEXT: Fatty liver disease is one of the most common forms of chronic liver disease. The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of fatty liver. OBJECTIVE: Determine the relationship between fatty liver and aldosterone in a large cohort study. DESIGN: Community-based, observational cohort study of African Americans. SETTING: The original Jackson Heart Study cohort enrolled African American participants from the Jackson, Mississippi, metropolitan area in Hinds, Madison, and Rankin Counties. PARTICIPANTS: Our study population consisted of 2507 Jackson Heart Study participants (1625 women and 882 men) who had liver attenuation measured per computed tomography scans, had aldosterone measurements, and were not taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or mineralocorticoid receptor antagonists. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURE: Liver attenuation on computed tomography scans. RESULTS: Univariate regression analysis demonstrated a statistically significant correlation between aldosterone levels and liver attenuation. Each doubling of aldosterone was associated with 1.08 Hounsfield unit decrease (95% confidence interval, 1.47 to -0.69, P < 0.001). A multivariable model adjusted for body mass index, age, alcohol intake, and homeostatic model assessment of insulin resistance determined that the association was statistically significant only for women. CONCLUSION: Our data demonstrate a positive association between aldosterone levels and fatty liver in African American women.

Milestone Weight Loss Goals (Weight Normalization and Remission of Obesity) after Gastric Bypass Surgery: Long-Term Results from the University of Michigan.

BACKGROUND: Rates of weight normalization and obesity remission after Roux-en-Y gastric bypass (GB) are unknown. This study evaluated weight loss, rates of achieving body mass index (BMI) <25 or 30 kg/m2, recidivism, and predictors of success following GB. METHODS: We retrospectively studied weight and BMI at baseline, 2 and 6 months, and annually at 1-7 years in 219 patients undergoing GB at the University of Michigan from January 2008 to November 2010. RESULTS: Follow-up was excellent for a population traditionally associated with high attrition rates with data availability of 157/219, 145/219, 144/219, 134/219, 123/219, 82/161, and 29/64 patients at 1-7 years, respectively. Mean baseline BMI was 47.0 kg/m2. Weight normalization (BMI <25 kg/m2) occurred in 2.3-6.8% of patients. More importantly, 47% of patients achieved remission of obesity (BMI <30 kg/m2) at some time point and 24% (52/219) at the last observed time point. BMI <30 kg/m2 was associated with a lower initial BMI and follow-up for more than 2 years. CONCLUSIONS: Rates of weight normalization are low after GB; however, a large number of patients achieved BMI <30 kg/m2. While the percent total weight loss and excess weight loss are both quite high in the entire cohort and this is likely associated with significant health benefits, our results still underscore the need to address obesity with intensive clinical attention earlier in its course.

Roux-En-Y Gastric Bypass Vs. Sleeve Gastrectomy: Balancing the Risks of Surgery with the Benefits of Weight Loss.

BACKGROUND: The purpose of the study was to compare weight loss, metabolic parameters, and postoperative complications in patients undergoing Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG). METHODS: We retrospectively studied 30-day postoperative complications as well as change in weight, blood pressure, cholesterol, hemoglobin, hemoglobin A1C, and creatinine from baseline to 2, 6, 12, and 24 months postoperatively in 383 patients undergoing GB and 336 patients undergoing SG at the University of Michigan from January 2008 to November 2013. For a study population which typically has high attrition rates, there were excellent follow-up rates (706/719 at 2 months, 566/719 at 6 months, 519/719 at 12 months, and 382/719 at 24 months). RESULTS: Baseline characteristics were similar in both groups except for higher weight and BMI in the SG group. The GB group experienced greater total body weight loss at 6, 12, and 24 months (41.9 vs. 34.6 kg at 24 months, p < 0.0001). Excess weight loss was 69.7 and 51.7 % following GB and SG respectively at 24 months (p < 0.0001). BP improved significantly in both groups. Surgical complication rates were greater after GB (10.1 vs. 3.5 %, p = 0.0007) with no significant difference in life-threatening or potentially life-threatening complications. CONCLUSIONS: Weight loss was greater following GB compared to SG at 2 years. The risk for surgical complications was greater following GB. Surgical intervention should be tailored to surgical risk, comorbidities, and desired weight loss.

Diabetes Mellitus and the Skin: Recognition and Management of Cutaneous Manifestations.

Diabetes mellitus (DM) is a heterogeneous condition characterized by hyperglycemia as a consequence of defects in insulin secretion and variable degrees of insulin resistance. DM is the most common endocrine disorder in the United States, affecting 9.3% of the population (29.1 million people) in 2014. Skin disorders are present in 79.2% of patients with DM, and cutaneous disease may appear as the first sign of DM or develop at any time in the course of the disease. Given the increasing incidence and prevalence of DM in the United States, primary care physicians should be aware of the associated cutaneous manifestations. This clinical review provides a brief guide to primary care physicians for recognizing and managing skin conditions that they may encounter when caring for patients with DM.

Prediction of Incident Diabetes in the Jackson Heart Study Using High-Dimensional Machine Learning.

Statistical models to predict incident diabetes are often based on limited variables. Here we pursued two main goals: 1) investigate the relative performance of a machine learning method such as Random Forests (RF) for detecting incident diabetes in a high-dimensional setting defined by a large set of observational data, and 2) uncover potential predictors of diabetes. The Jackson Heart Study collected data at baseline and in two follow-up visits from 5,301 African Americans. We excluded those with baseline diabetes and no follow-up, leaving 3,633 individuals for analyses. Over a mean 8-year follow-up, 584 participants developed diabetes. The full RF model evaluated 93 variables including demographic, anthropometric, blood biomarker, medical history, and echocardiogram data. We also used RF metrics of variable importance to rank variables according to their contribution to diabetes prediction. We implemented other models based on logistic regression and RF where features were preselected. The RF full model performance was similar (AUC = 0.82) to those more parsimonious models. The top-ranked variables according to RF included hemoglobin A1C, fasting plasma glucose, waist circumference, adiponectin, c-reactive protein, triglycerides, leptin, left ventricular mass, high-density lipoprotein cholesterol, and aldosterone. This work shows the potential of RF for incident diabetes prediction while dealing with high-dimensional data.

Diabetic muscle infarction: a systematic review.

CONTEXT: Diabetic muscle infarction (DMI) is a rare complication associated with poorly controlled diabetes mellitus. Less than 200 cases have been reported in the literature since it was first described over 45 years ago. There is no clear 'standard of care' for managing these patients. EVIDENCE ACQUISITION: PubMed searches were conducted for 'diabetic muscle infarction' and 'diabetic myonecrosis' from database inception through July 2014. All articles identified by these searches were reviewed in detail if the article text was available in English. EVIDENCE SYNTHESIS: The current literature exists as case reports or small case series, with no prospective or higher-order treatment studies available. Thus, an evidence-based approach to data synthesis was difficult. The available literature is presented objectively with an attempt to describe clinically relevant trends and findings in the diagnosis and management of DMI. CONCLUSIONS: Early recognition of DMI is key, so appropriate treatment can be initiated. MRI is the radiological study of choice. A combination of bed rest, glycemic control, and non-steroidal anti-inflammatory drug therapy appears to yield the shortest time to symptom resolution and the lowest risk of recurrence.

Impact of left ventricular assist device on diabetes management: an evaluation through case analysis and clinical impact.

BACKGROUND: Diabetes is a major risk factor for the development of heart failure (HF). In patients with advanced HF, left ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. It has been our observation that, post-LVAD implantation, diabetes management improves dramatically. OBJECTIVE: We evaluated insulin requirements in a group of type 2 diabetes patients after LVAD implantation, compared them to a small control group, and performed a pertinent literature review. METHODS: Relevant clinical and biochemical data were collected by chart review of 11 patients with known type 2 diabetes mellitus and HF who underwent LVAD implantation. Patients treated only with insulin were evaluated and compared with 5 control patients undergoing other cardiac procedures. RESULTS: Insulin requirement decreased by 73% at 6 months from the pre-LVAD dose despite no significant changes in weight or glomerular filtration rate. Mean hemoglobin A1c reduced post-LVAD to 6.4% from 8.6%. Patients undergoing other cardiac procedures showed no significant changes in hemoglobin A1c or insulin requirements. CONCLUSION: Patients with diabetes undergoing LVAD implantation demonstrated a significant reduction in insulin requirements. This finding underscores the importance of HF in the progression of insulin resistance.

Analysis of adipose tissue lipid using mass spectrometry.

Mass spectrometry technology has enabled significant advances in detailing the alterations of the lipidome in response to pathological conditions or experimental manipulations. Lipids comprise a wide range of compounds with functions that include structural, intracellular signaling, trafficking, and storage. Characterization of lipid species has evolved significantly over recent years due to the progress made in the area of mass spectrometry. This chapter details the methods used for the analysis of lipids tailored to the intrinsic characteristics of adipose tissue. Particular attention is given to the analysis of triglycerides, diacylglycerols, and phospholipid.

Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2 mutations.

Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is characterized by the absence of adipocytes and development of severe insulin resistance. In the current study, we investigated the adipogenic defect associated with AGPAT2 mutations. Adipogenesis was studied in muscle-derived multipotent cells (MDMCs) isolated from vastus lateralis biopsies obtained from controls and subjects harboring AGPAT2 mutations and in 3T3-L1 preadipocytes after knockdown or overexpression of AGPAT2. We demonstrate an adipogenic defect using MDMCs from control and CGL human subjects with mutated AGPAT2. This defect was rescued in CGL MDMCs with a retrovirus expressing AGPAT2. Both CGL-derived MDMCs and 3T3-L1 cells with knockdown of AGPAT2 demonstrated an increase in cell death after induction of adipogenesis. Lack of AGPAT2 activity reduces Akt activation, and overexpression of constitutively active Akt can partially restore lipogenesis. AGPAT2 modulated the levels of phosphatidic acid, lysophosphatidic acid, phosphatidylinositol species, as well as the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor cyclic phosphatidic acid. The PPARγ agonist pioglitazone partially rescued the adipogenic defect in CGL cells. We conclude that AGPAT2 regulates adipogenesis through the modulation of the lipome, altering normal activation of phosphatidylinositol 3-kinase (PI3K)/Akt and PPARγ pathways in the early stages of adipogenesis.

A role for 1-acylglycerol-3-phosphate-O-acyltransferase-1 in myoblast differentiation.

AGPAT isoforms catalyze the acylation of lysophosphatidic acid (LPA) to form phosphatidic acid (PA). AGPAT2 mutations are associated with defective adipogenesis. Muscle and adipose tissue share common precursor cells. We investigated the role of AGPAT isoforms in skeletal muscle development. We demonstrate that small interference RNA-mediated knockdown of AGPAT1 expression prevents the induction of myogenin, a key transcriptional activator of the myogenic program, and inhibits the expression of myosin heavy chain. This effect is rescued by transfection with AGPAT1 but not AGPAT2. Knockdown of AGPAT2 has no effect. The regulation of myogenesis by AGPAT1 is associated with alterations on actin cytoskeleton. The role of AGPAT1 on actin cytoskeleton is further supported by colocalization of AGPAT1 to areas of active actin polymerization. AGPAT1 overexpression was not associated with an increase in PA levels. Our observations strongly implicate AGPAT1 in the development of skeletal muscle, specifically to terminal differentiation. These findings are linked to the regulation of actin cytoskeleton.

Role of FoxO1 in FFA-induced oxidative stress in adipocytes.

Reactive oxygen species (ROS) production has recently been established as an essential contributor in the pathogenesis of obesity-associated insulin resistance. The FoxO1 pathway plays a role not only in nutrient sensing but also in regulating ROS production. We exposed adipocytes to free fatty acids (FFA) and demonstrated that FoxO1 protein levels decrease in a dose-dependent manner. The FoxO1 downregulation correlated with an increase in the production of ROS and a proinflammatory adipokine pattern characterized by a decrease in adiponectin and an increase in IL-6, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1 mRNA expression levels. Similarly, a decrease in FoxO1 protein levels was seen in adipocytes of db/db mice compared with controls. Treatment with the sirtuin agonist resveratrol, which translocates FoxO1 to the nucleus, increased FoxO1 protein levels in adipocytes exposed to FFA. This correlated with a decrease in the generation of ROS and a partial reversal of the proinflammatory adipokine pattern. Together these results indicate that the insulin-resistant adipocyte produced by the exposure to a high concentration of fatty acids is characterized by decreased levels of FoxO1. These data also suggest that modulation of the Sirt1/FoxO1 pathway is a potentially useful therapeutic target for the obesity-induced dysfunctional adipocyte.