Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1 min-1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. CONCLUSIONS: These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.

The National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study Cohort: Rationale, Methods, and Baseline Characteristics.

BACKGROUND: Although bariatric procedures are commonly performed in clinical practice, long-term data on the comparative effectiveness and safety of different procedures on sustained weight loss, comorbidities, and adverse effects are limited, especially in important patient subgroups (eg, individuals with diabetes, older patients, adolescents, and minority patients). OBJECTIVE: The objective of this study was to create a population-based cohort of patients who underwent 3 commonly performed bariatric procedures-adjustable gastric band (AGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG)-to examine the long-term comparative effectiveness and safety of these procedures in both adults and adolescents. METHODS: We identified adults (20 to 79 years old) and adolescents (12 to 19 years old) who underwent a primary (first observed) AGB, RYGB, or SG procedure between January 1, 2005 and September 30, 2015 from 42 health systems participating in the Clinical Data Research Networks within the National Patient-Centered Clinical Research Network (PCORnet). We extracted information on patient demographics, encounters with healthcare providers, diagnoses recorded and procedures performed during these encounters, vital signs, and laboratory test results from patients' electronic health records (EHRs). The outcomes of interest included weight change, incidence of major surgery-related adverse events, and diabetes remission and relapse, collected for up to 10 years after the initial bariatric procedure. RESULTS: A total of 65,093 adults and 777 adolescents met the eligibility criteria of the study. The adult subcohort had a mean age of 45 years and was predominantly female (79.30%, 51,619/65,093). Among adult patients with non-missing race or ethnicity information, 72.08% (41,248/57,227) were White, 21.13% (12,094/57,227) were Black, and 20.58% (13,094/63,637) were Hispanic. The average highest body mass index (BMI) recorded in the year prior to surgery was 49 kg/m2. RYGB was the most common bariatric procedure among adults (49.48%, 32,208/65,093), followed by SG (45.62%, 29,693/65,093) and AGB (4.90%, 3192/65,093). The mean age of the adolescent subcohort was 17 years and 77.5% (602/777) were female. Among adolescent patients with known race or ethnicity information, 67.3% (473/703) were White, 22.6% (159/703) were Black, and 18.0% (124/689) were Hispanic. The average highest recorded BMI in the year preceding surgery was 53 kg/m2. The majority of the adolescent patients received SG (60.4%, 469/777), followed by RYGB (30.8%, 239/777) and AGB (8.9%, 69/777). A BMI measurement (proxy for follow-up) was available in 84.31% (44,978/53,351), 68.09% (20,783/30,521), and 68.56% (7159/10,442) of the eligible adult patients at 1, 3, and 5 years of follow-up, respectively. The corresponding proportion was 82.0% (524/639), 49.9% (174/349), and 38.8% (47/121) in the adolescent subcohort. CONCLUSIONS: Our study cohort is one of the largest cohorts of patients with bariatric procedures in the United States. Patients are geographically and demographically diverse, which improves the generalizability of the research findings and allows examination of treatment effect heterogeneity. Ongoing and planned investigations will provide real-world evidence on the long-term benefits and risks of these most commonly used bariatric procedures in current clinical practice.