Oxyntomodulin and Glicentin May Predict the Effect of Bariatric Surgery on Food Preferences and Weight Loss.

BACKGROUND: Alterations in several gastrointestinal hormones are implicated in the postoperative suppression of food intake leading to weight loss after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). The aim was to evaluate changes in responses of gastrointestinal hormones after RYGB and SG and the associations of these changes with weight loss, energy intake, and food preferences. METHODS: Forty-two subjects with severe obesity were included (32 RYGB; 10 SG). Postprandial responses of glicentin, oxyntomodulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin were measured before and 6 months after surgery. Energy intake and energy density were assessed before and 6 months after surgery using a buffet meal test and weight loss was assessed 18 months after surgery. RESULTS: Postprandial concentrations of glicentin, oxyntomodulin, GLP-1, and ghrelin differed between RYGB and SG (all P ≤ .02). Enhanced responses of glicentin and oxyntomodulin predicted a greater weight loss (both P < .01) and were associated with a larger decrease in energy density (P ≤ .04). No associations were found for GLP-1, PYY, and ghrelin, and changes were not associated with changes in energy intake. When combing all hormones, 60%, 19%, and 33% of the variations in weight loss, energy intake, and energy density, respectively, could be explained. CONCLUSION: Postprandial responses of gastrointestinal hormones differed between RYGB and SG. Enhanced responses of glicentin and oxyntomodulin predicted a better weight loss and were associated with a decreased preference for energy-dense foods. Replication of these results could imply an opportunity to identify patients in need of additional support after surgical treatments of obesity.

Circulating levels of gastrointestinal hormones in response to the most common types of bariatric surgery and predictive value for weight loss over one year: Evidence from two independent trials.

AIMS: Bariatric surgery leads to profound and sustainable weight loss. Gastrointestinal hormones are involved in energy and glucose homeostasis, thus postoperative changes of their circulating levels may be mediating future weight loss. To investigate how the circulating concentrations of gastrointestinal hormones change in response to the most common types of bariatric operation and whether these changes can predict future weight loss. MATERIALS AND METHODS: We measured circulating GLP-1, GLP-2, oxyntomodulin, glicentin, glucagon, major proglucagon fragment (MPGF), ghrelin, GIP, PYY after overnight fasting and/or after a mixed meal test (MMT) in: a) 14 subjects that have undergone either an adjustable gastric banding [AGB] (n = 9) or a Roux-en-Y bypass (RYGB) (n = 5) (Pilot study 1), b) 28 subjects that have undergone either a vertical sleeve gastrectomy (n = 17) or a RYGB (n = 11) before and three, six and twelve months after surgery. RESULTS: In addition to the expected associations with GLP-1, the most robust increases were observed in postprandial levels of oxyntomodulin and glicentin three months after VSG or RYGB (but not after AGB) and are associated with degree of weight loss. Oxyntomodulin and glicentin levels at the third and sixth month postoperative visit are positively associated with feeling of satiety which may be underlying the observed associations with future weight loss. CONCLUSION: Beyond GLP-1, early postprandial changes in circulating oxyntomodulin and glicentin are predictors of weight loss after bariatric surgery, possibly through regulation of satiety. Further studies should focus on underlying mechanisms, and their potential as attractive therapeutic tools against obesity and related comorbidities.

Fasting levels of glicentin are higher in Roux-en-Y gastric bypass patients exhibiting postprandial hypoglycemia during a meal test.

BACKGROUND: Post-bypass postprandial hypoglycemia (PPH) is a frequent complication of Roux-en-Y Gastric Bypass (RYGB) but predictors remain poorly identified and are needed to assess individual risk. After RYGB, exaggerated secretion of glucagon-like peptide-1 (GLP-1) and insulin could lead to PPH, but other proglucagon-derived peptides, including glicentin and glucagon, could also contribute to this phenomenon. OBJECTIVES: To identify biological hypoglycemia in relation to the secretion of proglucagon-derived peptides during a mixed-meal test (MMT) in RYGB patients. SETTING: University hospital. METHODS: Twenty RYGB patients reporting symptoms consistent with PPH were examined 36.9 ± 5.1 months after surgery. Plasma levels of glucose, c-peptide, glucagon, GLP-1 and glicentin were assessed before and during MMT. Patients with postprandial hypoglycemia ≤3 mM (54 mg/dL) during MMT were assigned to HYPO group and compared with patients not exhibiting hypoglycemia (NONHYPO group). RESULTS: Seven patients displayed hypoglycemia ≤3 mM (HYPO) during the MMT. Lower fasting glycemia (4.5 mM versus 5.3 mM, P<.05) and higher fasting glicentin (22.6 pM versus 14.0 pM, P<.05) were observed in HYPO versus NONHYPO patients. Fasting glicentin was inversely correlated with postprandial nadir glucose. Examining the receiver-operating characteristics curve analysis, a cutoff of 17.2 pM for fasting glicentin identified PPH with 85.7% sensitivity and 53.8% specificity. All patients exhibited a similar increase of postprandial GLP-1, glucagon, and glicentin secretions that correlated with each other. CONCLUSIONS: These results suggest that fasting glicentin is a potential biomarker to examine in operated-obese patients at risk of developing PPH. Further studies are needed before proposing fasting glicentin as a predictive factor of PPH.

Decreased serum glicentin concentration in patients with severe and morbid obesity.

Background Proglucagon-derived hormones represent a family of peptides mainly produced in the pancreas and the intestine. While several proglucagon-derived peptides play key roles in metabolic diseases, little is known about glicentin. The aim of the present study was to investigate serum glicentin concentrations in individuals with adult obesity and to study its potential link with various metabolic parameters. Methods Fifty-two individuals with normal body mass index (BMI < 25 kg/m2) and 39 patients with severe or morbid obesity (BMI > 35 kg/m2) were prospectively included at the University Hospital of Nice between January 2014 and April 2016. Clinical data were recorded, and a fasting blood sample was collected to measure glicentin, glucose, insulin, C-peptide, total cholesterol, triglyceride, LDL and HDL-cholesterol. In addition, a homeostasis model assessment for insulin resistance (HOMA2-IR) was also calculated. Results Patients with severe and morbid obesity had significantly higher plasma glucose, together with higher serum concentrations of insulin, C-peptide, HOMA2-IR, triglyceride, LDL-cholesterol and lower serum concentrations of HDL-cholesterol compared with individuals with a normal body mass index. The obese patients displayed significantly lower fasting serum concentrations of glicentin compared with subjects with a normal body mass index (12 pmol/L vs. 24 pmol/L, P < 0.0001). In the total population, fasting glicentin concentrations did not correlate with BMI, glycaemic parameters (glucose, insulin, C-peptide, HOMA-IR) or lipid parameters (total cholesterol, triglyceride, LDL and HDL-cholesterol). Conclusion To the best of our knowledge, this is the first study reporting serum glicentin concentrations in healthy lean and obese adult subjects. We found that fasting serum glicentin concentrations are decreased in patients with severe or morbid obesity suggesting the potential interest of this peptide in obesity and metabolic-related disorders.

Fasting Circulating Glicentin Increases After Bariatric Surgery.

INTRODUCTION: Bariatric surgery including the Roux-en-Y gastric bypass (RYGB) and the laparoscopic sleeve gastrectomy (LSG) is a well-established therapeutic option for patients with morbid or severe obesity. Metabolic modifications observed after bariatric surgery are thought to be, at least partly, linked to hormonal changes. While variation of several proglucagon-derived peptides during bariatric surgery is well documented, little is known about glicentin. The aim of this study was to investigate circulating glicentin variations after bariatric surgery. MATERIAL AND METHODS: Thirty patients eligible for bariatric surgery (18 RYGB and 12 LSG procedures) were prospectively included in the University Hospital of Nice. Clinical data and fasting biological parameters were recorded preoperatively, at 3, 6, and 12 months after bariatric surgery. RESULTS: The median age of patients was 51 years (35-56) with 33.3% men. Fasting glicentin concentration increased progressively after bariatric surgery from 6 months and was more marked at 12 months (14 ± 3.6 pmol/L at baseline vs 19.7 ± 2.7 pmol/L at 12 months for RYGB and 12.5 ± 1.4 vs 16.4 ± 1.8 pmol/L for LSG, respectively). Compared to preoperative values, the fold increase of glicentin at 12 months was 2 ± 0.2 in the RYGB group and 1.6 ± 0.3 in the LSG group. Glicentin variation after surgery did not correlate with anthropometric, glycemic, or lipid parameter modifications. CONCLUSION: Fasting glicentin level increases after bariatric surgery suggesting the potential interest of this peptide as a player and/or a marker of physiological changes after bariatric surgery.

Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes.

CONTEXT: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM). OBJECTIVE: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated. DESIGN: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT). SETTING: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden. PATIENTS AND PARTICIPANTS: Adolescents with obesity, age 10-18 years, with normal glucose tolerance (NGT, n = 23), impaired glucose tolerance (IGT, n = 19), or T2DM (n = 4) and age-matched lean adolescents (n = 19) were included. MAIN OUTCOME MEASURES: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin. RESULTS: Adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT (0.25 vs 0.53 pM, P < .05; 18.2 vs 23.6 pM, P < .01) and adolescents with obesity and T2DM had higher fasting glucagon levels (18.1 vs 10.1 pM, P < .01) than those with NGT. During OGTT, glicentin/glucagon ratios were lower in adolescents with obesity and NGT than in lean adolescents (P < .01) and even lower in IGT (P < .05) and T2DM (P < .001). CONCLUSIONS: Obese adolescents with IGT have lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, whereas GLP-1 and glicentin levels are maintained low. During OGTT, adolescents with obesity have more products of pancreatically than intestinally cleaved proglucagon (ie, more glucagon and less GLP-1) in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.

The peculiar processing of pancreatic hormone glucagon seen in traumatized patients.

BACKGROUND/AIM: The kinetics of the pancreatic hormone glucagon in traumatized patients has not been minutely investigated as well as that of insulin, despite its significant influence on energy metabolism. In the present study, we examined the kinetics of glucagon and glucagon-related peptides assessed by radioimmunoassay, and the molecular forms of these peptides using gel filtration chromatography. In addition, we discuss glucagon processes in the pancreas and intestine in traumatized patients in the early operative days. METHODOLOGY: Twelve traumatized patients who had undergone emergency surgery were enrolled in this study (group S). Ten healthy volunteers were also enrolled as normal control subjects (group C). The serum level of glucagon and glucagon-related peptides were assessed in the early morning fasting state in both groups, on the second postoperative day in group S, using the glucagon nonspecific N-terminal (glucagon-like immunoreactivity [GLI]) and specific C-terminal (immunoreactive glucagon [IRG]) radioimmunoassays. The molecular forms of these peptides were also estimated using the gel filtration chromatography method. RESULTS: Serum IRG in group S was significantly high compared with that of group C (P < .05). Serum GLI was not significantly different between both groups. In all 12 patients in group S, a peculiar glicentin-like peptide (GLLP: MW approximately 8000 Da) other than pancreatic glucagon was seen on gel filtration chromatography, which was not seen in group C. CONCLUSIONS: The kinetics and processing of glucagon in traumatized patients was different from those of healthy subjects. In traumatized patients, the peculiar processing of glucagon was processed in the intestine, which is different from the ordinary glucagon processing either in the pancreas or the intestine, generating a peculiar glicentin-like peptide (GLLP).

Changes in glucagon kinetics and processing in patients with acute pancreatitis.

BACKGROUND/AIMS: The kinetics of the pancreatic hormone glucagon in patients with acute pancreatitis have not been investigated as carefully as those of insulin, in spite of its crucial influence on energy metabolism. In the present study, we studied the kinetics of glucagon and glucagon-related peptides assessed by radioimmunoassay. Furthermore, the molecular forms of these peptides were examined using gel filtration chromatography, and the glucagon processes in the pancreas and intestine in the early stage in patients with acute pancreatitis were investigated. METHODOLOGY: Fourteen patients with acute pancreatitis were enrolled in this study. Eight had severe pancreatitis (group S) and six had mild pancreatitis (group M). Ten healthy volunteers were also enrolled as the normal control (group C). Serum levels of glucagon and glucagon-related peptides were assessed on the second admission day in groups S and M, and in an early morning fasting state in group C, using glucagon non-specific N-terminal (glucagon-like immunoreactivity: GLI) and specific C-terminal (immunoreactive glucagon: IRG) radioimmunoassays. The molecular forms of these peptides were also estimated using gel filtration chromatography. We then discuss the glucagon processes based on these findings. RESULTS: Serum GLI and IRG in groups S and M were significantly higher than those of group C (P < 0.01), while those in group S were also significantly higher than those in group M (P < 0.05). In all patients in groups S and M, except for only three in group S, a peculiar glicentin-like peptide (GLLP: MW about 8000) other than pancreatic glucagon was observed in IRG gel filtration chromatography, which was clearly absent from group C. CONCLUSIONS: The kinetics and processing of glucagon in patients with acute pancreatitis were quite different from those of healthy subjects. In patients with acute pancreatitis, the peculiar processing of glucagon proceeded in the intestine quite differently from ordinary glucagon processing either in the pancreas or in the intestine, generating a peculiar GLLP.

Effects of extremely early enteral feeding on plasma glicentin levels in very-low-birthweight infants.

AIM: Glicentin, an active component of enteroglucagon, is considered to have a significant trophic action on the intestinal mucosa. We examined the effects of extremely early enteral feedings on the postnatal and postprandial changes in plasma glicentin levels in very-low-birthweight (VLBW) infants. METHODS: We measured the plasma glicentin concentrations before and after feedings at 1 or 2 days, 5 or 6 days and 14 days after birth in 21 VLBW infants. The subjects were randomly divided into an extremely early feeding group, which was started on breast milk within 24 h after birth, and a control group, which was started on breast milk more than 24 h after birth. RESULTS: Plasma basal concentrations of glicentin at 5 or 6 days and at 14 days after birth were significantly higher than those at 1 or 2 days after birth in the early feeding group. The basal glicentin level at 14 days after birth was significantly higher than that at 1 or 2 days. The basal levels at 5 or 6 days and at 14 days after birth in the early feeding group were significantly higher than those in the control group. Plasma glicentin concentrations after feeding were significantly higher than those before feeding at 5 or 6 days and 14 days after birth in the early feeding group, but those levels were significantly higher only at 14 days after birth in the control group. CONCLUSION: Our results suggest that extremely early enteral feedings may play an important role in the development of glicentin secretion and intestinal mucosal growth in the early period of life in VLBW infants.