Pancreatic and gut hormone responses to mixed meal test in post-chronic pancreatitis diabetes mellitus

AIMS Bile acids (BA) regulate post-prandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The post-prandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effect of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on post-prandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon and ghrelin. METHODS Twelve healthy volunteers underwent a mixed meal test 60 minutes after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg) or no BA in a randomised cross-over study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin and fibroblast growth factor 19 were measured prior to BA administration at -60, 0 (just prior to mixed meal) and 15, 30, 60, 120, 180 and 240 minutes after the meal. RESULTS UDCA and CDCA provoked differential gut hormone responses: UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced post-prandial secretion of GIP, with an associated reduction in post-prandial insulin secretion. CONCLUSIONS Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmedin obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions.

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Abnormal Non Esterified Fatty Acid Suppression After a Mixed Meal Test in Patients With Partial Lipodystrophy

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.003 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A1-A2

Author(s):

Maria Cristina Foss de Freitas ◽

Baris Akinci ◽

Elif A Oral

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Adipose Tissue ◽

Meal Test ◽

Mixed Meal ◽

Partial Lipodystrophy ◽

Mixed Meal Test

Abstract Elevated levels of non-esterified fatty acids (NEFA) have been observed in individuals with several clinical scenarios of insulin resistance, such as in diabetes mellitus and lipodystrophy. Insulin is a well-known stimulator of de novo lipogenesis. Despite the reduction of adipose tissue mass, paradoxically elevated circulating NEFA concentrations have been observed in patients with different lipodystrophy syndromes. Aiming to understand the behavior of NEFA in lipodystrophy versus common Type 2 diabetes mellitus during feeding, we compared NEFA kinetics during a mixed meal test in patients with partial lipodystrophy (PL) and Type 2 diabetes mellitus (DM). We reviewed data from 17 PL patients (13F/4M, ages 12–64) matched by gender and BMI to 20 DM patients (13F/7M, ages 24–72). All patients were evaluated during fasting state and then underwent a mixed meal test (MMT). Blood samples were collected before (fasting) and at 30, 60, 90, 120, and 180 minutes post-meal to measure glucose, insulin, non-esterified free fatty acids (NEFA), and triglyceride levels. Adipose tissue insulin resistance (ADIPO-IR) and homeostatic model of insulin resistance (HOMA-IR) were calculated from the fasting measurements, and the area under the curve (AUC) and maximum percentage of change from baseline were calculated from the MMT data. Fasting insulin and triglyceride (Tg) levels were lower in the DM group compared to the PL group (Insulin: 24.4±13.7 vs. 68.0±67.2 pmol/L, p=0.003 and Tg: 168.0±107.7 vs. 1378.3±1927.3 mg/dL, p<0.001). HOMA-IR was significantly higher in the PL group compared to the DM group (6.0±2.1 vs. 3.3±1.5, p=0.005), as well as ADIPO-IR (297.0±241.1 vs. 115.3±80.1, p=0.03). NEFA, glucose and triglyceride AUC were significantly higher in the PL group compared to the DM group. Patients with PL had higher glucose and triglyceride levels throughout the MMT at all-time points. Interestingly, NEFA levels were similar in both groups at baseline, but the PL group suppressed NEFA less than DM group (54.9±13.3% vs. 69.2±11.1%, p=0.002) despite higher insulin levels. Additionally, we divided the PL group according to the presence of a pathogenic variant in the lamin A gene (n=8) versus those without mutations in this gene (n=9), but there were no notable differences among these subgroups with respect to NEFA levels at baseline or during the meal. These findings support the need to better understand and address the origins of abnormal NEFA kinetics and adipose tissue insulin resistance in PL patients.

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Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis

Pancreas ◽

10.1097/mpa.0000000000001168 ◽

2018 ◽

Vol 47 (10) ◽

pp. 1239-1243 ◽

Cited By ~ 12

Author(s):

Phil A. Hart ◽

Dana K. Andersen ◽

Kieren J. Mather ◽

Alicia C. Castonguay ◽

Mandeep Bajaj ◽

...

Keyword(s):

Pancreatic Cancer ◽

Chronic Pancreatitis ◽

Meal Test ◽

Mixed Meal ◽

Pancreatogenic Diabetes ◽

Mixed Meal Test

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Exenatide Treatment Causes Suppression of Serum Ghrelin Levels following Mixed Meal Test in Obese Diabetic Women

Journal of Diabetes Research ◽

10.1155/2016/1309502 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Figen Topyildiz ◽

Sinem Kiyici ◽

Zulfiye Gul ◽

Deniz Sigirli ◽

Metin Guclu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Area Under The Curve ◽

Meal Test ◽

Mixed Meal ◽

Female Patients ◽

Mixed Meal Test ◽

Serum Ghrelin

Aim. To investigate the effect of exenatide treatment on serum ghrelin levels in obese female patients with type 2 diabetes mellitus.Methods. Fourteen female patients with type 2 diabetes mellitus being treated with metformin and exenatide were enrolled. A mixed meal test was applied to the patients while continuing with their daily medications. Blood samples were taken before and at 60, 120, and 180 minutes following mixed meal test to measure serum total ghrelin, glucose, and insulin levels. The following week, exenatide treatment of the patients was paused for 24 hours and the same experimental procedures were repeated.Results. Serum ghrelin levels were suppressed significantly at 180 minutes with exenatide treatment compared with baseline (294.4±57.5versus234.5±59.4 pg/mL) (p<0.001). Serum ghrelin levels at 180 minutes were statistically different when percentage change in serum ghrelin levels after mixed meal tests with and without exenatide usage were compared (p=0.001). Estimated total area under the curve values for serum ghrelin concentrations was also significantly lower with exenatide compared with omitted treatment (p=0.035).Conclusion. These results suggest that the effect of exenatide on weight loss may be related with the suppression of serum ghrelin levels, which is an orexigenic peptide.

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Gut Hormone Responses to Mixed Meal Test in New-Onset Prediabetes/Diabetes After Acute Pancreatitis

Hormone and Metabolic Research ◽

10.1055/a-0802-9569 ◽

2018 ◽

Vol 51 (03) ◽

pp. 191-199 ◽

Cited By ~ 4

Author(s):

Sayali Pendharkar ◽

Ruma Singh ◽

Aya Cervantes ◽

Steve DeSouza ◽

Sakina Bharmal ◽

...

Keyword(s):

Acute Pancreatitis ◽

Body Fat ◽

Liver Fat ◽

Inhibitory Peptide ◽

Mixed Meal ◽

Gastric Inhibitory Peptide ◽

Gut Hormone ◽

Mixed Meal Test ◽

Hormone Responses ◽

New Onset

AbstractThe study was aimed to investigate gut hormone responses to mixed meal test in individuals with new-onset prediabetes or diabetes after acute pancreatitis (cases) compared with healthy controls, and the effect of body fat parameters. A total of 29 cases and 29 age- and sex-matched healthy controls were recruited. All participants were given standard mixed meal drink and blood samples were collected to measure dipeptidyl peptidase IV, gastric inhibitory peptide, glucagon like peptide-1, insulin, oxyntomodulin, and peptide YY. Body fat parameters were measured using magnetic resonance imaging. Repeated measures and linear regression analyses were conducted in unadjusted and adjusted models. Gastric inhibitory peptide levels were significantly higher whereas oxyntomodulin levels were significantly lower in cases compared with controls in both the unadjusted (p<0.001 and p<0.001, respectively) and adjusted (p<0.001 and p<0.001, respectively) models. In cases, liver fat % contributed up to 13.4% (vs. 2.9% in controls) to variance in circulating levels of gastric inhibitory peptide whereas body mass index - up to 20.8% (vs. 9.9% in controls) in circulating levels of oxyntomodulin. New-onset prediabetes/diabetes after acute pancreatitis is characterised by increased levels of gastric inhibitory peptide and decreased levels of oxyntomodulin. Further, liver fat % and body mass index appear to be the body fat parameters that contribute most significantly to gastric inhibitory peptide and oxyntomodulin levels, respectively.

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Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis

Pancreas ◽

10.1097/mpa.0000000000001215 ◽

2019 ◽

Vol 48 (1) ◽

pp. e9

Keyword(s):

Pancreatic Cancer ◽

Chronic Pancreatitis ◽

Meal Test ◽

Mixed Meal ◽

Pancreatogenic Diabetes ◽

Mixed Meal Test

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Appetite, Glycemia, and Entero-Insular Hormone Responses Differ Between Oral, Gastric-Remnant, and Duodenal Administration of a Mixed-Meal Test After Roux-en-Y Gastric Bypass

Diabetes Care ◽

10.2337/dc17-2515 ◽

2018 ◽

Vol 41 (6) ◽

pp. 1295-1298 ◽

Cited By ~ 2

Author(s):

Daniel Gero ◽

Robert E. Steinert ◽

Hanna Hosa ◽

David E. Cummings ◽

Marco Bueter

Keyword(s):

Gastric Bypass ◽

Gastric Remnant ◽

Meal Test ◽

Mixed Meal ◽

Mixed Meal Test ◽

Hormone Responses

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Pancreatic Hormone Responses to Mixed Meal Test in New-onset Prediabetes/Diabetes After Non-necrotizing Acute Pancreatitis

Journal of Clinical Gastroenterology ◽

10.1097/mcg.0000000000001145 ◽

2020 ◽

Vol 54 (2) ◽

pp. e11-e20 ◽

Cited By ~ 9

Author(s):

Sayali A. Pendharkar ◽

Ruma G. Singh ◽

Sakina H. Bharmal ◽

Marie Drury ◽

Maxim S. Petrov

Keyword(s):

Acute Pancreatitis ◽

Meal Test ◽

Mixed Meal ◽

Mixed Meal Test ◽

Hormone Responses ◽

Pancreatic Hormone ◽

New Onset

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Predictors of Postprandial Hypoglycemia After Gastric Bypass Surgery: a Retrospective Case-Control Study

Obesity Surgery ◽

10.1007/s11695-021-05277-1 ◽

2021 ◽

Author(s):

Elric Zweck ◽

Matthias Hepprich ◽

Marc Y. Donath

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Gastric Bypass Surgery ◽

Glycosylated Hemoglobin ◽

Relative Weight ◽

Meal Test ◽

Retrospective Case ◽

Mixed Meal ◽

Absolute Weight ◽

Mixed Meal Test

Abstract Background Postprandial hypoglycemia after bariatric surgery is an exigent disorder, often impacting the quality of life. Distinguishing clinically relevant hypoglycemic episodes from symptoms of other origin can be challenging. Diagnosis is demanding and often requires an extensive testing such as prolonged glucose tolerance or mixed-meal test. Therefore, we investigated whether baseline parameters of patients after gastric bypass with suspected hypoglycemia can predict the diagnosis. Methods We analyzed data from 35 patients after gastric bypass with suspected postprandial hypoglycemia and performed a standardized mixed-meal test. Hypoglycemia was defined by the appearance of typical symptoms, low plasma glucose, and relief of symptoms following glucose administration. Parameters that differed in patients with and without hypoglycemia during MMT were identified and evaluated for predictive precision using receiver operating characteristic (ROC) areas under the curve (AUC). Results Out of 35 patients, 19 (54%) developed symptomatic hypoglycemia as a result of exaggerated insulin and C-peptide release in response to the mixed-meal. Hypoglycemic patients exhibited lower glycosylated hemoglobin A1c (HbA1c) and higher absolute and relative weight loss from pre-surgery to study date. HbA1c and absolute weight loss alone could achieve acceptable AUCs in ROC analyses (0.76 and 0.72, respectively) but a combined score of absolute weight loss divided by HbA1c (0.78) achieved the best AUC. Conclusions HbA1c and weight loss differed in patients with and without symptomatic hypoglycemia during mixed-meal test. These baseline parameters could be used for screening of postprandial hypoglycemia in patients after gastric bypass and may facilitate the selection of patients requiring further evaluation. Graphical abstract

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Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals

British Journal Of Nutrition ◽

10.1017/s0007114516004475 ◽

2017 ◽

Vol 117 (1) ◽

pp. 48-55 ◽

Cited By ~ 20

Author(s):

Siôn A. Parry ◽

Jennifer R. Smith ◽

Talitha R. B. Corbett ◽

Rachel M. Woods ◽

Carl J. Hulston

Keyword(s):

Glycaemic Control ◽

High Energy ◽

Tolerance Test ◽

High Fat ◽

Short Term ◽

Mixed Meal ◽

Gut Hormone ◽

Before And After ◽

Hormone Responses ◽

Mixed Meal Tolerance Test

AbstractObesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding. Nine healthy individuals (five males, four females) performed a mixed meal tolerance test (MTT) before and after consuming a high-fat (65 %), high-energy (+50 %) diet for 7 d. Measurements of plasma glucose, NEFA, acylated ghrelin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and serum insulin were taken before (fasting) and at 30-min intervals throughout the 180-min MTT (postprandial). Body mass increased by 0·79 (sem 0·14) kg after high-fat overfeeding (P<0·0001), and BMI increased by 0·27 (sem 0·05) kg/m2 (P=0·002). High-fat overfeeding also resulted in an 11·6 % increase in postprandial glucose AUC (P=0·007) and a 25·9 % increase in postprandial insulin AUC (P=0·005). Acylated ghrelin, GLP-1 and GIP responses to the MTT were all unaffected by the high-fat, high-energy diet. These findings demonstrate that even brief periods of overeating are sufficient to disrupt glycaemic control. However, as the postprandial orexigenic (ghrelin) and anorexigenic/insulintropic (GLP-1 and GIP) hormone responses were unaffected by the diet intervention, it appears that these hormones are resistant to short-term changes in energy balance, and that they do not play a role in the rapid reduction in glycaemic control.

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