Speed Of Gastric Emptying Research Articles

197-OR: ADO09, a Coformulation of Insulin A21G and Pramlintide (Pram), Improves Blood Glucose Control and Reduces Body Weight in Subjects with T1D

ADO09 is a co-formulation of Pram and insulin A21G developed to deliver the positive effects of Pram without additional injections. This double-blind randomized cross-over trial investigated the effects of pre-meal ADO09 vs. insulin aspart (ASP) on mixed meal tolerance tests (MMTT) and CGM over 24 days in 16 T1D subjects (BMI 30.5 ± 3.1 kg/m²) using daily prandial insulin doses of 45-75 U. ADO09 reduced incremental AUC glucose 0-4h during MMTT by 69% (p=0.006) and deltaPG 1h by 82 mg/dL (p<0.001) vs. ASP (figure). Post-meal glucagon levels were lowered by up to 85% and speed of gastric emptying (acetaminophen absorption) reduced by >50% with ADO09. CGM over the final 3 weeks showed higher time in range (+58 min), lower time >180 mg/dL (-71 min) and slightly higher time <70 mg/dL (+13mins) with ADO09. Body weight decreased by 1.6 kg with ADO09 (p=0.007) as did daily prandial insulin doses (-12 U vs. ASP, median 35.0 U vs. 47.3; p=0.0004). Slightly more hypoglycemic episodes were noted with ADO09 (n=96 vs. 79) with no difference in nocturnal hypoglycemia. While more adverse events (AEs) occurred with ADO09 (22 vs. 10), most AEs were mild and of gastro-intestinal nature (nausea, decreased appetite).In conclusion, ADO09 improved blood glucose control and reduced both body weight and prandial insulin doses vs. insulin aspart in T1D subjects with high prandial insulin needs.View largeDownload slideView largeDownload slide DisclosureG. Meiffren: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. J. Devries: Advisory Panel; Self; ADOCIA, Novo Nordisk Inc., Zealand Pharma A/S, Speaker’s Bureau; Self; Novo Nordisk Inc. T. Heise: Advisory Panel; Self; Novo Nordisk A/S, Valbiotis, Research Support; Self; ADOCIA, Afon Technology Ltd., AstraZeneca, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, Julphar, Mylan N. V., Nestlé, Neuraly, Nordic Bioscience, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker’s Bureau; Self; Novo Nordisk A/S. G. Andersen: None. R. Eloy: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. C. Mégret: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. S. Famulla: None. C. Seroussi: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. Y. Chan: Employee; Self; ADOCIA. M. Gaudier: Employee; Self; ADOCIA, Stock/Shareholder; Self; ADOCIA. O. Soula: Employee; Self; ADOCIA, Employee; Spouse/Partner; ADOCIA, Stock/Shareholder; Self; ADOCIA, Stock/Shareholder; Spouse/Partner; ADOCIA.

**-Postprandial pancreatic [11C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release

Purpose[S-methyl-11C]-L-methionine ([11C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [11C]MET uptake.MethodsNineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [11C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated.ResultsThe uptake of [11C]MET in the pancreas was significantly higher (p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects (p < 0.0001). Paracetamol AUC30 correlated with the SUVmax increment between 15 and 30 minutes (R2 = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [11C]MET. Total integrated SUVmax correlated with insulin AUC60 (R2 = 0.66,p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC60 and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of 11C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R2 = 0.78, p < 0.0001).ConclusionPostprandial [11C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function.

First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying

Background—Ethanol undergoes a first pass metabolism (FPM) in the stomach and liver. Gastric FPM of ethanol primarily depends on the activity of gastric alcohol dehydrogenase (ADH). In addition, the speed...

The role of gastrointestinal factors in alcohol metabolism.

Although the liver is the major organ responsible for ethanol metabolism, such metabolism also occurs in the gastrointestinal (GI) tract. However, compared to the liver, GI metabolism of ethanol is quantitatively much lower. Various enzyme systems have been characterized in GI mucosal cells including various isozymes of alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP 2E1) and catalase. Gastric ADH activity is one factor by which first pass metabolism (FPM) is influenced and its activity is modulated by genetics, gender, age, drugs and gastric morphology. Another important factor in FPM of ethanol is the speed of gastric emptying. In addition to mucosal ethanol metabolism, ethanol can also be oxidized by many bacterial species in the upper GI tract including oropharynx and stomach as well as in the large intestine. GI metabolism of ethanol may influence systemic bioavailability of ethanol and may lead to local toxicity most likely mediated by acetaldehyde. Such toxicity could be of importance in ethanol-associated carcinogenesis.

The Influence of Pregnancy and Contraceptive Steroids on the Biliary Tract and Its Reference to Cholesterol Gallstone Formation

The evidence that pregnancy and the use of contraceptive steroids are associated with increased risk of cholesterol gallstones is reviewed from a physiologic viewpoint. Hepatobiliary functions known to be involved in gallstone formation are physical and chemical composition of bile; nucleation retention and crystal growth; decreased gallbladder motility; enterohepatic circulation of bile acids; speed of gastric emptying and intestinal transit time. In pregnancy many changes in bile acid concentration and pool size have been documented in animals and women with conflicting results. Late pregnant women have enlarged gall bladders that empty slowly in response to food and prolonged intestinal transit time but not gastric emptying has been reported. Cholesterol saturation of bile is increased. Estrogens are known to bind to receptors in hepatocytes and gall bladder. During estrogen administration cholesterol saturation in bile increases the bile acid pool size decreases synthesis of bile acids declines and recycling of bile acids increases with increased fecal losses of bile acids. Progestins have the opposite effects favoring bile acid synthesis. Progesterone has a quieting effect on smooth muscle possibly causing some of the complaints of pregnancy and oral contraception such as heartburn and constipation. These changes with the possibility that emptying of the gall bladder is incomplete give cause for the association between oral contraception and gallstones.

Relative role of pyloroplasty size, truncal vagotomy, and milk meal volume in canine gastric emptying.

The gastric emptying of 10, 20, or 40 ml/kg body mass milk meals was measured before and after Heineke-Mikulicz pyloroplasty of 3, 5, or 7 cm (6 dogs) or truncal vagotomy (3 dogs). The pyloroplasty group then underwent vagotomy, following which the tests were repeated. Initial gastric emptying (in the first 10 min) was increased after 5-and 7-cm pyloroplasties (P<0.01) and particularly after vagotomy with all sizes of pyloroplasty (P=0.001). Regardless of the volume of meal used, after vagotomy and pyloroplasty there was a 51–63% decrease in intragastric volume within the first 10 min. Increased duodenogastric reflux occurred in those dogs who showed rapid initial gastric emptying. After the first 10 min all groups were shown to have virtually normal gastric emptying, except the truncal vagotomy group in which gastric emptying was delayed (P<0.05). It is the combination of pyloroplasty with vagotomy which is required to produce the very rapid initial gastric emptying of a liquid meal following vagotomy with pyloroplasty. It is concluded that two mechanisms control the gastric emptying of a milk meal. The first acts quickly, is dependent on an intact pylorus, and is influenced by the intragastric volume; the second is a more slowly acting mechanism, requiring up to 10 min to have its effect, and is not dependent on an intact pylorus or the intragastric volume. After vagotomy and pyloroplasty, the speed of gastric emptying in the first 10 min is proportional to the original meal volume, and therefore the therapy of postvagotomy diarrhea and dumping with small frequent meals seems rational.