Rapid Gastric Emptying of a Solid Pancake Meal in Type II Diabetic Patients

Schwartz, Joyce G.; Green, G M; Guan, Difu; McMahan, C. Alex; Phillips, William T.

doi:10.2337/diacare.19.5.468

Cited by 106 publications

(72 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[114][115][116] Mismatch between the rate of glucose appearance in the systemic circulation and the rate of glucose disappearance can account for as much as 34% of the variability in peak postprandial glucose concentrations following glucose ingestion in normal glucose tolerant subjects. 114,117,118 The normal physiologic response to hypoglycemia is to accelerate gastric emptying. This increases nutrient delivery into the systemic circulation and restores normal plasma glucose concentrations.…”

Section: Correction Of Accelerated Gastric Emptyingmentioning

confidence: 99%

“…Despite hyperglycemia, newly diagnosed T2DM patients often have an accelerated rate of gastric emptying that can exceed the rate of gastric emptying in NGT subjects by 25%-30%. [116][117][118][119] GLP-1, which is deficient and to which the beta cell is resistant in T2DM, is a potent inhibitor of gastric emptying, and slows the rate of glucose appearance in the systemic circulation. 86 GLP-1 agonists, such as exenatide, delay gastric emptying in healthy, nondiabetic subjects 93 and in individuals with T2DM.…”

Section: Correction Of Accelerated Gastric Emptyingmentioning

confidence: 99%

“…In contrast, patients with newly diagnosed T2DM, despite hyperglycemia, often have an abnormally accelerated gastric emptying rate. 42 In this review, we first explore the use of pioglitazone for the treatment of T2DM, and then examine therapies designed to augment plasma GLP-1 levels.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment

Triplitt¹,

Cersósimo²,

DeFronzo³

2010

VHRM

View full text Add to dashboard Cite

Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in type 2 diabetes mellitus (T2DM). Pioglitazone is a potent insulin sensitizer, improves pancreatic beta cell function and has been shown in several outcome trials to lower the risk of atherosclerotic and cardiovascular events. Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. Alogliptin is a new DPP-4 inhibitor that reduces glycosylated hemoglobin (HbA 1c ), is weight neutral, has an excellent safety profile, and can be used in combination with oral agents and insulin. Alogliptin has a low risk of hypoglycemia, and serious adverse events are uncommon. An alogliptin-pioglitazone combination is advantageous because it addresses both insulin resistance and islet dysfunction in T2DM. HbA 1c reductions are significantly greater than with either monotherapy. This once-daily oral combination medication does not increase the risk of hypoglycemia, and tolerability and discontinuation rates do not differ significantly from either monotherapy. Importantly, measures of beta cell function and health are improved beyond that observed with either monotherapy, potentially improving durability of HbA 1c reduction. The alogliptin-pioglitazone combination represents a pathophysiologically sound treatment of T2DM.

show abstract

Section: Correction Of Accelerated Gastric Emptyingmentioning

confidence: 99%

Section: Correction Of Accelerated Gastric Emptyingmentioning

confidence: 99%

See 1 more Smart Citation

Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment

Triplitt¹,

Cersósimo²,

DeFronzo³

2010

VHRM

View full text Add to dashboard Cite

show abstract

“…Gastroparesis can occur secondary to drugs or systemic disease as a complication of diabetes or remain idiopathic (21). Accelerated gastric emptying is also observed in subsets of patients with symptoms suggestive of functional dyspepsia, or dumping, as well as in a subset of patients with diabetes particularly early after diagnosis (12,25). Accelerated gastric emptying is also observed in animal models of diabetes (7).…”

mentioning

confidence: 92%

A gamma variate model that includes stretched exponential is a better fit for gastric emptying data from mice

Bajzer

Gibbons

Coleman

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Bajzer Ž, Gibbons SJ, Coleman HD, Linden DR, Farrugia G. A gamma variate model that includes stretched exponential is a better fit for gastric emptying data from mice. Am J Physiol Gastrointest Liver Physiol 309: G162-G170, 2015. First published June 4, 2015; doi:10.1152/ajpgi.00280.2014.-Noninvasive breath tests for gastric emptying are important techniques for understanding the changes in gastric motility that occur in disease or in response to drugs. Mice are often used as an animal model; however, the gamma variate model currently used for data analysis does not always fit the data appropriately. The aim of this study was to determine appropriate mathematical models to better fit mouse gastric emptying data including when two peaks are present in the gastric emptying curve. We fitted 175 gastric emptying data sets with two standard models (gamma variate and power exponential), with a gamma variate model that includes stretched exponential and with a proposed two-component model. The appropriateness of the fit was assessed by the Akaike Information Criterion. We found that extension of the gamma variate model to include a stretched exponential improves the fit, which allows for a better estimation of T 1/2 and Tlag. When two distinct peaks in gastric emptying are present, a two-component model is required for the most appropriate fit. We conclude that use of a stretched exponential gamma variate model and when appropriate a two-component model will result in a better estimate of physiologically relevant parameters when analyzing mouse gastric emptying data. motility; smooth muscle; gastrointestinal tract; empirical mathematical models THE MEASUREMENT OF GASTRIC emptying in human subjects and animal models of disease is an important technique for understanding the changes in gastric motility that occur under normal physiological conditions, in disease, or in response to drugs. Acute physiological changes in gastric emptying can be identified in response to the content and nature of a meal including the effects of calories, osmolarity, lipid, protein, and carbohydrate content (9). Determination of gastric emptying has clinical relevance since the delay of gastric emptying of solids is required for positive diagnosis of gastroparesis. Gastroparesis can occur secondary to drugs or systemic disease as a complication of diabetes or remain idiopathic (21). Accelerated gastric emptying is also observed in subsets of patients with symptoms suggestive of functional dyspepsia, or dumping, as well as in a subset of patients with diabetes particularly early after diagnosis (12,25). Accelerated gastric emptying is also observed in animal models of diabetes (7). Prokinetic agents have been identified and studied by using gastric emptying tests in experimental animals and candidate drugs have been tested for unwanted effects on gastric emptying (24).Several noninvasive tests have been developed to follow gastric emptying in humans including scintigraphy and breath tests (5, 29), and some of these tests have been applied for ...

show abstract

“…GLP-1 is secreted in response to a meal or glucose challenge by the L-cells of the intestine lining the colon and ileum [Ørskov et al, 1986;Holst, 1999;Drucker, 1998]. The glucoregulatory effects of GLP-1 include enhanced glucose-dependent insulin secretion, suppression of glucose-dependent glucagon secretion (in the postmeal state), and regulation of gastric emptying, which can be paradoxically accelerated in some patients with diabetes [Holst, 1999;Zander et al, 2002;Parkes et al, 2001;Rayner et al, 2001;Schwartz et al, 1996]. Furthermore, in cell lines, isolated pancreatic islets, and animal models, GLP-1 promotes neogenesis and cell proliferation.…”

Section: The Incretin Effectmentioning

confidence: 99%

Management of type 2 diabetes: the role of incretin mimetics

Holcombe¹,

Kim²,

Stonehouse³

et al. 2006

Drug Development Research

View full text Add to dashboard Cite

Current strategies for the treatment of type 2 diabetes target deficient insulin secretion and insulin resistance, but have not been shown to correct the progressive b-cell dysfunction characteristic of the disease. Traditionally, type 2 diabetes is treated in a stepwise manner with medical nutrition therapy, oral anti-diabetes therapies, and ultimately exogenous insulin. These therapies improve glycemic control, but are unable to prevent or delay either deterioration in glucose control or the decline of b-cell function. Despite the use of current anti-diabetes therapies, patients with type 2 diabetes are likely to experience deteriorating glycemic control and substantial weight gain. In addition to these issues, patients treated with insulin secretogogues such as sulfonylureas and exogenous insulin are subject to an increased risk of hypoglycemia. Moreover, insulin-based therapies do not fully address the complex hormonal irregularities, such as glucagon hypersecretion, that characterize type 2 diabetes. In view of the drawbacks associated with current treatment strategies, new therapies are being developed that may provide more durable glycemic control with associated reductions in body weight. These new therapies include the incretin mimetics, agents that share many of the glucoregulatory effects of the incretin hormones such as glucagon-like peptide-1 (GLP-1). Leveraging the physiological functions of incretin hormones such as GLP-1 may potentially benefit the ever growing number of patients with type 2 diabetes. Drug Dev. Res. 67:545-552, 2006.

show abstract

Rapid Gastric Emptying of a Solid Pancake Meal in Type II Diabetic Patients

Abstract: Type II diabetic patients with no clinical evidence of neuronal dysfunction have a significantly more rapid rate of gastric emptying of a solid high-carbohydrate meal when compared with nondiabetic control subjects.

Cited by 106 publications

References 7 publications

Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment

Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment

A gamma variate model that includes stretched exponential is a better fit for gastric emptying data from mice

Management of type 2 diabetes: the role of incretin mimetics

Contact Info

Product

Resources

About