Normal and disordered gastric emptying in diabetes: recent insights into (patho)physiology, management and impact on glycaemic control

Abstract

Gastric emptying is a major determinant of postprandial blood glucose, accounting for ~35% of variance in peak glucose in both healthy individuals and those with type 2 diabetes. Gastric emptying is frequently disordered in individuals with diabetes (both abnormally delayed and accelerated). Delayed gastric emptying, i.e. diabetic gastroparesis, may be linked to upper gastrointestinal symptoms for which current treatment remains suboptimal; pharmacological acceleration of delayed emptying is only weakly associated with symptom improvement. Accordingly, the relationship between symptoms and delayed gastric emptying is not simply ‘cause and effect’. In insulin-treated patients, disordered gastric emptying, even when not associated with gastrointestinal symptoms, can cause a mismatch between the onset of insulin action and the availability of absorbed carbohydrate, leading to suboptimal glycaemic control. In patients with type 2 diabetes, interventions that slow gastric emptying, e.g. glucagon-like peptide-1 receptor agonists, reduce postprandial blood glucose. This review focuses on recent insights into the impact of gastric emptying on postprandial blood glucose, effects of diabetes therapy on gastric emptying and the management of disordered gastric emptying in diabetes. In view of the broad relevance of gastric emptying to diabetes management, it is important that future clinical trials evaluating novel therapies that may affect gastric emptying should quantify the latter with an appropriate technique, such as scintigraphy or a stable isotope breath test. Graphical abstract

Prevalence of gastroparesis in diabetic patients: a systematic review and meta-analysis

“…Due to the lack of standardised diagnostic criteria, it is frequently misdiagnosed as a gastrointestinal disorder, leading to inadequate treatment. DM-DGP affects the absorption and metabolism of oral medication, leading to poor glycemic control and further accelerating the course of diabetes, creating a vicious cycle 11 . Therefore, this meta-analysis was conducted to comprehensively analyse the prevalence of DGP in DM globally to help shape healthcare policy.…”

Review article: An analysis of the pharmacological rationale for selecting drugs to inhibit vomiting or increase gastric emptying during treatment of gastroparesis

“…Symptoms may depend on whether the ingested meal is preferentially distributed to the proximal or distal stomach, 3 potentially reflecting their different structures and functions, and how vagal signalling from these regions is interpreted within the brain 4 . The delayed gastric emptying can make it difficult to manage patients, especially those with diabetic gastroparesis, affecting the availability of ingested carbohydrate and delivery of drugs needed to optimise glycaemic control 5 . When gastric emptying of meals is within normal range, without identified cause, patients are diagnosed with chronic unexplained nausea and vomiting (CUNV), or ‘gastroparesis‐like’ 6 .…”

“…4 The delayed gastric emptying can make it difficult to manage patients, especially those with diabetic gastroparesis, affecting the availability of ingested carbohydrate and delivery of drugs needed to optimise glycaemic control. 5 When gastric emptying of meals is within normal range, without identified cause, patients are diagnosed with chronic unexplained nausea and vomiting (CUNV), or 'gastroparesis-like'. 6 Gastroparesis and functional dyspepsia (FD) may be interchangeable.…”

The novel GIP, GLP‐1 and glucagon receptor agonist retatrutide delays gastric emptying

“…6 GE is a major determinant of glycemic response after food intake. 7 Delayed GE may reduce food intake and subsequently impact weight loss. 8 While GLP-1 RAs and the GIP/GLP-1 RA tirzepatide transiently delay GE, the effects of retatrutide are unknown.…”