The rate of gastric emptying is a critical determinant of postprandial glycaemia and, accordingly, is fundamental to maintaining blood glucose homeostasis. Disordered gastric emptying occurs frequently in patients with longstanding type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM). A complex bidirectional relationship exists between gastric emptying and glycaemia--gastric emptying accounts for ∼35% of the variance in peak postprandial blood glucose concentrations in healthy individuals and in patients with diabetes mellitus, and the rate of emptying is itself modulated by acute changes in glycaemia. Clinical implementation of incretin-based therapies for the management of T2DM, which diminish postprandial glycaemia, in part by slowing gastric emptying, is widespread. Other therapies for patients with T2DM, which specifically target gastric emptying include pramlintide and dietary-based treatment approaches. A weak association exists between upper gastrointestinal symptoms and the rate of gastric emptying. In patients with severe diabetic gastroparesis, pathological changes are highly variable and are characterized by loss of interstitial cells of Cajal and an immune infiltrate. Management options for patients with symptomatic gastroparesis remain limited in their efficacy, which probably reflects the heterogeneous nature of the underlying pathophysiology.

In healthy subjects exogenous GLP-1 increases meal retention in the distal stomach and, even when administered in a "low" dose, frequently induces "gastroparesis," and the effects of GLP-1 on postprandial glycemia are predictable on the basis of its effect on GE, supporting the concept that GE is a major target mechanism for the clinical use of incretin mimetics.

The clustering of cardiovascular risk factors associated with abdominal obesity is well established. Although currently lacking a universal definition, the metabolic syndrome describes a constellation of metabolic abnormalities, including abdominal obesity, and was originally introduced to characterize a population at high cardiovascular risk. Adipose tissue is a dynamic endocrine organ that secretes several inflammatory and immune mediators known as adipokines. Dysregulation of adipokine secretion, free fatty acid toxicity, and the site-specific differences in abdominal (visceral) versus subcutaneous fat support abdominal obesity as a causal factor mediating the insulin resistance, increased risk of diabetes, and cardiovascular disease in the metabolic syndrome.

The incretin hormones glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the intestine following oral ingestion of nutrients. Incretins promote insulin secretion, while GLP-1 also inhibits glucagon release and gastric emptying, minimizing postprandial glucose excursions. The incretins share similar effects on the pancreatic β cell; however, there are a number of differences in extrapancreatic actions. Type 2 diabetes (T2DM) is associated with abnormal incretin physiology, and although treatment with GIP is ineffective, GLP-1 effects are preserved. The current incretin-based approaches to T2DM include the GLP-1 agonists that are resistant to the serine protease dipeptidylpeptidase-4 (DPP4), which normally rapidly degrades the incretins, and DPP4 inhibitors (DPP4i). Incretin-based treatments have provoked much interest due to use-associated weight loss (GLP-1 agonists), minimal hypoglycemia, and potential for positive effects on pancreatic β cell biology and the cardiovascular system. However, the long-term safety of these agents has yet to be established. This review outlines the current understanding of incretin biology, available data pertaining to incretin-based treatment in T2DM, and differences between GLP-1 and DPP4i therapy.

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BackgroundHyperglycaemia occurs frequently in critically ill patients without diabetes. We conducted a systematic review and meta-analysis to evaluate whether this ‘stress hyperglycaemia’ identifies survivors of critical illness at increased risk of subsequently developing diabetes.MethodsWe searched the MEDLINE and Embase databases from their inception to February 2016. We included observational studies evaluating adults admitted to the intensive care unit (ICU) who developed stress hyperglycaemia if the researchers reported incident diabetes or prediabetes diagnosed ≥3 months after hospital discharge. Two reviewers independently screened the titles and abstracts of identified studies and evaluated the full text of relevant studies. Data were extracted using pre-defined data fields, and risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled ORs with 95 % CIs for the occurrence of diabetes were calculated using a random-effects model.ResultsFour cohort studies provided 2923 participants, including 698 with stress hyperglycaemia and 131 cases of newly diagnosed diabetes. Stress hyperglycaemia was associated with increased risk of incident diabetes (OR 3.48; 95 % CI 2.02–5.98; I2 = 36.5 %). Studies differed with regard to definitions of stress hyperglycaemia, follow-up and cohorts studied.ConclusionsStress hyperglycaemia during ICU admission is associated with increased risk of incident diabetes. The strength of this association remains uncertain because of statistical and clinical heterogeneity among the included studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1471-6) contains supplementary material, which is available to authorized users.

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Gastrointestinal symptoms and disordered gut motility occur frequently in the diabetic population and are generally regarded as manifestations of gastrointestinal "autonomic dysfunction," although the relationships between both symptoms and dysmotility with abnormal cardiovascular autonomic function are weak. It is now recognized that the blood glucose concentration is both a determinant of and determined by gastrointestinal function. An improved definition of the underlying pathophysiology should facilitate the development of therapies that are targeted more effectively.