Diabetic gastroparesis: pathophysiology and impact on insulin timing choices.

Authors

Francesco Galeano, Andrea Tumminia, Vittorio Oteri, Rosario Le Moli, Tommaso Piticchio, Sabrina Scilletta, Maurizio Di Marco, Antonino Di Pino, Francesco Frasca

Published in

Endocrine. Volume 91. Issue 1. Jun 23, 2026. Epub Jun 23, 2026.

Abstract

Diabetic gastroparesis (DGP) is a chronic and frequently underrecognized complication of diabetes mellitus, characterized by delayed gastric emptying in the absence of mechanical obstruction. It represents a clinically significant manifestation of diabetic autonomic neuropathy and arises from a complex interplay of sustained hyperglycemia, oxidative and nitrosative stress, advanced glycation end-product accumulation, impaired insulin/IGF-1 signaling, lipid dysmetabolism, and inflammatory activation. These mechanisms converge to damage autonomic and enteric neurons, reduce interstitial cells of Cajal density, and disrupt gastric smooth muscle function, ultimately leading to impaired and unpredictable gastric motility. Beyond gastrointestinal symptoms, DGP profoundly affects metabolic control. The altered timing and variability of gastric emptying disturb the physiological coordination between nutrient absorption and insulin pharmacokinetics, generating a temporal mismatch that predisposes patients to early postprandial hypoglycemia followed by late hyperglycemia. This pattern increases glycemic variability, complicates insulin dose adjustment, and contributes to oxidative stress and vascular risk. In this narrative review, we examine the current understanding of DGP pathophysiology and its clinical implications for insulin therapy. We discuss diagnostic strategies, nutritional interventions, and pharmacological treatments, with particular attention to insulin timing modulation. We also analyze the emerging role of diabetes technologies, including continuous glucose monitoring and automated insulin delivery systems, as well as future perspectives such as glucose-responsive insulins and regenerative approaches targeting gastric neuromuscular dysfunction. A mechanism-based, personalized therapeutic strategy may improve metabolic stability and patient outcomes.

PMID:
42334698
Bibliographic data and abstract were imported from PubMed on 23 Jun 2026.

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