Gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, is a recognized complication of long-standing diabetes. Its pathophysiology involves, amongst other mechanisms, autonomic dysfunction due to vagal nerve damage, impaired smooth muscle contractility, and hormonal dysregulation of intestinal motility. During Ramadan, fasting causes significant dietary changes due to prolonged fasting and the consumption of large meals for Iftar (breaking of fast), which may unmask or worsen gastroparesis symptoms in individuals with diabetes. Symptoms such as early satiety, bloating, nausea, and glycemic fluctuations can further complicate diabetes management during fasting. This paper highlights the relationship between Ramadan fasting and gastroparesis in individuals with diabetes, exploring underlying mechanisms, clinical manifestations, diagnostic approaches, and management strategies. A multidisciplinary approach involving dietary modifications, medication adjustments, lifestyle changes, and individualized medical counseling is essential for safe fasting, alongside the option to avoid fasting in individuals who are deemed too high at risk for fasting. Further research is needed to assess the prevalence of subclinical gastroparesis in fasting individuals with diabetes and to optimize risk stratification and management in these patients.

Delayed gastric emptying is a substantial challenge for people with diabetes, affecting quality of life and blood glucose regulation. The complication is underdiagnosed, and current diagnostic tests are expensive or time consuming or have modest accuracy. The assessment of glycemic variations has potential use in gastroparesis screening. The aim of this study was to investigate the differences in glycemic variability between type 1 diabetes patients with gastroparesis and without a diagnosis of gastroparesis and the potential for using a classification model to differentiate between groups.

Continuous glucose monitoring (CGM) from 425 patients with diabetes was included in the analytic cohort, including 16 patients with a diagnosis of gastroparesis and 409 without a known gastroparesis diagnosis. Sixteen features (9 daytime features and 7 nighttime features) describing glucose dynamics were extracted to assess differences between patients with and without a diagnosis of gastroparesis. A logistic regression model was trained using forward selection and cross-validation.

In total, 3 features were included in the model utilizing forward selection of features and cross-validation: mean absolute glucose (MAG), span, and standard deviation during the night. The Receiver operating characteristic (ROC) AUC for the classification model was 0.76.

Gastroparesis seems to have an impact on glucose variability, especially during the night. Moreover, CGM could possibly be used as a part of the screening process for delayed gastric emptying, but more studies are needed to determine a realistic accuracy.

Gastroparesis is associated with unpredictable gastric emptying and can lead to erratic glucose profiles and negative impacts on quality-of-life. Many people with gastroparesis are unable to meet glycemic targets and there is a need for new approaches for this population. Hybrid closed-loop systems improve glucose control and quality-of-life but evidence for their use in people with diabetic gastroparesis is limited.

We present a narrative review of the challenges associated with type 1 diabetes management for people with gastroparesis and present a case series of 7 people with type 1 diabetes and gastroparesis. We compare glycemic control before and during the first 12 months of hybrid closed-loop therapy. Data were analyzed using electronic patient records and glucose management platforms. We also discuss future advancements for closed-loop systems that may benefit this population.

Five of 7 patients had data available for time in range before and during hybrid closed-loop therapy, and all had an improvement in percentage time in target glucose range, with the overall mean time in range increasing from 26.0% ± 15.7% to 58.4% ± 8.6% during HCL use, (P = .004). There were significant reductions in HbA1c (83 ± 9 mmol/mol to 71 ± 14 mmol/mol) and mean glucose from 13.0 ± 1.7 mmol/L (234 ± 31 mg/dL) to 10.0 ± 0.7 mmol/L (180 ± 13 mg/dL) with use of a hybrid closed-loop system. Importantly, this was achieved without an increase in time in hypoglycemia (P = .50).

Hybrid closed-loop systems may represent a valuable approach to improve glycemic control for people with type 1 diabetes and gastroparesis. Prospective studies are required to confirm these findings.

In addition to the continuous use, the intermittent use of continuous glucose monitoring (CGM) is an application of CGM, expanding the typical medical use cases. There are a variety of reasons and occasions that speak in favor of using CGM only for a limited time. To date, these circumstances have not been sufficiently discussed. In this article, we define discontinuous or intermittent CGM use, provide reasons for using it, and expand on the benefits and possibilities of using CGM on a temporary basis. We aim to draw attention to this important topic in the discussion of CGM use and give examples for a different method of CGM use. As well, we would like to foster the allocation of CGM to the right patient groups and indications, especially in cases of limited resources. From a global point of view, intermittent CGM use is more likely to occur than continuous use, primarily for economic reasons.

This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.

Management of a patient's blood glucose or metabolism in nuclear medicine studies has become an integral aspect of daily work primarily due to the increasing use of F-18 flurodeoxyglucose (FDG) positron emission tomography (PET). Newer tracers such as F-18 Fluciclovine and C-11 Choline, are in theory subject to metabolic shifts and changes based on patients' insulin levels, and also require attention to achieving optimum patient preparation. Metabolic derangements can also affect other studies, such as gastric emptying (GE), the results of which are dependent upon the patient's blood glucose level during the time of imaging. The growing variety of diabetic medications has increased the complexity of the instructions which need to be given to patients. Current guidelines for patient preparation were developed in the past and have only slowly evolved with the introduction of newer oral medications. In addition to older insulin formulations newer formulations with different profiles of onset, duration, and consistency of action are being used. The wide spectrum of newer drugs now in use for treating diabetes has not been accompanied by any updated consensus on how to manage these drugs for imaging studies which require blood glucose level management. In this article we review these newer diabetes medications primarily to raise awareness of the changing landscape. Our focus will be on suggestions to optimize patient preparation and management for these studies. For each scenario, our suggestions will be given as summary proposals for best patient management. Our hope is that this discussion will stimulate multicenter studies to provide data to support new practice guidelines for metabolically dependent nuclear medicine procedures.

This study aimed to investigate the effect of AMPK on apoptosis and energy metabolism of gastric smooth muscle cells in diabetic rats and to explore the role of AMPK in the pathogenesis of diabetic gastroparesis (DGP). After establishment of a diabetic rat model, rats were divided into normal control (NC), 4-week (DM4W), 6-week (DM6W), and 8-week (DM8W) diabetic model groups. The gastric residual pigment ratio, intestinal transit rate, and intestinal propulsion rate in each group were detected to confirm the successful establishment of the DGP model. The spontaneous contraction in isolated gastric smooth muscle strips of the NC and DM8W groups was experimentally observed. The expression of phospho-AMPK, AMPK, phospho-LKB1, LKB1, phospho-TAK1, TAK1, and CaMMKβ in rat gastric smooth muscle tissues was detected by western blot analysis; ADP, AMP, ATP contents, and the energy charge were detected using Elisa; and apoptosis of gastric smooth muscle cells was detected by flow cytometry. The rat gastric smooth muscle cells were cultured in vitro, and treated with an AMPK inhibitor and an agonist. At 24 and 48 h, the effects of AMPK on apoptosis and energy metabolism of gastric smooth muscle cells were observed. Reduced spontaneous contractions, AMPK activation, cell apoptosis, and energy metabolism disorders were observed in gastric smooth muscle tissues of a diabetic rat, and AMPK activation was associated with an increased ratio of ADP/ATP, AMP/ATP, LKB1 activity, and CaMMKβ expression. From in vitro cell culture experiments, we found that AMPK activation of high-glucose conditions promoted cell apoptosis. Inhibition of AMPK had no obvious effect on apoptosis at the early stage with high glucose, but the inhibitory effect was significant at the late stage with high glucose. AMPK can regulate both mitochondrial metabolism and glycolysis pathways under high-glucose conditions. During the early stage with high glucose, AMPK was the main promotion factor of the mitochondrial metabolism pathway, but did not increase the ATP production, AMPK also promoted the glycolysis pathway. During the late stage with high glucose, AMPK was a major inhibitor of the mitochondrial pathway, and still played a role in promoting the glycolytic pathway, which acted as the main regulator. Apoptosis and energy metabolism disorders were present in gastric smooth muscle cells during the occurrence of DGP. Under high-glucose condition, AMPK was activated, which can promote apoptosis, change the energetic metabolism pathway of cells, inhibit mitochondrial energy metabolism, and promote glycolysis.

This article is a comprehensive review of diabetic gastroparesis, defined as delayed or disordered gastric emptying, including basic principles and current trends in management. This review includes sections on anatomy and physiology, diagnosis and differential diagnosis as well as management and current guidelines for treatment of diabetic gastroparesis. Diabetic gastroparesis (DGp) is a component of autonomic neuropathy resulting from long-standing poorly controlled type 1 and type 2 diabetes. The diagnostic workup of DGp first excludes obstruction and other causes including medications that may mimic delayed/disordered gastric emptying. Targeting nutrition, hydration, symptomatic relief and glycemic control are mainstays of treatment for DGp. Additionally, optimal treatment of DGp includes good glycemic management, often involving customizing insulin delivery using basal-bolus insulin and technology, including sensor-augmented pumps and continuous glucose monitoring systems. Prokinetic medications may be helpful in DGp symptoms, although only limited number of medications is currently available in the USA. Selected medication-refractory patients with DGp may benefit from gastric neuromodulation, and some from surgical interventions including pyloric therapies that can also be done endoscopically. As is true of any of the diabetic complications, prevention of DGp by early and optimal glycemic control is more cost-effective.Funding: Hansa Medcell, India.

To better understand the prevalence and impact of gastroparesis in the T1D Exchange clinic registry database.

The analysis included 7107 adult participants with T1D across 45 sites (median age 46years. and median duration 24years). Linear and logistic regression models were used to assess the association of gastroparesis vs. no gastroparesis (obtained from medical record) with demographic characteristics, glycemic control and diabetes complications.

Among 7107 registry participants, 340 (4.8%) had a clinical diagnosis of gastroparesis. Females were more likely to have gastroparesis compared with males (5.8% vs. 3.5%, P<0.001). Participants with gastroparesis compared with those without gastroparesis were older (median age 49.4 vs. 45.3years, P<0.001), had a longer duration of T1D (median duration 32 vs. 23years, P<0.001), higher mean HbA1c (8.1% vs. 7.7% [65 vs. 61mmol/mol], P<0.001), more frequent severe hypoglycemia (25% vs. 11% with ≥1 event in the past 12months, P<0.001), lower socio-economic status, less likely to be using CGM and insulin pump and greater prevalence of microvascular and neuropathic complications than participants without gastroparesis.

Gastroparesis is associated with higher risk of severe hypoglycemia despite higher HbA1c levels than in T1D patients without gastroparesis. The increased presence of multiple long-term complications and overall poor glycemic control in these subjects emphasizes the need to establish diagnostic protocols for earlier diagnosis, achieve tighter glycemic control with more extensive use of insulin pumps and continuous glucose monitoring, and the need for wider availability of medical therapies for treatment of diabetic gastroparesis.

In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients.

Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes.

At baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life.

Baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.

In type 1 diabetic patients, insulin secretory capacity, meals and physical activity correlate with glycemic variability. Autonomic function associated with gastrointestinal motility and counterregulatory hormone secretion is another candidate which correlates with glucose variability. The aim of this study is to clarify a new clinical parameter associated with glycemic variability in insulin-depleted patients with type 1 diabetes.

We studied 31 inpatients with type 1 diabetes. We evaluated glycemic variability calculated by continuous glucose monitoring, clinical parameters and the coefficient of variation of R-R interval (CVR-R). Glycemic variability was also assessed during the daytime and nighttime.

The CVR-R showed a significant negative correlation with the whole-day standard deviation (SD) (r = -0.50, p = 0.007), mean amplitude of glycemic excursions (MAGE) (r = -0.47, p=0.011), M-value (r = -0.38, p = 0.048) and mean of daily differences (MODD) (r = -0.59, p = 0.001). The CVR-R also showed a significant negative correlation with the nighttime SD (r = -0.59, p = 0.001), MAGE (r = -0.47, p=0.011), M-value (r = -0.53, p = 0.004) and MODD (r = -0.65, p = 0.0003). And furthermore, the CVR-R also showed a significant negative correlation with the daytime SD (r = -0.44, p = 0.019) and MAGE (r = -0.50, p = 0.006), but not with the daytime M-value or MODD. The nighttime SD was significantly higher in patients with diabetic polyneuropathy than in patients without it (p = 0.016), while the CVR-R was significantly lower in patients with polyneuropathy than in patients without it (p = 0.009).

CVR-R is closely correlated with glycemic variability, especially during nighttime, in insulin-depleted patients with type 1 diabetes. Measuring CVR-R may help us to presume the degree of glycemic variability in those patients.

Gastroparesis is a well-known diabetic complication. The pathogenesis is not fully understood. However, it is important to early diagnose these patients. This study evaluated the plasma glucose response after a test meal, and gastrointestinal (GI) symptom severity in patients with clinical suspicion of diabetic gastroparesis, and assessed its usefulness to predict gastroparesis. In all, 83 subjects with insulin-treated diabetes mellitus (DM) type 1 and 2 were included; 53 subjects had gastroparesis and 30 had normal gastric emptying determined by gastric scintigraphy. GI symptom severity during the preceding 2 weeks was evaluated with a validated questionnaire. The test meal consisted of 100 g meat, 40 g pasta, 150 g carrot, and 5 g oil. The subjects ingested the meal under fasting conditions, and plasma glucose was followed during 180 minutes. Patients with gastroparesis demonstrated a blunted plasma glucose response after a test meal versus patients with normal gastric emptying (P < .005), reflected by lower maximum increase in plasma glucose response and incremental area under the curve of the plasma glucose, but a similar time to the maximum plasma glucose level. All GI symptoms were more severe in patients with gastroparesis. GI symptom severity had the best discriminative value to identify patients with gastroparesis with an area under the receiver operating curve of 0.83 (optimal cutoff: sensitivity 87%, specificity 80%). Patients with diabetic gastroparesis have a blunted postprandial plasma glucose response. Combining this information with the presence of GI symptoms can help clinicians identify diabetic patients with gastroparesis.

Colesevelam's glucose-lowering mechanism of action is not completely understood. Clinical trials of colesevelam suggest that its mechanism, and often adverse effects, differ from those of other oral antidiabetes drugs. Colesevelam does not affect insulin sensitivity (unlike thiazolidinediones), insulin secretion (unlike sulfonylureas and meglitinides), or early insulin response or glucagon (unlike dipeptidyl peptidase-4 inhibitors). Colesevelam may have some effect on glucose absorption, but likely via a different mechanism than α-glucosidase inhibitors. Colesevelam and metformin have similarities regarding hepatic glucose production, but divergent effects on gluconeogenesis versus glycogenolysis, suggesting differing mechanisms of drug action for improving glycemic control. Colesevelam is thought to be a portal glucagon-like peptide-1 (GLP-1) secretagogue with primarily hepatic effects. Bile acid binding by colesevelam leads to TGR5 activation, increased secretion of GLP-1 or other incretins, and inhibition of hepatic glycogenolysis. Colesevelam's mechanism of action appears to be atypical of other antidiabetes medications, making it a potentially suitable component of many combination regimens in the treatment of type 2 diabetes.

Gastroparesis is a common disorder that produces symptoms of gastric retention in the absence of physical obstruction. Extensive research into the clinical features, pathophysiology, diagnostic evaluation, and therapy of gastroparesis in the past several years has offered insight into the condition. This review provides updated information on gastroparesis focusing on new findings from the past few years.

Large database studies have characterized clinical profiles in idiopathic and diabetic gastroparesis and are defining roles of gastric and extragastric factors in symptom genesis. Dietary deficiencies in gastroparesis have been clarified. Histologic study of full thickness gastric tissue in severe gastroparesis shows heterogeneous enteric neuronal, smooth muscle, interstitial cell, and inflammatory abnormalities. Advances in gastric emptying testing include wireless motility capsules and nonradioactive breath tests. The importance of glycemic control in diabetic gastroparesis is a focus of current investigation. Novel therapies include new prokinetics (ghrelin agonists), increased focus on antiemetic agents including antidepressants, and next generation gastric stimulators. Studies are being initiated to delineate the natural history of gastroparesis.

Much has been learned recently on the causes, clinical presentations, and management of gastroparesis. Current ongoing investigation provides promise for further gains in the years ahead.

The molecular mechanisms of cellular changes responsible for diabetic gastroparesis, primarily seen in middle-aged women, still remain incompletely defined. We hypothesized that a decrease in the expression, dimerization, and post-translational modification of neuronal nitric oxide synthase alpha (nNOSα) is estrogen mediated and responsible for the gender-specific prevalence of this malady.

We induced diabetes by injecting male and female rats with streptozotocin. Male diabetic rats without gastroparesis were then injected with estrogen for 3 weeks and evaluated for gastroparesis development. Gastric tissues were analyzed for the elucidation of biochemical events associated with diabetes and gastroparetic dysfunction.

Although male diabetic, gastroparetic (either streptozotocin- or estrogen-induced) rats exhibited similarity in disease pathology to that of females, the molecular mechanisms of development were different. Our results indicate that slow gastric emptying in both male diabetic, gastroparetic rat groups was not associated with the level of expression of nNOSα in gastric tissues. However, nNOSα dimerization, which reflects nNOSα activation, did decline slightly in the antrum of diabetic males with estrogen-induced gastroparesis, suggesting a possible estrogen role. Females with diabetic gastroparesis, in contrast, demonstrated significantly impaired levels and dimerization of nNOSα in the antrum and pylorus. Although the precise mechanism remains unknown, nNOSα dimerization impairment in female antrum is apparently associated with reduced phosphorylation of Ser(1416) in the activation loop of nNOSα.

Taken together, these results demonstrate that gender and estrogens may be leading factors, through molecular changes involved in nitric oxide synthesis down-regulation, within the antrum and pylorus of female diabetic, gastroparetic rats.

Patients with gastroparesis often present a challenge to the treating physician. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also cause significant disruptions to social activities that often center around food. While the definition of gastroparesis focuses on impaired gastric emptying, treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic nature of the illness with a common history of abuse, and coexisting anxiety or depression show parallels with other functional disorders of the gastrointestinal tract. These parallels provided the rationale for some initial studies investigating alternative therapies that target the brain rather than the stomach. This emerging shift in medical therapy comes at a time when clinical studies suggest that gastric electrical stimulation may exert its effects by modulating visceral sensory processing rather than altering gastric motility. Physiologic and detailed anatomic investigations also support a more complex picture with different disease mechanisms, ranging from impaired accommodation to apparent visceral hypersensitivity or decreased interstitial cells of Cajal to inflammatory infiltration of myenteric ganglia. Delayed gastric emptying remains the endophenotype defining gastroparesis. However, our treatment options go beyond prokinetics and may allow us to improve the quality of life of affected individuals.