An orchestrated function of all these components is required for the appropriate propulsive movement of the food in the gastrointestinal tract. Gastroparesis, a pathological slowing-down of gastric emptying, is a result of the damage to the tissue elements involved in the regulation of motility. Gastroparesis is one of the well-known complications of longstanding diabetes mellitus.
Although it is rarely a lifethreatening complication, it has a deteriorating effect on the quality of life, leads to unpredictable oscillation of the blood glucose level, and increases the time required for the absorption of food and medicines.
This review describes the clinical characteristics of diabetic gastroparesis and summarizes the organic and functional motility abnormalities caused by this This article is part of the Topical Collection on Microvascular Complications—Neuropathy V.
Kempler e-mail: kempler.
Evaluation of Diagnostic Methods and Dietary Treatment of Diabetic Gastroparesis
Lengyel : T. Várkonyi 1st. Lengyel e-mail: lecs in1st. Várkonyi e-mail: varkonyitamas gmail. Finally, the currently available and potential future therapeutic approaches are summarized.
Keywords Diabetes mellitus. Interstitial cells of Cajal. Neural elements. Furthermore, a normal gastric motility rate does not exclude the possibility that the complaints originate from motility disorders, while a slower gastric motility is not always associated with symptoms .
It is important to emphasize that the only manifestation of gastroparesis in some patients without GI symptoms is poor glycemic control, whereas in gastroparesis diet for diabetics cases, the completely opposite phenomenon may be experienced: the presence of obvious symptoms are not related to dysglycemia .
Due to delayed food absorption, postprandial hypoglycemia might be a characteristic feature of gastroparesis among insulin-treated diabetic patients. Although slower stomach emptying in a case of long-standing diabetes mellitus rarely leads to life-threatening complications and does not increase mortality , it increases the risk of an electrolyte imbalance, as well as hypo- or hyperglycemia.
Gastroparesis should also be considered as the underlying mechanism among patients thought to have brittle diabetes. As in various other areas of medicine, the severity of the disease may be characterized by different scoring systems. Further investigations are gastroparesis diet for diabetics to test whether these questionnaires are sufficiently valuable to guide the proper therapeutic approach or how well these scores lead to an estimate of the gastroparesis diet for diabetics of the gastric complication.
The mixing and the propulsive movement of liquid and solid food arriving into the esophagus and the lower parts of the gastrointestinal GI tract require the well-coordinated work of five basic tissue elements: smooth muscle, extrinsic and intrinsic neurons, glial cells, hormonal elements, and the interstitial cells of Cajal ICCs.
Damage to any of these elements leading to an imbalance of the neuromuscular unit will deteriorate the propulsive movement of food to some extent.
The degrees to which these elements gastroparesis diet for diabetics involved determine the degree and nature of the functional disorder. The stomach, positioned in the upper tract of the GI system, has a unique role in the processing of food, since it accommodates to the volume of the aliments, stores them, grinds them into small pieces, and transmits the food toward the duodenum.
Under physiological conditions, the movement of low-calory liquid food, especially water, toward gastroparesis diet for diabetics duodenum depends on its volume and the pressure pump function of the stomach . Low-calory solid food such as bread spends 20—30 min in the stomach, while a continuous peristaltic movement starts at the mid-upper corpus of the greater curvature of the stomach, spreads toward the antral region usually 3—5 times per minute , and presses the pieces of food to the almost closed pylorus.
This way, the stomach comminutes the solid food and makes it accessible to the digestive enzymes. Hyperosmotic, acidic, or nutrient-rich food makes stomach emptying much slower . The over-slow emptying of solid food from the stomach for a nonmechanical reason is defined as gastroparesis .
Gastroparesis was one of the first complications of diabetes described , and some ancient doctors, such as Aretaeus of Cappadocia, thought that diabetes was a disease of the stomach.
The etiology of gastroparesis cannot be identified in about a third of the cases .
The symptoms in all cases are chronic and recur frequently , including epigastric burning sensation, bloating, early satiety, abdominal discomfort, nausea, and vomiting. Diabetic gastroparesis occurs more frequently in women, in obese patients with poor glycemic control, and in patients where other complications of diabetes have already appeared. Nonetheless, an obvious relationship between the higher glycated hemoglobin HbA1c level and the development and severity of gastroparesis has not been clearly established .
The connection between symptoms and motility disorders related to gastroparesis is rather poor [17, 18]. An increased rate of stomach emptying is a characteristic finding in patients with a relatively short diabetes history less than 2 years and without the signs and symptoms of diabetic neuropathy .
Faster than normal stomach emptying can be observed even in long-term type 1 diabetes mellitus . In animal models, insulin therapy in a subtherapeutic dosage normalized increased stomach emptying .
The most important consequence of faster gastric emptying in clinical practice is sudden postprandial hyperglycemia shortly following food intake. It is also possible that this increased rate of stomach emptying is a preliminary phase of later slower stomach emptying .
Diabetic Gastroparesis: Functional/Morphologic Background, Diagnosis, and Treatment Options
Diabetic gastroparesis involves a severe delay of stomach emptying of both solid and liquid food . In a survey, type 2 diabetic patients with delayed emptying were older, had higher body mass index, and exhibited more intensive nausea and early satiety, as compared with type 1 diabetic patients Curr Diab Rep with impaired gastric motility .
Several functional changes can be found in the background of slower stomach emptying [21—24]. However, acute and chronic hyperglycemia have different effects on stomach motility. In healthy volunteers, severe artificial hyperglycemia causes slowing-down of the emptying of nutrient-containing liquid and solid food .
In type 1 diabetic patients with diabetic autonomic neuropathy, hyperglycemia increases the frequency of rhythmic activity in the stomach, resulting in tachygastria . Obvious deleterious effects of hyperglycemia cannot be confirmed on ICCs cells generate and propagate electrical activity in the stomach and the GI tract .
Interestingly, in type 1 diabetic patients without autonomic neuropathy, the stomach emptying can be significantly decreased even if the postprandial blood glucose elevation does not exceed the physiological range . Chronic hyperglycemia in diabetes can also be responsible for all of the above-mentioned motility disorders.
However, it is important to consider that diabetes is associated not only with elevated blood glucose levels, but additionally with an absolute or relative absence of insulin. The importance of this phenomenon is revealed by in vitro experimental data demonstrating the deteriorating effect of the absolute absence of insulin on stomach ICCs and the smooth muscle cells .
In general, slower movement of solid food from the stomach in diabetes is more frequent than slower movement of liquids. The impaired pyloric pressure pump function also has an effect on solid food emptying , and the dilatation of the distal stomach also relates to the antral hypomotility .
It is probably important that the slow waves gastroparesis diet for diabetics the stomach generated by the ICCs are modified by a number of factors, such as the sympathetic—parasympathetic balance, eating, and medicines. Any disturbance in these factors can worsen the effectivity of the peristalsis . The reasons for the discrepancy between the symptoms and detectable motility disorders are not clear; a possible explanation is the viscero-sensory functional defect related to diabetic autonomic neuropathy.
The increased activity or sensitivity of these neuronal systems in the proximal stomach might explain the generation of nausea, vomiting, early satiety, and epigastrial pain experienced in type 1 diabetic patients without substantial motility disorders .
Various factors can damage different tissues, including hyperglycemia and an absolute or Page 3 of 9, relative lack of insulin. The increase in mitochondrial superoxide activity caused by the increased glucose burden can be an important factor in the development of chronic morphologic complications of diabetes .
The increased oxidative stress-related decrease in nitric oxide NO concentration, together with the reduced activity of heme oxygenase, is an important feature of the pathogenetic background at the cellular level . Carbon monoxide produced by heme oxygenase has a protective effect on the ICCs . Histological changes in long-standing diabetes can also be studied. In a human investigation in antrum samples, mild lymphocytic infiltration in the myenteric plexus was a characteristic finding of diabetic gastroparesis .
Significant reductions in the numbers of neuronal elements and the Gastroparesis diet for diabetics in the antrum wall were detected . In another investigation, the loss of neuronal elements was proven in diabetic samples from the mucosal layer . In a larger study , the most frequent abnormality was damage to or loss of the ICCs and the decrease in the number of NO synthase NOS positive neurons. However, the loss of the NOS-positive neurons was more characteristic for idiopathic gastroparesis.
Electromicroscopic investigations detected a significant increase in the amount of connective tissue.
Overall, the most characteristic histopathological change in diabetic gastroparesis is the loss of or damage to the ICCs. The pathophysiologic steps leading to ICC damage are complex.
The ICCs are very sensitive to the lack of insulin, despite the absence of insulin receptors and insulin-like growth factor-1 IGF-1 receptors on these cells . The explanation of this paradoxical situation was provided by experiments  that revealed that the smooth muscle cells of the stomach have insulin and IGF-1 receptors and these cells produce the stem cell factor SCF that is essential for the development and maintenance of the network of ICCs.
The smooth muscle atrophy that develops in the lack of insulin is responsible for the decreased production of SCF and, hence, for the damage to the ICC network [27, 40].
The exact mechanism of Gastroparesis diet for diabetics damage is still not clear, and several questions remain to be answered [42, 43]. The most characteristic histological findings and symptoms of diabetic gastroparesis are listed in Tables 1 and 2.
The parasympathetic regulation can exert both excitatory and inhibitory effects, while the sympathetic input is generally inhibitory, with the exception of its propulsive influence on the lower esophageal sphincter . In accordance with the previous description, GI autonomic neuropathy is the result of a complex pathophysiological process that involves organic and functional impairments of the neuronal cells and a progressive imbalance of various autonomic regulations.
The changes include reduced numbers of ICCs, extrinsic autonomic neurons, and smooth muscle cells with altered inhibitory neurotransmission . In patients with diabetic gastroparesis, a reduction in the intraneuronal levels of NO has also been observed . It is assumed that the leading pathophysiologic abnormality is the impairment of parasympathetic function in autonomic neuropathy.
Sham feedinginduced gastric acid production or pancreatic polypeptide response to hypoglycemia is decreased in diabetic patients as well. Since both the gastroparesis diet for diabetics secretory function and pancreatic polypeptide secretion are under vagal control, these observations support the role of parasympathetic damage in the development of diabetic gastroparesis [46, 47].
The progression of the impaired gastric emptying seems to be slower than the progression of the autonomic cukorbeteg diéta 160 grammos . Besides the chronic metabolic exposure, acute hyperglycemia can also alter GI vagal functions . Moreover, current hyperglycemia affects parasympathetic cardiac functions even in healthy subjects, pointing to cukorbeteg melyik vakcinát kaphatja importance of the physiological condition of all those factors that possibly affect the vagal control in the regulation of gastric emptying .
The emptying of the stomach might Curr Diab Rep be slower when the balance between the excitatory and inhibitory gastroparesis diet for diabetics of the autonomic system gastroparesis diet for diabetics disturbed . Parasympathetic function becomes abnormal earlier during the progression of autonomic neuropathy than does the sympathetic function, leading to weakening of the excitatory parasympathetic innervation of the stomach and a relative strengthening of the inhibitory sympathetic effects .
The alteration in the sympathetic function can also have detrimental effect on gastric emptying. Several important processes are regulated by the sympathetic nervous system, which may also partially affect the gastric motility visceral reflexes, nausea, vomiting, and abdominal pain. Despite the well-known general consequences of the parasympathetic and sympathetic impairments, it is still not clear how these alterations act directly on the motility of the stomach in diabetic patients.
Besides the normal extrinsic autonomic neuronal functions, intact central neuronal regulation is also mandatory for the integrity of gastric emptying. Abnormal visceral hypersensitivity diabétesz kezelésére egy újszülött a result of an altered afferent central function is a newly documented source of various digestive symptoms that are responsible for an impaired quality of life .
In line with this, a recent study demonstrated altered central sensory processing in diabetic patients with upper abdominal symptoms . A few clinical observations suggest the role of the central neuronal system in cukorbetegség seb regulation of certain visceral functions, including gastric motility .
The severity of the autonomic neuronal damage in humans is not yet measurable directly; therefore, reproducible and sensitive cardiovascular and sensory tests are applied to estimate the neuronal dysfunctions in patients with abnormal gastric emptying or GI symptoms.
In some of these tests, correlations have been found between neuropathy and stomach motility. The overall autonomic neuropathy score calculated from cardiovascular reflex tests correlated positively with the scintigraphic gastric emptying rate of solids in patients with long-standing type 1 diabetic patients . Two heart rate tests of the five cardiovascular tests consistently correlated with the cukorbetegség genetikai okai of an isotope-labeled solid meal from the stomach in long-standing type 1 diabetes .
These heart rate tests, the heart rate response to deep kezelésére arthropathiát cukorbetegség, and the Valsalva maneuver are regarded as sensitive indicators of the parasympathetic function that become abnormal during the early course of neuropathy.
These data support the hypothesis that the insufficiency of the excitatory effect of the vagal nerve on the postprandial phase of the stomach functions leads to delayed emptying in type 1 diabetic patients with long duration.
Reduced heart rate variability, a well-known indicator of the autonomic dysfunction, was associated with GI complaints in diabetic patients with sensorimotor neuropathy, suggesting a concomitant role of various manifestations of neuropathy in the pathogenesis of digestive complications . Although several studies have documented correlations between neuropathy tests and gastric emptying, numerous Curr Diab Rep other studies did not discern any relationship .
This might be explained in terms of the restricted methodology of the measurement of the complex GI neuronal dysfunctions, the heterogeneity of the tests applied in the various studies, and the importance of pathophysiological factors other than neuropathy in the pathogenesis of gastroparesis. The Role of Nitric Oxide Synthase in the Development of Diabetic Gastroparesis The NOS-positive gastroparesis diet for diabetics identified in the GI tract have a crucial role in the inhibitory regulation of the motility functions and, hence, in the relaxation of the different sphincters.
It has been confirmed in animal models that inhibition of neuronal NOS results in slower stomach emptying. Human investigations have revealed that the endogenous NO inhibits the propulsive movement in the stomach . The clinical observation that diabetic gastroparesis predominantly affects women might be related to the fact that impairment of the nitrergic system is more pronounced in females . It has been revealed in animal models that the number of NOSpositive neurons decreases in diabetes and, in parallel with the loss of these neurons, the regulation of pyloric relaxation, just as the antral tone deteriorates.
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Early treatment with insulin led to rearrangement of the presence of NOS-positive neurons and their synthetic function .
A possible future therapeutic approach may be to transplant stem cells that can differentiate into NOS-positive enteral neurons . The Role of Enteral Hormones in the Development of Diabetic Gastroparesis The role of these hormones in the pathomechanism of diabetic gastroparesis is still controversial. The effects of the hormones that stimulate e.
One of the most frequently investigated enteral hormone is GLP-1, since dipeptidyl-peptidase-IV inhibitors and GLP-1 diabetes and heart disease statistics and agonists are increasingly more widely used in clinical practice.
The consequences of elevations or reductions of this peptide in diabetes have been analyzed, and an association was proven between the effect of GLP-1 on gastric emptying and the elevation of postprandial glucose levels .
Ghrelin has also been a target molecule in recent investigations. Although in a species-specific manner, ghrelin promotes the antro-pyloric Page 5 of 9, coordination and can thereby improve stomach emptying [64, 65].