Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastroparesis is the most severe form of gastric neuromuscular dysfunction along a continuum that encompasses gastric visceral hypersensitivity, gastric dysrhythmias, and pylorospasm. Gastroparesis may present with vague dyspepsia symptoms or with vomiting of undigested food and weight loss. A careful history and physical examination may suggest the diagnosis of gastroparesis, but symptoms associated with gastric neuromuscular disorders are non-specific. Gastroparesis in patients with diabetes, particularly type 2 diabetes, is more common than appreciated. If gastroparesis is confirmed, then reversible causes such as mechanical obstruction of stomach and chronic mesenteric ischemia must be excluded. ''Idiopathic'' gastroparesis may follow viral infections or be due to degenerative processes that affect gastric enteric neurons, smooth muscle, and/or interstitial cells of Cajal. An approach to the diagnosis and treatment of gastroparesis and gastric neuromuscular disorders is reviewed including dietary counselling and new medical devices.
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PMID:Gastroparesis and neuromuscular disorders of the stomach. 1648 77

In most Western countries, diabetic nephropathy (DN) has become the single most common condition found in patients with end-stage renal disease (ESRD). This is to some extent due to better survival of diabetic patients with renal failure, but mostly due to the dramatic increase in the prevalence of type 2 diabetes. The majority of type 2 diabetic patients with renal failure suffer from nodular glomerulosclerosis (Kimmelstiel-Wilson); but ischemic nephropathy, irreversible acute renal failure (mostly acute on chronic) and diabetes co-existing with primary renal diseases are common as well. Classical DN evolves in a sequence of stages. After a period of glomerular hyperfiltration, increased urinary albumin excretion [microalbuminuria (MA)] i.e. 30-300 mg/day or 20 - 200 microg/minute indicates the onset of overt DN. Risk factors for development of DN are positive family history, hyperglycemia in the mother during pregnancy, high blood pressure, obesity and insulin resistance. Poor glycemic control (HbAlc) and elevated systolic blood pressure (> 135 mm Hg) interact in enhancing the risk of DN. Proteinuria and smoking are major promoters of progression. The risk of onset of microalbuminuria can be reduced by lowering of blood pressure and specifically by blockade of the renin angiotensin system (RAS). In patients with established DN, the target systolic blood pressure should be <130 mm Hg and RAS blockade is obligatory. Treating all cardiovascular risk factors is a high priority. Antihypertensive management is rendered difficult by extreme volume sensitivity, pronounced activation of the RAS and autonomic neuropathy. Cardiac events are excessively frequent, glycemic control becomes difficult and autonomic diabetic neuropathy with gastroparesis and diabetic foot are additional problems. Hemodialysis or continuous ambulatory peritoneal dialysis should be started relatively early. In the absence of contraindications, transplantation (renal transplantation, combined kidney/pancreas transplantation or pancreas after kidney transplantation) is the treatment of choice.
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PMID:Diabetic nephropathy. 1718 81

The worldwide epidemic of type 2 diabetes mellitus (T2DM) is a substantial economic and social burden. Although gastroparesis associated with type 1 diabetes mellitus (T1DM) has been recognized for years, only recently have studies shown that patients with T2DM also have high rates of gastroparesis. Individuals with T2DM constitute 90% to 95% of the diabetic population. Unique characteristics that distinguish this population are obesity, insulin resistance, and associated comorbidities. These features highlight the importance of investigating gastric emptying in individuals with T2DM and upper gastrointestinal symptoms. The purpose of this review is to examine the literature pertaining to diabetes and the effect of diabetes on gastric neuromuscular function, with a focus on T2DM. An understanding of gastric motility in T2DM is important to diagnose gastroparesis, to treat upper gastrointestinal symptoms, and to restore normal gastric motility, which may lead, in turn, to improved glucose control.
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PMID:Gastroparesis in type 2 diabetes mellitus: prevalence, etiology, diagnosis, and treatment. 1788 73

Diabetic neuropathy is a common chronic complication of diabetes and cause of significant morbidity and mortality, because it may involve the autonomous and peripheral nervous systems. Autonomic diabetic neuropathy is a challenging chronic complication of long-standing diabetes manifested with hypotension, syncope, gastroparesis, diarrhea, constipation, bladder dysfunction, sexual dysfunction, cardiac arrest, and/or sudden death. We present a case of diabetic gastroparesis in an older woman. The patient was an 83-year-old woman with a 40-year history of type 2 diabetes who was admitted with hypoglycemia, malnutrition, persistent vomiting, and obstinate constipation. After several unsuccessful attempts with different therapies, we administered intravenous azithromycin (500 mg/day). After 3 days of treatment, vomiting was resolved and the patient evacuated normal feces, with notable improvement in the general conditions and metabolic control. Because diabetic gastroparesis frequently is difficult to manage clinically and there are few beneficial therapeutic choices available at present, the macrolide antibiotic azithromycin, which has strong prokinetic properties, may be a useful option in the treatment of this complex condition.
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PMID:Azithromycin in an older woman with diabetic gastroparesis. 1822 58

Gastric emptying is frequently abnormal in patients with long-standing type 1 and type 2 diabetes mellitus. Symptoms commonly associated with disordered gastric emptying include nausea, vomiting, bloating and epigastric pain, while patients are also at risk of malnutrition, weight loss, impaired drug absorption, disordered glycaemic control and poor quality of life. Although often attributed to the presence of irreversible autonomic neuropathy, acute hyperglycaemia represents a potentially reversible cause of gastric dysfunction in diabetes. Scintigraphy represents the gold standard for measuring gastric emptying. The management of diabetic gastroparesis is less than optimal, partly because the pathogenesis has not been clearly defined. Treatment approaches include dietary modification and optimization of glycaemia, and the use of prokinetic drugs, while novel therapies such as gastric electrical stimulation are the subject of ongoing investigation.
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PMID:Diabetic gastroparesis: diagnosis and management. 1949 27

It is long known that both type 1 and type 2 diabetes can be associated with changes in gastric emptying; a number of publications have linked diabetes to delayed gastric emptying of variable severity and often with poor relationship to gastrointestinal symptomatology. In contrast, more recent studies have reported accelerated gastric emptying when adjusted for glucose concentration in patients with diabetes, indicating a reciprocal relationship between gastric emptying and ambient glucose concentrations. This review proposes that gastroparesis or gastroparesis diabeticorum, a severe condition characterized by a significant impairment of gastric emptying accompanied by severe nausea, vomiting, and malnutrition, is often overdiagnosed and not well contrasted with delays in gastric emptying. The article offers a clinically relevant definition of gastroparesis that should help differentiate this rare condition from (often asymptomatic) delays in gastric emptying. The fact that delayed gastric emptying can also be observed in non-diabetic individuals under experimental conditions in which hyperglycaemia is artificially induced suggests that a delay in gastric emptying rate when blood glucose concentrations are high is actually an appropriate physiological response to hyperglycaemia, slowing further increases in blood glucose. The article discusses the strengths and weaknesses of various methodologies for assessing gastric emptying, especially with respect to the diabetes population, and reviews newer diabetes therapies that decelerate the rate of gastric emptying. These therapies may be a beneficial tool in managing postprandial hyperglycaemia because they attenuate rapid surges in glucose concentrations by slowing the delivery of meal-derived glucose.
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PMID:Diabetes mellitus and gastric emptying: questions and issues in clinical practice. 1961 Jan 28

The prevalence of obesity is growing, is driving an increase in the prevalence of diabetes, and is creating a major public health crisis in the United States. Lifestyle and behavior therapy rarely give durable weight loss. There are few medications approved for the treatment of obesity. Those that exist are limited in efficacy and using them in combination does not result in greater weight loss. Surgical treatments for obesity are effective and give durable weight loss, but are accompanied by measurable morbidity and mortality. Several pacing approaches are being tried and are an outgrowth of pacing for gastroparesis. The Transcend(R) pacemaker blocks vagal efferents and delays gastric emptying, giving a 40% loss of excess body weight, if certain screening procedures are employed. The Tantulus pacemaker is still in development but increases antral muscular contractions and delays gastric emptying by stimulation during the absolute refractory period. Weight loss has been 30% of excess body weight, and glycohemoglobin decreased 1.6% in a trial of obese type 2 diabetes. Stimulation to the subdiaphragmatic sympathetics, vagal nerve stimulation with or without unilateral vagotomy, and intestinal pacing are other approaches that are still being evaluated preclinically. Clearly a safe, effective, and durable treatment for obesity is desperately needed. Electrical pacing of the gastrointestinal tract is promising therapeutically, and because pacemakers work through different mechanisms, combining pacemaker treatments may be possible. Rapid progress is being made in the field of electrical stimulation as a treatment for obesity and even greater progress can be expected in the foreseeable future.
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PMID:Electrical stimulation as treatment for obesity and diabetes. 1988 14

A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a. The unique post-translational modification of O-n-octanoylation at serine 3 is the first in peptide discovery history and is essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation at serine 3, is also produced in the stomach and remains the major molecular form secreted into the circulation. The third ghrelin gene product, obestatin, a novel 23-amino acid peptide identified from rat stomach, was found by comparative genomic analysis. Three ghrelin gene products actively participate in modulating appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach. To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins. GOAT may provide a critical molecular target in developing novel therapeutics for obesity and type 2 diabetes.
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PMID:Ghrelin gene products and the regulation of food intake and gut motility. 2003 70

Gastroparesis, or chronic delayed gastric emptying without mechanical obstruction, affects about 40% of patients with type 1 diabetes and up to 30% of patients with type 2 diabetes. Diabetic gastroparesis (DGP) typically causes nausea, vomiting, early satiety, bloating, and postprandial fullness. These symptoms can be extremely troubling and result in poor quality of life. The diagnosis of DGP is made by documenting the presence of chronic upper gastrointestinal (GI) symptoms, ruling out mechanical obstruction, and demonstrating delayed gastric emptying. The usual treatment for DGP includes dietary modifications, prokinetic agents, and antiemetic agents. Although the majority of patients have mild-to-moderate disease that can be managed using these measures, a substantial percentage of patients have severe DGP that is characterized by inadequate oral intake, malnutrition, weight loss, and frequent hospitalizations. Optimal management of these patients presents a difficult challenge for the clinician, although emerging treatment options, such as gastric neurostimulation, are encouraging. Patients with DGP often present with gastric comorbidities, including gastroesophageal reflux disease, intestinal dysmotility, and fungal and bacterial infections of the GI tract. This monograph will present an overview of the pathophysiology of DGP, review diagnostic testing with a discussion of emerging technology, and present the latest research in treatment options for DGP. In addition, management strategies for refractory DGP and gastric comorbidities will be described.
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PMID:Treatment of patients with diabetic gastroparesis. 2073 35

Diabetic gastroparesis is a disorder that occurs in both type 1 and type 2 diabetes. It is associated with considerable morbidity among these patients and with the resultant economic burden on the health system. It is primarily a disease seen in middle-aged women, although the increased predisposition in women still remains unexplained. Patients often present with nausea, vomiting, bloating, early satiety and abdominal pain. The pathogenesis of this complex disorder is still not well understood but involves abnormalities in multiple interacting cell types including the extrinsic nervous system, enteric nervous system, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The primary diagnostic test remains gastric scintigraphy, although other modalities such as breath test, capsule, ultrasound, MRI and single photon emission CT imaging show promise as alternative diagnostic modalities. The mainstay of treatment for diabetic gastroparesis has been antiemetics, prokinetics, nutritional support and pain control. In recent years, gastric stimulation has been used in refractory cases with nausea and vomiting. As we better understand the pathophysiology, newer treatment modalities are emerging with the aim of correcting the underlying defect. In this review, what has been learned about diabetic gastroparesis in the past 5 years is highlighted. The epidemiology, pathogenesis, diagnosis and treatment of diabetic gastroparesis are reviewed, focusing on the areas that are still controversial and those that require more studies. There is also a focus on advances in our understanding of the cellular changes that underlie development of diabetic gastroparesis, highlighting new opportunities for targeted treatment.
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PMID:Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years. 2087 Nov 31


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