Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Jejuno-ileal bypass has been performed in 226 massively obese patients, 190 of whom have been followed for a minimum of 1 year. End-to-side and end-to-end anastomoses were compared and no difference in the weight reduction achieved by either technique was seen throughout the 5-year follow-up. There was no significant difference in weight reduction achieved between groups of patients in which the jejunal length varied from 10 to 35 cm and the ileal length from 35 to 10 cm. The weight reduction achieved in the entire series averaged 36-7 +/- 9-4 per cent at 2 years, after which no further loss occurred. Good psychological benefits were recorded. Remission of diabetes occurred in 12 of 13 patients and marked long term lowering of serum lipids was seen. Side effects included fluid and electrolyte disturbances and fatty changes in the liver during the first year, improving thereafter. Early cirrhosis of the liver occurred in 8-6 per cent. Other side effects included abdominal bloating, arthralgia and renal colic. The operative mortality was 0-9 per cent and the late mortality directly attributable to the jejuno-ileal bypass, 3-1 per cent. In 19 patients the bypass was discontinued because of severe side effects.
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PMID:The management of gross refractory obesity by jejuno-ileal bypass. 48 7

Delayed gastric emptying, gastroparesis, is one of the sequelae of diabetes mellitus. Symptoms may include postprandial nausea, epigastric pain, bloating, vomiting, early satiety and unpredictable blood sugar fluctuations. Nowadays diagnosis is made by the measurement of gastric emptying with a radionuclide test meal. Using this technique some 50% of diabetic patients show signs of disordered gastric emptying. Relief is best delivered by agents promoting gastric emptying. In phase II single-dose studies metoclopramide, domperidone, cisapride, erythromycin and renzapride were all able to enhance gastric evacuation of solid and liquid meals in patients with diabetic gastroparesis. A few short term studies support the efficacy of domperidone and renzapride, but long term trials are lacking. Erythromycin, mimicking the potent gastrokinetic effect of motilin, may hold considerable promise for the future. Experience with erythromycin in diabetic gastroparesis is nonetheless very limited. To some extent the therapeutic effectiveness of metoclopramide and cisapride has been established in placebo-controlled trials. In trials with a placebo-controlled crossover design, however, only metoclopramide showed a sustained positive effect. Metoclopramide, which combines gastrokinetic and antiemetic properties seems, so far, the best therapeutic option in diabetic gastroparesis. Cisapride may be considered as a good alternative in cases where limited efficacy or side effects preclude the use of metoclopramide.
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PMID:Diabetic gastroparesis. A critical reappraisal of new treatment strategies. 128 Oct 70

Octreotide is an analogue of somatostatin. Like endogenous somatostatin, it exerts a potent inhibitory effect on the release of anterior pituitary growth hormone and thyroid-stimulating hormone, and peptides of the gastroenteropancreatic endocrine system, while overcoming some of the shortcomings of exogenously administered somatostatin, namely a short duration of action, a need for intravenous administration and postinfusion rebound hypersecretion of hormone. Clinical studies have shown that octreotide is effective in the treatment of acromegaly and thyrotrophinomas. In comparative trials octreotide was significantly superior to bromocriptine in patients with acromegaly. Octreotide also appears to provide a significant advantage over existing therapies in the management of the carcinoid syndrome and offers considerable therapeutic potential in reversing carcinoid crises which may be life-threatening. Trials in patients with tumours producing vasoactive intestinal peptide demonstrated that octreotide may be an effective first-line choice for this condition, which has usually metastasised and become refractory to traditional symptomatic therapy. In limited studies in patients with high-output secretory diarrhoea, including cryptosporidium-related diarrhoea associated with AIDS and in patients with small bowel fistulas, octreotide has been shown to be effective in reducing stool/fistula output. However, well-designed clinical trials are still required to confirm its long term usefulness in these disorders. Similarly, although the use of octreotide in other conditions such as neonatal hypoglycaemia caused by nesidioblastosis, reactive pancreatitis, insulin-dependent diabetes mellitus, postprandial hypotension and the dumping syndrome has provided encouraging preliminary results, more studies are needed to clarify the place of octreotide in their treatment. Overall, octreotide appears to be well tolerated with the most frequently reported reactions being pain at the site of injection and gastrointestinal symptoms such as abdominal cramps, nausea, bloating, flatulence, diarrhoea and steatorrhoea. These adverse effects usually abate with time. Additionally, octreotide, like endogenous somatostatin, may also result in cholelithiasis, presumably by altering fat absorption and possibly by decreasing motility of the gallbladder. Thus, octreotide represents a new departure from traditional therapies in the treatment of various pathophysiological states associated with excessive peptide production and secretion. It offers a significant advantage over existing therapies in the medical management of patients with acromegaly, thyrotrophinomas, the carcinoid syndrome, tumours producing vasoactive intestinal peptide and severe secretory diarrhoea in whom conventional management options have either become exhausted or have provided suboptimal symptomatic relief.
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PMID:Octreotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. 268 36

Acarbose is an alpha-glucosidase inhibitor proposed for the treatment of diabetic patients. It acts by competitively inhibiting the alpha-glucosidases in the intestinal brush border. The principal action of these enzymes is to convert nonabsorbable dietary starch and sucrose into absorbable monosaccharides (e.g. glucose). Enzyme inhibitors delay this conversion, slowing the formation and consequently the absorption of monosaccharides, and thus reducing the concentration of postprandial blood glucose. Both starch and sucrose are influenced, whereas lactose and glucose are not. Many studies in experimental animals, healthy volunteers and patients with non-insulin-dependent diabetes mellitus (NIDDM) have shown that acarbose decreases postprandial blood glucose, with a lesser reduction of fasting blood glucose, plasma triglycerides and postprandial insulin levels. In long term studies in NIDDM patients, acarbose significantly reduced glycosylated haemoglobin levels. Acarbose is only minimally absorbed from the gut and no systemic adverse effects have been demonstrated after long term administration. The drug allows undigested carbohydrates to pass into the large bowel where they are fermented causing flatulence, bloating and diarrhoea. These symptoms, which occur in approximately 30 to 60% of patients, tend to decrease with time and seem to be dose-dependent. They are minimised by starting therapy with low doses (such as 50mg 3 times daily) which may be effective in many patients. An increase in serum hepatic transaminases observed in earlier studies in the US, where doses of acarbose up to 900mg daily were used, has been not reported with the lower doses of the drug actually recommended [150 to 300mg (up to 600mg) daily]. In conclusion, acarbose may be useful in patients with NIDDM when diet alone is no longer able to maintain satisfactory blood glucose control. Furthermore, it may be a valid alternative to sulphonylurea or biguanide therapy when these drugs are contraindicated and insulin administration may be delayed. Acarbose seems also to be a useful adjunct to hypoglycaemic oral agents but its precise role in this field has not been fully clarified.
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PMID:A risk-benefit appraisal of acarbose in the management of non-insulin-dependent diabetes mellitus. 772 53

Recent cohort and case control studies of low-dose combined oral contraceptives (COCs) containing the new generation of progestogens have allowed classification of adverse effects into those which are rare but serious and should be considered risks and those which are more frequent but are less of a threat to health. Low-dose COCs continue to affect coagulation in a complex way, but the risk is less than with the older preparations, and it can be minimized by screening women for a personal or familial history of early or unusual thrombosis and for levels of protein C, S, and antithrombin III. Women with true migraine with focal signs should also avoid using COCs. The relative risk of myocardial infarction (MI) may increase from 4:1 in women with one risk factor (age, smoking, hypertension, hyperlipidemia, and diabetes) to 20:1 with two risk factors and 128:1 with three or more risk factors. In the absence of all risk factors, a recent study indicated that the relative risk of MI with COC use was 1.9 for current and past use. COC use also causes a slight increase in hypertension in most women, especially those who are older or have a family history of hypertension. While the COC can affect carbohydrate and lipid metabolism, the new generation of progestogens has reduced these effects. The COC may accelerate presentation of gallbladder disease in predisposed women. The COC protects against benign breast disease but may increase the risk of breast cancer and cervical cancer slightly. There is a strong link between hepatocellular adenoma and COC use, but the incidence is low. Return to fertility after use has not been a problem. Both estrogenic adverse effects (nausea, dizziness, irritability, weight gain, bloating) and progestogenic adverse effects (vaginal dryness, acne, hirsutism, weight gain, depression, loss of libido) can occur in 50% of women, but these generally disappear after a few months of use. In conclusion, the low-dose, third generation COCs are associated with minimal risks in the absence of other risk factors and have many beneficial effects such as the prevention of ovarian and endometrial cancer; a decrease in pelvic inflammatory disease and ectopic pregnancies; and protection from anemia, primary dysmenorrhea, functional ovarian cysts, and benign breast disease as well as from the morbidity and mortality associated with pregnancy.
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PMID:The combined oral contraceptive. Risks and adverse effects in perspective. 776 40

The efficacy and tolerability of acarbose was studied in 14 type-2-diabetic patients poorly controlled with diet and sulfonylureas. Acarbose was given in addition to sulfonylureas in a single-blind, placebo-controlled study for three times three months (acarbose-placebo-acarbose). At the beginning of the study and every three months body weight, HbA1c and biochemical and hematological safety parameters were measured. The patients controlled their mid morning urine glucose and two to four times daily their blood glucose concentration with a memory glucometer. Diabetic control improved significantly: HbA1c was 8.5 +/- 1.4% at the beginning, 6.5 +/- 1.1% after three months with acarbose (p < 0.001), 7.2 +/- 0.9% after three months placebo (p < 0.01) and 6.7 +/- 1.3% again after three months with acarbose (p < 0.05). Thus, the effect of acarbose alone accounts for 0.7 or 0.5% respectively, whereas the effect of teaching and diet in a special diabetes unit (the difference from the study to placebo) accounts for 1.3% of HbA1c. Home monitored blood and urine glucose values were improved: The postprandial blood glucose concentrations, the postprandial differences, the mean blood glucose concentrations and the glycosuria were decreased during acarbose treatment in comparison with placebo. The preprandial blood glucose concentrations before breakfast and supper were not influenced by acarbose. Hematological and biochemical safety parameters as well as blood pressure and heart rate were unchanged. Meteorism and flatulence as typical side effects decreased during treatment. Acarbose is a safe and effective adjunct treatment for type-2-diabetic patients uncontrolled with diet and sulfonylurea alone.
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PMID:[Effectiveness and tolerance of long-term acarbose therapy in diabetic patients with threatened secondary failure of sulfonylurea drug treatment]. 801 32

Autonomous neuropathy in patients with diabetes is associated with dysmotility and abdominal discomfort. The disturbances resemble to some extent those seen in patients with functional dyspepsia. To gain further insight into the disorders, we compared patients with long-standing diabetes, patients with functional dyspepsia, and healthy individuals with respect to abdominal symptoms, width of gastric antral area, and autonomic nerve function. We investigated 42 type I diabetic outpatients by structured interview for abdominal discomfort, ultrasonography of the gastric antrum, assessment of vagal and sympathetic nerve function by respiratory sinus arrhythmia and skin conductance, and measurement of blood sugar and HbA1c. Immediately after a standard meal of soup with meat, 21 (50%) of the 42 patients with diabetes complained of abdominal discomfort (pain, bloating, fullness), which was significantly less frequent (95% CI of difference 0.03-0.5) than previously seen in patients with functional dyspepsia (76%), and significantly more frequent (95% CI of difference 0.3-0.6) than that seen in healthy individuals (4%). Bloating was the most marked postprandial complaint. Mean fasting antral area was significantly wider in patients with diabetes (mean 4.9 cm2, SD 1.7) compared to healthy individuals (mean 3.5 cm2, SD 1.2), 95% CI of difference 0.6-2.2 cm2. Mean postprandial antral area was 14.8 cm2 (SD 4.6) in the patients with diabetes, which is insignificantly wider than in patients with functional dyspepsia (mean 13.0 cm2, SD 4.0) but significantly wider (95% CI of difference 1.9-6.5 cm2) than that seen in healthy individuals (mean 10.6 cm2, SD 3.8). The mean respiratory sinus arrhythmia was 0.7 beats/min (SD 0.7) in the patients with diabetes, which was insignificantly lower than that seen in patients with functional dyspepsia (2.1 beats/min, SD 4.5), and significantly lower (99% CI of difference 3.8-7.1 beats/min) compared to healthy individuals (6.2 beats/min, SD 3.8). It is concluded that patients with diabetes have a wider gastric antrum and more discomfort after a meal than healthy individuals. Compared to patients with functional dyspepsia, patients with diabetes have a wider postprandial antrum but fewer symptoms. The very low vagal tone seen in patients with diabetes may play an important role in the pathogenesis of their gastric motility disturbance and postprandial abdominal discomfort.
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PMID:Wide gastric antrum and low vagal tone in patients with diabetes mellitus type 1 compared to patients with functional dyspepsia and healthy individuals. 856 73

Gastroparesis is delayed gastric emptying of either solids or liquids, which occurs in the absence of mechanical obstruction. Although associated with many diseases, the most frequent cause of gastroparesis is diabetes mellitus. It is estimated that up to 50% of diabetic patients may have this problem. Symptoms of gastroparesis include postprandial nausea, epigastric pain/burning, bloating, early satiety, excessive eructation, anorexia and vomiting. The vomiting associated with gastroparesis often has the following two features: (1) emesis of undigested foods ingested more than four hours previous; and (2) emesis of undigested foods in the middle of the night or in the morning prior to eating breakfast. It is important to recognize and treat gastroparesis not only to decrease symptoms but also to prevent bezoar formation and nutritional deficiencies as well as to improve glycemic control in brittle diabetics. The purpose of this article is to review the physiology of gastric emptying and to use this information to understand the pharmacological therapies for this debilitating problem.
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PMID:Gastroparesis: current management. 878 40

Disordered gastric emptying occurs in 30-50% of patients with diabetes mellitus. Although the rate of gastric emptying is dependent on the integration of motor activity in different regions of the stomach, there is limited information about the function of the proximal stomach in diabetes mellitus. In the present study the response of the proximal stomach to a liquid meal was examined in eight diabetic patients with autonomic neuropathy and gastrointestinal symptoms and in 10 healthy volunteers, using an intragastric bag connected to an electronic barostat. Postprandial relaxation of the proximal stomach was measured as an increase of intragastric bag volume at a constant pressure level of 1 mm Hg above the intraabdominal pressure. During the experiment the blood glucose levels were maintained within the euglycemic range. Before ingestion of the meal the intragastric bag volume was larger in the diabetic patients than in the healthy volunteers, 234.4 +/- 29.1 ml vs 155.3 +/- 15.3 ml (P = 0.06). The maximum volume was not different in diabetics compared to the healthy controls (386.3 +/- 45.2 ml versus 399.0 +/- 35.2 ml). However, the maximum volume increase was significantly less in diabetics (143.7 +/- 38.6 ml) compared to the controls (231.4 +/- 30.5 ml, P < 0.04). Bloating was inversely correlated with the volume changes, which suggests that impaired relaxation of the proximal stomach may play a role in the genesis of this sensation. In conclusion, this study shows a lower fasting fundal tone and a decrease in volume change of the gastric fundus after a nutrient drink in patients with autonomic neuropathy due to type I diabetes mellitus. These abnormalities may play a role in the abnormal distribution of food, disordered liquid gastric emptying, and in the genesis of the sensation of bloating observed in these patients.
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PMID:Proximal gastric motor activity in response to a liquid meal in type I diabetes mellitus with autonomic neuropathy. 953 42

The purpose of this clinical study was to determine the efficacy, tolerability, and impact on quality of life of domperidone--a specific peripherally acting dopamine antagonist--in the management of symptoms of gastroparesis, a common and potentially debilitating condition in patients with diabetes mellitus. In the first phase of this multicenter, two-phase withdrawal study, 287 diabetic patients with symptoms of gastroparesis of at least 6 months' duration received domperidone 20 mg QID in a single-masked fashion for 4 weeks. Efficacy was evaluated using a four-point rating scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) for each of the following symptoms: nausea, abdominal distention/bloating, early satiety, vomiting, and abdominal pain. At the end of the first phase, patients with sufficient improvement in their total symptom score (a score < or = 6 and a decrease in score of > or = 5 units from the baseline [selection] visit) were eligible for the 4-week, randomized, placebo-controlled, double-masked withdrawal phase of the study. The impact of domperidone on quality of life was determined using the Medical Outcomes Study Short Form-36 (SF-36). Of 269 patients with data from the single-masked phase, 208 (77%) qualified for entry into the double-masked phase based on a statistically significant improvement in total symptom score, from a mean score of 10.32 at baseline (initial visit) to 3.79 after 4 weeks of single-masked domperidone therapy. During the double-masked phase, patients in the placebo group had significantly greater deterioration in total symptom scores compared with patients in the domperidone group (mean changes of 1.84 and 0.85, respectively). Similar significant differences in favor of domperidone were seen in the secondary efficacy variables (i.e., patients' diary scores and global assessments of symptoms). The tolerability profile of domperidone was similar to that of placebo. Patients who responded to domperidone experienced significant improvements in quality of life, as indicated by the SF-36 physical and mental component summary scores. During the double-masked phase, patients who were randomized to placebo experienced a significant deterioration in the physical component summary score compared with patients in the domperidone group. The results of this study suggest that domperidone 20 mg QID provides significant improvement in the upper gastrointestinal symptoms of diabetic gastroparesis and is well tolerated in patients with this condition.
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PMID:Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. DOM-USA-5 Study Group. 966 60


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