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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a biometrically planned, randomised double blind crossover study the influence of a glucosidase inhibitor, acarbose, (Bay g 5421, pseudotetrasaccharide) on the blood glucose in a total of 10 dieting obese NIDDM patients was compared with placebo. There were no significant differences between the groups with regard to age, height, body weight and duration of diabetes. After a 2-week preliminary period 5 patients received Bay g 5421 for 4 weeks and then placebo for a further 4 weeks. After the same preliminary period the other 5 patients received placebo for 4 weeks and then Bay g 5421 for the second period of 4 weeks. On average, the blood glucose profiles were lower after Bay g 5421 than after placebo. This was statistically almost significant (p less than or equal to 0.09) for the area of the profiles, i.e., the average value of the 13 points of the daily profiles. The fraction of glycosylated hemoglobins (Hb A1a-c) was also lower during the period when the patients were treated with Bay g 5421 than with placebo. There was, however, no statistically significant difference. In contrast, the glucosuria-decrease during the Bay g 5421 period was significant. The serum cholesterol and serum triglycerides did not show any therapy-dependent difference. Thus it may be concluded that Bay g 5421 effectively reduces the blood glucose concentration, in particular, postprandial hyperglycemia in dieting diabetic patients type 2.
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PMID:[Effect of glucosidase inhibitor, Bay g 5421 (acarbose), on the blood glucose in obese diabetic patients ty pe 2 (NIDDM) (author's transl)]. 719 Dec 99

The treatment of type II diabetes should not only concentrate on blood glucose levels but also should take symptoms like insulin resistance, hyperinsulinemia, low HDL-cholesterol, high VLDL, and systemic hypertension into consideration. These symptoms are well described by the metabolic syndrome and are known to be risk factors of macroangiopathy. In obese type II diabetic patients weight loss by caloric restriction is the most essential therapeutic step. Retarding intestinal carbohydrate uptake glucosidase-inhibitors are able to lower postprandial blood glucose levels without stimulating insulin secretion. The biguanide metformin is suitable to diminish peripheral insulin resistance, gluconeogenesis, and intestinal glucose absorption on cellular mechanisms others than betacytotropic effects. In non obese type II diabetic patients sulfonylureas are advantageous because of meal related stimulation of endogenous insulin which runs the physiological way with first pass through the liver. Therefore, sulfonylurea treatment should be continued when secondary failure indicates the need for exogenous insulin. In accordance with the course of type II diabetes in secondary failure insulin should be added to sulfonylureas in as small amounts as possible to ameliorate poor metabolic control. Thus iatrogenic hyperinsulinemia and resulting insulin resistance can be largely avoided. If there is any long term benefit when different oral antidiabetic agents are administered together with insulin has to be evaluated in further clinical studies.
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PMID:[Combination therapy of oral antidiabetic drugs with insulin]. 847 36

The progress of knowledge relating to non-insulin-dependent diabetes mellitus (NIDDM) is associated with new therapeutic developments. Their different respective targets allow to classify them in drugs stimulating insulin secretion (glimepiride, repaglinide, glucagon-like peptide 1), medications reducing insulin resistance (thiazolidinediones) or in insulinmimetic agents (vanadium). Alpha glucosidase inhibitors, available in France since 1993, constitute another therapeutic approach, reducing postprandial hyperglycemia by delaying the digestion of complex carbohydrates. These new medications, safer and sometimes effective in a single daily administration, represent an alternative to classic oral antidiabetic agents allowing therapeutic combinations and a more global management of NIDDM.
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PMID:[New therapies in type 2 diabetes]. 978 90

The pseudooligosaccharide acarbose is a potent inhibitor of amylases, glucosidases, and cyclodextrin glycosyltransferase and is clinically used for the treatment of so-called type II or insulin-independent diabetes. The compound consists of an unsaturated aminocyclitol, a deoxyhexose, and a maltose. The unsaturated aminocyclitol moiety (also called valienamine) is primarily responsible for the inhibition of glucosidases. Due to its structural similarity to maltotetraose, we have investigated whether acarbose is recognized as a substrate by the maltose/maltodextrin system of Escherichia coli. Acarbose at millimolar concentrations specifically affected the growth of E. coli K-12 on maltose as the sole source of carbon and energy. Uptake of radiolabeled maltose was competitively inhibited by acarbose, with a Ki of 1.1 microM. Maltose-grown cells transported radiolabeled acarbose, indicating that the compound is recognized as a substrate. Studying the interaction of acarbose with purified maltoporin in black lipid membranes revealed that the kinetics of acarbose binding to LamB is asymmetric. The on-rate of acarbose is approximately 30 times lower when the molecule enters the pore from the extracellular side than when it enters from the periplasmic side. Acarbose could not be utilized as a carbon source since the compound alone was not a substrate of amylomaltase (MalQ) and was only poorly attacked by maltodextrin glucosidase (MalZ).
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PMID:Acarbose, a pseudooligosaccharide, is transported but not metabolized by the maltose-maltodextrin system of Escherichia coli. 1019 28

1. We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with effects to inhibit alpha-1, 6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. 2. The infarct size as a percentage of area at risk was not reduced by pre-ischaemic treatment with 1 mg kg(-1) miglitol (42.7+/-4.0%, n=10) compared with the saline control group (41.7+/-2.3%, n=10). However, it was significantly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 mg kg(-1) of miglitol (25.7+/-4. 5%, n=10, and 14.6+/-2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing effect after pre-reperfusion treatment with 10 mg kg(-1) of miglitol (35.0+/-3.0%, n=10). 3. Another 40 rabbits given 1, 5 and 10 mg kg(-1) of miglitol or saline before ischaemia (n=10 in each) were sacrificed at 30 min of ischaemia for biochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. 4. Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose-dependent effect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be beneficial for coronary heart disease as well as diabetes mellitus.
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PMID:A novel anti-diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits. 1058 21

Nephrogenic diabetes insipidus (DI) secondary to chronic urinary tract obstruction is a rare disease. The exact cause is unknown but it is likely that increased collecting duct pressures cause damage to the tubular epithelium, resulting in insensitivity to the action of arginine-vasopressin (AVP). A 77-year-old man complaining of polyuria and polydipsia was treated with alpha glucosidase inhibitor under the impression of polyuria due to diabetes mellitus. But his symptoms did not improve. Water deprivation and AVP administration study revealed that the patient had nephrogenic DI. Urinary tract obstruction due to an enlarged prostate was suggested as a principal cause of nephrogenic DI. The patient underwent transurethral resection of the prostate and bilateral subcapsular orchiectomy. After surgery, the urine osmolarity was normalized and the patient became symptom-free. We report a case of nephrogenic DI due to obstructive uropathy which was cured by surgery eliminating obstruction.
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PMID:A case of nephrogenic diabetes insipidus caused by obstructive uropathy due to prostate cancer. 1073 36

Type 2 diabetes is responsible for various micro and macro-vascular complications, appearing early in the course of the disease. The UKPDS results clearly demonstrate the interest of an early and intensive treatment of hyperglycaemia to reduce theses microvascular complications and, to a lesser extent, macrovascular complications. The UKPDS also demonstrate the limits of the current management of type 2 diabetes: delayed diagnosis when several complications already exist, difficulties to maintain an adequate glucose control over the time, particularly with monotherapy, need for an intensive combination treatment policy, unwanted effects of this intensive treatment (weight gain, hypoglycaemias). The 3 classes of oral antidiabetic agents currently available (sulfonylureas and meteglinide analogues, metformin, a-glucosidase inhibitors) imperfectly cover the current therapeutic needs. Thus, the new class, the thiazolidinediones, acting on key physiopathological components, appears as a welcome addition to the treatment of type 2 diabetes. The association of metformin (or a sulfonylurea) and a thiazolidinedione should permit to obtain early a better glycaemic control without the hypoglycaemic risk associated with intensive therapy at an early stage of type 2 diabetes.
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PMID:[Is a new therapeutic class justified in the treatment of type 2 diabetes?]. 1203 11

The exponential expansion of the publicly available human DNA sequence database has increasingly facilitated cloning by homology of genes for biochemically defined, functionally similar proteins. We hypothesized that an as-yet uncloned human alpha-glucosidase (human neutral alpha-glucosidase C or GANC) is a previously uncharacterized member of a paralogous human glycosyl hydrolase gene family 31, sharing sequence homology and related, but not identical, functions with other cloned human alpha-glucosidases. We now report both the in silico and physical cloning of two alleles of human neutral alpha-glucosidase (designated GANC on the human gene map). This cloning and correct identification and annotation as GANC was successful only because of the application of the biochemical and genetic information we had previously developed regarding this gene to the results of the in silico method. Of note, this glucosidase, a member of family 31 glycosyl hydrolases, has multiple alleles, including a "null" allele and is potentially significant because it is involved in glycogen metabolism and localizes to a chromosomal region (15q15) reported to confer susceptibility to diabetes.
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PMID:Computer assisted cloning of human neutral alpha-glucosidase C (GANC): a new paralog in the glycosyl hydrolase gene family 31. 1237 Apr 36

The treatment approach of diabetes mellitus during pregnancy requires a combination of diet, exercise, multiple home glucose determinations and intensive insulin regimens. During the last decade there was an increased interest in the use of oral antihyperglycemic agents (OAHAs) as an alternative to insulin in achieving good glycemic control. OAHAs are divided into four groups: derivatives of sulfonylurea, biguanides, glucosidase inhibitors and thiazolidinediones. This review describes the possible teratogenic effects of the use of OAHAs during pregnancy and the effects of these drugs during lactation. Animal and human studies assessing the teratogenic effects of OAHAs have yielded conflicting data because the risk of major malformations in infants of mothers with diabetes appears to be related to maternal glycemic control rather than the antidiabetic therapy. A major concern with the use of OAHAs during pregnancy is neonatal hypoglycemia, which may be severe and persist for days. Therefore, insulin is still the drug of choice because it has not been implicated as a teratogen in human pregnancies. In addition, because of the lack of data regarding the use of OAHAs in pregnancy, we cannot draw firm conclusions about all of the available drugs. However, OAHAs, especially glibenclamide (glyburide), may be beneficial in a situation where the proper use of insulin is problematic. Because there are very limited clinical data on the exposure of OAHAs to the infant via breast milk, and the potentially serious effect of neonatal hypoglycemia, the safest recommendation is not to breast feed while taking OAHAs. Well-conducted, prospective, controlled studies regarding the feasibility of OAHAs in pregnant women with diabetes and during lactation are needed.
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PMID:Oral antihyperglycemic agents during pregnancy and lactation: a review. 1239 47

The recent advance of the carotid artery echotomography indicates the intima media thickness(IMT) of the carotid artery as one of surrogate endpoints of atherosclerosis in subjects with multiple risk factors, such as hypertension, hyperlipidemia, and diabetes mellitus. IMT is shown to be increased in subjects with hyperlipidemia, type 1 and 2 diabetes mellitus, and other several diseases. Also, increase in IMT is related with the prevalence of cerebral infarction and coronary artery diseases. The carotid artery plaques including soft or calcified plaques were shown to predict appearance of strokes. Several drugs, such as anti-diabetogenic drugs(insulin-sensitizer, biguanides, and alfa-glucosidase inhibitor), hypotensive drugs(ACEI, Ca-blocker), and anti-platelet drugs were shown to attenuate the progression of IMT. Recently, we have shown that an anti-platelet drug arrested the progression of IMT and significantly reduced appearance of asymptomatic cerebral infarction in subjects with type 2 diabetes. These data clearly indicate the usefulness of the carotid artery echography in subjects with atherosclerosis and IMT could evaluate the effects of treatment for atherosclerosis.
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PMID:[Evaluation of carotid artery lesion by echography]. 1473 40


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