Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin dependent (IDD) and non-insulin dependent diabetes (NIDD) are separate disorders. Twin studies show that IDD cannot be entirely due to genetic causes as concordance is no more than about 50%, but there is some inherited predisposition to it as shown by HLA patterns. NIDD, on the other hand, is predominantly due to genetic causes since identical twins are nearly always concordant. Many cases of NIDD show chlorpropamide alcohol flushing (CPAF), a dominantly inherited feature which may precede the appearance of diabetes and thus act as a genetic marker for this type of diabetes. Diabetics who show chlorpropamide acohol flushing are less likely to develop retinopathy than those who do not. Genetic factors must therefore affect the incidence and severity of diabetic retinopathy. Chlorpropamide alcohol flushing is due to sensitivity to enkephalin. Enkephalin and other opioids affect carbohydrate metabolism and insulin release. It is possible therefore that they act as neurotransmitters and cause NIDD by a sympathetically mediated effect on the liver and pancreas--in other words, that as far as NIDD is concerned Claude Bernard's views on the cause of diabetes may have been right.
 ...
PMID:Diabetes: the genetic connections. 39

Chlorpropamide (CP), a sulfonylurea-type oral hypoglycemic agent, is known to provoke a flushing reaction reminiscent of the disulfiram-ethanol reaction in certain individuals. This is manifested in rodents by an increase in blood acetaldehyde levels after ethanol administration. When the sulfonamide N1-nitrogen of CP was substituted with an ethyl group, the product, N1-ethylchlorpropamide, was found to be three times as active as CP in raising ethanol-derived blood acetaldehyde. However, whereas CP lowered fasting blood glucose in rats measured over 6 h, N1-ethylchlorpropamide was devoid of hypoglycemic activity, suggesting that the latter might be potentially useful as an alcohol deterrent agent.
 ...
PMID:A nonhypoglycemic chlorpropamide analog that inhibits aldehyde dehydrogenase. 305 78

Chlorpropamide/alcohol flushing (CPAF), found in many patients with non-insulin-dependent diabetes (NIDD), can be blocked by indomethacin in most patients who are free of vascular complications but not in those with such complications. Since indomethacin is a prostaglandin inhibitor this finding suggests that prostaglandins may be involved in the aetiology of vascular diseases in NIDD. All 6 pairs of identical twins with CPAF, of whom 2 pairs were disocrdant for diabetes, were concordant for indomethacin blocking, which suggests that the block has a genetic basis. The difference in the response of CPAF to indomethacin in diabetic patients with and without vascular complications is probably the first indication of a metabolic difference between these two types of patient.
 ...
PMID:Blockade of chlorpropamide-alcohol flushing by indomethacin suggests an association between prostaglandins and diabetic vascular complications. 610 37

Chlorpropamide-alcohol flushing may be due to sensitivity to endogenous opiates. To investigate this possibility the plasma met-enkephalin and beta-endorphin responses to sherry with and without chlorpropamide were studied in six patients with non-insulin dependent diabetes and in six normal subjects. After chlorpropamide all patients showed a rise in met-enkephalin concentrations from a basal level of 50 +/- 7.2 ng/l to a peak of 75 +/- 8.1 ng/l (p less than 0.001). In contrast, before chlorpropamide treatment was started met-enkephalin values did not change after alcohol. No significant changes in beta-endorphin values were observed. In six normal subjects pretreated with chlorpropamide the met-enkephalin concentration also rose from a basal level of 72 +/- 15 ng/l to a peak of 103 +/- 9.4 ng/l (p less than 0.002). Again, the met-enkephalin rise was not observed after placebo. Neither beta-endorphin concentrations nor facial temperature changed significantly. These data suggest that endogenous opiates may be implicated in CPAF. Furthermore, this is the first study in which a significant change in circulating met-enkephalin values has occurred.
 ...
PMID:Chlorpropamide alcohol flush and circulating met-enkephalin: a positive link. 626 88

Twelve maturity-onset diabetic subjects were treated with chlorpropamide once daily, glibenclamide once daily, or glibenclamide twice daily in a crossover design study. Doses were increased until the fasting blood glucose concentrations became less than 6 mmol/L (108 mg/dl), at which time the patients were admitted for a 24-h study period. There was little difference between the plasma glucose and insulin responses to chlorpropamide or glibenclamide given twice daily (mean doses 489 and 11 mg/day, respectively). When glibenclamide was given once daily (mean dose 9 mg/day), similar plasma glucose concentrations during the day were obtained with slightly higher plasma glucose concentrations during the night. Four patients had chlorpropamide-induced flushing with alcohol, and six patients had postprandial hypoglycemia on glibenclamide. Chlorpropamide once daily or glibenclamide twice daily are suitable for control based on fasting blood glucose measurements.
 ...
PMID:Comparison of chlorpropamide and glibenclamide treatment of maturity-onset diabetes: control assessed by fasting plasma glucose concentrations. 678 74

Seventy patients with non-insulin dependent diabetes (NIDD) were studied for the chlorpropamide-alcohol flush (CPAF), first degree family history of diabetes, macroangiopathy and for peripheral neuropathy. Positive CPAF challenge tests were found in 65% of the tested subjects and in 77% if there was a family history of diabetes. Signs of macroangiopathy (loss of foot pulses) were significantly (p less than 0.05) less common in the CPAF positive than in the CPAF negative diabetics with a duration of diabetes of ten years or less. With a longer duration this difference between the two groups was reduced. Also signs of peripheral neuropathy (abnormal vibration sense) were less common (p less than 0.05) in the CPAF positive diabetics than in the CPAF negative. Previously a low prevalence of retinopathy in teh CPAF positive non-insulin dependent diabetics has been reported. We have shown that this is also true of peripheral macroangiopathy and peripheral neuropathy. Chlorpropamide-alcohol flushing seems to be related to a relative protection against late complications in diabetes and the test might be used to find patients at risk.
 ...
PMID:Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes. 695 48

Chlorpropamide-alcohol flushing (CPAF) has been advanced and challenged as a specific marker for familial noninsulin dependent diabetes mellitus. The previous studies assay flushing reactions employing arbitrarily defined critical threshold values of rise and rate of rise in facial temperature. Since these methods ignore the curvilinear relationship between skin temperature and cutaneous blood flow, errors of analysis obtained, Further, the role of baseline facial temperature is obfuscated. The method of malar thermal circulation index derived from the relationship between skin temperature and cutaneous blood flow provides a more accurate assay method and permits the characterization of the role of baseline facial temperature. Baseline facial temperature is less in subjects with CPAF and noninsulin dependent diabetes than in normal subjects. The lower baseline facial temperature alone may account for the reported differences in the parameters of the CPAF test.
 ...
PMID:Chlorpropamide-alcohol flushing, malar thermal circulation index, and baseline malar temperature. 712 Dec 66

Chlorpropamide alcohol flushing (CPAF) in non-insulin-dependent diabetics (NIDDs) has been reported to be associated with a lower tendency to develop late complications. The flush was thought to be mediated by enkephalins and prostaglandins. Early studies could not correlate CPAF to increased levels of acetaldehyde in blood and the flush was not regarded as an antabuse-like reaction. In this study, the increase of plasma acetaldehyde during the flush in 13 CPAF positive diabetics was significantly (P less than 0.005) higher than in the 13 CPAF negative diabetics during a CPAF challenge test. The increase of plasma acetaldehyde was reduced to the level of CPAF negative diabetics in three CPAF positive diabetics when they were exposed to alcohol without premedication with chlorpropamide and they did not flush. The normal breakdown of ethanol to acetic acid via acetaldehyde appears to be inhibited by chlorpropamide in the flushers. Acetaldehyde measurement is an objective method to study the chlorpropamide alcohol flush and it appears superior to the measurement of skin temperature.
 ...
PMID:Increase of plasma acetaldehyde. An objective indicator of the chlorpropamide alcohol flush. 726 73