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)

Decisions to resect small aortic aneurysms or employ non-operative treatment for aorto-iliac occlusive disease must depend on current rather than historical surgical results. To assess current morbidity and mortality, we reviewed 200 consecutive aortic resections in two groups of patients treated from 1981 to 1989: those undergoing elective aortofemoral bypass for occlusive disease (AFB, no. 100) or resection of infrarenal abdominal aortic aneurysms (AAA, no. 100). Indications for AFB included claudication (54%), rest pain (32%), and gangrene (13%). AAA size ranged from 3 to 14 cm (mean 6.5 +/- 2.4 cm); 45% presented with abdominal or back pain. Patients undergoing AFB were younger (AFB 61.5 +/- 10 years vs AAA 68.7 +/- 8.9 years) with a higher incidence of some atherosclerotic risk factors, diabetes mellitus 30% vs 10%, tobacco use 77% vs 49%, hyperlipidemia 21% vs 7%; p less than 0.001). Coronary artery disease (CAD) was more prevalent in AAA patients (49% vs 34%; p less than 0.001). Postoperative mortality was not different in occlusive or aneurysmal disease (3% AFB vs 2% AAA), nor was the occurrence of serious complications such as myocardial infarction (2% vs 1%) or pulmonary embolism (2% vs 3%). Improvements in patient selection, perioperative care and surgical technique have lowered the mortality of elective aortic surgery. Given the current standard of care, an aggressive approach to AAA even in high risk patients is appropriate. The low morbidity of AFB for occlusive disease mandates a critical appraisal of less effective nonoperative therapies.
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PMID:Current results of elective aortic reconstruction for aneurysmal and occlusive disease. 221 95

An electrophoretic variant of the lactate dehydrogenase (LDH)-B(H) subunit was discovered in a patient with diabetes mellitus. His LDH activity in serum was slightly lower than normal and the LDH isozyme pattern showed an abnormal migration indicating an LDH-B subunit variant of the fast type. The LDH containing the variant subunit revealed a decreased heat stability. DNA analysis of the variant allele detected a base substitution, an A to G transition, at codon 6 (AAA-->GAA). The mutation resulted in the replacement of a lysine by a glutamic acid (K6E). The change may cause the heat instability and affect the net charge of the variant subunit, resulting in an electrophoretic LDH-B subunit variant of the fast type.
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PMID:Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit. 831 53

Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The objective of this study was to search for mutations in the Kir6.2 gene that might be associated with NIDDM or related to altered insulin secretion, insulin action, or glucose metabolism in healthy subjects. Using polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) on genomic DNA from 69 Danish NIDDM patients and 66 matched control subjects, we report the finding of three missense polymorphisms in otherwise conserved codons and three silent polymorphisms in the gene encoding Kir6.2: codon 23 (GAG/AAG), Glu-->Lys; codon 190 (GCT/GCC), Ala-->Ala; codon 267 (CTC/CTG), Leu-->Leu; codon 270 (CTG/GTG), Leu-->Val; codon 337 (ATC/GTC), Ile-->Val; codon 381 (AAG/AAA), Lys-->Lys. The codon 23 and codon 337 amino acid polymorphisms were always coupled. The allelic frequencies of the polymorphisms were similar in NIDDM patients and control subjects. The amino acid polymorphisms were not associated with altered insulin secretion after intravenous glucose or tolbutamide injections or with altered glucose effectiveness in a phenotype study of 346 young healthy subjects. However, carriers of the maximal load of amino acid variants, the compound homozygous codon 23/337 and heterozygous codon 270, had on average a 62% higher insulin sensitivity index (P = 0.006), compared with noncarriers. We conclude that a combination of common Kir6.2 amino acid variants may contribute to the genetic background behind the large variation of the insulin sensitivity index in the general population.
Diabetes 1997 Mar
PMID:Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM. 903 10

During a recent 30-month period, we repaired 10 ruptured abdominal aortic aneurysms (RAAA) at our institution. To evaluate the survival, postoperative morbidity, and financial impact of treating RAAA, we compared these patients with 10 randomly selected patients undergoing elective AAA (EAAA). Both groups were comparable for age, gender, and incidence of diabetes, hypertension, coronary artery disease, chronic obstructive pulmonary disease (COPD), and renal failure. Although we have noted a dramatic increase in survival for RAAA (90%), the morbidity continues to be unacceptably high (60%). Efforts should be made toward better detection of AAA prior to rupture as well as development of strategies to minimize or prevent these major complications. Potential average savings accrued from one patient undergoing EAAA repair rather than RAAA repair ($93,139. 21) can be used to perform screening abdominal ultrasound tests in patients at increased risk of having an AAA.
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PMID:Ruptured versus elective abdominal aortic aneurysm repair: outcome and cost. 1054 16

The objective of this report was to analyze the current surgical results of operative treatment in patients suffering ruptured AAA (abdominal aortic aneurysms) and to define those independent predictive factors for mortality. During a period of 2 years, from January 1996 to December 1997, 144 patients operated on for ruptured AAA in 10 hospitals were included in a multicenter retrospective study. Among the collected variables concerning each patient, those with potential relation to surgical mortality were studied: gender, age, diabetes, hypertension, cardiopathy, pulmonary obstructive disease, preoperative renal dysfunction, symptomatic cerebrovascular disease, peripheral vascular disease, hematocrit on admission, preoperative hypotension < 80 mmHg, loss of consciousness, cardiac arrest, aortic aneurysm location (infrarenal versus non-infrarenal), iliac involvement, aneurysm size, type of rupture, left renal vein ligature, ligature of a patent inferior mesenteric artery, place of aortic cross-clamping, type of grafting, exclusion of both hypogastric arteries, venous technical complications, associated surgery, use of cell saver, intraoperative blood loss, and postoperative complications (renal failure, sepsis, coagulopathy, cardiac complications, pulmonary complications, colon ischemia, prosthetic graft complications, and need for reoperation). Those variables with statistical significance in the univariate analysis were introduced into a multivariate logistic regression model to determine the independent predictors of death. From our results we concluded that surgery for ruptured abdominal aortic aneurysms continues to have an excessively high mortality rate. Even though some preoperative variables could be identified as predictors of mortality, an absolute mortality risk has not yet been determined and the decision to negate surgery should be individualized rather than taken on that basis only. Early diagnosis and treatment of symptomatic aneurysms would improve mortality figures and selective screening should be contemplated.
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PMID:Factors increasing the mortality rate for patients with ruptured abdominal aortic aneurysms. 1176 39

Open abdominal aortic aneurysm repair has been reported to be associated with impairment of sexual function in men, most likely because of autonomic nerve injury and pelvic blood flow changes. Endovascular aneurysm repair does not involve dissection in the area of the iliac bifurcation and therefore may be associated with lower incidence of sexual dysfunction as compared to open repair. We conducted a retrospective study of males after open and endovascular abdominal aortic aneurysm repair to determine if there is a significant difference in the incidence of sexual dysfunction between the two procedures. A modified International Index of Erectile Function Questionnaire was used to access sexual function before and after aneurysm repair. The questionnaire was mailed to all male patients who underwent abdominal aortic aneurysm repair from January 1, 1999 to July 15, 2002. The questionnaire asked patients questions regarding their sexual function before and 3 months after the repair. Questionnaire scores for domains of sexual function (erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction) as well as the total questionnaire score were analyzed. The chi-square and Wilcoxon's signed ranks test were used for statistical comparisons, with p < 0.05 considered significant. Logistic regression was used to examine association. Two hundred ninety-three questionnaires were mailed and 90 were returned completed. There was no difference for the total questionnaire score or the erectile function score before the procedure. Based on the questionnaire score, erectile function worsened after open AAA repair ( p = 0.002). Orgasmic function also deteriorated after open AAA repair ( p = 0.001). Endovascular repair was not accompanied by decreased erectile or orgasmic function ( p = 0.057 and p = 0.068, respectively). Impairment of erectile function was not associated with age, diabetes, or the number of patent hypogastric arteries after aneurysm repair, but there was a significant association between impaired erectile function and open aneurysm repair ( p = 0.036). Endovascular repair of abdominal aortic aneurysms is associated with significantly less impairment of erectile and orgasmic function than that with open repair. Preservation of sexual function after endovascular as compared to open repair should be among the factors considered when weighing treatment options for an abdominal aortic aneurysm in a sexually active male.
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PMID:Erectile function after open or endovascular abdominal aortic aneurysm repair. 1450 65

ATP-sensitive K+ channels (K(ATP) channels) control electrical activity in beta-cells and therefore are key players in excitation-secretion coupling. Partial suppression of beta-cell K(ATP) channels in transgenic (AAA) mice causes hypersecretion of insulin and enhanced glucose tolerance, whereas complete suppression of these channels in Kir6.2 knockout (KO) mice leads to hyperexcitability, but mild glucose intolerance. To test the interplay of hyperexcitability and dietary stress, we subjected AAA and KO mice to a high-fat diet. After 3 months on the diet, both AAA and KO mice converted to an undersecreting and markedly glucose-intolerant phenotype. Although Kir6.2 is expressed in multiple tissues, its primary functional consequence in both AAA and KO mice is enhanced beta-cell electrical activity. The results of our study provide evidence that, when combined with dietary stress, this hyperexcitability is a causal diabetic factor. We propose an "inverse U" model for the response to enhanced beta-cell excitability: the expected initial hypersecretion can progress to undersecretion and glucose-intolerance, either spontaneously or in response to dietary stress.
Diabetes 2004 Dec
PMID:Diet-induced glucose intolerance in mice with decreased beta-cell ATP-sensitive K+ channels. 1556 46

Using B-mode ultrasound, we studied the prevalence of abdominal aortic aneurysm (AAA; diameter > or =3 cm) and its predictive risk factors in 109 consecutive patients who were >60 years of age and had coronary artery disease (CAD). A group of 60 age-matched patients who did not have CAD served as controls. The prevalence of AAA was higher in the CAD group than in the control group (14%, 16 of 109, vs 3%, 2 of 60, p <0.05). By multivariate analysis, only smoking was strongly associated with AAA (odds ratio 4.86, 95% confidence interval 1.55 to 15.25). In contrast, presence of diabetes mellitus was negatively associated with AAA in univariate analysis (odds ratio 0.11, 95% confidence interval 0.01 to 0.83) and a strong trend of inverse association remained in multivariate analysis (odds ratio 0.12, 95% confidence interval 0.01 to 1.03). Thus, systematic screening can detect AAA in 1 of 7 patients who are >60 years of age and have CAD. AAA shares some, but not all, risk factors of atherosclerosis.
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PMID:Frequency of abdominal aortic aneurysm in patients >60 years of age with coronary artery disease. 1667 3

Mono-O-glycosylations post-translationally regulate the activity of nucleocytoplasmic proteins. We showed that glucosamine and an inhibitor of deglycosylation (PUGNAc) induced O-glycosylation of FoxO1, resulting in increased expression of a glucose-6-phosphatase reporter gene. This effect was independent of FoxO1 re-localisation, since it was also observed with constitutively nuclear FoxO1-AAA mutant. Moreover, in HepG2 cells, glucosamine and PUGNAc have a synergistic effect on the glucose-6-phosphatase reporter gene, and this effect was inhibited by FoxO1 siRNAs. Since glucose-6-phosphatase plays a key role in hepatic glucose production, our observation may be of importance with regard to glucotoxicity associated with chronic hyperglycaemia in diabetes.
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PMID:O-glycosylation of FoxO1 increases its transcriptional activity towards the glucose 6-phosphatase gene. 1828 Feb 54

Carotid duplex ultrasonography (DUS) is routinely performed prior to coronary artery bypass graft surgery (CABG) on all patients > 65 years old because of the reported associated risk of finding concomitant carotid artery stenosis. Identifying risk factors that correlate with severe carotid stenosis may result in more cost-effective screening for patients with asymptomatic carotid artery disease prior to CABG. We performed a retrospective study to identify risk factors for significant carotid artery disease in patients scheduled to undergo CABG between March 2005 and March 2008 at the Massachusetts General Hospital. Patients with carotid stenosis >or= 70% identified by DUS (n = 50) were matched by age and sex to control patients who had < 50% stenosis (n = 50). Data were analyzed using the chi-squared test or analysis of variance as appropriate. Logistic regression was used to examine multivariate correlates of carotid stenosis. A total of 643 patients were screened to arrive at the patient cohorts described below. This produced a prevalence of 7.7% for significant (> 70%) carotid disease. The patient cohorts were predominantly male with no significant difference in the incidence of diabetes, hypertension, extent of coronary artery disease (CAD) (i.e. left main coronary artery disease (LMCA) and one, two-, or three-vessel CAD) or lipid abnormalities in the two groups. Univariate analysis identified the presence of peripheral arterial disease (PAD, p = 0.001), a cervical bruit (p < 0.0001), a prior neurological event (p = 0.020), and the presence of an abdominal aortic aneurysm (AAA; p = 0.046) as significant predictors of >or= 70% internal carotid artery stenosis. Logistic regression analysis revealed that the presence of a carotid bruit (p = 0.0068) and PAD (p = 0.0194) were associated with an increased risk of significant carotid artery disease. In conclusion, the presence of a carotid bruit or PAD predicts an increased likelihood of significant carotid artery disease in patients undergoing CABG. Unlike previous studies, LMCA or extent of CAD did not correlate with significant carotid artery disease. Using these predictive models, a prospective outcomes trial is required to validate these criteria.
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PMID:Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting--a case control study. 1965 73


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