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

The SHROB rat is a unique strain with genetic obesity, hypertriglyceridemia, hyperinsulinemia, renal disease with proteinuria, and genetically determined hypertension, characteristics paralleling human Syndrome X. The obese phenotype results from a single homozygous recessive trait, designated faK, and is allelic with the Zucker fatty trait (fa), but of distinct origin. The faK mutation is a premature stop codon in the extracellular domain of the leptin receptor, resulting in a natural receptor knockout. The SHROB are glucose intolerant compared to heterozygous or wild-type SHR, but retain fasting euglycemia even on a high sucrose diet, suggesting that diabetes requires polygenic interaction with additional modifier genes. Insulin-stimulated phosphorylation of tyrosine residues on the insulin receptor and on the associated docking protein IRS-1 are reduced in skeletal muscle and liver compared to SHR, due mainly to diminished expression of insulin receptor and IRS-1 proteins. Despite multiple metabolic derangements and severe insulin resistance, hypertension is not exacerbated in SHROB compared to SHR. Thus, insulin resistance and hypertension are independent in this model. Increased activity of the sympathetic nervous system may be a common factor leading by separate pathways to hypertension and to insulin resistance. We studied the chronic effects of sympathetic inhibition with moxonidine on glucose metabolism in SHROB. Moxonidine (8 mg/kg/day), a selective I1-imidazoline receptor agonist, not only reduced blood pressure but also ameliorated glucose intolerance. Moxonidine reduced fasting insulin by 47% and plasma free fatty acids by 30%. Moxonidine enhanced expression and insulin-stimulated phosphorylation of IRS-1 in skeletal muscle by 74 and 27%, respectively. Thus, central sympatholytic therapy not only counters hypertension but also insulin resistance, glucose tolerance, and hyperlipidemia in the SHROB model of Syndrome X.
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PMID:Molecular pathology in the obese spontaneous hypertensive Koletsky rat: a model of syndrome X. 1084 68

The age-related patterns of clustering of cardiovascular risk variables of Syndrome X from childhood to adulthood were examined in a community-based sample of black and white children (aged 5-10 years, n = 2,389), adolescents (aged 11-17 years, n = 3,371), and young adults (aged 18-37 years, n = 2,115). In the analysis of clustering, insulin resistance index, BMI, triglycerides/ HDL cholesterol ratio, and mean arterial pressure were used either as categorical variables (age-, race- and sex-specific values >75th percentiles) to calculate risk ratios (observed frequency/expected frequency) or as continuous variables (normal scores based on ranks) to compute intraclass correlations. In the total sample, the risk ratio for clustering of adverse levels of all 4 variables was 9.8 for whites (P < 0.01) versus 7.4 for blacks (P < 0.01); the intraclass correlation was 0.33 for whites (P < 0.001) versus 0.26 for blacks (P < 0.001). Both the risk ratio and intraclass correlation were significantly higher in whites than in blacks in the total sample. The intraclass correlations of the 4 variables were significant (P < 0.001) in all race and age-groups, and they were higher during preadolescence and adulthood than during adolescence. Furthermore, unlike risk ratios, intraclass correlations showed a continuous increase with age during adulthood. When BMI was adjusted, the intraclass correlations involving the other 3 variables were reduced by approximately 50%, and the age-related pattern was no longer evident. These results suggest that the degree of clustering of risk variables of Syndrome X varies with age from childhood to adulthood and is likely influenced by the age-related changes in obesity and the attendant insulin resistance.
Diabetes 2000 Jun
PMID:Age-related patterns of the clustering of cardiovascular risk variables of syndrome X from childhood to young adulthood in a population made up of black and white subjects: the Bogalusa Heart Study. 1086 58

The cocaine- and amphetamine-regulated transcript (CART) peptide is a recently characterized neuropeptide implicated in the control of appetite. We hypothesized that genetic variation in CART may contribute to human obesity. The entire coding region of CART was determined by nucleotide sequencing in 91 unrelated subjects with severe early-onset obesity. A novel amino acid change, Ser66Thr, was found in 2 probands and in 0 of 100 control subjects but did not cosegregate with obesity in family studies. Two common polymorphisms were found in the 3'-untranslated region (A1475G and deltaA1457). An effect of these polymorphisms on body composition and intermediate phenotypes related to obesity was examined in a large Caucasian population in the U.K. Neither polymorphism showed any significant relationship with obesity; however, men heterozygous for the A1475G variant had significantly lower waist-to-hip ratio (WHR), fasting plasma insulin, and fasting triglycerides. Regression analysis indicated that the effects on insulin and triglycerides were likely to be secondary to the effects on WHR. Thus, we have conducted the first systematic study of the CART gene in human obesity, and although no clear association with obesity was found, the data suggest that genetic variation in the CART locus might influence fat distribution and variables related to syndrome X.
Diabetes 2000 May
PMID:The CART gene and human obesity: mutational analysis and population genetics. 1090 99

The low detection rate and undertreatment of depression in general medical practice is pervasive. The persistence of this problem suggests that doubt remains within elements of the medical profession that depression is a medical condition meriting medical treatment, as opposed to an existential state, inevitable for the human condition. Depression is a physical and psychological clinical disorder which affects every aspect of human physiology. As such it deserves consideration as a comorbid medical illness requiring treatment as does hypertension in relation to diabetes. This article will illustrate how clinical depression is a comorbid medical illness requiring detection and treatment through the analysis of depression's impact on two conditions called Syndrome X. Conditions labeled Syndrome X in endocrinology and cardiology demonstrate how depression amplifies the pathophysiology of endocrine and cardiac disease and diminishes functional variability (regularizes variance) found in normal physiology.
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PMID:Syndrome X, depression, and chaos: relevance to medical practice. 1090 97

Multiple metabolic syndrome (MMS) implies a frequent coincidence of four basic serious metabolic risk factors for subsequent manifestation of cardiovascular disease. The latter include: central type obesity, arterial hypertension, dyslipoproteinaemia and diabetes mellitus type II (non-insulin-dependent diabetes mellitus--NIDDM). MMS is also described as syndrome X, Reaven's syndrome, insulin resistance syndrome, metabolic syndrome or as the "deadly quartet". NIDDM in humans is conceived as a syndrome the pathogenesis of which is multifactorial and it is not an unequivocal nosological unit. It many epidemiological studies reliable evidence was provided that in the aetiology of NIDDM a marked genetic influence is involved. Its genetic predisposition is conditioned by the interaction of candidate genes and a complex of influences of the external environment. Evidence was provided that MMS phenotypes cumulate only in members of some families. The mode of genetic transmission of NIDDM remains obscure.
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PMID:[Genetic predisposition for multiple metabolic syndrome. Part 1. Diabetes mellitus type 2--incidence and prevalence]. 1095 28

Insulin-resistance is associated with a number of disease states such as diabetes, syndrome X, and hypertension. These situations may be coupled to insulin-resistance through the insulin signaling system as a common pathway. The purpose of this study was to investigate the receptor binding alterations in streptozotocin-induced diabetic rats, spontaneously hypertensive rats and aortocaval shunted rats (eccentric cardiac hypertrophy). A physical model describing a 1:1 stoichiometry of ligand binding with its receptor is proposed describing reversible binding of [(125)I]insulin or [(125)I]IGF-1 at the microvascular endothelial as well as with the cardiac myocytes after CHAPS-treatment. Analysis of the collected effluents are curve-fitted with a conservation equation and a first-order Bessel function which allowed the calculation of the forward binding constants (k(n)), the reversible constants (k(-n)), the dissociation constants (k(d)) and the residency time constants (tau). The results showed that streptozotocin-induced diabetic rats showed insulin-resistance through alterations in the kinetics of insulin receptor binding. The normotensive controls of the spontaneously hypertension rats (SHR) carry themselves insulin-resistant receptors whose binding to insulin worsens in the hypertensive SHR. Negative cooperativity between insulin-like growth factor IGF-1 and insulin receptors could be a causative factor predisposing for insulin-resistance in the aortocaval shunted rats to insulin resistance. The defects may be occurring at the receptor level in insulin-dependent diabetes mellitus, Wistar-Kyoto rats and spontaneously hypertensive rats. In conclusion, alterations in the kinetics of insulin binding to its receptor seem to play a central role for the initiation of insulin-resistance during the various pathophysiological states.
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PMID:Characterization of insulin-resistance: role of receptor alteration in insulin-dependent diabetes mellitus, essential hypertension and cardiac hypertrophy. 1103 73

Syndrome X, defined as typical angina with positive exercise test results and normal coronary angiographic findings, represents a multifactorial pathophysiologic state that may range from abnormalities in pain perception to abnormalities in endothelial- and nonendothelial-dependent coronary flow reserve associated with myocardial ischemia. Treatment begins with accurate diagnosis by means of a comprehensive coronary vascular reactivity evaluation. This may lay the groundwork for appropriate treatment. The management of patients with syndrome X is challenging, and it may be necessary to attempt various medications depending on the patient's response. We feel that the first step in the treatment is accurate diagnosis. This is done by performing a functional angiogram (assessment of endothelial-dependent and endothelial-independent coronary flow reserve). In those without evidence of coronary flow reserve abnormalities, reassurance might be curative; however, in those who continue to have symptoms, a trial of imipramine therapy at a dose of 50 mg/d may be attempted, provided other organic disorders (in particular gastrointestinal disorders) are excluded. Those who demonstrate evidence of abnormal coronary vascular reactivity are approached as outlined in Figure 1. Patients are advised to avoid medications that may cause coronary "spasm." We routinely refer our patients to the cardiovascular health clinic for risk factor management and an exercise program. Our first choice of medications usually consists of slow-release calcium channel blockers. We tend to start with a once-a-day regimen, and based on the response, we occasionally change the regimen to twice a day. If the functional angiogram reveals concomitant epicardial disease, then nitrates are added to the medical regimen. Angiotensin-converting enzyme inhibitors are part of the treatment if the patient has hypertension or diabetes or if calcium channel blocker therapy fails. l-Arginine at an initial dosage of 1 g three times daily is added and may be increased to 3 g three times daily if no contraindications are present. Because there are no data regarding the effect of l-arginine, which may affect insulin secretion, in patients with diabetes, we use caution in this patient population. There is no "gold standard" therapy for syndrome X, so each patient may respond differently to the initial medical therapy. Thus, we follow these patients closely to monitor their response to treatment.
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PMID:Syndrome X. 1109 12

Patients with type 2 diabetes (formerly known as non-insulin-resistant diabetes) have a significantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients. By inducing endothelial changes, hyperglycemia contributes directly to atherosclerosis. Type 2 diabetes is also associated with atherogenic dyslipidemias. This form of diabetes, or the precursor state of insulin resistance, commonly occurs as a metabolic syndrome (formerly known as syndrome X) consisting of hypertension, atherogenic dyslipidemia and a procoagulant state, in addition to the disorder of glucose metabolism. All cardiovascular risk factors except smoking are more prevalent in patients with type 2 diabetes. In addition to exercise, weight control, aspirin therapy and blood pressure control, therapy to modify lipid profiles is usually necessary. The choice of agent or combination of statin, bile acid sequestrant, fibric acid derivative and nicotinic acid depends on the lipid profile and characteristics of the individual patient.
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PMID:Attenuating cardiovascular risk factors in patients with type 2 diabetes. 1114 70

The cardiovascular risk factors that accompany postrenal transplantation include an atherogenic lipid profile, hypertension, new-onset diabetes mellitus, and a chronic prothrombotic state. This picture describes the dysmetabolic syndrome or syndrome X, which can significantly aggravate not only the risk of cardiovascular disease and death in this population, but also the progression of allograft dysfunction. The recognition and aggressive management of the dysmetabolic syndrome in postrenal allograft recipients may have a favorable impact on the incidence of cardiovascular morbidity and mortality in these patients and prolong allograft function.
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PMID:Syndrome X following renal transplantation. 1127 92

Hypertension and diabetes are the basic risk factors of atherosclerosis and its complications. At present new associations are sought which will enable us to describe more satisfactorily the mutual relationship of hypertension, metabolic disorders and cardiovascular disease. One of the systems involved in all substantial physiological processes is the autonomic nervous system. Stimulation of the sympathetic nervous system by chronic stress causes in addition to an elevated pulse rate and cardiac minute output also activation of another important pressor mechanism--the renin-angiotensin-aldosterone system. Increased activity of the sympathetic nervous system plays a part also in the development of impaired glucose and lipid metabolism, which are very frequent in hypertonic subjects. Hyperinsulinaemia, hypertriglyceridaemia and reduced HDL-cholesterol concentration are associated with a decline of the insulin capacity to take up glucose and deposit glycogen and together with a raised blood pressure create the so-called metabolic syndrome of insulin resistance (syndrome X, Reaven's syndrome).
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PMID:[Stress-induced hypertension and diabetes mellitus]. 1139 76


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