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The present report analyzes the prevalence of the cluster of metabolic abnormalities defined as syndrome X (high blood glucose, high blood pressure, low high density lipoprotein (HDL) cholesterol, and high triglycerides) and its impact on cardiovascular disease mortality in a large cohort of men and women (22,561 men and 18,495 women). These individuals were participants in a series of epidemiologic investigations of cardiovascular disease conducted in Italy between 1978 and 1987. They were followed for an average of 7 years, during which time a total of 1,218 deaths occurred (1,003 in men and 215 in women). Deaths were coded according to the International Classification of Diseases, 9th Revision (ICD-9). The prevalence of the full cluster of metabolic abnormalities (syndrome X) was low in the population as a whole, with only 3.0 percent of men and 3.4 percent of women exhibiting the full cluster of abnormalities that comprise syndrome X. The risk of death from all causes and cardiovascular disease increased with increased numbers of metabolic abnormalities in both men and women. Mortality from cancer was significantly increased in women (but not in men) with syndrome X, compared with women with no metabolic abnormalities. Population attributable risks for all cause mortality and cardiovascular disease mortality were 0.06 and 0.09 in men and 0.04 and 0.48 in women when assessed by population cutpoints. These data from a large population-based epidemiologic investigation indicate that the presence of a full cluster of metabolic abnormalities from syndrome X is an important risk factor for cardiovascular disease and all-cause mortality in both men and women, but that the low prevalence of such a cluster in the population reduces the public health impact of syndrome X. The majority of individuals who die from cardiovascular disease present elevations in any one, two, or three of the metabolic abnormalities. The notion of the cluster of metabolic abnormalities (syndrome X) should not distract our attention from established individual risk factors that have been proven to be major causes of cardiovascular disease death and disability in our society.
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PMID:Syndrome X and mortality: a population-based study. Risk Factor and Life Expectancy Research Group. 982 67

Increased activity of the sympathetic nervous system may be a critical factor in the development of impaired insulin secretion and insulin resistance. We studied the chronic effects of sympathetic inhibition with moxonidine on glucose metabolism in the spontaneously hypertensive genetically obese rat (SHROB). This unique animal model closely resembles human syndrome X, expressing insulin resistance, genetic obesity, spontaneous hypertension, and hyperlipoproteinemia. Moxonidine, a selective imidazoline receptor agonist, was administered to lean spontaneous hypertensive rats (SHR) and SHROBs for 90 days in food at 8 mg/kg/day and significantly reduced mean blood pressure. Moxonidine treatment reduced fasting insulin levels by 71% in SHROB and lowered plasma free fatty acids by 25%. In SHR, moxonidine treatment decreased free fatty acids by 17% compared with controls. During an oral glucose tolerance test, blood glucose levels in moxonidine-treated SHROB were reduced relative to untreated controls from 60 min onwards. Insulin secretion was facilitated at 30 min (83% greater) and 60 min (67% greater) postchallenge compared with control SHROB. In skeletal muscle, moxonidine treatment increased the expression of the insulin receptor beta subunit by 19% in SHROB but was without effect in SHR. The level of insulin receptor substrate-1 (IRS-1) protein was decreased by 60% in control SHROB compared with lean SHR. Moxonidine treatment enhanced the expression and insulin-stimulated phosphorylation of IRS-1 protein in skeletal muscle in SHROB by 74 and 27%, respectively, and in SHR by 40 and 56%, respectively. Moxonidine increased the levels of expression of IRS-1 protein in liver in SHR by 275% and in SHROB by 260%. These findings indicate that chronic inhibition of sympathetic activity with moxonidine therapy can lower free fatty acids and significantly improve insulin secretion, glucose disposal, and expression of key insulin signaling intermediates in an animal model of obese hypertension.
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PMID:Mechanisms of antihyperglycemic effects of moxonidine in the obese spontaneously hypertensive Koletsky rat (SHROB). 986 64

Few prospective studies have examined associations of lifestyle factors or variables in the insulin resistance syndrome (syndrome X) with incidence of elevated blood pressure (BP) in black subjects and women. This report estimates the 10-year incidence of high blood pressure (HBP) and high normal blood pressure (HNBP) in the biracial cohort of the Coronary Artery Risk Development in (Young) Adults Study (CARDIA), and examines lifestyle factors and four syndrome X variables, measured at baseline, as predictors. CARDIA examined 5115 black and white men and women aged 18-30 years in 1985-1986, and re-examined them at 2, 5, 7, and 10 years. The 10-year incidence of HBP was 16.4% in black men, 7.8% in white men, 13.1% in black women, and 3.2% in white women, while the 10-year incidence of HBP or HNBP was 29.5%, 16.2%, 19.2%, and 6.3%, respectively, in the four sex-race subgroups. Predictors included body mass index, waist circumference, physical activity, alcohol intake, pulse rate, cigarette smoking, education, fasting insulin, triglycerides, uric acid, and high-density lipoprotein cholesterol, as well as age and systolic BP. In univariate analyses, each of these variables was significantly related to incidence in at least one of the four sex-race groups. In multivariate analyses that included control for age and systolic pressure, independent predictors included fasting insulin in white men and women, triglycerides in white men, uric acid and pulse rate in black men, waist circumference in white men and black women, and education (inverse) in white men and black and white women. These results suggest that lower socioeconomic status, as assessed by education level, and one or more syndrome X variables, ie, fasting insulin, triglycerides, uric acid, may be associated with development of elevated BP in young adults.
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PMID:Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study. Coronary Artery Risk Development in (Young) Adults. 992 47

Insulin resistance, characterized by reduced responsiveness to normal circulating levels of insulin, leads to hyperglycemia and hyperinsulinemia resulting in a deadly quartet of non-insulin dependent diabetes mellitus, obesity, hypertension and dyslipidemia These complications, also referred to as 'Syndrome X' have been associated with an increased risk of coronary heart disease. A number of non-pharmacological and pharmacological interventions are available for prevention and treatment of insulin resistance. However, introduction of thiazolidinediones, the new orally active class of drug, has proved to be a major breakthrough in this field. These agents have been shown to reduce insulin resistance by a novel mechanism of action. By interacting with a family of nuclear receptors known as peroxisome proliferator activated receptors thiazolidinediones are thought to enhance the actions of insulin, thereby increasing insulin dependent glucose disposal and reducing hepatic glucose output. A series of animal and clinical studies in patients with impaired Glucose Tolerance and NIDDM have demonstrated the safety and effect of various thiazolidinediones including ciglitazone, pioglitazone and troglitazone. Thus, thiazolidinediones by unlocking insulin resistance act as a key to glycemic control and hence are likely to prove a useful and rational therapy in NIDDM and possibly other disorders resulting from insulin resistance.
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PMID:Thiazolidinediones--the new insulin enhancers. 1005 51

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.
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PMID:Relation between the serum level of C-peptide and risk factors for coronary heart disease and diabetic microangiopathy in patients with type-2 diabetes mellitus. 1007 54

Insulin resistance is an early and major feature in the development of non-insulin-dependent diabetes mellitus(NIDDM). It is also associated with hyperlipidemia, hypertension, obesity and cardiovascular disease. It is the clustor of the risk factors for atherosclerosis and recognized as 'insulin-resistance syndrome' (Syndrome X). Central (abdominal) obesity is much more strongly associated with insulin resistance than overall obesity. The increase of both the influx of free fatty acid to liver and the production of TNF-alpha in adipose tissue may play an important role in mechanism of insulin resistance associated with central obesity. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Exercise training also improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat. The new 'glitazones' (thiazolidinediones) is used clinically to improve insulin sensitivity.
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PMID:[Syndrome X]. 1019 44

Hypertension and insulin resistance are often part of a complex set of abnormalities including obesity, hyperlipidemia, and glucose intolerance, described as syndrome X. Besides a common genetic basis, insulin resistance and hypertension might be linked by excessive activity of the sympathetic nervous system. We studied the effects of chronic inhibition of sympathetic activity with the antihypertensive agent moxonidine on glucose metabolism in the genetically obese SHR Koletsky rat (SHROB), a unique animal model which closely resembles human syndrome X, expressing genetic obesity, hypertension, and hyperlipidemia. Moxonidine, a selective I1-imidazoline receptor agonist, was administered to SHROB and SHR for 90 days in food at 8 mg/kg/day. Moxonidine not only lowered blood pressure, but also reduced fasting insulin levels by 49% in SHROB, and reduced plasma free fatty acids by 30%. In lean SHR, moxonidine treatment decreased circulating free fatty acids by 33% compared to controls. During oral glucose tolerance tests, blood glucose levels in moxonidine-treated SHROB were reduced from 60 min onwards, and there was a sharply higher insulin secretion post-challenge compared to control SHROB. Western blot analysis of insulin signaling proteins showed that IRS-1 was decreased 42% in control SHROB compared with SHR. Moxonidine treatment enhanced the expression of IRS-1 protein in skeletal muscle by 74% in SHROB and 40% in SHR. Moxonidine increased expression of IRS-1 protein in liver by 245% in SHROB and 268% in SHR. Long-term inhibition of sympathetic activity with moxonidine therapy lowered free fatty acids and significantly improved insulin secretion, glucose disposal, and expression of key insulin signaling intermediates. Thus, moxonidine should be considered for the treatment of multiple metabolic and cardiovascular abnormalities associated with syndrome X.
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PMID:Anti-hyperglycemic activity of moxonidine: metabolic and molecular effects in obese spontaneously hypertensive rats. 1032 53

The purpose of this investigation was to determine the prevalence and correlates of abnormal urinary albumin excretion and to examine the possible additive effects of cardiovascular risk factors on urinary albumin excretion in African Americans with type 2 diabetes mellitus. One hundred fifty-one African-American subjects who met WHO criteria for type 2 diabetes were included in this cross-sectional analysis. Subjects were identified through computerized medical records from a family medicine clinic and a community health center. Urinary albumin excretion ratios (UAER) were determined from overnight samples. The prevalence of abnormal urinary protein excretion was 51%. Of those with abnormal protein excretion, 36% had microalbuminuria and 15% had macroalbuminuria. Diabetes duration, waist to hip ratio, blood pressure, and total- and LDL cholesterol were significantly higher in subjects with macroalbuminuria. Regression analysis indicated that mean arterial blood pressure, diabetes duration and total cholesterol were independently associated with UAER. Mean UAER significantly increased with the addition of one or more syndrome X risk factors to pure diabetes. Our results indicate that African Americans with type 2 diabetes mellitus have a high prevalence of abnormal urinary protein excretion, which is associated with a clustering of additional cardiovascular risk factors. The fact that this increased risk was associated with hypertension indicates that screening for albuminuria in this population is essential and that a majority of African Americans with diabetes may be at risk for developing cardiovascular complications.
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PMID:Abnormal urinary protein excretion in African Americans with type 2 diabetes mellitus. 1035 70

The prevalence of obesity has increased over the past three decades, in children as well as in adults. When obesity develops in the childhood years, excess adiposity generally continues into adult years, and adult obesity with childhood onset is frequently more severe. The health consequences of obesity in adults are well established, including greater rates of hypertension, non-insulin dependent diabetes mellitus, and heart disease. This paper will discuss the risk factors for these adult disorders that are detectable in obese children. Compared to normal weight children, obese children have higher blood pressure, higher plasma insulin levels, and a more atherogenic lipid pattern. Thus, the characteristic features of Syndrome X, or the insulin resistant syndrome, can be detected in obese children and adolescents. The vascular consequences of exposure to these metabolic risk factors beginning in childhood have yet to be completely determined. However, it is very likely that childhood obesity does contribute significantly to cardiovascular disease. For these reasons, greater efforts should be mounted to reduce the currently rising rates.
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PMID:Obesity and other risk factors in children. 1042 Oct 92

Obesity poses a serious health hazard and its treatment is often disappointing. Major advances have been made during recent years in the understanding of body weight regulation, with the discovery of leptin, a protein produced by adipocytes and acting on the central nervous system to reduce food intake, and that of beta-3 adrenergic receptors and uncoupling proteins which contribute to stimulate energy expenditure. Numerous metabolic complications are associated with abdominal obesity and most of them, such as diabetes mellitus, dyslipidaemias and arterial hypertension, appear to be linked to insulin resistance and may be part of the socalled metabolic syndrome or syndrome X. While very-low-calorie diets are usually effective in the short-term, they cannot, in the long-term and for most patients, solve the problem of severe obesity. Pharmacological antiobesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. All of these pharmacological approaches have potential efficacy, but unfortunately serious limitations. This is also the case of mechanical means, such as intragastric balloons. Consequently, bariatric surgery may be considered as a valuable alternative therapy in well-selected patients with morbid obesity refractory to classical treatments. In conclusion, obesity is a chronic disease and should be treated as such with reasonable expectations.
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PMID:Medical aspects of obesity. 1042 50


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