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Type II diabetes and hypertension are two pathologies which are frequently associated in adults, especially in developed countries. All the more so when patients are also obese: obesity is today, and will be in the next future, a true epidemic in these countries. These three pathologies imply a risk for cardiovascular complications much higher than that due to an isolated arterial hypertension. This increased risk is probably due to many factors: hyperglycemia, a dismetabolic syndrome (hyperlipemia, hyperuricemia, thrombophilia, altered Na(+)-H+ membrane exchanges = syndrome X) and hyperinsulinemia which favor atherosclerosis and clinical events. Consequently non-pharmacological and aggressive pharmacological therapy is necessary. Even if the trials done in the last years are questionable and not totally convincing, all researchers agree that lowering blood pressure to normality is the best way to improve prognosis of these patients. Usually for this purpose we need a therapy with more than one drug. Among the antihypertensive drugs, ACE-inhibitors (and perhaps also angiotensin receptor blockers) are preferred, especially in those hypertensives with diabetes who have also microalbuminuria or a frank proteinuria.
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PMID:[Diabetes and arterial hypertension]. 1177 8

Metabolic Syndrome X is a cluster of abnormalities including insulin resistance, hyperlipidemia, hypertension, and obesity. We sought to determine if excess plasma glucagon and free fatty acids (FFA) might contribute to the insulin resistance in the obese spontaneous hypertensive rat (SHROB), a unique animal model of leptin resistance and metabolic Syndrome X. SHROB were extremely hyperinsulinemic and mildly glucose intolerant compared with lean SHR. SHROB had elevated fasting plasma glucagon and FFA, and showed paradoxical responses to an oral glucose challenge, with increased glucagon at 30 and 60 min postchallenge (200% plus minus 45% and 91% plus minus 13%, respectively; n = 9). In lean SHR, glucagon was nearly unchanged by glucose loading (<30% increase, P > 0.05; n = 5). Plasma FFA were not affected by a glucose load in SHROB, whereas SHR showed a decrease of 40% plus minus 6% (n = 5--9). The I/G molar ratio changed in opposite directions in the two genotypes, with a decrease in SHROB at 30 and 60 min, in contrast to the appropriate increase at 30 and 60 min postchallenge in the lean SHR (P < 0.01; n = 5--9). Administration of 500 ng/kg exogenous glucagon to SHR raised glucagon 56% plus minus 5% to a level that was similar to fasting SHROB. This level of circulating glucagon was sufficient to elevate glucose and insulin during the 7 hr of observation (n = 9). Based on these results, we suggest that fasting hyperglucagonemia and impaired suppression of glucagon secretion and FFA in response to an oral glucose load may contribute to insulin resistance and glucose intolerance in the SHROB model of metabolic Syndrome X.
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PMID:Plasma glucagon and free fatty acid responses to a glucose load in the obese spontaneous hypertensive rat (SHROB) model of metabolic syndrome X. 1185 14

'Visceral fat syndrome' is a clinical entity compatible with Syndrome X, Deadly quartet, and insulin resistance syndrome. All of these entities express the pathophysiology of multiple risk factor syndrome in which multiple risks of arteriosclerosis, i.e., hypertension, hyperlipidemia, and glucose intolerance, cluster in an individual. The accumulation of visceral fat plays a crucial role in the pathogenesis of visceral fat syndrome. On the other hand, familial combined hyperlipidemia (FCHL) is a common hyperlipidemia associated with premature arteriosclerosis. The pathogenesis of FCHL is not fully elucidated but the visceral fat accumulation may play an important role in the pathophysiology of FCHL. In this review, we will discuss the relationship between visceral fat syndrome and FCHL.
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PMID:[Disorder of lipid metabolism in visceral fat syndrome--relation to familial combined hyperlipidemia]. 1202 87

Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to increased levels of free fatty acids in plasma, increased flux of free fatty acids back to the liver, enhanced production of TGs, decreased proteolysis of apo B-100, and increased VLDL production. Decreased removal of postprandial TGs often accompanies these metabolic abnormalities. Genes regulating the expression of the major players in this metabolic cascade, such as LPL, cholesterol ester transfer protein, and hepatic lipase, can modulate the expression of small, dense LDL but these are not the major defects. New candidates for major gene effects have been identified on chromosome 1. Regardless of their fundamental causes, small, dense LDL (compared with normal LDL) particles have a prolonged residence time in plasma, are more susceptible to oxidation because of decreased interaction with the LDL receptor, and enter the arterial wall more easily, where they are retained more readily. Small, dense LDL promotes endothelial dysfunction and enhanced production of procoagulants by endothelial cells. Both in animal models of atherosclerosis and in most human epidemiologic studies and clinical trials, small, dense LDL (particularly when present in increased numbers) appears more atherogenic than normal LDL. Treatment of patients with small, dense LDL particles (particularly when accompanied by low HDL and hypertriglyceridemia) often requires the use of combined lipid-altering drugs to decrease the number of particles and to convert them to larger, more buoyant LDL. The next critical step in further reduction of CAD will be the correct diagnosis and treatment of patients with small, dense LDL and the dyslipidemia that accompanies it.
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PMID:Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. 1241 79

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40-80% of the CHD patients were diabetic and 50-80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins - apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested.
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PMID:Diabetic dyslipidaemia in Kuwait. 1244 10

We measured serum leptin levels in two groupings of wild male baboons, one with access to abundant quantities of food from gardens and garbage dumps near human habitations (Garbage; n = 11) and one without access (No Garbage; n = 10). A Garbage subgroup had high leptin levels (Garbage HL), whereas the rest of the Garbage group had low leptin levels (Garbage LL) similar to those in the No Garbage group. The Garbage HL individuals were obese, with higher mass, body mass index, and leptin to mass ratios; were insulin to resistant, with elevations in serum insulin, glucose, and insulin to glucose ratios; and were hyperlipidemic. This syndrome X-like condition occurred only in the Garbage HL subset. The Garbage LL subset did not differ from the No Garbage individuals in mass, body mass index, leptin to mass ratio, insulin, glucose, or insulin to glucose ratios. The highest cholesterol levels, however, occurred in the Garbage LL individuals, suggesting that susceptibility to hyperlipidemia is distinguishable from susceptibility to obesity and insulin resistance. The differences were not explained by age or social status. These results show that a subgroup of wild baboons is susceptible to developing obesity and insulin resistance and that this susceptibility is not related to age or social rank.
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PMID:Serum leptin levels as a marker for a syndrome X-like condition in wild baboons. 1262 12

Hypertension often coexists with hyperlipidemia, insulin resistance, and glucose intolerance, a comorbidity known as metabolic syndrome X. Different antihypertensives have mixed effects on these associated abnormalities. We compared three antihypertensives in the spontaneously hypertensive obese rat model of syndrome X. Moxonidine (4 mg/kg), an imidazoline and alpha2-adrenergic agonist, alpha-methyldopa (200 mg/kg), an alpha2-adrenergic agonist, or the vasodilator hydralazine (10 mg/kg) was given orally for 15 d. All three agents lowered blood pressure equally. Moxonidine significantly reduced fasting plasma insulin, glucagon, cholesterol, triglycerides, and free fatty acids (FFA) compared with untreated controls. In contrast, syndrome X markers were not affected by alpha-methyldopa treatment, and hydralazine reduced only glucagon and FFA. Relative to untreated controls, moxonidine improved glucose tolerance as shown by reduced glucose area under the curve (AUC) (13.6 +/- 2.4 versus 42.5 +/- 9.9 g x min/dl). Insulin AUC was increased (7.4 +/- 0.9 versus 3.9 +/- 1.8 microg x min/ml) as was the plasma C-peptide response to the glucose load. In contrast, alpha-methyldopa and hydralazine worsened glucose tolerance (68 +/- 26 and 110 +/- 21 g x min/ml, respectively) and significantly reduced insulin AUC (2.5 +/- 0.8 and -2.3 +/- 1.0 microg x min/ml, respectively) compared with controls. Moxonidine reduced but alpha-methyldopa and hydralazine elevated glucagon levels after the glucose load. Contrary to the "hemodynamic hypothesis" for the metabolic actions of antihypertensives, which predicts roughly equal benefits, only moxonidine had a positive impact on comorbidities. This unique action suggests a role for direct stimulation of imidazoline receptors.
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PMID:Contrasting metabolic effects of antihypertensive agents. 1455 73

Type 2 diabetes is characterized by the association of insulin resistance and progressive failure of the beta cell function. This disease is frequently associated with the so-called syndrome X or polymetabolic syndrome which includes many cardiovascular risk factors: hyperinsulinism, hyperglycemia, postprandial hyperglycemia, hyperlipidemia and various anomalies of the coagulation system. Glycemic control is fundamental and the goals have been defined to reach them; it is necessary to start with diet and to introduce various oral hypoglycemic agents given alone or in association, if necessary. Insulin treatment is often started late in the course of the disease and this strategy is questionable. Blood pressure must reach 130-80 mmHg and polytherapy is often required to reach this target. The treatment choices will be based on the clinical status of each patient and according to the presence of additional cardiovascular risk factors, increased levels of microalbuminuria or a history of myocardial infarction. Hyperlipidemia is frequent in type 2 diabetes. Statins or fibrates will be prescribed according to predominant lipid anomalies. Clearly, the management of such patients implies many drugs and compliance is difficult. In the near future, some drugs associations will be on the market and they will certainly make the treatment of type 2 diabetes easier and compliance better.
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PMID:[Treatment of type 2 diabetes]. 1505 51

Bardet-Biedl syndrome (BBS) is an autosomal recessive condition with a wide spectrum of clinical features. The principal manifestations are rod-cone dystrophy (sometimes called atypical retinitis pigmentosa), postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction. The clinical diagnosis of syndrome X defines a patient with abnormal glucose metabolism, hypertension, hyperlipidemia and obesity. We report here a 15 year-old girl with BBS presenting with syndrome X.
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PMID:Bardet-Biedl syndrome with syndrome X: a patient report. 1527 Apr 11

In 1980, the term non-alcoholic steatohepatitis was coined to describe a new syndrome occurring in patients who usually were obese (often diabetic) females who had a liver biopsy picture consistent with alcoholic hepatitis, but who denied alcohol use. The causes of this syndrome were unknown, and there was no defined therapy. More than two decades later, this clinical syndrome is only somewhat better understood, and still there is no Food and Drug Administration-approved or even generally accepted drug therapy. Patients with primary non-alcoholic steatohepatitis typically have the insulin resistance syndrome (synonymous with the metabolic syndrome, syndrome X, and so forth), which is characterized by obesity, diabetes, hyperlipidemia, hypertension, and, in some instances, other metabolic abnormalities such as polycystic ovary disease. Secondary non-alcoholic steatohepatitis may be caused by drugs such as tamoxifen, certain industrial toxins, rapid weight loss, and so forth. The cause of non-alcoholic steatohepatitis remains elusive, but most investigators agree that a baseline of steatosis requires a second hit capable of inducing inflammation, fibrosis, or necrosis for non-alcoholic steatohepatitis to develop. Our research group has focused its efforts on the interactions of nutritional abnormalities, cytokines, oxidative stress with lipid peroxidation, and mitochondrial dysfunction in the induction of steatohepatitis, both alcoholic and non-alcoholic in origin. Research findings from other laboratories also support the role of increased cytokine activity, oxidative stress, and mitochondrial dysfunction in the pathogenesis of non-alcoholic steatohepatitis. The objectives of this article are to review the (1) definition and clinical features of non-alcoholic steatohepatitis, (2) potential mechanisms of non-alcoholic steatohepatitis, and (3) potential therapeutic interventions in non-alcoholic steatohepatitis.
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PMID:Mechanisms of non-alcoholic steatohepatitis. 1567 Jun 68


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