Metabolic syndrome, sometimes known by other names, is a clustering of at least three of the Insulin resistance, metabolic syndrome, and prediabetes are closely related to one . The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. to an increased risk of hypertension, atherosclerosis and diabetes. The metabolic syndrome, then, is both associated with inflammation and . WA) noted the association of metabolic syndrome with type 2 diabetes and with There is a high correlation between insulin sensitivity and intra-abdominal fat (47 ). Visit for more related articles at Journal of Diabetes & Metabolism Type 2 diabetes mellitus is a complex disorder complicated by microvascular and.
The increased hazard ratio was modest and the reduction in HbA1c following insulin or sulfonylurea therapy did not significantly decrease myocardial infarction or stroke, although long-term follow up did demonstrate a significant reduction in atherosclerotic cardiovascular events.
The results of the Hoorn Study, 8 years of follow-up, subjects died; 98 of cardiovascular causes. Fasting plasma glucose was only predictive in the diabetic range, although the risks started to increase at about 6.
These increased risks were mostly, but not completely, attributable to known cardiovascular risk factors [ 47 ]. Insulin and Atherosclerosis Several in vivo and in vitro studies have demonstrated that insulin can promote atherogenesis. Insulin promotes de novo lipogenesis and increases hepatic VLDL synthesis, via the stimulation of sterol regulatory element- binding protein-1c and by the inhibition of acetyl- CoA carboxylase [ 16 - 21 ].
Insulin administration prevented regression of coronary atherosclerosis, when low-cholesterol diet was instituted. Alloxaninduced diabetic rabbits fed with a high-cholesterol diet have developed marked hypercholesterolaemia, but their aorta remained free of atherosclerotic plaques [ 22 ]. Finally, insulin therapy is frequently associated with weight gain. This is of major concern since the current diabetes epidemic is being driven by obesity, a major risk factor for CVD [ 23 - 26 ].
Nitric oxide production is impaired because nitric oxide synthase is activated by the same PI-3 kinase pathway, resulting in endothelial dysfunction and accelerated atherosclerosis. Diabetes and Vascular Smooth Muscle Function The impact of diabetes mellitus on vascular function is not limited to the endothelium.
In patients with type 2 diabetes mellitus, the vasodilator response to exogenous NO donors is diminished. Moreover, vasoconstrictor responsiveness to exogenous vasoconstrictors, such as endothelin-1, is reduced.
Dysregulation of vascular smooth muscle function is exacerbated by impairments in sympathetic nervous system function. The underlying mechanism is not known. Insight into the differences in endocrine and lipoprotein metabolism may provide further evidences.
This indicates that a difference in appetite control is responsible for the lower caloric intake and weight gain in DR rats [ 43 ].
One of the common features of obesity in humans is dyslipidemia which occurs in rat model of diet-induced obesity and is frequently associated with hypertension [ 38 ]. I have decided to ignore molecular mechanisms of hypertension in OP rat because of limited space. However, hypertension developed in OP, but not OR, rats, is a multifactorial disorder and diet is not the major factor that causes the high blood pressure in this model.
According to Barker hypothesis, adult metabolic diseases are programmed during fetal life [ 44 ]. To investigate the mechanisms by which altered intrauterine milieu predisposes to later development of MetS, different animal models have been developed see review [ 45 ]. Interestingly, offspring of rats fed high saturated fats during pregnancy have fetal IR [ 46 ], abnormal cholesterol metabolism [ 47 ] and raised adult blood pressure [ 48 ].
Insulin Resistance, Type 2 Diabetes and Atherosclerosis
Furthermore, the outbred Sprague-Dawley DIO and DR rats have been selectively bred over time such that their future body weight response to a HFD is known in utero, allowing the researcher to look early in life prior to the onset of obesity for genetic traits that may later predispose them to their DIO or DR phenotypes [ 3749 ].
The inbred obese Zucker diabetic fatty ZDF rat is high-fidelity model with close resemblance to human case in obesity and T2D. The female ZDF rat is also suitable model mimics pre-diabetic state in humans because she shows a prolonged period of insulin sensitivity prior to the onset of diet-induced diabetes [ 51 ]. The ZDF rats show profound dyslipoproteinaemia with increased TC and TGs levels and lower chylomicra disposal rates that mimics conditions occurred in human case of obesity [ 52 ].
Although normal rats are not ideal model of cardiovascular disease research since they typically have very low levels of TC and LDL-C but high levels of HDL-C, they are mild diet-responsive. The ability of rats to sustain their cholesterol profile even in the face of high-cholesterol diets means that very little actual atherosclerosis develops [ 16 ].
A mixture of high levels of dietary cholesterol with 0. More recently, Zaragosa and colleagues introduced various animal models of cardiovascular diseases see review [ 56 ]. Surprisingly rat does not develop atheroma in the process of atherosclerosis see review [ 56 ]. Generally rats are highly resistant to the development of atherosclerosis because they lack physiological resemblance on many aspects with humans that are pathophysiologically important [ 57 ].
For example, HDL is dominating lipoprotein in these animals and rat platelets are generally resistant in hyperlipidemic condition see review [ 58 ]. Rats are potentially practical model for studying hypercholesterolemia along with hypertension see review [ 58 ].
They exhibit augmented thrombotic response and develop coronary atherosclerotic lesions under hypertensive and hyperlipidemic conditions e. Triglyceride-rich diets containing various amounts of cholesterol, with or without cholic acid have been used to induce hypercholesterolemia in rats.
The fat sources vary from lard to soybean, canola or sunflower oils.
Insulin Resistance, Type 2 Diabetes and Atherosclerosis | OMICS International
Nevertheless, the question of the caloric value of the employed diets has not yet been considered properly since their high fat content, which is the strategy used in order to induce hypercholesterolemia, leads to lower ingestion by the animals and induces malnutrition.
Roberts and colleagues presented a rat model of diet-induced syndrome X and they explored potential mechanisms of hypercholesterolemia in diet-induced syndrome X [ 61 ]. To induce syndrome X, female Fischer rats were fed a high-fat primarily from lard plus a small amount of corn oilrefined-carbohydrate sucrose diet for 20 months [ 61 ]. Sampey and colleagues [ 62 ] have demonstrated that the CAF is a more robust model of MetS than lard-based HFD and that the rapid-onset of weight gain, obesity, multiorgan dysfunctions and pathologies observed in the CAF model more closely reflect the modern human condition of early onset obesity.
However, they did not repot possible lipid-lipoprotein disorders that may be occurred in their model. Recently, Manting and colleagues [ 63 ] have shown that a combination of chronic stress and HFD The hamster models Hamsters are another animal model can be used to assess some aspects of MetS.
The combination of high dietary SF and cholesterol is commonly used to promote atherosclerosis in these animals and atherosclerotic lesions similar to those found in humans can be found after prolonged feeding periods [ 65 ]. Actually, cholesterol itself may not always be necessary for this phenotype, since a purified diet with no cholesterol but high concentrations of SF can promote more aortic cholesterol accumulation compared to a diet with both cocoa butter and 0.
Cholesterol-fed hamsters have been used to screen therapeutic anti-atherosclerotic and hypolipidemic properties of phyto medicines e. Hamsters have been proposed as an animal model to evaluate diet-induced atherosclerosis since the s [ 69 ]. Relative to other normal rodent models, hamsters have a low rate of endogenous cholesterol synthesis, cholesteryl ester transfer protein CETP activity and tissue specific editing of apolipoprotein apo B mRNA and secretion of apo B from the liver and apo B from the small intestine.
The morphology of aortic foam cells and lesions in hamsters fed atherogenic diets was reported to be similar to human lesions [ 70 ]. Recently, in a systematic review Dillard and colleagues concluded that the Golden-Syrian hamster does not appear to be a constructive model to determine the mechanism s of diet-induced development of atherosclerotic lesions see review [ 71 ] however the authors only concentrated on atherogenecity of cholesterol- and fat-rich diets in hamster models of atherosclerosis.
Leung and colleagues investigated intestinal lipoprotein production and the response to insulin sensitization in the high fat-fed Syrian Golden hamster for 5 weeks [ 72 ].
An appropriate dyslipidemic animal model that has diabetes would provide an important tool for research on the treatment of diabetic dyslipidemia. Ten days of high fat feeding in golden Syrian hamsters resulted in a significant increase in IR and baseline serum lipid levels accompanied by a prominent dyslipidemia.
Various diet formula, fat resources and time tables have been found to induce some aspects of MetS in the literature. For example, a diet consisted of 80 g of anhydrous butterfat, g of corn oil, 20 g of Menhaden fish oil and 1. F1B hamster is a genetically-defined hamster, derived from two highly inbred lines, namely by crossbreeding between Bio F1B hamster is an exciting animal model for hyperlipidemic-related applications.
Metabolic syndrome in relationship to type 2 diabetes and atherosclerosis.
Dietary fatty acid chain length, degree of saturation and cis-trans conformation have been shown to alter several metabolic pathways involving cholesterol throughout the body, the combined effect of which is reflected in plasma lipid and lipoprotein profiles see review [ 76 ].
Interestingly, intake of trans-fatty acids in shortenings and margarines has been linked to increased risk of cardiovascular disease through effects on lipoprotein metabolism and substituting trans-fatty acids for either saturated or polyunsaturated fatty acids results in more deleterious lipid-lipoprotein profiles [ 77 ].
Hamsters are candidate model to investigate cardiometabolic risks of different fat resource and fat-rich diets [ 78 ]. Similarity with the human LDL receptor gene, makes hamster ideal to study LDL receptor antagonists and also useful for drugs which interfere with CETP activities and reverse cholesterol transport RCT from peripheral tissues to the liver for biliary and fecal excretion [ 79 ].
A considerable amount of experimental attention is currently directed at understanding the in vivo mechanisms of RCT. Although not established in vivo, RCT is thought to be impaired in patients with MetS, in which liver steatosis prevalence is relatively high.
In vivo RCT was assessed by intraperitoneally injecting 3 H-cholesterol labeled macrophages. Finally their results indicate a significant increase in macrophage-derived cholesterol fecal excretion, which may not compensate for the diet-induced dyslipidemia and liver steatosis [ 80 ]. They induced this model by feeding hamsters a high-fat, high-cholesterol, inadequate methionine- and choline-containing diet.
All these strains are derived from inbred or outbred Golden-Syrian hamster. Interestingly, hamsters fed high-sucrose diets did not have elevated TG levels and developed only mild IR relative to those fed diets high in fructose [ 72 ]. Avramoglu and colleagues reviewed mechanisms of metabolic dyslipidemia in insulin resistant states see review [ 82 ].
They developed an explanatory fructose-fed hamster model of insulin resistance to study hepatic lipid metabolism as its lipoprotein metabolism as described previously [ 8384 ]. Hamsters exhibit obesity, hypertriglyceridemia, increase plasma FFAs concentration and IR if fed fructose-rich diet for a two week period.
The microsomal triglyceride transfer protein plays a pivotal role in VLDL assembly and its activity showed a striking 2. The apoB production also has been increased in the fructose-fed hamsters [ 73 ]. Fructose-fed hamster also has been introduced as an exploratory animal model to excavate role of intestinal lipoprotein overproduction in the dyslipidemia of insulin-resistant states [ 74 ].
The authors have shown that fructose feeding for 3 weeks increases secretion of apoBcontaining lipoproteins in the fasting state and during steady state fat feeding. They showed that hamsters fed the high-fructose diet showed significantly increased VLDL—triglyceride Fructose feeding induced a Compositional changes were associated with reduced LDL diameter.
Metabolic syndrome in relationship to type 2 diabetes and atherosclerosis.
In contrast, fructose feeding caused elevations in all HDL fractions. The guinea pig models A number of seminal reviews on the details of the criteria that make guinea pigs suitable animal models for studying lipoprotein metabolism are available see reviews [ 85 - 87 ] and a summary will be presented here. As humans, guinea pigs have higher concentrations of free compared to esterified cholesterol found in the liver and they show evidence of moderate rates of hepatic cholesterol synthesis and catabolism.
Guinea pigs have been used as models to dissect the mechanisms by which various dietary fat resources influences plasma lipid-lipoprotein profiles. In contrast to hamsters they do not possess a fore-stomach fermentation which modifies dietary macronutrients before reaching the small intestine [ 89 ]. Guinea pigs are not only superior models for studying the mechanisms by which statins [ 90 ], cholestyramine [ 91 ], apical sodium bile acid transport inhibitors [ 92 ] and microsomal transfer protein inhibitors [ 93 ] lower plasma LDL-C but also are selected to investigate the mechanisms by which certain drugs or toxins affect lipid-lipoprotein metabolism e.
Guinea pigs respond to dietary fat saturation, dietary cholesterol and dietary fiber by alterations in LDL-C see review [ 87 ]. The suitability of guinea pigs as models of atherosclerosis is augmented by an array of review and assessment features see review [ 59 ]. However, guinea pigs do not develop advanced atherosclerotic lesions, and are not an entrenched model for atherosclerosis progression [ 96 ].
High plasma level of lipoprotein a also called Lp a is associated with coronary heart disease and other forms of atherosclerosis in humans see review [ 97 ]and as primates, hedgehogs [ 98 ] and guinea pigs possess Lp a among normal animal models [ 99 ]. Initial atherosclerosis induced by various formula of HFD in guinea-pigs. High SF diet supplemented with high cholesterol 0. Yang and colleagues [ ] introduced a hyperlipidemic guinea pig model in a comparative investigation.
It seems that chronic dyslipidemia associated with hypertriglyceridemia may reduce auditory function. However, for international comparisons and to facilitate the etiology, it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes.
There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. The previous definitions of the metabolic syndrome by the International Diabetes Federation  and the revised National Cholesterol Education Program are very similar and they identify individuals with a given set of symptoms as having metabolic syndrome.
There are two differences, however: However, this potentially excludes any subject without increased waist circumference if BMI is less than Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria.
Also, the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography. IDF[ edit ] The International Diabetes Federation  consensus worldwide definition of the metabolic syndrome is: Central obesity defined as waist circumference with ethnicity-specific values AND any two of the following: Reproductive disorders such as polycystic ovary syndrome in women of reproductive ageand erectile dysfunction or decreased total testosterone low testosterone-binding globulin in men can be attributed to metabolic syndrome.
Both psoriasis and psoriatic arthritis have been found to be associated with metabolic syndrome.Diabetes Type II Pathophysiology
These include increased physical activity such as walking 30 minutes every day and a healthy, reduced calorie diet. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily due to a lack of compliance with lifestyle and diet changes.
Diet[ edit ] Dietary carbohydrate restriction reduces blood glucose levels, contributes to weight loss, and reduces the use of several medications that may be prescribed for metabolic syndrome. Phillips developed the concept that risk factors for myocardial infarction concur to form a "constellation of abnormalities" i.
He suggested there must be an underlying linking factor, the identification of which could lead to the prevention of cardiovascular disease; he hypothesized that this factor was sex hormones.
Reaven proposed insulin resistance as the underlying factor and named the constellation of abnormalities syndrome X. Reaven did not include abdominal obesity, which has also been hypothesized as the underlying factor, as part of the condition. The name "syndrome X" also has other meanings.
Controversy[ edit ] The clinical value of using "metabolic syndrome" as a diagnosis has previously been debated due to different sets of conflicting and incomplete diagnostic criteria. These concerns have led the American Diabetes Association and the European Association for the Study of Diabetes to issue a joint statement identifying eight major concerns on the clinical utility of the metabolic syndrome diagnosis.