Insulin resistance triglycerides metabolism

PPARy is a transcription factor which controls the expression of enzymes and proteins involved in fat and glucose metabolism. More importantly, stimulation of this receptor induces differentiation of preadipocytes to adipose cells. It is believed that the formation of additional, small fat cells lowers free fatty acids and hepatic triglycerides, thereby collecting insulin resistance. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

Patients with metabolic syndrome are twice as likely to develop type 2 diabetes and four times more likely to develop CHD.3,11 These individuals are usually insulin resistant, obese, have hypertension, are in a prothrombotic state, and have atherogenic dyslipidemia characterized by low HDL cholesterol and elevated triglycerides, and an increased proportion of their LDL particles are small and dense.3... 

ATP III recognizes the metabolic syndrome as a secondary target of risk reduction after LDL-C has been addressed. This syndrome is characterized by abdominal obesity, atherogenic dyslipidemia (elevated triglycerides, small LDL particles, low HDL cholesterol), increased blood pressure, insulin resistance (with or without glucose intolerance), and prothrom-botic and proinflammatory states. If the metabolic syndrome is present, the patient is considered to have a CHD risk equivalent. 

Manco, M., Mingrone, G., Greco, A. V., Capristo, E., Gniuli, D., De Gaetano, A., Gasbarrini, G. Metabolism 49, 2000, 220-224. Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides. 

Details of plasma lipoproteins and their metabolism are given in Section 5.5. Most of the cholesterol in the blood is carried as part of low density lipoprotein (LDL) or high density lipoprotein (HDL), whereas most triglyceride, in the fasting state, is carried by very low density lipoprotein (VLDL). The relative concentrations of these lipoproteins constitute the lipid profile and determine CVD risk. Diabetics are more likely to show an unhealthy profile with elevated concentrations of LDL and triglyceride but reduced HDL concentration. This pattern can be partly explained by enhanced fatty acid liberation from adipocytes as a consequence of insulin resistance in that tissue and due to reduced removal from the circulation of triglycerides, which is also insulin dependent. 

Low LPL activity can also be found secondary to metabolic dysregulation, notably in insulin resistance and type 2 diabetes mellitus. In fact, diabetic hypertriglyceridemia is caused in part by decreased LPL secretion in response to reduced insulin action. Another preanalytical pitfall results from the high affinity of LPL for triglyceride-rich lipoproteins. When extremely hypertriglyceridemic plasma is prepared by cen-... 

A major study tracked 4,637 men and women ages eighteen to thirty for fifteen years. People in the top fourth in terms of magnesium consumption from foods and supplements were less likely to develop high blood pressure, as well as other components of the metabolic syndrome that includes high triglycerides and insulin resistance, a precursor to diabetes. 

Although the primary target of risk-reduction therapy is LDL-C, the ATP III recognized the metabolic syndrome, a constellation of several risk factors (increased triglycerides, decreased HDL-C, obesity, hypertension, and insulin resistance), as a secondary target of therapy. By definition, those with three or more of these risk factors are considered to have the metabolic syndrome. The specific criteria for the chnical identification of the metabolic syndrome are listed in Table 26-17. 

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