Hypercholesterolemia diabetes mellitus

GR is a 68-year-old African-American male who presents to the emergency department with dizziness and loss of speech that began 1 hour ago. His past medical history is significant for hypertension, diabetes mellitus, hypercholesterolemia, and benign prostatic hypertrophy (BPH). Social history is significant for smoking 1 pack per day for the last 38 years. Current medications include metoprolol 50 mg twice daily, insulin NPH 20 units twice daily, and simvastatin 20 mg daily. 

Father is living and has hypertension. Mother is living and has diabetes mellitus and hypercholesterolemia. Both parents are obese. 

Familial dysbetalipoproteinemia (type III) is characterized by the accumulation of chylomicron and VLDL remnants, which are enriched in cholesterol compared to their precursors. The primary molecular cause of familial dysbetalipoproteinemia (type III) is the homozygous presence of the apolipoprotein E2 (apoE2) isoform, which is associated with recessive inheritance of the disorder [62]. However, only 1 in 50 homozygotes for apoE2 will develop type III hyperlipoproteinemia, which is clinically characterized by palmar and tuberous xanthomas, arcus lipoides, and premature atherosclerosis of coronary, peripheral, and cerebral arteries. Precipitating factors include diabetes mellitus, renal disease, hemochromatosis, but also familial hypercholesterolemia. In addition, some rare mutations in the apoE gene have been found to cause dominant and more penetrant forms of type III hyperlipoproteinemia. 

The measurement of serum cholesterol is one of the most common tests performed in the clinical laboratory. Hypercholesterolemia (high blood cholesterol levels) can be the result of a variety of medical conditions. Among the conditions implicated are diabetes mellitus, atherosclerosis, and diseases of the endocrine system, liver, or kidney. High blood cholesterol levels do not point to a specific disease determination of cholesterol is used in conjunction with other clinical measurements mainly for confirmation of a particular diseased condition, rather than for diagnosis of a specific ailment. 

Braunwald (1997) points out that fully half of all patients with CHD do not have any of the conventional risk factors (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus, marked obesity and physical inactivity). Further, up to two-thirds of patients with CHD have what may be considered normal serum cholesterol levels (see references in Parodi, 2004). These facts suggest that the role of plasma cholesterol in CHD has been overemphasized and oversimplified. 

Davi G, Gresele P, Violi F, Basili S, Catalano M, Giammarresi C, Volpato R, Nend GG, Ciabattoni G, Patrono C. Diabetes mellitus, hypercholesterolemia, and hypertension but not vascular disease per se are assodated with persistmt platelet activation in vivo. Evidence derived from the study of periibe arterial disease. Circulation 1997 96 69-75... 

Kakoki M, Hirata Y, Hayakawa H,Tojo A, Nagata D, Suzuki E, Kimura K, Goto A, Kikuchi K, NaganoT, Omata M Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney. Circulation 99 1242-8,1999... 

Other athrombogenic factors (e.g., anticardiolipin antibodies, thrombocytosis, sickle cell disease, polycythemia, diabetes mellitus, hypercholesterolemia, hyperhomocysteinemia)... 

Since hypercholesterolemia (in particular, LDL cholesterol) increases the risk of CHD, it seems reasonable to lower cholesterol levels in patients whose levels put them at risk. Before treatment, other risk factors such as hypertension, cigarette smoking, obesity, and glucose intolerance need to be evaluated and corrected. Disorders that exacerbate hyperlipoproteinemia (e.g., chronic ethanol abuse, hypothyroidism, diabetes mellitus) need to be treated before lipid-lowering measures are taken (discussed earlier. Table 20-7). 

In addition to diabetes mellitus, Mr. Applebod has a hyperlipidemia (high blood lipid level—elevated cholesterol and triacylglycerols), another risk factor for cardiovascular disease. A genetic basis for Mr. Applebod s disorder is inferred from a positive family history of hypercholesterolemia and premature coronary artery disease in a brother. 

Among various types of fat deposition, visceral fat type obesity is one risk factor for metabolic diseases such as diabetes mellitus, hypercholesterolemia, hyperlipidemia, hypertension, and atherosclerosis. The risk of diseases such as diabetes mellitus and coronary heart disease, as well as all-cause mortality, increases in proportion to the increase in body adipose above optimal, but intra-abdominal distribution of fat in the body is associated more closely with disease risk. 

A familial history of diabetes has been reported several times in carbohydrate inducible hyperlipemia as well as in the later discussed familial hypercholesterolemia with hypertriglyceridemia . The relationships of abnormal carbohydrate metabolism in these diseases and of the defect in diabetes mellitus are not clear. 

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