Diabetes mellitus is very often associated with hypercholesteremia and atherosclerosis

living in the lundra regions (e.g. polar bear) brown fat is found in very great amount. It acts in the following way Within the uterus, the temperature was around 38°C. When the fetus is delivered in a bleak cold environment (temp, say, - 30°C), an exposure to severe cold occurs. This causes sympathetic stimulation and catecholamine liberation from the medulla of the new born, which in turn causes adipose tissue tipolysis so that glycerol and fatty acids are formed. The glycerol is removed by blood but the fatty acids combine with glycerol 3 phos (obtained from glucose metabolism) to form triglyceride again. This releases tremendous energy and the newborn is saved. Brown fat is one of the most scintillating examples of teleologic principle. In human newborns also some vestiges of brown fat is seen, specially in the nape of neck. Some traces of brown fat is seen in adult human beings too. APPLIED BIOCHEMISTRY Atherosclerosis Atherosclerosis, the "captain of men of Death", is the single biggest killer at least in the Western World. It is an ancient disease. Mummy of Amenhotep II shows unmistakable signs of the disease. Animals, specially captive animals of zoo, suffer from it. Inspite of tremendous amount o global research, its exact cause remains unknown and therefore preventive and curative measures are unsatisfactory. Pathology The student is referred to the portion dealing with the histology of aorta (chap. 6, sec. V, fig. 5.6.1) in this book. To repeat in short, a big artery like aorta has three coats - (i) tunica intima, (ii) tunica media and (iii) tunica edventitia. The earliest lesions are fatty streaks which are formed within the sub intima. Chemically, the streaks consist practically entirely of cholesterol esters. Subsequently the streaks may or may not progress to the next stage of development, the 'fibrous plaque'. A fibrous plaque consists of large amount of lipid (mostly cholesterol ester), collagen fibers and smooth muscle cells. The lipids are mostly extracellular. Fibrous plaques are bigger than the fatty streaks and often cause the overlying intima to bulge, causing partial obliteration of, the lumen. Calcium deposition frequently occurs in the fibrous plaque, and the overlying intima may be ulcerated and on the ulcer, thrombus formation may occur. Thrombus or a part of the ulcerated intima may be detached and cause embolism in a distal part. Such fibrous plaques are formed in the aorta (specially abdominal aorta) or in such vital arteries like coronary, cerebral or renal artery. Plaques can also appear in smaller arteries supplying the lower limb. However, they do not develop in the smaller vessels like arterioles. The major dangers are occlusion of blood supply, which may be gradual or acute; block of a vital artery leading to death of the area supplied can occur. This may cause myocardial infarction (in heart), death of an area of brain, of a limb and so on. Risk factors Some factors popularly called 'risk factors' are specially predisposing factors of the disease . Thus, (i) strong family history, (ii) hypertension, (iii) cigarette smoking, (iv) diabetes mellitus and (v) obesity, (vi) high intake of saturated (animal hydrogenated) fats, and (vii) bad serum lipid profile (high cholesterol/ high triglyceride/high apohpoprotein B : A ratio, see p. 413) etc, are well known risk factors . Sex Females o reproductive ages seldom suffer from atherosclerosis unless they have very strong risk factors like smoking, diabetes of hypertension. Surprisingly enough, oral contraceptive pills, containing high estrogen, make them susceptible to atherosclerotic disorder. Consequently, the content of estrogen in the pills have been lowered since the last few years. Etiology The principal factor is disorder of cholesterol metabolism. Aorta and other arteries can synthesize cholesterol. It is possible that in atherosclerotic subjects, excess cholesterol is synthesized in the arteries. Or, plasma cholesterol esters may infiltrate in the intima; the presence of hypertension may help in this. Other contributing factors are damage of the intima by stress and strain, which may be caused or aggravated by hypertension. Platelet deposition on the damaged endothelium aggravates the condition. Diabetes mellitus is very often associated with hypercholesteremia and atherosclerosis. The mechanism (so as to how diabetes precipitates submtimal deposition of cholesterol) at molecular level has been described in connection with the insulin (chap 6.6). Further, the basic fault may he with the apohpoproteins (for details, see chap 8 sec VII). Preventive measures The aims are to avoid hypercholesteremia/ hyperhpidemia and the known risk factors. If the serum cholesterol is high, the subject should take up anticholesteremic measures which have been discussed earlier in this chapter. Storage disease This is another class of disorder of hpid metabolism. In these diseases the amount of synthesis of the particular lipid in question is normal but its removal is defective owing to lack of the necessary hydrolytic enzymes. As a result, the hpid accumulates in various tissues. Well known examples are: (i) Gaucher's disease Storage of cerebrosides occur (due to lack of cerebrosidase) in liver, spleen and brain. Clinically there is hepatosplenomegaly (enlarged liver and spleen) and mental deficiency. Niemann - Pick disease Deposition of sphmgomyelin (due to lack of sphinogomyelinase) occurs in liver and spleen. Clinically there is hepato splenomegaly. Death occurs in early life. SUMMARY & HIGHLIGHTS Major phosphohpids in our body are, (i) lecithin, (ii) cephalins (phosphatidyl serine and phosphalidy