LM World

Very L o w Dens it y Lipoprotein:             The function of VLDL is to transport e ndogenously synthesized triglycerides and chole s ter o l into the p e ripheral ti s su e s. These lipids, fatty acids can be utilized for energy or st o red as triglyceri de s. W hen VLDL parti c les enter the syste m ic c i rc u l ation t h eir triglyceride core is hydrolyzed by LPL. The re m aining VLDL r e m nant is called Inter m ediate Density L i p oprot e i n. Unlike t h e chylo m icron remnant IDL contains Apo b-100 rather than ApoB-48.So m e of t he larger p a rticles appear to be directly re m oved from the circ u l ation The rest of the particles e n t e r t h e casca d e in which they are con v ert e d to IDL and ev e ntually to L DL.

Chylomicrons:             Chylomicrons are the largest of the lipoproteins. Their primary function is to transport the dietary or exogenous triglycerides and cholesterol from the intestinal lumen to sites of metabolism or storage. In the lumen of the GI tract, dietary fat is degraded into free fatty acids and monoglycerides. These substances enter the intestinal villi, where they are reconstructed into a triglyceride particle.             The triglycerides and cholesterol esters are then combined with Apolipoproteins-B-48, A I and A IV within the intestinal wall to form chylomicron particles.             The nascent chylomicrons enter the systemic circulation by the way of the lymphatics. Apos E and C are then added to the particles. Normally the chylomicrons are cleared rapidly from the blood and are virtually absent in the fasting state. The cleaning of the chylomicrons is modulated by the enzyme lipoprotein lipase (LPL). The chylomicron remnants are cleared rapidly

Lipoprotein Classification: Lipoprotein can be classified based on Hydrated density: Gof m an in 1954 separated lipopro t eins by ultracentrifugation i n to five m ajor density classes. Eletroph o retic m obility: Teselius (1947), Frederickson and colleagues (1967) reported existence of two lipoprotein classes separat e d by moving boundary electrophoresis. Apo-Lipoprotein content: Alaupovic and colleagues             As the p ro p ortion of lipid to pr o t e ins in lipo p rot e in co m plexes in c re a ses, t h e density of the m acro m olecule decreases. This property is used in separating the various lipopr o t ei n s in the plasma by ultracentrifugat i on .The rate at which each lipoprotein floats through a solution of sodium chloride (sp.gra v ity-1.063) is expressed as “Svedberg” (Sf) unit of floatation. One S f unit is equal to 1 0 -13 c m /s/dyne/g at 26 0 C.    

Factors which increases likelihood of insulin resistance 1.       A   Strong fa m ily history of diabetes 2.       A   History of gestational diabetes 3.       A   Polycystic o varian d i sease 4.       A   I m paired glucose m etabolism 5.       A   Obesity, BMI of > 30 kg / m 2 6.       A   Increased waist hip ratio (WHR), 0.9 to 1 in m en and 0.8 in wo m en.             Detection of insulin resistance was shown by Burgland et. Al and it is as follows. If we get know a persons BMI in kg / m2 and serum triglycerides in millimoles / L than insulin sensitivity index (ISI) can be calculated.             Possibility of insulin resistance                          Insulin sensitive Value             High                                                                       < 3.5             Moderate                                                               3.5 – 10             Low                                          

The features of insulin resistance syndrome detectable clinically             The third report of expert panel on de t ection, evaluation and treat m ent of high blood cholesterol detected in adults has put forth the following guidelines. The diagnosis of m etabolic syndro m e is made when three or more ri s k deter m inants given below are present. Risk Factors D ef ining L e vel 1. Abdominal Obesity Waist circumference a)   Men > 102 cms (>40 inches) b)   Women > 88 cms (>34.5 inches) 2. Triglycerides > 150mg /dl 3. HDL cholesterol a)   Men < 40mg /dl B) Women < 50 mg/dl 4. Blood Pressure > 130 / M85 mmHg 5. Fasting glucose > 110 mg/ dl

Insul i n Resis t ance Syndrome             The   various   studies   d o ne   world   wide   show   that   diab e tes   is   a   m ulti f actori a l disease. The Neele’s thrifty genotype or fasting or fea s ting hypothesis shows that an individual harbors the genes for diabetes at birth which bec o m es expre s sive when t h e apt environ m ent arrives. T he probable cause for Indian e p i d e m ic of diabetes is at the int r aut e rine level.             Most of the Indian new born babies are s m all c o mpared to the western new born babies. However the m ajor deficit was in the n o n fat issue that is the a b do m inal vi s cera and skel e t a l muscle. But the f at a t s u bscapul e r s k in f old was well pr e ser v ed; t h is sug g ests that besides the obligatory preservation of brain, the m al-nourished fetus favors adipose tissue deposition at the expense of muscle a nd the

Pathogenesis of Typ e -2-Diabetes Genetic factors: The s e are of greater importance in type -2-diabetes than in type -1- diabetes. Among the identi c al twins the concordance rate is above 90%.             However, like type-1-diabeties it is not HLa a s s o ciated exce p t a weak li n k a m ong the Pima Indian .   There is no evidence of autoimmune mechanism except a few subgroups. The m ode of inheritance is largely unknown in the m aturity onset diabetes which is a u toso m al do m inant and linked to chro m oso m es 7, 20 and 12. The defect in chro m osome has been traced to m utations in gene encoding the g l ucose phosphorylati o n enzy m e glucokinase which serves as part of glucose sensing mechanism regulating insulin secretion in pancreatic beta cells. There is also evidence that a subgroup of patients with type-2-diabetes between poly m o r phic alleles of glycogen