RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
SYNOPSIS
OF
DISSERTATION
" STUDY OF LIPID PROFILE IN
TYPE 2 DIABETES MELLITUS
IN A.I.M.S , RURAL SETUP-
A COMPARATIVE STUDY"
Submitted by
Dr. MITHUN SOMAIAH C.S. M.B.B.S
POST GRADUATE
GENERAL MEDICINE (M.D)
Under the guidance of
Dr. SHASHIKANTHA M.B.B.S M.D
PROFESSOR
DEPARTMENT OF GENERAL MEDICINE
DEPARTMENT OF GENERAL MEDICINE
ADICHUNCHANAGIRI INSTITUTE OF MEDICAL SCIENCES,
B.G.NAGARA-571448
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / NAME OF THE CANDIDATEAND ADDRESS
(in block letters) / Dr. MITHUN SOMAIAH C.S.
P.G (GENERAL MEDICINE)
ADICHUNCHUNAGIRI INSTITUTE OF
MEDICAL SCIENCES.B.G NAGARA,
MANDYA DISTRICT -571448
2. / NAME OF THE INSTITUTION /
ADICHUNCHANAGIRI INSTITUTE OF
MEDICAL SCIENCES, B.G.NAGARA.3. / COURSE OF STUDY AND SUBJECT /
M.D. ( GENERAL MEDICINE)
4. / DATE OF ADMISSION TO COURSE / 24th May, 20105. / TITLE OF THE TOPIC / " STUDY OF LIPID PROFILE IN
TYPE 2 DM IN A.I.M.S RURAL SETUP-
A COMPARATIVE STUDY”
6. / BRIEF RESUME OF INTENDED WORK
6.1 NEED FOR THE STUDY
6.2 REVIEW OF LITERATURE
6.3 OBJECTIVES OF THE STUDY / APPENDIX-I
APPENDIX-IA
APPENDIX-IB
APPENDIX-IC
7 / MATERIALS AND METHODS7.1 SOURCE OF DATA
7.2 METHOD OF COLLECTION OF DATA : (INCLUDING SAMPLING PROCEDURE IF ANY)
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER ANIMALS, IF SO PLEASE DESCRIBE BRIEFLY.
7.4 HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3 / APPENDIX-II
APPENDIX-IIA
APPENDIX-IIB
YES
APPENDIX-IIC
YES
8. / LIST OF REFERENCES /APPENDIX – III
9. / SIGNATURE OF THE CANDIDATE /10. /
REMARKS OF THE GUIDE
/ WITH THE RISING NUMBER OF DIABETICS IN INDIA, THE FOLLOW UP OF LIPID PROFILE HAS CERTAINLY EMERGED AS AN IMPORTANT PROGNOSTICATION TOOL TO ASSESS CARDIOVASCULAR RISK FACTORS IN THESE PATIENTS SO AS TO REDUCE MOBIDITY AND MORTALITY IN THEM. HENCE THE STUDY WILL GIVE US AN INSIGHT INTO RISK STRATIFICATION WHICH CAN BE CORELATED WITH THE ALTERATIONS IN LIPID PROFILE11 / NAME AND DESIGNATION
(in Block Letters)
11.1 GUIDE / Dr. SHASHIKANTHA . M.B.B.S, M.D
PROFESSOR,
DEPARTMENT OF GENERAL MEDICINE
AIMS, B.G. NAGARA-571448
11.2 SIGNATURE OF THE GUIDE
11.3 CO-GUIDE (IF ANY) / -
11.4 SIGNATURE / -
11.5 HEAD OF DEPARTMENT / Dr JAGANNATHA. K M.B.B.S,M.D
PROFESSOR and HOD
DEPARTMENT OF GENERAL MEDICINE
AIMS, B.G. Nagara-57144811.6 SIGNATURE
12 / 12.1 REMARKS OF THE CHAIRMAN
AND PRINCIPAL
12.2 SIGNATURE
APPENDIX-I
6 . BRIEF RESUME OF THE INTENDED WORK:
APPENDIX –I A
6.1. NEED FOR THE STUDY:
Diabetes as a metabolic disorder is rising at an alarming rate all over the world and has
been a reason for concern due to the complications associated with it . With India having
the highest number of diabetic patients in the world, the sugar disease is posing an
enormous health problem in the country. Calling India the diabetes capital of the
world, the International Journal of Diabetes in Developing Countries says that there
is alarming rise in prevalence.
The International Diabetes Federation estimates that the number of diabetic
patients in India more than doubled from 19 million in 1995 to 40.9 million in 2007.
It is projected to increase to 69.9 million by 2025. Currently, up to 11 per cent
of India’s urban population and 3 per cent of rural population above the age of 15
have diabetes. Diabetes affects all people in the society, not just those who live with
it. The World Health Organization estimates that mortality from diabetes and heart
disease cost India about $210 billion every year and is expected to increase to $335
billion in the next ten years. These estimates are based on lost productivity, resulting
primarily from premature death.
Various studies have shown that the high incidence of diabetes in India is
mainly because of sedentary lifestyle, lack of physical activity, obesity, stress and
consumption of diets rich in fat, sugar and calories.
Dyslipidemia is commonly seen in diabetes. Type 2 diabetes mellitus is one of
the most common secondary cause of hyperlipidemia.The relationship between
hyperlipidemia and vascular complication of diabetes has long been of interest
because both tend to occur with greater frequency in type 2 diabetes mellitus. Insulin
resistance and obesity combine to cause dyslipidemia.and hyperglycemia and
hyperlipidemia has additive cardiovascular risk.. Diabetes,particularly type 2 diabetics
have higher lipid levels than non-diabetics and those patients with poor diabetic
control exaggerate this11.
.
There are several reasons for this association. Firstly, insulin plays an important role in
the regulation of intermediary lipid metabolism (Nikkila, E.A, 1974) and fluctuations in the
degree of diabetic control thus produce a variable effect on plasma lipoprotein metabolism.
Secondly, many non-insulin dependent diabetic patients are obese, and obesity leads to the
development of hyperlipidemia(Bierman, E.L1968). Thirdly ,although diabetes and
hyperlipidemia represent different genetic disorders, each of these disorders is common in the
population and the two disorders may co-exist by chance in thesame individual (Brunzell, J.D 1975).
Hence identification, critical evaluation, follow up of serum lipid profile in type 2
diabetes mellitus continue to be important and help in the prognostication of
cardiovascular risk.
APPENDIX –I B
6.2 REVIEW OF LITERATURE
HISTORY AND REVIEW OF LITERATURE
Diabetes mellitus is a group of metabolic diseases in which a person has high blood
sugar, either because the body does not produce enough insulin, or because cells do not
respond to the insulin that is produced resulting in polyuria( frequent urination), polydipsia
(increased thirst) and polyphagia( increased hunger).
The term diabetes was coined by Aretaeus of Cappadocia. It was derived from the
Greek verb, itself formed from the prefix dia-, "across, apart," and the verb bainein, "to walk,
stand." The verb diabeinein meant "to stride, walk, or stand with legs asunder"; hence, its
derivative diabētēs meant "one that straddles," or specifically "a compass, siphon." The sense
"siphon" gave rise to the use of diabētēs as the name for a disease involving the discharge of
excessive amounts of urine. Diabetes is first recorded in English, in the form diabete, in a
medical text written around 1425. In 1675, Thomas Willis added the word mellitus, from the
Latin meaning "honey", a reference to the sweet taste of the urine. This sweet taste had been
noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians. In 1776,
Matthew Dobson confirmed that the sweet taste was because of an excess of a kind of sugar in
the urine and blood of people with diabetes.
Sushruta (6th century BCE) identified diabetes and classified it as Medhumeha. He
further identified it with obesity and sedentary lifestyle, advising exercises to help "cure" it.
The ancient Indians tested for diabetes by observing whether ants were attracted to a person's
urine, and called the ailment "sweet urine disease" (Madhumeha). The Chinese, Japanese and
Korean words for diabetes are based on the same ideographs which mean "sugar urine
disease".
Medicine first recognized the existence of abnormal fatty content of the
circulating blood through the milky appearance observed during the days when blood
letting was widely practiced. The term lipemia was formulated by Babington in the 18th
century, when he showed that fats were responsible for giving this milky appearance
to the serum.The presence of lactescent serum with diabetes was first noted by Mariet
in 1799 and in 1958 by Thannhauser.S.J.
Owing to lack of research facilities no further advance was made till the
beginning of the 20th century. The deficiency in knowledge was made evident in 1903
when Fischer reviewed the subject. He listed all the conditions where doctors had
earlier observed milky appearance of blood. These included apoplexy, peritonitis,
malaria, jaundice, leprosy, etc. He finally retained diabetes and alcoholic lipaemia as
being genuine. In the years that followed data accumulated about hyperlipemia
accompanying diabetes. Man and Peters (1935) found that triglyceride was the
primary lipid to be elevated. Harries et al (1952) found elevations of serum lipid levels
in diabetic acidosis.
More recently, Chaturvedi et al1(2001) found elevation in triglyceride rich VLDL
to be a common abnormality. In a study of Lowy A.D et al (1957) found a significant
increase in the incidence of hyperlipidemia in association with poor diabetic control.
In a study of the significance of blood lipid alterations in diabetes mellitus,
Mazzone,T et al (2000) 2 measured plasma triglyceride and cholesterol levels in a
large series of diabetic and non-diabetic subjects of all ages. Their results showed that
plasma triglycerides increase with age in diabetics but not in nondiabetics, while
cholesterol levels increase with age in both groups.
Bagdade et.al. (1967) 3 studied five patients with chronic symptomatic diabetes
and minimal ketoacidosis who had marked hyperlipidemia and concluded that diabetic
lipemia can be considered to be a reversible form of dietary fat induced lipemia
secondary to chronic insulin deficiency.
Nikkila EA and Hormila P (1978) 4, concluded that the average serum lipid and
lipoprotein pattern of insulin treated chronic diabetic patients was not_more
atherogenic than non-diabetic subjects of similar age and sex. On the contrary the
increase in HDLc levels which they found, should make them less liable to develop
coronary heart disease. Thus they felt that the increased incidence of cardiovascular
disease in type II diabetes must be accounted for by some other factors.
Chance et.al. (1969)5 studied serum lipids and lipoproteins in 135 diabetic
children prior to treatment and found elevated serum total lipids in 64% of the patients
and elevated cholesterol in 43%. Abnormal lipoprotein patterns were found in 77%, the
commonest anomaly being increase in pre P-lipoprotein.
Strisower E H et al (1958)6 found significant increase in serum cholesterol, LDL
and VLDL values in poorly controlled insulin treated diabetics, which returned to
normal on achieving rigid control
Dewind et. al. (1952) carried out studies in patients with advanced diabetic
atherosclerosis and found no obvious correlation between any of the lipid fractions
although the mean serum cholesterol values were significantly higher in diabetics than
in non-diabetic elderly controls.
Hokanson JE, et al (1996) 7 stated that plasma triglyceride is an independent
risk factor for the development of cardiovascular disease.
Sharma D et.al. (1970)8 studied serum lipid profile in type 2I diabetic patients
below 40 years of age and found significant elevations in the level of serum
cholesterol, phospholipids, esterified fatty acids and triglyceride as compared to a
control group.
In the study of Barr et al (1951) HDL concentrations were Strikingly reduced
in some atherosclerotic diabetic patients. In a recent Study of HDLc in diabetics by
P.K.Bijlani et.al. (1983), it was found that the HDLc values in diabetics and subjects
with impaired glucose tolerance were significantly lower than normal controls. Females
in all groups had higher HDLc than males. Higher HDLc values were also observed in
diabetics on insulin therapy and with better glycemic control.
V.J. Retnam et al (1983) 9 reported hyperlipoproteinemia in a study of 152
adult diabetics on treatment. They found that 20 out of 70 controlled patients and 48
of 82 uncontrolled patients had hyperlipoproteinemia.
Over the past years there has been increasing awareness on the part of the
physicians and general population of the potential benefits of detecting and treating
hypercholesterolemia. This is particularly important in diabetics for two reasons:
1.There already is an increased risk of premature coronary heart disease
In patients with diabetes independent of raised plasma cholesterol levels.
2.Alterations in plasma lipoprotein metabolism are common in diabetes
as they tend to exaggerate any pre-existing tendencies towards elevated lipid levels.
The new recommendations by the National Cholesterol Education Program
have provided guidelines for practicing physicians in treatment of
hypercholesterolemia. These guidelines can be easily applied to patients with diabetes
and optimal. care of diabetic patients require that these recommendations be followed.
However it is also important to understand the effect of diabetes on lipoprotein
metabolism,because in many cases it may be more appropriate to make a change in
diabetic treatment rather than treat the hyperlipidemia.
DYSLIPIDEMIA AND DIABETES
Dyslipidemia is a relatively common problem in patients with poorly
controlled diabetes mellitus. It has been estimated that the frequency of elevated
plasma lipid levels in diabetic patients is between 20 and 90 %. (Billimoria, J.D 1976,
Chance.G.W 1969, Chase. H.P 1976) 5 . Diabetes,particularly type 2 diabetics have
higher lipid levels than non-diabetics and those patients with poor diabetic control
exaggerate this. There are several reasons for this association.
Firstly, insulin plays an important role in the regulation of intermediary lipid
metabolism (Nikkila, E.A, 1974) and fluctuations in the degree of diabetic control thus
produce a variable effect on plasma lipoprotein metabolism.
Secondly, many non-insulin dependent diabetic patients are obese, and obesity
leads to the development of hyperlipidemia(Bierman, E.L1968). Third,although
diabetes and hyperlipidemia represent different genetic disorders, each of these
disorders is common in the population and the two disorders may co-exist by chance
in the same individual (Brunzell, J.D 1975).
TYPE 2 DIABETES AND ITS EFFECT ON LIPID PROFILE
The most common abnormality in type-2 diabetes is hypertriglyceridemia
caused by increase in VLDL. The effect of type-2 diabetes on TG is moderate and
increases in plasma TO >500 mg/dl is caused by the coexistence of a genetic form of
hypertriglyceridmeia aggravated by the hyperglycemia.
Type-2 diabetes causes both overproduction and impaired clearance of
VLDL triglyceride. The mechanism of overproduction of VLDL - TG most likely is
because of increased flow of glucose and free fatty acids to the liver. The removal
defect is caused by impaired lipoprotein lipase activity, but is minimal except in poorly
controlled type-2 diabetes. VLDL overproduction and lipoprotein lipase levels can be
controlled with normalization of glucose levels .
There is also increased production of VLDL apoprotein -B which may be