EVALUATION OF FASTING AND POSTPRANDIAL PLASMA

ACYLATED GHRELIN LEVEL IN OBESE AND NORMAL

WEIGHT TYPE 2 DIABETES MELLITUS PATIENT IN UYO

BY

DR. ANIETIE ARTHUR ETUK

(MBBch, CALABAR)

DEPARTMENT OF CHEMICAL PATHOLOGY UNIVERSITY

OF UYO TEACHING HOSPITAL
UYO

A PROPOSAL SUBMITTED FOR DISSERTATION IN PARTIAL

FULFILLMENT FOR THE AWARD OF FELLOWSHIP
(FMCPath) OF THE NATIONAL POSTGRADUATE MEDICAL
COLLEGE OF NIGERIA
 Chapter one

1.1 STATEMENT OF THE PROBLEM

1.2 JUSTIFICATION OF STUDY

 CHAPTER THREE

AIMS AND OBJECTIVE

3.1 AIMS
To evaluate fasting and postprandial acylated ghrelin in normal
weight and in obese type 2 diabetes mellitus patient.

3.2 OBJECTIVES
1. To measure fasting acylated ghrelin in Type 2 Diabetes Mellitus
(T2DM)
2. To evaluate post prandial acylated ghrelin in Type 2 Diabetes
Mellitus (T2DM)
3. To compare fasting and post prandial in obese Type 2 Diabetes
Mellitus (T2DM)
4. To compare fasting and post prandial in normal weight Type 2
Diabetes Mellitus (T2DM)
 INTRUDUCTION

Diabetes mellitus is a diverse group of metabolic disorders that is often

associated with a high disease of implication and outbreak in
developing countries including Nigeria (1).
It’s a heterogeneous disturbance of metabolism with chronic
hyperglycemia as it major complication due to insulin secretion
impaired in both from the B-cell of Pancreas (2, 7, 6, 3).

Diabetes mellitus is clinically classified into; Type 1 Diabetes Mellitus

(T1DM), Type 2 Diabetes Mellitus (T2DM) and Gestational Diabetes
with T2DM, accounting for over 90 – 95% of all cases of Diabetes
Mellitus worldwide (1, 2).
In 2011, the International Diabetes Federation (IDF) estimated the
global prevalence of Diabetes Mellitus to be 366million, with an
increase 422million in 2014, 415million in 2015.
It was estimated at 425million in 2017 within the age group of 20 – 79
years.

In 2030, it’s expected to increase to 522million and 629million by the

year 2040.
In Nigeria, the estimated prevalence are grossly undocumented. In
Akwa Ibom State, the records are unavailable on the present
prevalence of Diabetes Mellitus (7, 8, 4).
Over weight and obesity with physical inactivity are the strongest risk
factor of T2DM globally.
There are 2 categories – modifiable and non-modifiable risk factor.
Modifiable risk factors includes: Diet rich in saturated fat and
carbohydrates, impaired glucose tolerance, Hypertension >140/90,
Hypertriglyceridemia >250mg/dl and low level of physical activity.
Non-modifiable factors include: Age 48 years
Family history of Diabetes Mellitus, ethnicity and gestational DM from a
T2DM patient (8, 4, 3, 5) .

Inflammatory markers and its activations are risk factors for the
development of T2DM in the presence of obesity (10).
Complication for T2DM could be microvascular (e.g. nephropathy,
neuropathy and retinopathy), macro vascular (e.g. pulmonary artery
disease (CAD), peripheral artery disease (PAD), cerebrovascular
disease). (3, 4, 8, 5).

Ghrelin is a 28 amino acid gastric peptide hormone with an orexigenic

property which stimulates appetites and regulate energy balance. Its
Synthesized by the endocrine XIA- like cells of the fundus mucosa (9, 12, 14,
17, 11)

There are of 2 forms: Acylated ghrelin (AG) [active form] and

Deacylated ghrelin (DAG) [inactive form] with both playing a role in the
development of Metabolic Syndrome (MS) and Type 2 Diabetes
Mellitus(T2DM) (9, 13, 12) .
It production involves transcriptional, translational and post
translational modification of the ghrelin gene (13) .
Evidence suggest that Ghrelin and it genetic variations plays an
important role in cardiovascular system, development of Metabolic
Syndrome, T2DM and control glucose metabolism (9, 13) .
Plasma ghrelin concentration level is reduced in a fasting state and
obese patient than in a normal weight patient and this is due to the
presence of possible genetic component in the regulation of ghrelin
plasma level (9) .
In non-diabetic, there are differences in the fasting and post prandial
ghrelin circulation level in both obesed and normal weight patient (9) .
Post prandial plasma ghrelin level is suppress in normal weight but not
in obese patient which suggest food intake fails to suppress ghrelin
level in obese patient (9).
Studies shows that the plasma ghrelin as well as the Deacylated ghrelin
with prevalence of metabolic syndrome is lower in obese patient than
normal weight patient and this is due to high Body Mass Index (BMI)
with adiposity (9, 20) .

Total ghrelin, Acylated ghrelin (AG) or Deacylated ghrelin (DAG) level

are also lower in overweight and obese patient with insulin resistance
compared to insulin sensitive patient, and no difference in normal
weight patient. (9, 20, 15) .
The energy that catalysis AG which is synthesis by the hypothalamus is
Ghrelin-o- acyl Transference (GOAT) and it signals is transmitted via the
central and peripheral pathway of the vagus nerve (12, 13) .
AG, a target of obesity therapy using the GOAT inhibitor is activated by
the arcuate nucleus (12) .
It is metabolized by GOAT to DAG and plays an active role in the
pathogenesis of obesity. AG stimulate appetite, increase growth
secretion, decrease insulin from the pancreas, reduce in energy
consumption by the body and effects on growth to peripheral
metabolism (15) .

Obesity a complex disease caused by the interplay between

environmental and genetic factors, is a global public health problem
and a major risk factor for the development of metabolic syndrome
(MS) and Type 2 Diabetic Mellitus (T2DM) (9) .
It strongly associated with oxidative stress due to imbalance between
oxidants and antioxidants (13) .
Obesity is a risk factor for chronic disease such as hear and blood vessel
disease, diabetes mellitus and cancer (12) .
Obesity results from a positive energy balance or energy intake to
exceeding energy expenditure (12) .
Obesity is the excessive accumulation of body fat caused by energy
imbalance between calories Consumed and calories Expanded (12) .
Obesed individuals have higher AG than normal weight (AG increase
the risk of obesity) (12) .
Plasma AG concentration is higher before and after eating at all time
points regardless of food type in obese individuals (12) .
The increase in AG and decrease in total ghrelin occur because the AG
hormonal content circulating in the plasma is only 10% of the total
existing ghrelin (12) .
The American Obesity Association (AOA) estimates that 15% of children
between age 6 – 19 years meets the criteria for obesity (13, 29) .
Insulin resistance (IR), hypertension, glucose intolerance and T2DM
have all been implicated in childhood obesity and the concomittant
Occurrence of these abnormalities (metabolic syndrome) is a risk for
the development of cardiovascular disease, diabetes and non-alcoholic
fatty liver disease during early adulthood (13, 29, 30) .
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