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Islamic University of Gaza Postgraduate Deanship Faculty of Science Biological Sciences Master Program Medical Technology Department

Detection of Some Enzymes and Transferrin as Early Diagnostic Markers

for Diabetic Nephropathy among Type-2 Diabetic Patients in Gaza

By

Shimaa Waleed Shubair

Supervisor: Prof. Mohammad E. Shubair

A thesis submitted in partial fulfillment of the requirements for the degree of master of biological sciences / Medical Technology

1429 2008

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DECLARATION I hereby declare that this manuscript is my own work and that, to the best of my

knowledge and belief, it contains no material previously published, or written by

another person, nor material which to a substantial extent has been accepted

for the award of any other degree of the university or other institute, except

where due a acknowledgment has been made in the text.

Author Shimaa W. Shubair

Signature: Date:

All Right Reserved 2008. No part of this work can be copied, translated or stored in retrieval system, without prior permission of the author.

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Detection of some enzymes and transferrin as early diagnostic markers for diabetic nephropathy among type-2 diabetic patients in Gaza

Abstract Kidney Function assessment is important in diabetic patients and early

detection of diabetic nephropathy in preclinical stage of disease and will

contribute to decreasing morbidity and mortality rates.

This study focused on the determination of N-acetyl--D-glucosaminidase

(NAG) and gamma glutamyl transferase (GGT) enzymes, transferrin (TRF) and

creatinine (CR) in urine of type-2 diabetic subjects and controls of healthy

subjects for detection of the relationship between these markers and diabetic nephropathy in type-2 diabetic patients in Gaza.

Early morning urine samples were collected from 100 diabetic patients,

their age range was from 40-60 years and some of them have hypertension and

from 80 control non diabetic subjects with the same age. All the 180 subjects

did not suffer from urinary tract infection, liver or renal diseases. In addition, the

control subjects did not suffer hypertension, or abnormalities in carbohydrate

metabolism. NAG and GGT were measured in urine samples using colorimetric

assay kits while TRF was assayed using a turbidimetric immunoassay kit. CR

was assayed using the alkaline picrate method.

Urinary TRF concentration, NAG and GGT activities showed significant

differences between diabetic patients and control. The study showed also that

these markers did not have significant difference between hypertensive and

non-hypertensive diabetic patients and no significant difference between males

and females of patients group. Furthermore, the study showed that 32% have

shown elevated NAG excretion but GGT excretion was found elevated only in

15% of cases and TRF was found higher in 29% of patients. One female patient

had abnormally elevated levels of TRF, NAG and GGT. No correlations was

found between age, body mass index (BMI), smoking, duration of diabetes,

systolic or diastolic pressure and these markers. This study indicates that the

appearance of the NAG, GGT and TRF in urine may be useful as a non-

invasive surrogate test in detecting diabetic nephropathy at an early stage.

Key words: Diabetic nephropathy, N-acetyl--D-glucosaminidase, Gamma glutamyl transferase, Transferrin, Gaza.

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colorimetric assay

Turbidimetric Immunoassay .

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LIST OF ABBREVIATIONS

AAP

Abs

ACE

ACR

AD

AER

AFR

AGEs

AIDS

AMG

AngII

AP

ARBs

BC

Beta-G1

BMG

BMI

CDC

CHD

CR

CVD

DAP

DKA

DM

DN

EMME

ESRD

EUR

GDM

GFR

Alanine aminopeptidase

Absorbance

Angiotensin converting enzyme

Albumin/ creatinine ratio

Anno domini after Christ birth

Albumin excretion rate

Africa

Advanced glycosylation end products

Acquired immunodeficiency syndrome

Alpha 1-microglobulin

Angiotensin II

Alkaline phosphatase

Angiotensin receptor blockers

Before Christ birth

Beta-glucuronidase

Beta 2-microglobulin

Body mass index

Center for disease control and prevention

Coronary heart disease

Creatinine

Cardiovascular disease

Dipeptidyl aminopeptidase IV

Diabetic ketoacidosis

Diabetes mellitus

Diabetic nephropathy

Eastern Mediterranean and middle east region

End stage renal disease

European region

Gestational diabetes mellitus

Glomerular filtration rate

v

GGT

GSH

HbA1c

HHNKC

HIV

HOT

hTRF

IDF

LA

LAP

LDH

LDL

MAU

min

MOH

NA

NAG

NCDs

NDDG

NIDDM

PCBS

PHC

RBP

SACA

SEA

SPSS

TER

TGF

TRF

TRFR

UKPDS

UPMRC

Gamma glutamyl transpeptidase / transferase

Glutathione

Glycosylated (or glycated) hemoglobin

Hyperosmolar hyperglycemic nonketotic coma

Human immunodeficiency virus

Hypertension optimal treatment

Human serum transferrin

International diabetes federation

lactic acidosis

leucine aminopeptidase

lactate dehydrogenase

low-density lipoprotein

Microalbuminuria

minute

Ministry of Health-Palestine

North American region

N-acetyl--D-glucosaminidase

Non-communicable diseases

National diabetes data group

Non-insulin-dependent diabetes

Palestinian central bureau of statistics

Primary health care department

Retinol binding protein

South and central America region

South-East Asian Region

Statistical package for social science

Transferrin excretion rates

Transforming growth factor beta

Transferrin

Transferrin receptors

United kingdom prospective diabetes study group

Union of Palestinian medical relief committee

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U.S.

WHO

WP

United states

World health organization

Western pacific region

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ACKNOWLEDGMENTS

I would like to thank .

The Islamic University of Gaza and the Faculty of Science for giving me the

opportunity and knowledge so that I achieve this research.

My supervisor Prof. Mohammad shubair, who stood for me, step by step, during

this journey to be sure that every detail will be correct .

My family for strengthening my self confidence and encouraging me always to

pursue my goal.

Dr. Samir Safi for his help in the statistical background of this research.

Mr. Yusif Al Arqan for facilitating the task of sample-testing in his own

laboratory.

The employees of the diabetes clinic at Remal Health Center for all the help

they provided during sample collection process.

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Dedication

This thesis is dedicated to my father and mother who have

supported me all the way since the beginning of my study .

Also, this thesis is dedicated to my husband who has been a great

source of motivation and inspiration and his loving and kind

family.

Finally, dedication continues to my beloved Palestinian

community, especially diabetes patients.

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Chapter I Introduction 1.1 Background of the problem 1.2 Diabetes in Palestine

1.2.1 Prevalence of diabetes mellitus

1.2.2 Cost of anti diabetic drugs in MOH

1.2.3 Mortality of diabetes mellitus

1.3 Global prevalence of diabetes mellitus 1.4 Aim of the study 1.5 Significance Chapter II literature Review 2.1 Diabetes mellitus 2.1.1 History of diabetes mellitus

2.1.2 Definition and description of diabetes mellitus

2.1.3 Classification of diabetes mellitus

2.1.3.1 Type-1 diabetes

2.1.3.2 Type-2 diabetes

2.1.3.3 Gestational diabetes mellitus (GDM)

2.1.4 The insulin

2.1.5 Diet and exercise in diabetes

2.1.5.1 Principles of diet therapy in diabetes

2.1.5.2 Exercise and diabetes

2.2 Complications of diabetes mellitus 2.2.1 Acute glycemic complications 2.2.1.1 Diabetic ketoacidosis (DKA)

2.2.1.2 Hyperosmolar hyperglycemic