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Glycated albumin versus glycated
hemoglobin as glycemic indicator in
hemodialysis patients with diabetes mellitus.
Thesis

Submitted for partial fulfillment
of doctor degree in internal medicine
Submitted By

Ayman Noureldeen Mostafa
Master Degree Of Internal Medicine

Assistant lecture Of Internal Medicine And Nephrology
Al-Azhar University Hospital-Assiut

SUPERVISED BY

Dr.Mohamad Abbas Sobh
Professor Of Internal Medicine And Nephrology
Assuit University

Dr. Ashraf Mohamad Mohamad Alkabeer
Lecturer Of Internal Medicine
Faculty Of Medicine, ALAzhar University Assuit
2013
Introduction
The global incidence of diabetes mellitus is rising
exponentially and diabetic nephropathy is now the predominant
cause of chronic kidney disease (CKD) (Zimemet P et al;
(2010

Diabetic nephropathy causing end-stage kidney disease
(ESKD) accounts for 30–50% of all new patients commencing
renal replacement therapy (RRT). So diabetic nephropathy
considers as the most common aetiology of end-stage kidney
.(disease (ESKD). (Collins AJ et al 2012
Strict glycaemic control reduces the development and
progression of diabetes-related complications, and there is
evidence that improved metabolic control improves outcomes
in diabetic subjects with advanced chronic kidney disease
((CKD). (Ohkubo Y et al; 2011
Glycaemic control in people with kidney disease is
complex. Changes in glucose and insulin homeostasis may
occur as a consequence of loss of kidney function and dialysis.
The reliability of measures of long-term glycaemic control is
affected by CKD and the accuracy of glycated haemoglobin
(HbA1c) in the setting of CKD and ESKD is questioned.
(( Chalmers J et al;2012
The validity of indicators of longer term glycaemic control
has been the focus of increased recent research. They found
that HbA1c and glycated albumin levels are both independently
associated with serum glucose level. However, HbA1c level
unlike glycated albumin level
was also influenced by
hemodialysis, hemoglobin level, and erythropoietin dose.
Although we agree that glycated albumin level could be a
better indicator of glycemic control than HbA1c level in
patients on hemodialysis who have diabetes and anuria, this
conclusion might not be applicable to patients with massive
proteinuria or to those on peritoneal dialysis. (Rohlfing CL et al;
.(2011
Glycated hemoglobin (HbA1c) level, which indicates the
percentage of circulating hemoglobin that has chemically
reacted with glucose, reflects the blood glucose level over the
120 days preceding the test; glucose levels during the 30 days
before the test have the biggest impact on HbA1c level.
( Gerich JE et al;2010)
The lack of specific guidelines for assessing glycemic
control in patients who are receiving hemodialysis has resulted
in the HbA1c assay which is widely used in the general
population being the test of choice in this setting. However, in
patients with diabetes who are on hemodialysis, factors such as
anemia (due to reduced erythrocyte life span or iron
deficiency), recent transfusions, metabolic acidosis, and
administration of erythropoietin affect the accuracy of the
HbA1c assay. By increasing the proportion

of young

erythrocytes in the blood, both anemia and erythropoietin can
falsely lower HbA1c levels, which could in turn lead to a
failure to diagnose hyperglycemia. Approximately 90% of
patients on hemodialysis worldwide undergo erythropoietin
treatment; therefore, HbA1c might be an unsuitable marker for
glycemic control in the hemodialysis setting.( Mak RH et al;
2012)
Aim of the study
Our study is a cross sectional study aiming to compare between
glycated hemoglobin and glycated albumin as glycemic indicator in
hemodialysis patients with diabetes.

Patients and methods
A cross sectional study of 50 chronic uraemic diabetic patients who
are currently undergoing hemodialysis three sessions per week for more
than 3 months in the dialysis unit. The study will be conducted through a
period of time spanning 3 months.
Study procedure
All patients will be subjected to :1. Full history taking (including the duration on dialysis , aetiology
of chronic renal failure , duration of diabetes and smoking).
2. Thorough clinical examination ( including body mass index,…).
3. Measurement of blood glucose level 3 times weekly for three
months.
4. Measurement of glycated albumin every 3 weeks for 3 months.
5. Measurement of glycated hemoglobin at the end of the three
months.
Inclusion criteria
All chronic renal failure diabetic patients who are undergoing
hemodialysis for more than 3 months.
Exclusion criteria
1. Patients with acute renal failure.
2. Active malignancy.
3. Pregnancy.
4. Active major bleeding in the prior month.

• A written consent will be taken from the patients in order to be
eligible in the study.
• All results will be statiscally analyzed and tabulated.
References
1.

Chalmers J , and et al. Intensive blood glucose control on
hemodialysis N Engl J Med 2012;358:2560-2572.

2.

Collins AJ, Foley R, Herzog C and et al. Excerpts from the

United States Renal Data System 2012 annual data report:
atlas of end-stage renal disease in the United States. JAMA
2012;307 No 17:1809-1816.
3.

Gerich JE, meyer C, Woerle HJ, and et al. impact of blood

glucause results of thr last 30 dayes on HbA(1c). Care
2010;24:382-391.
4.

Mak RH, and et al. Impact of end-stage renal disease and

dialysis on glycemic control. Semin Dial 2012;13:4-8.
5.

Ohkubo Y, Kishikawa H, Araki E,and et al. Intensive

hypoglycemic therapy prevents the progression of diabetic
microvascular
complications.
Diabetes
Res
Clin
Pract2011;28:103-117.

6.

Rohlfing CL, Wiedmeyer HM,Little RR,and et al. Defining

the relationship between plasma glucose and HbA(1c):
analysis of glucose profiles and HbA(1c) in the Diabetes
patient on hemodialysis Trial. Diabetes Care 2002;25:275278.
‫‪Zimemet P,Alberti KG ,Shaw J. Global and societal‬‬

‫.7‬

‫29:)2(11;0102 .‪implications of the diabetes epidemic. Nature‬‬‫.99‬

‫مقدمة‬
‫إن المعدل العالمى لتنتشار مرض السسسكرى قسسد تزايسسد بشسسكل ملحسسوظ فسسى السسسنوات‬
‫ ً‬
‫اليخيرة وأصبح العتلل الكلوى السكرى من أكسسثر أسسسباب الفشسسل الكلسسوى شسسيوعا‬
‫حيث أن تنسبة تسستراوح مسسا بيسسن 03 % السسى 05% مسسن المصسسابين بمسسرض الفشسسل‬
‫ ً‬
‫الكلوى المزمن حول العالم تكون تنتيجة للصابة بالعتلل الكلوى السكرى .وتنظرا‬
‫لن التحكم الصارم فى مستوى السسسكر بالسسدم لمرضسسى السسسكرى يعتسسبر مسسن المسسور‬
‫المعقدة ويخاصة فسسى مرضسسى الستصسسفاء السسدموى.ففسسى مرضسسى السسسكرى تنسسستطيع‬
‫التعرف على مدى إتنتظسسام مسسستوى السسسكر بالسسدم يخلل الثل ث شسسهور السسسابقة عسسن‬
‫طريق إيختبار تنسبة الهيموجلوبين السكرى بالدم .ولكن فى مرضى السكرى تحسست‬
‫الستصفاء الدموى يكون المر مختلفسا حيسسث ان تنسسسبة الهيموجلسسوبين فسسى هسسؤلء‬
‫ ً‬
‫المرضى تكون سريعة التغير وذلك لعدة أسباب منها تعرض هسسؤلء المرضسسى لفقسسد‬
‫كميات من السسدم اثنسساء عمليسسة الستصسسفاء السسدموى وكسسذلك بعسسض هسسؤلء المرضسسى‬
‫يحتاجون بصفة مسسستمرة لعمليسسة تنقسسل السسدم اليهسسم وكمسا أن فسسترة حيسساة كسسرات السسدم‬
‫الحمسسراء تتسساثر بمسسرض الفشسسل الكلسسوى وكسسذلك معظسسم هسسؤلء المرضسسى يحتسساجون‬
‫لهرمون الريثروبيوتين الذى يحفز تكوين كرات دم حمراء جديدة.مما يجعل تنتائسسج‬
‫إيختبار تنسبة الهيموجلوبين السكرى فى هؤلء المرضى غير دقيقة.وتنظسسرا لكسسل مسسا‬
‫ ً‬
‫سبق فإن تنسبة اللبومين بالسسدم فسسى مرضسسى السسسكرى تحسست الستصسسفاء السدموى‬
‫تكون تكون اكثر ثباتا من تنسبة الهيموجلوبين وفى هذة الرسالة تنقوم بقارتنة تنتائج‬
‫ ً‬
‫المستوى العشوائى للسكر بالدم بكل من مستوى تنسبة الهيموجلسسوبين السسسكرى و‬
‫مستوى تنسبة اللبومين السكرى بالدم لمعرفة أى من المستويين يمكسسن اسسستخدامة‬
‫ ٍ‬
‫.كمؤشر دقيق لمستوى السكر بالدم لهؤلء المرضى‬

‫مقارتنة بين اللبومين السكري والهيموجلوبين السكري‬
‫كمؤشر لمستوي السكر بالدم لمرضي الستصفاء الدموي‬
‫والمصابين بداء السكري‬
‫بروتوكول رسالة‬
‫توطئة للحصول على درجة الدكتوراة فى‬
‫الباطنه العامة‬
‫مقدمة من‬

‫الطبيب/ ايمن نورالدين مصطفي‬
‫ماجستير امراض الباطنة العامة‬
‫مدرس مساعد أمراض الباطنة والكلي‬
‫كلية طب الهزهر أسيوط‬

‫تحت إشراف‬
‫ا.د/محمدعباس صبح‬
‫أستاذ أمراض الباطنه العامة والكلى بطب أسيوط‬
‫د/اشرف محمد محمد الكبير‬
‫مدرس أمراض الباطنة العامة‬
‫كلية الطب – جامعة الهزهر– أسيوط‬

‫3102‬
‫د/اشرف محمد محمد الكبير‬
‫مدرس أمراض الباطنة العامة‬
‫كلية الطب – جامعة الهزهر– أسيوط‬

‫3102‬

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Protocol 1 final copy

  • 1. Glycated albumin versus glycated hemoglobin as glycemic indicator in hemodialysis patients with diabetes mellitus. Thesis Submitted for partial fulfillment of doctor degree in internal medicine Submitted By Ayman Noureldeen Mostafa Master Degree Of Internal Medicine Assistant lecture Of Internal Medicine And Nephrology Al-Azhar University Hospital-Assiut SUPERVISED BY Dr.Mohamad Abbas Sobh Professor Of Internal Medicine And Nephrology Assuit University Dr. Ashraf Mohamad Mohamad Alkabeer Lecturer Of Internal Medicine Faculty Of Medicine, ALAzhar University Assuit 2013
  • 2. Introduction The global incidence of diabetes mellitus is rising exponentially and diabetic nephropathy is now the predominant cause of chronic kidney disease (CKD) (Zimemet P et al; (2010 Diabetic nephropathy causing end-stage kidney disease (ESKD) accounts for 30–50% of all new patients commencing renal replacement therapy (RRT). So diabetic nephropathy considers as the most common aetiology of end-stage kidney .(disease (ESKD). (Collins AJ et al 2012 Strict glycaemic control reduces the development and progression of diabetes-related complications, and there is evidence that improved metabolic control improves outcomes in diabetic subjects with advanced chronic kidney disease ((CKD). (Ohkubo Y et al; 2011 Glycaemic control in people with kidney disease is complex. Changes in glucose and insulin homeostasis may occur as a consequence of loss of kidney function and dialysis. The reliability of measures of long-term glycaemic control is affected by CKD and the accuracy of glycated haemoglobin (HbA1c) in the setting of CKD and ESKD is questioned. (( Chalmers J et al;2012 The validity of indicators of longer term glycaemic control has been the focus of increased recent research. They found that HbA1c and glycated albumin levels are both independently associated with serum glucose level. However, HbA1c level unlike glycated albumin level was also influenced by hemodialysis, hemoglobin level, and erythropoietin dose. Although we agree that glycated albumin level could be a
  • 3. better indicator of glycemic control than HbA1c level in patients on hemodialysis who have diabetes and anuria, this conclusion might not be applicable to patients with massive proteinuria or to those on peritoneal dialysis. (Rohlfing CL et al; .(2011 Glycated hemoglobin (HbA1c) level, which indicates the percentage of circulating hemoglobin that has chemically reacted with glucose, reflects the blood glucose level over the 120 days preceding the test; glucose levels during the 30 days before the test have the biggest impact on HbA1c level. ( Gerich JE et al;2010) The lack of specific guidelines for assessing glycemic control in patients who are receiving hemodialysis has resulted in the HbA1c assay which is widely used in the general population being the test of choice in this setting. However, in patients with diabetes who are on hemodialysis, factors such as anemia (due to reduced erythrocyte life span or iron deficiency), recent transfusions, metabolic acidosis, and administration of erythropoietin affect the accuracy of the HbA1c assay. By increasing the proportion of young erythrocytes in the blood, both anemia and erythropoietin can falsely lower HbA1c levels, which could in turn lead to a failure to diagnose hyperglycemia. Approximately 90% of patients on hemodialysis worldwide undergo erythropoietin treatment; therefore, HbA1c might be an unsuitable marker for
  • 4. glycemic control in the hemodialysis setting.( Mak RH et al; 2012) Aim of the study Our study is a cross sectional study aiming to compare between glycated hemoglobin and glycated albumin as glycemic indicator in hemodialysis patients with diabetes. Patients and methods A cross sectional study of 50 chronic uraemic diabetic patients who are currently undergoing hemodialysis three sessions per week for more than 3 months in the dialysis unit. The study will be conducted through a period of time spanning 3 months. Study procedure All patients will be subjected to :1. Full history taking (including the duration on dialysis , aetiology of chronic renal failure , duration of diabetes and smoking). 2. Thorough clinical examination ( including body mass index,…). 3. Measurement of blood glucose level 3 times weekly for three months. 4. Measurement of glycated albumin every 3 weeks for 3 months. 5. Measurement of glycated hemoglobin at the end of the three months. Inclusion criteria All chronic renal failure diabetic patients who are undergoing hemodialysis for more than 3 months. Exclusion criteria 1. Patients with acute renal failure. 2. Active malignancy. 3. Pregnancy.
  • 5. 4. Active major bleeding in the prior month. • A written consent will be taken from the patients in order to be eligible in the study. • All results will be statiscally analyzed and tabulated.
  • 6. References 1. Chalmers J , and et al. Intensive blood glucose control on hemodialysis N Engl J Med 2012;358:2560-2572. 2. Collins AJ, Foley R, Herzog C and et al. Excerpts from the United States Renal Data System 2012 annual data report: atlas of end-stage renal disease in the United States. JAMA 2012;307 No 17:1809-1816. 3. Gerich JE, meyer C, Woerle HJ, and et al. impact of blood glucause results of thr last 30 dayes on HbA(1c). Care 2010;24:382-391. 4. Mak RH, and et al. Impact of end-stage renal disease and dialysis on glycemic control. Semin Dial 2012;13:4-8. 5. Ohkubo Y, Kishikawa H, Araki E,and et al. Intensive hypoglycemic therapy prevents the progression of diabetic microvascular complications. Diabetes Res Clin Pract2011;28:103-117. 6. Rohlfing CL, Wiedmeyer HM,Little RR,and et al. Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes patient on hemodialysis Trial. Diabetes Care 2002;25:275278.
  • 7. ‫‪Zimemet P,Alberti KG ,Shaw J. Global and societal‬‬ ‫.7‬ ‫29:)2(11;0102 .‪implications of the diabetes epidemic. Nature‬‬‫.99‬ ‫مقدمة‬ ‫إن المعدل العالمى لتنتشار مرض السسسكرى قسسد تزايسسد بشسسكل ملحسسوظ فسسى السسسنوات‬ ‫ ً‬ ‫اليخيرة وأصبح العتلل الكلوى السكرى من أكسسثر أسسسباب الفشسسل الكلسسوى شسسيوعا‬ ‫حيث أن تنسبة تسستراوح مسسا بيسسن 03 % السسى 05% مسسن المصسسابين بمسسرض الفشسسل‬ ‫ ً‬ ‫الكلوى المزمن حول العالم تكون تنتيجة للصابة بالعتلل الكلوى السكرى .وتنظرا‬ ‫لن التحكم الصارم فى مستوى السسسكر بالسسدم لمرضسسى السسسكرى يعتسسبر مسسن المسسور‬ ‫المعقدة ويخاصة فسسى مرضسسى الستصسسفاء السسدموى.ففسسى مرضسسى السسسكرى تنسسستطيع‬ ‫التعرف على مدى إتنتظسسام مسسستوى السسسكر بالسسدم يخلل الثل ث شسسهور السسسابقة عسسن‬ ‫طريق إيختبار تنسبة الهيموجلوبين السكرى بالدم .ولكن فى مرضى السكرى تحسست‬ ‫الستصفاء الدموى يكون المر مختلفسا حيسسث ان تنسسسبة الهيموجلسسوبين فسسى هسسؤلء‬ ‫ ً‬ ‫المرضى تكون سريعة التغير وذلك لعدة أسباب منها تعرض هسسؤلء المرضسسى لفقسسد‬ ‫كميات من السسدم اثنسساء عمليسسة الستصسسفاء السسدموى وكسسذلك بعسسض هسسؤلء المرضسسى‬ ‫يحتاجون بصفة مسسستمرة لعمليسسة تنقسسل السسدم اليهسسم وكمسا أن فسسترة حيسساة كسسرات السسدم‬ ‫الحمسسراء تتسساثر بمسسرض الفشسسل الكلسسوى وكسسذلك معظسسم هسسؤلء المرضسسى يحتسساجون‬ ‫لهرمون الريثروبيوتين الذى يحفز تكوين كرات دم حمراء جديدة.مما يجعل تنتائسسج‬ ‫إيختبار تنسبة الهيموجلوبين السكرى فى هؤلء المرضى غير دقيقة.وتنظسسرا لكسسل مسسا‬ ‫ ً‬ ‫سبق فإن تنسبة اللبومين بالسسدم فسسى مرضسسى السسسكرى تحسست الستصسسفاء السدموى‬ ‫تكون تكون اكثر ثباتا من تنسبة الهيموجلوبين وفى هذة الرسالة تنقوم بقارتنة تنتائج‬ ‫ ً‬
  • 8. ‫المستوى العشوائى للسكر بالدم بكل من مستوى تنسبة الهيموجلسسوبين السسسكرى و‬ ‫مستوى تنسبة اللبومين السكرى بالدم لمعرفة أى من المستويين يمكسسن اسسستخدامة‬ ‫ ٍ‬ ‫.كمؤشر دقيق لمستوى السكر بالدم لهؤلء المرضى‬ ‫مقارتنة بين اللبومين السكري والهيموجلوبين السكري‬ ‫كمؤشر لمستوي السكر بالدم لمرضي الستصفاء الدموي‬ ‫والمصابين بداء السكري‬ ‫بروتوكول رسالة‬ ‫توطئة للحصول على درجة الدكتوراة فى‬ ‫الباطنه العامة‬ ‫مقدمة من‬ ‫الطبيب/ ايمن نورالدين مصطفي‬ ‫ماجستير امراض الباطنة العامة‬ ‫مدرس مساعد أمراض الباطنة والكلي‬ ‫كلية طب الهزهر أسيوط‬ ‫تحت إشراف‬ ‫ا.د/محمدعباس صبح‬ ‫أستاذ أمراض الباطنه العامة والكلى بطب أسيوط‬
  • 9. ‫د/اشرف محمد محمد الكبير‬ ‫مدرس أمراض الباطنة العامة‬ ‫كلية الطب – جامعة الهزهر– أسيوط‬ ‫3102‬
  • 10. ‫د/اشرف محمد محمد الكبير‬ ‫مدرس أمراض الباطنة العامة‬ ‫كلية الطب – جامعة الهزهر– أسيوط‬ ‫3102‬