different complications and cause of complications

1. Presented by Guide
Mr. Gogawale Vinayak G.
M.Pharm. (Semester-II)
(Department of Pharmacology)
Dr. U.M.Aswar
(Pharmacology)
SINHGAD INSTITUTE OF PHARMACY, NARHE
PATHOBIOLOGY OF DIABETIC
COMPLICATIONS
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2. CONTENTS
• Introduction .
• Complications in diabetes .
• Pathogenesis of complications of diabetes.
• References.
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3. • Diabetes mellitus is a group of chronic disorders
characterize by the hyperglycemia.
• Types of diabetes:
1. Type I diabetes mellitus
2. Type II diabetes mellitus
3. Gestational diabetes mellitus
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INTRODUCTION

4. • Type I diabetes mellitus:
- It is characterized by the bodies disability to
produce insulin due to autoimmune destruction
of beta cells of pancreas.
-It generally occur in the childhood and in
adults at late 30s or early 40s.
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5. 4/4/2015 5
Mechanism of type I diabetes mellitus

6. • Type II diabetes mellitus:
-It is caused due to lack of insulin secretion
and insulin resistance action of body which
cause hyperglycemia.
-
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7. 4/4/2015 7
Mechanism of type II diabetes mellitus

8. Complications in diabetes mellitus
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9. • s complications
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Types of diabetes complications
Eye:
• Retinopathy
Heart:
• Cardiomyopathy
Kidney:
• Nephropathy
Neuropathy

10. Retinopathy:
• Diabetic retinopathy characterized by the growth of
new blood vessels on the retina and posterior surface
of the vitreous.
• It causes the loss of vision of both eyes.
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Eye

11. Eye
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12. • Stages of retinopathy:
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Retinopathy
Mild nonproliferative retinopathy
Moderate nonproliferatve retinopathy
Severe nonproliferative retinopathy
Proliferative retinopathy

13. Cardiomyopathy
• It is a disorder in which the myocardium get affects and
shows left ventricular hypertrophy.
• Diastolic and systolic dysfunction or in combination.
• Patients who suffer from the coronary artery diseases as
well as hypertension they shows synergic adverse effect.
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Heart

14. 4/4/2015 14
Heart

15. Heart
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16. Nephropathy
• Diabetic nephropathy is clinical syndrome characterized
by decreasing glomerular filtration rate, glomerular
hypertrophy, tubulointerstitial fibrosis, decreased
excretion of albumin and decreased creatinine clearance.
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Kidney

17. • Stages of Nephropathy:
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Nephropathy
Glomerular hypertrophy
Mesangial expansion
Micro albuminuria
Overt-proteinuria Hypertension
End stage renal disease

18. Neuropathy
Neuropathy
• It is the symptoms of dysfunction of the peripheral
nerve which resembles in pain.
• Changes in the blood vessels supplying the peripheral
nerves underlie the mechanisms involved in micro
vascular damage and hypoxia.
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19. Neuropathy
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20. Pathways causes complications of diabetes
• Polyol pathway
• Advanced glycation end product formation
• Protein kinase C
• Hexosamine pathway.
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Pathogenesis of complications of diabetes

21. Increased polyol pathway flux
• Aldose reductase is the enzyme in the polyol pathway.
• It is cytosolic, monomeric oxidoreductase that catalyses the
NADPH dependent reduction of wide variety of carbonyl
compounds including glucose.
• The metabolism of the glucose from this pathway is in
small percentage than the total glucose use.
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22. • The polyol pathway involves two enzymatic reactions
the first is the reduction of glucose to sorbitol by the
action of aldose reductase and the second oxidation of
sorbitol to fructose by the action of sorbitol
dehydrogenase.
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Increased polyol pathway flux

23. Increased polyol pathway flux
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24. Advanced glycation end product formation
• It is a non enzymatic reaction in free amino acids and
carbonyl compounds or carbonyl groups of reducing
sugar called as Millard reaction.
• It is three stage reaction as follows:
1. Early stage
2. Intermediate stage
3. Late stage
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25. Advanced glycation end product formation
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26. Protein Kinase C
• Diacylglycerol is produced as well as inosytol
triphosphate whenever receptor induced phosphotidyl
inositol hydrolysis occurs.
• The main effect of diacylglycerol is to activate
memabrane bound protein kinase which catalyses the
phosphorylation of intracellular proteins
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27. Protein Kinase C
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28. Hexosamine pathway
• Fructose 6 phosphate is converted glucosamine 6
phosphate,catalysed by first and end relating enzyme
glutamine fructose 6 phosphate amidotransferase
(GFAT). The major end product is UDP N
acetylglucosamine (UDP-GlcNAc) require to
formation of O- linked glycoprotein
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29. Hexosamine pathway
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30. References
• Schalkwijk C. G., Stehouwer C. D., “Vascular Complications In Diabetes
Mellitus: The Role Of Endothelial Dysfunction”, Clinical Science (2005) 109,
143–159.
• Sharma V., Sharma P.L., “Role of Different Molecular Pathways in the
Development of Diabetes-Induced Nephropathy” ISSN(2013) 2155-6156 JDM.
• Zychowska M.,et al. “Mechanisms And Pharmacology Of Diabeticneuropathy –
Experimental And Clinical Studies.”ISSN(2013)1601-1610.
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31. References
• Singh V. P. et al., “Advanced Glycation End Products and
Diabetic Complications” , Korean J Physiol Pharmacol(2014)
vol 18,1-14.
• Brownlee M., “Biochemistry and molecular cell biology of
diabetic complications”, Nature (2001) vol 414, 813-820.
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