PATHOPHYSIOLOGY OFPATHOPHYSIOLOGY OF

DIABETES MELLITUS DIABETES MELLITUS

By Prarit AroraBy Prarit Arora

IntroductionIntroduction

Diabetes Mellitus is a metabolic disorder tes Mellitus is a metabolic disorder characterized by persistent hyperglycemia (high characterized by persistent hyperglycemia (high blood sugar level).blood sugar level).Resulting either from inadequate secretion of Resulting either from inadequate secretion of hormone insulin, an adequate response of target hormone insulin, an adequate response of target cell to insulin or combination of these factors.cell to insulin or combination of these factors.Glucose level in the blood is controlled by Glucose level in the blood is controlled by several hormone .several hormone .Insulin is the major hormone which controls the Insulin is the major hormone which controls the level of glucose in blood.level of glucose in blood.Insulin is secreted by beta-cells of Islet of Insulin is secreted by beta-cells of Islet of langerhans of pancreas. langerhans of pancreas.

Diabetes Mellitus is a metabolic disorder tes Mellitus is a metabolic disorder characterized by persistent hyperglycemia (high characterized by persistent hyperglycemia (high blood sugar level).blood sugar level).Resulting either from inadequate secretion of Resulting either from inadequate secretion of hormone insulin, an adequate response of target hormone insulin, an adequate response of target cell to insulin or combination of these factors.cell to insulin or combination of these factors.Glucose level in the blood is controlled by Glucose level in the blood is controlled by several hormone .several hormone .Insulin is the major hormone which controls the Insulin is the major hormone which controls the level of glucose in blood.level of glucose in blood.Insulin is secreted by beta-cells of Islet of Insulin is secreted by beta-cells of Islet of langerhans of pancreas. langerhans of pancreas.

Diabetes Mellitus is of two types:Diabetes Mellitus is of two types:

TYPE-1 –IDDM TYPE-1 –IDDM

(Insulin Dependent Diabetes Mellitus)(Insulin Dependent Diabetes Mellitus)

TYPE-2 –NIDDMTYPE-2 –NIDDM

(Non-Insulin Dependent Diabetes Mellitus)(Non-Insulin Dependent Diabetes Mellitus)

TYPE-3 –Gestational Diabetes TYPE-3 –Gestational Diabetes

TYPE-1 –IDDMTYPE-1 –IDDM

It is characterized by loss of the insulin producing beta-It is characterized by loss of the insulin producing beta-cells of islet of langerhans of the pancreas.cells of islet of langerhans of the pancreas.Sensitivity and responsiveness to insulin are usually Sensitivity and responsiveness to insulin are usually normal.normal.This type of Diabetes Mellitus comprises up to 10%.This type of Diabetes Mellitus comprises up to 10%.Type-1 IDDM can affect childrens or adults.Type-1 IDDM can affect childrens or adults.Common causesCommon causes::Loss of beta-cells leading to Type-1 IDDM is Loss of beta-cells leading to Type-1 IDDM is autoimmune destruction or by antibodies directed autoimmune destruction or by antibodies directed against insulin and Islet proteins.against insulin and Islet proteins.

TYPE-2 - NIDDMTYPE-2 - NIDDM

Type-2-NIDDM is due to combination of Type-2-NIDDM is due to combination of defective insulin secretion and defective defective insulin secretion and defective responsiveness to insulin or reduced responsiveness to insulin or reduced insulin sensitivity.insulin sensitivity.

It is quite common ; comprising 90% or It is quite common ; comprising 90% or more of cases in many population.more of cases in many population.

TYPE-3 GESTATIONAL DIABETESTYPE-3 GESTATIONAL DIABETES

It involves combination of inadequate insulin secretion and secretion and responsiveness .responsiveness .It develops during pregnancy and improve or disappear after It develops during pregnancy and improve or disappear after delivery.delivery.Individuals at higher risk for Gestational Diabetes include :Individuals at higher risk for Gestational Diabetes include :

I.I. Obese woman.Obese woman.II.II. Those with previous history of glucose intolerance.Those with previous history of glucose intolerance.III.III. Any pregnant woman who has elevated fasting, or casual, blood Any pregnant woman who has elevated fasting, or casual, blood

glucose level.glucose level.IV.IV. Those with a history of gestational diabetes mellitus.Those with a history of gestational diabetes mellitus.V.V. Those with a history of large for gestational –age-babies.Those with a history of large for gestational –age-babies.VI.VI. Strong family history of diabetes mellitus.Strong family history of diabetes mellitus.

PATHOGENESIS OF TYPE-1-PATHOGENESIS OF TYPE-1-IDDMIDDM

Three main factors are involved:-Three main factors are involved:-

a)a) Genetic Genetic

b)b) Environmental Environmental

c)c) Auto-ImmunityAuto-Immunity

Discussion of TYPE-1 IDDM Discussion of TYPE-1 IDDM Genetic Factors :Genetic Factors :

i.i. It accounts for about 1/3It accounts for about 1/3rdrd of the susceptibility. of the susceptibility.ii.ii. In a genetic susceptibility person ; there is a development of Auto-antigen receptors In a genetic susceptibility person ; there is a development of Auto-antigen receptors

lead to destruction of beta-cells.lead to destruction of beta-cells.

• Environmental Factors :Environmental Factors :i.i. Such as viruses ; are mainly involved .Such as viruses ; are mainly involved .ii.ii. The environmental factors changes structure features with beta-cell and leads to The environmental factors changes structure features with beta-cell and leads to

destruction of beta-cell.destruction of beta-cell.

• Auto-Immunity Factors :Auto-Immunity Factors :i.i. Type-1 IDDM is a slow T-cell mediated Auto-immune disease.Type-1 IDDM is a slow T-cell mediated Auto-immune disease.ii.ii. Destruction of the insulin secretion cell in the pancreatic islets takes place over many Destruction of the insulin secretion cell in the pancreatic islets takes place over many

years.years.iii.iii. The pathological changes in the pre-diabetic pancreas in Type-1 IDDM is The pathological changes in the pre-diabetic pancreas in Type-1 IDDM is

characterized by characterized by InsulinitisInsulinitis. . iv.iv. It is the infiltration of Islet with mono-nuclear cells containing activated It is the infiltration of Islet with mono-nuclear cells containing activated

macrophages ,helper cytotoxic T-lymphocytes, Natural Killer cells, B-lymphocytes.macrophages ,helper cytotoxic T-lymphocytes, Natural Killer cells, B-lymphocytes.

PATHOGENESIS OF TYPE -2 PATHOGENESIS OF TYPE -2 NIDDMNIDDM

It is more common than Type-1 IDDM.It is more common than Type-1 IDDM.

There is no evidence of immune There is no evidence of immune activationactivation

It results mainly due to two defects -:It results mainly due to two defects -:

I.I. Insulin resistance.Insulin resistance.

II.II. Pancreatic beta-cell failure. Pancreatic beta-cell failure.

DISCUSSION OF TYPE-2 NIDDMDISCUSSION OF TYPE-2 NIDDM

Insulin resistance Insulin resistance ::Increased hepatic production of glucose and resistance to action of insulin.Increased hepatic production of glucose and resistance to action of insulin.Insulin resistance may be any one of three general causes :-Insulin resistance may be any one of three general causes :-Out of these three; Out of these three; target tissuetarget tissue defect is the most common cause of Insulin defect is the most common cause of Insulin

resistance is Type-2 –NIDDM.resistance is Type-2 –NIDDM.

• Pancreatic beta-cell failure :-Pancreatic beta-cell failure :-I.I. There is only moderate reduction in the total mass of pancreatic Islet There is only moderate reduction in the total mass of pancreatic Islet

tissues.tissues.II.II. Which inconsistent with a measurable fall in plasma insulin Which inconsistent with a measurable fall in plasma insulin

concentration.concentration.III.III. When related to blood glucose level; beta-cell number is reduced and When related to blood glucose level; beta-cell number is reduced and

glucagon secretion is increased which may contribute to hyperglycemia glucagon secretion is increased which may contribute to hyperglycemia and caused Type-2-NIDDM.and caused Type-2-NIDDM.

IV.IV. Possible mechanism for beta-cell decomposition include genotoxicity , Possible mechanism for beta-cell decomposition include genotoxicity , Intrinsic failure of Insulin production and degranulation of beta-cells.Intrinsic failure of Insulin production and degranulation of beta-cells.

LATE COMPLICATION OF LATE COMPLICATION OF DIABETES MELLITUS / DIABETES MELLITUS /

SECONDARY COMPLICATIONSECONDARY COMPLICATION

RETINOPATHYRETINOPATHY

NEPHROPATHYNEPHROPATHY

NEUROPATHYNEUROPATHY

ATHEROSCLEROSISATHEROSCLEROSIS

DISCUSSION OF SECONDARY DISCUSSION OF SECONDARY COMPLICATIONS OF DIABETES COMPLICATIONS OF DIABETES

MELLITUSMELLITUSRETINOPATHY :RETINOPATHY : It is characterized by retinal damage such as bleeding in retina It is characterized by retinal damage such as bleeding in retina due to this retinal damage or retinal detachment occurs from normal position due to this retinal damage or retinal detachment occurs from normal position which ultimately leads to cataract or glaucoma.which ultimately leads to cataract or glaucoma.

DIABETIC NEPHROPATHY : DIABETIC NEPHROPATHY : In this renal capillaries become leaky ; due to this In this renal capillaries become leaky ; due to this proteins appear in the filterate or urine which is known as proteinurea leads to proteins appear in the filterate or urine which is known as proteinurea leads to nephron syndrome. It may cause other kidney disorders such as renal nephron syndrome. It may cause other kidney disorders such as renal atherosclerosis leads to renal failure. Nephropathy occurs due to Advance atherosclerosis leads to renal failure. Nephropathy occurs due to Advance Glycation End Product (AGE) accumulation. Glycation mainly occur of collagen Glycation End Product (AGE) accumulation. Glycation mainly occur of collagen and other proteins. Initially ; it is reversible , but later on become irreversible ,but and other proteins. Initially ; it is reversible , but later on become irreversible ,but this deposit on renal capillaries. this deposit on renal capillaries.

NEUROPATHYNEUROPATHY : Defect in peripheral Nervous System mainly involves nerves : Defect in peripheral Nervous System mainly involves nerves and these become non-functional symptoms include:and these become non-functional symptoms include:

I.I. Disturbance in urinary bladder functioning.Disturbance in urinary bladder functioning.II.II. Disturbance in bowel functioning.Disturbance in bowel functioning.

• ATHEROSCLEROSIS : ATHEROSCLEROSIS : Occurs also due to AGE accumulation in blood vessels. Occurs also due to AGE accumulation in blood vessels.