Diabetes Mellitus - B. Pharma 2nd Semester Pathophysiology notes pdf

Diabetes Mellitus


       Diabetes Mellitus

       Normal insulin physiology

       Type I Diabetes Mellitus

       Type II Diabetes Mellitus


At the end of this PDF Notes, student will be able to

         Define the term “Diabetes Mellitus”

         Classify Diabetes mellitus

        Describe the normal physiology of Insulin

         Explain the etio-pathogenesis of type I DM

         Explain the etio – pathogenesis if type II DM

Diabetes Mellitus (DM)

       Chronic metabolic disorder

       Characterized by hyperglycemia due to deficiency of insulin or defective response of tissues to insulin

Classification of Diabetes Mellitus

Primary (idiopathic) DM

       Primary disorder by itself

       Type – I (Insulin dependent DM/ IDDM)

       Type – II (Non- Insulin dependent DM/NIDDM)

Secondary DM

       Due to identifiable cause – pancreatitis, endocrine disorder

       Gets corrected/ reversed when primary disorder is controlled

Etio-pathogenesis of Diabetes Mellitus

Normal Insulin Physiology

Regulated by 3 processes

       Glucose production by liver

       Uptake and utilization of glucose by peripheral tissues

       Insulin secretion

Normal Insulin Physiology

       Pre proinsulin – precursor for insulin

       Synthesized from insulin mRNA in rough ER of pancreatic β cells

       Delivered to golgi complex

       Series of proteolytic cleavage

       Pre proinsulin to pro insulin

       Finally to  mature insulin + C- peptide

       Mature insulin + C- peptide – stored in equimolar concentration in secretory granules

       Glucose – important stimulus that triggers the syntheis & release of insulin

       Glucose taken up by pancreatic β cells through GLUT-2

       Immediate release of insulin

       Phase I of insulin secretion

       Released insulin is taken up by the insulin receptors present on the surface of tissues

       Series of intracellular reactions

       Activation of insulin dependent GLUT 4 transporter

       Uptake of glucose

Any defects in the above steps – Diabetes mellitus

Action of Insulin

Type I Diabetes Mellitus

       Insulin dependent DM

       Absolute lack of insulin

       Reduction in β cell mass

       Starts at childhood, becomes sever at puberty

       Dependent on daily injections of insulin

       Hence, insulin dependent DM

Involves 3 interconnected mechanism

       Genetic susceptibility

       Auto immunity

       Environmental factors

Genetic susceptibility

       Linked to race

       High among identical twins

       Susceptibility gene encodes class II antigen on  MHC on chromosome 6p21 (HLA-D)

       Affects degree of immune response against pancreatic β cells

Auto immunity

       Onset of type I DM is abrupt

       Usually results from chronic auto immune attack of β cells

       Clinical manifestations occur after 90% of β cells mass has been destroyed by auto antibodies

Environmental factors

       Viral infections such as Measles, Mumps,

       Infection by COX sackie virus , Cytomegalo virus, Rubella virus

       Toxins – Pentamidine, Alloxan, Streptozotocin

Summary of pathogenesis of Type I DM

Type II DM

       Non insulin dependent DM

       Insulin therapy is not mandatory

       Disease is not linked to HLA gene

       Collection of multiple genetic defects

       Modified with environment factors

Pathogenesis of Type II DM

2 metabolic defects that characterize type II DM

       Derangement in β cell production of insulin

       Decreased response of peripheral tissues to insulin, rapid insulin resistance

Derangement in β cell production of insulin

Decreased secretion of insulin from β cell Due to

       β cell damage  on persistant stimulation

       Chronic hyperglycemia exhaust the ability of β cell  to function

Decreased response of peripheral tissues to insulin, rapid insulin resistance

       Reduced responsiveness of peripheral tissues

       Leads to complications

       Insulin resistance due to reduction in no. of receptors

       Sensitivity of insulin receptor decreases in obesity & pregnancy

Summary of pathogenesis of type II DM


       Diabetes is a chronic metabolic disorder characterized by hyperglycemia due to deficiency of insulin or defective response of tissues to insulin

       DM is categorized as Type I and Type II

       Type I DM is dependent on insulin and occurs mainly due to the destruction of beta cells of pancreas

       Type II DM is independent of insulin and occurs either due to decreased insulin secretion or due to decreased sensitivity of insulin receptors

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