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

Diabetes Mellitus

Contents

•       Diabetes Mellitus

•       Normal insulin physiology

•       Type I Diabetes Mellitus

•       Type II Diabetes Mellitus

Objectives  

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 βcells 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 βcells 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

Summary

•       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