Diabetes mellitus, commonly known as diabetes, is a chronic metabolic disorder that affects the body’s ability to regulate blood sugar (glucose) levels. It results from either insufficient production of insulin, resistance to its action, or a combination of both. This disorder has become a global health concern due to its prevalence and potential complications.

• 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

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

Frequently Asked Questions (FAQ) about Diabetes Mellitus:

Q1: What is diabetes mellitus? Diabetes mellitus is a chronic condition characterized by elevated blood sugar levels. It results from problems with insulin, a hormone that helps regulate blood sugar by allowing cells to absorb and use glucose for energy.

Q2: What are the common types of diabetes? The two most common types of diabetes are:

Type 1 Diabetes: This results from the immune system attacking and destroying insulin-producing cells in the pancreas. People with Type 1 diabetes require lifelong insulin replacement.
Type 2 Diabetes: This is characterized by insulin resistance, where cells don’t respond effectively to insulin. It is often associated with lifestyle factors and may be managed with lifestyle changes, medication, or insulin.

Q3: What is the role of insulin in diabetes? Insulin is a hormone produced by the pancreas that regulates blood sugar. It allows cells to take in glucose from the bloodstream, lowering blood sugar levels. In diabetes, there’s either insufficient insulin production or resistance to its effects.

Q4: What are the common symptoms of diabetes? Common symptoms include excessive thirst, frequent urination, unexplained weight loss, fatigue, blurred vision, and slow wound healing. However, some individuals with Type 2 diabetes may not exhibit symptoms initially.

Q5: How is diabetes diagnosed? Diabetes is diagnosed through blood tests that measure fasting blood sugar levels, oral glucose tolerance tests, or HbA1c levels. Healthcare professionals use these tests to determine blood sugar control and the type of diabetes.

Q6: How is diabetes managed and treated? Management and treatment strategies depend on the type and severity of diabetes. They may include dietary modifications, regular exercise, medication, insulin therapy, blood sugar monitoring, and lifestyle changes to control the condition and prevent complications.

Q7: What are the potential complications of diabetes? Diabetes can lead to a range of complications, including heart disease, kidney disease, eye problems (retinopathy), nerve damage (neuropathy), and foot problems. Uncontrolled diabetes can also result in life-threatening situations like diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS).

Q8: How can diabetes be prevented? Preventing Type 2 diabetes involves maintaining a healthy weight, engaging in regular physical activity, and adopting a balanced diet. Regular medical check-ups and early intervention for individuals at risk can also help.

Q9: Can diabetes lead to other health issues? Diabetes is associated with an increased risk of other health problems, including high blood pressure, high cholesterol, and an elevated risk of heart disease. Controlling blood sugar levels is crucial for minimizing these risks.

Q10: Is diabetes manageable, and can people with diabetes live a normal life? Yes, diabetes is manageable. With proper treatment, blood sugar control, and a healthy lifestyle, individuals with diabetes can lead normal, fulfilling lives. Regular monitoring, medication, and lifestyle modifications are key to managing the condition effectively.