diabetes

Question 1

What discovery did Mering and Minkowski make in 1889?

Answer 1

They removed the pancreas from dogs, leading to diabetes, demonstrating the pancreas’s role in glucose regulation.

Question 2

What did Banting and Best discover in 1921?

Answer 2

They isolated insulin, proving that insulin deficiency causes diabetes, and showed that pancreas removal results in diabetes, which could be reversed with a purified pancreatic extract.

Question 3

What is diabetes mellitus?

Answer 3

It is an inability to regulate blood glucose, causing acute symptoms from high or low glucose and chronic damage to tissues like blood vessels, eyes, kidneys, and nerves.

Question 4

What were diabetes treatments like before insulin therapy in 1923?

Answer 4

Treatment involved starvation diets, with post-diagnosis survival typically under 5 years

Question 5

How did insulin therapy revolutionise diabetes treatment?

Answer 5

It allowed artificial regulation of blood glucose, significantly improving survival and quality of life for patients with diabetes.

Question 6

What is the difference between Type 1 and Type 2 diabetes in terms of cause?

Answer 6

Type 1: Caused by a failure of insulin secretion due to autoimmune destruction of beta cells.
Type 2: Caused by insulin resistance in tissues and eventual beta-cell failure.

Question 7

What are the characteristics of Type 1 diabetes?

Answer 7

Sudden onset, very low/absent insulin, high glucose levels, develops early in life, sometimes called juvenile diabetes, and is relatively rare (~5% of diabetes cases).

Question 8

What are the characteristics of Type 2 diabetes?

Answer 8

Gradual onset, insulin resistance, develops later in life, most common form of diabetes, and strongly associated with obesity.

Question 9

How does the autoimmune mechanism lead to Type 1 diabetes?

Answer 9

Cytotoxic CD8 T cells destroy pancreatic beta cells by recognising peptides from beta-cell proteins presented with MHC molecules.

Question 10

What genetic factors are associated with Type 1 diabetes?

Answer 10

HLA-DR3 and DR4, particularly the DR4-DQ8 haplotype in Caucasians.

Question 11

What are the symptoms of Type 1 diabetes due to the lack of insulin?

Answer 11

Inability to store glucose, fat, or protein.
Tissues cannot use glucose as fuel.
Hyperglycaemia causes dehydration, excessive urination, and thirst.
Ketoacidosis may develop, leading to acidotic coma.

Question 12

How does hyperglycaemia lead to dehydration in Type 1 diabetes?

Answer 12

High glucose enters the glomerular filtrate, increasing osmolarity, reducing water reabsorption, causing diuresis, dehydration, and excessive thirst.

Question 13

What are the primary aims of insulin therapy?

Answer 13

To regulate blood glucose levels by matching insulin doses with diet and monitoring blood sugar levels to avoid hyperglycaemic and hypoglycaemic episodes.

Question 14

What complications arise from repeated insulin injections at the same site?

Answer 14

Lipohypertrophy (fat deposition).
Unpredictable insulin absorption.
Poor glycaemic control.

Question 15

What are the forms of insulin used for therapy?

Answer 15

Animal insulin (porcine/bovine).
Human insulin.
Human insulin analogues (e.g., insulin lispro, insulin glargine).

Question 16

How does metformin help in Type 2 diabetes?

Answer 16

It suppresses glucose release from the liver, activates AMPK, promotes lipolysis, and improves insulin sensitivity.

Question 17

What is the mechanism of sulphonylureas in Type 2 diabetes therapy?

Answer 17

They block ATP-sensitive K+ channels in beta cells, causing depolarisation, opening Ca²⁺ channels, and triggering insulin secretion.

Question 18

What are GLP-1 receptor agonists, and how do they help in Type 2 diabetes?

Answer 18

They increase insulin secretion, protect beta cells, promote weight loss, and offer renal protection.

Question 19

How do SGLT-2 inhibitors work in diabetes treatment?

Answer 19

They promote glucose excretion in urine, lowering blood glucose and blood pressure, and inducing ketogenesis.

Question 20

What role do free fatty acids (FFAs) play in insulin resistance?

Answer 20

Excess FFAs form second messengers (DAG), activating PKC, which phosphorylates IRS-1, attenuating insulin receptor signalling.

Question 21

How do adipokines influence diabetes?

Answer 21

Pro-hyperglycaemic adipokines worsen insulin resistance, while anti-hyperglycaemic adipokines like adiponectin improve insulin sensitivity.

Question 22

What is the function of AMPK in diabetes therapy?

Answer 22

It promotes lipolysis, improves insulin receptor signalling, and enhances glucose uptake, aiding glucose regulation.

Question 23

What is the role of PPARγ in Type 2 diabetes?

Answer 23

It regulates adipocyte differentiation, promotes anti-hyperglycaemic adipokines, and improves insulin sensitivity.

Question 24

What long-term complications can diabetes cause?

Answer 24

Coronary artery disease, cerebrovascular disease, peripheral vascular disease, retinopathy, nephropathy, and neuropathy.

Question 25

How do advanced glycation end-products (AGEs) damage blood vessels?

Answer 25

AGEs crosslink with collagen, thicken the endothelium, trap LDL and IgGs, causing oxidation, inflammation, and vessel damage.

Question 26

What is the sequence of events in Type 2 diabetes pathogenesis?

Answer 26

Genetic/environmental predisposition → Insulin resistance → Hyperinsulinaemia → Beta-cell failure → Hyperglycaemia.

Question 27

How does obesity contribute to Type 2 diabetes?

Answer 27

Visceral fat produces FFAs and inflammatory cytokines, reduces adiponectin expression, and disrupts insulin signalling.

Question 28

What is ketoacidosis in diabetes?

Answer 28

It occurs when the lack of insulin leads to fatty acid metabolism, forming ketone bodies, lowering blood pH, and causing metabolic acidosis.

Question 29

What are the key differences in insulin secretion between Type 1 and Type 2 diabetes?

Answer 29

Type 1: Total failure of insulin secretion due to beta-cell destruction.
Type 2: Insulin is secreted but tissues are resistant, leading to eventual beta-cell failure.

Question 30

What is alpha-cell reprogramming in diabetes research?

Answer 30

A strategy to convert alpha cells into insulin-producing beta cells by overexpressing factors like MafA and Pdx1.