Diabetes

Question 1

Treatment to reduce DM rates

Answer 1

WEIGHT LOSS

5-7kg

Question 2

Natural history of T2DM

Answer 2

Impaired glucose tolerance –>
Post prandial hyperglycaemia –>
Phase 1 = insulin resistance –>
Phase 2 = Beta cell failure

Question 3

Insulin signalling

Answer 3

Insulin –> IRS1 or IRS2

  - -> MAP kinase --> cell growth and differentiation
  - -> PI-3 kinase --> aPKC --> lipid synthesis
  - -> Akt --> GLUT 4 --> transport to cell surface and glucose entry 
              - -> Protein metabolism

Question 4

Why do people become insulin resistance during times of inflammation or lipid overload

Answer 4

Adipocytes –> Free fatty acids and inflammatory cytokines which cause internalisation of IRS-1 –> insulin resistance

Question 5

Octet of T2 DM causes

Answer 5

Decreased insulin secretion
Increased glucagon secretion
Increased hepatic glucose production
Decreased incretin effect
Increased lipolysis
Increased glucose reabsorption in the kidney
Decreased glucose uptake in muscle
Neurotransmitter dysfunction

Question 6

Exenatide

Answer 6

Glucagon like peptide 1

• -> stimulates insulin secretion and suppresses glucagon production
• -> Slows gastric emptying
• -> improves insulin sensitivity

Exenatide
= GLP-1 receptor agonist
= S/C injection BD or ER = weekly
= HbA1c lower by 1%
= weight loss - modest
= S/Es nausea, vomiting diarrhoea
= can cause pancreatitis

Question 7

Liraglutide

Answer 7

GLP-1 analogue

Once daily injection or weekly slow release
Weight loss
Similar side effects as exenatide

Question 8

DPP-4 Inhibitors

Answer 8

DPP-4 breaks down GLP-1

Sitagliptin, Saxagliptin, Linagliptin
Oral 
Lower HbA1c by 0.5-1%
Weight neutral
S/Es: Nasal stuffiness, nausea, headache, allergy
Linagliptin = no dose adjustment in CKD

Question 9

SGLT-2 inhibitors

Answer 9

SGLT-2 = renal glucose transporter in the proximal tubule

Dapagliflozin and Empagliflozin
Oral
Not for renal or liver failure
Cause UTIs and genital infections
Linked with euglycaemic DKA

Question 10

Microvascular complications of DM

Answer 10

Diabetic retinopathy
- 50% T2DM at diagnosis

Peripheral neuropathy
- 50% of amputations could be avoided

Diabetic Nephropathy

• 40% of cases of ESRF
• 20-30% of people with T2DM have overt Diabetic nephropathy

RISK OF COMPLICATIONS DECREASES WITH HbA1C REDUCTION

Question 11

Glycaemic targets

Answer 11

Preprandial BGLs - 4.4-7.2
Post prandial <10

HbA1c <7

Question 12

Treatment

Answer 12

Metformin for all

• -> add sulfanylurea –> add DPP4 inhibitor or GLP-1 agonist or acarbose or thiazolidinedione
• -> OR add DPP4 inhibitor or GLP-1 agonist

Add insulin

Question 13

Type 1 DM epidemiology

Answer 13

Stable trend to diagnosis
Any age

Familial trend - HLA genes up to 50% of T1Dm

Autoimmune disease association:

• Graves and hashimotos
• Coeliac
• Pernicious anaemia

? environmental exposure - viral infection?

Question 14

Natural history of type 1 DM

Answer 14

Genetic predisposition

• -> insulinitis - destruction of beta cells by autoantibodies
• -> impaired glucose tolerance
• -> Hyperglycaemia
• -> DKA

Question 15

Associated autoantibodies?

Answer 15

GAD
Insulin
IA-2

Question 16

Why do intensive BGL modification?

Answer 16

DCCT trial showed reduced microvascular and macrovascular complications

Effects of intensive control extended past trial –> long term effects for controlling BGL in DM

Question 17

Treatments for Type 1 DM

Answer 17

Insulin:

• Short for pre-meals
• Long for basal bolus

Insulin pumps

• Reduced HbA1c
• Reduced Hypoglycaemia
• Improved QOL
• Reduced mortality
• EXPENSIVE

Pancreas transplant

Question 18

Late autoimmune diabetes of adulthood

Answer 18

Adult + DM + Antibodies

Usually have a period of insulin independence –> insulin dependent

Usually GAD antibody positive
Can have other autoimmune disease

? risk of DKA

Question 19

Features of MODY 1?

Answer 19

Gene = HNF4α 
Frequency = 5% 
Feature = β-cell dysfunction 
Other feature = Low TG 
Treatment = Sensitive to SU

Question 20

Features of MODY 2?

Answer 20

Gene = Glucokinase 
Frequency = 15-20% 
Feature = β-cell glucose sensing defect 
Other feature = Fasting hyperglycaemia 
Treatment = Diet

Question 21

Feature of MODY 3?

Answer 21

Gene = HNF1α 
Frequency = 30-50% 
Feature = β-cell dysfunction 
Other feature = Glycosuria 
Treatment = Sensitive to SU

Question 22

Features of MODY 5?

Answer 22

Gene = HNF1β
Frequency = 5% β-cell dysfunction R
Other feature = renal/genital anomalies and pancreatic hypoplasia
Treatment = Insulin