Endocrine Diseases

Question 1

Definition of Type 1 Diabetes Mellitus

Answer 1

Metabolic autoimmune disorder from destruction of insulin producing beta cells in the pancreas, results in absolute insulin deficiency.

Question 2

Epidemiology of Type 1 Diabetes Mellitus

Answer 2

5-10% of all patients with diabetes, European > Asian, commonly in youth.

Question 3

Risk Factors of Type 1 Diabetes Mellitus

Answer 3

Geographic region (European > Asian), genetic predisposition Family history of autoimmune disease (HLA-DR3 and HLA-DR4)
Past medical history of autoimmune disease (HLA-DR3 and HLA-DR4)
, infectious agents, dietary factors

Question 4

Pathophysiology of Type 1 Diabetes Mellitus

Answer 4

T1DM usually develops as a result of autoimmune pancreatic beta-cell destruction. Up to 90% will have autoantibodies to at least one of 3 antigens: glutamic acid decarboxylase; insulin; and islet auto-antigen-2.
Beta-cell destruction proceeds sub-clinically for months to years as insulitis. When 80-90% of beta cells have been destroyed, hyperglycaemia develops. Patients cannot utilise glucose in peripheral muscle and adipose tissues. This stimulates glucagon secretion which promotes gluconeogenesis, glycogenolysis, and ketogenesis in the liver. Hyperglycaemia and anion gap metabolic acidosis result. Long-term hyperglycaemia leads to complications (below).
Hyperglycaemia induces oxidative stress and inflammation. Oxidative stress can cause endothelial dysfunction by NO. Dysfunctional endothelium allows entry of LDLP into the vessel wall, which induces a slow inflammatory process and leads to atherosclerosis formation.

Question 5

Key presentations of Type 1 Diabetes Mellitus

Answer 5

Polyuria, polydipsia, blurred vision, fatigue or tiredness. DKA

Question 6

Signs and Symptoms of Type 1 Diabetes Mellitus

Answer 6

Weight loss
Caused by fluid depletion and breakdown of fat and muscle secondary to insulin deficiency
Causes polyphagia
Polyuria – excessive or abnormally large production/passage of urine
Result of osmotic diuresis that occurs when blood glucose levels exceed the renal tubular reabsorptive capacity (renal threshold)
Polydipsia – excessive thirst
Result of fluid and electrolyte loss
Other relate autoimmune diseases e.g. thyroid
PATIENTS MAY PRESENT WITH DKA

Question 7

1st line Ix of T1DM

Answer 7

Random glucose tolerance test if presenting to GP. >11.1mmol/L enough for diagnosis with symptoms
Fasting plasma glucose, 2-hour plasma glucose, plasma or urine ketones can all be measured.

Question 8

Gold Standard Ix of T1DM

Answer 8

HbA1c ≥48 mmol/mol (≥6.5%)

Question 9

Other investigations (not 1st line) to consider for T1DM

Answer 9

C peptide - low (produced when pro-insulin is processed)

Autoimmune markers

Question 10

DDx of T1DM

Answer 10

Other forms of diabetes:
MODY
T2DM
Neonatal
Latent

Question 11

Tx of T1DM

Answer 11

1st line: Basal-bolus insulin
Adjunct: Pre-meal insulin correaction dose (and amylin analogue)
2nd line: fixed-dose insulin

Question 12

Monitoring of T1DM

Answer 12

Check HbA1C 2x per annum
Blood pressure <140/90
No statins: Lipid profile screening 1st time then every 5 years
Diabetic complications screening…

Question 13

Complications of T1DM

Answer 13

DKA - uncontrolled
Hypoglycaemia
Microvascular: retinopathy, DD, neuropathy
CVD

Question 14

Prognosis of T1DM

Answer 14

Uncontrolled fatal DKA
Risk factor for blindness, renal failure, foot amputations etc.
CVD main cause of death

Question 15

Definition of T2DM

Answer 15

Type 2 diabetes mellitus is a combination of peripheral insulin resistance and less severe insulin deficiency

Question 16

Epidemiology of T2DM

Answer 16

Older (>40 years old) – some teenagers now getting T2DM
Obese
More common in racial groups e.g. African, Asian, Polynesian, American-Indian

Question 17

Aetiology of T2DM

Answer 17

Type 2 diabetes often presents on a background genetic predisposition and is characterised by insulin resistance and relative insulin deficiency. Insulin resistance is aggravated by ageing, physical inactivity, and overweight (body mass index [BMI] 25-29.9 kg/m²) or obesity (BMI >30 kg/m²).

Question 18

Risk Factors of T2DM

Answer 18

Obesity
Low physical activity
Hypertension
Hypercholesterolaemia
Family history or PMH of T2DM (higher association than T1DM)
Genetics– having a twin with DM increases the other twin’s risk of DM

Question 19

Pathophysiology of T2DM

Answer 19

Insulin resistance due to B-cell dysfunction (B cell mass typically reduced to ~50%) = hyperglycaemia due to reduced insulin secretion
Beta cell hypertrophy (increases in size) and hyperplasia (increase in number) result in more insulin in order to remove glucose from blood

Question 20

Key presentations of T2DM

Answer 20

Polydipsia
Polyuria
Glycosuria
Central obesity 
Slower onset

Question 21

1st Line Ix of T2DM

Answer 21

HbA1c >48mmol/mol (6.5%)
Fasting plasma glucose >6.9mmol/L (>125 mg/dL)
Random plasma glucose >11.1mmol/L (>200mg/dL)
2-hour post-load glucose after 75g oral glucose >11.1mmol/L

Question 22

DDx of T2DM

Answer 22

Other diabetes:

Pre diabetes, T1DM, LADA

Question 23

Mx of T2DM

Answer 23

1st line – Lifestyle Modification
1st line therapy – Metformin + manage hypertenstion!!!
If HbA1c still high consider dual therapy:
Metformin + DPP4 inhibitor (Gliptins.. Sitagliptin)
+ Pioglitazone (reduces peripheral insulin resistance)
+ Sulfonylureas (zides and mides… Glicazide)
+ SGLT-2i (flozins…)
4) Escalate to triple therapy
5) Insulin