Type 2 Diabetes mellitus

Question 1

What is T2DM?

Answer 1

Progressive disorder defined by deficits in insulin secretion and action that lead to abnormal glucose metabolism and related metabolic derangements.

Question 2

Which metabolic syndrome is T2DM associated with?

Answer 2

Central obesity 
HTN 
Hyperlipidaemia 
Decreased HDL cholesterol 
Disturbed haemostatic variables 
Modest increases in a no. of proinflammatory markers

Question 3

What causes T2DM?

Answer 3

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 obesity.
Insulin resistance affects primarily the liver, muscle, and adipocytes and it is characterised by complex derangements in cellular receptors.

Question 4

Pathophysiology of T2DM

Answer 4

Established diabetes is associated with hypersecretion of insulin by a depleted B cell mass but insulin still inadequate in restoring glucose homeostasis.
Hyperglycaemia and lipid excess is toxic to B cells (glucotoxicity) and causes further deterioration of glucose homeostasis which results in absolute insulin deficiency

Question 5

Complications of uncontrolled BP and hyperglycaemia

Answer 5

Uncontrolled BP and glucose increase the risk of microvascular and macrovascular complications such as retinopathy and nephropathy.

Question 6

Signs & symptoms of T2DM

Answer 6

Polyuria- due to osmotic diuresis that results when blood glucose levels exceed the renal threshold
Polydipsia- due to loss of fluid and electrolytes
Weight loss- due to fluid depletion and accelerated breakdown of fat and muscle secondary to insulin deficiency.
Ketouria is often present in young people and may progress to DKA.
Lethargy
Blurred vision
Pruritis vulvae or balanitis due to candida infection.

Question 7

Complications of T2DM

Answer 7

Staphylococcal skin infections
Retinopathy
Polyneuropathy causing tingling and numbness in the feet
Erectile dysfunction
Arterial disease resulting in MI or peripheral gangrene

Question 8

What is asymptomatic diabetes?

Answer 8

Glycosuria may be detected in routine examination in individuals.
More common in older people with raised renal threshold for glucose.
This is not diagnostic of diabetes, people may have familial renal glycosuria (1 in 400)

Question 9

Risk factors of T2DM

Answer 9

Older age 
Obesity 
Gestational diabetes
Pre-diabetes
African 
Physical inactivity 
PCOS 
HTN 
Dyslipidaemia 
CVD

Question 10

Physical examination in T2DM

Answer 10

Evidence of weight loss and dehydration
The breath may smell of ketones (nail polish)
Older patients may present with established complications.
Characteristic retinopathy.
Severe insulin resistance may present with acanthosis nigricans.

Question 11

Differentials of T2DM

Answer 11

Pre-diabetes
T1DM 
Latent autoimmune diabetes in adults (LADA) 
Monogenic diabetes 
Ketosis-prone diabetes 
Gestational diabetes

Question 12

Investigations of T2DM

Answer 12

Same as T1DM 
Random blood glucose measurement 
Fasting plasma glucose 
Oral glucose tolerance 
HbA1c 
Tests should be repeated before the diagnosis is made.

Question 13

Management of T2DM

Answer 13

The core of diabetes management is based on self-management by the patient, who is helped and advised by those with specialized knowledge.
Diet
Exercise
Pharmacological management: insulin sensitizers and secretions.

Question 14

Pharmacological management of T2DM

Answer 14

Biguanide (metformin)- 500mg OD initially, increase by 500 mg/day increments every week, maximum 1000mg TDS.
Sulphonylureas (gliclazide and glipizide):
Glipizide- 2.5-5 mg (immediate-release) OD initially, increase by 2.5-5 mg/day increments every 1-2 weeks, maximum 10 mg TDS OR 5 mg orally (extended-release) OD, increase 10 mg OD in 1-2 weeks if necessary.
Gliclazide: 40-80 mg OD, increase according to response, maximum 320 mg/day
Meglitinides (repaglinide, nateglinide)
Thiazolidinedione (pioglitazone, rosiglitazone)
DPP4 inhibitors (sitagliptin and linagliptin)
GLP1-agonists (exenatide, liraglutide and lixisenatide)
SLGT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin)
A-glucosidase inhibitors (acarbose)
Amylin analogue (pramlinitide)

Question 15

Biguanide (metformin)

Answer 15

Reduces the rate of liver gluconeogenesis and increases insulin sensitivity.
The primary treatment for T2DM
Side effects: Anorexia, diarrhoea, epigastric discomfort, nausea and lactic acidosis.
Lactic acidosis occurs in patients with severe hepatic or renal disease, metformin is CI in these patients.

Question 16

Sulphonylureas (Gliclazide and Glipizide)

Answer 16

Ineffective in patients without a B-cell mass.
Bind to sulphonylurea receptors which closes ATP-K+ channels which result in depolarisation causing increased secretion of insulin.
Side effects: Increased cardiovascular morbidity, Weight gain, hypoglycaemia

Question 17

Meglitinides (nateglitinide and repaglinide)

Answer 17

Meglitinides have the same effect as sulphonylureas but weaker and they promote insulin secretion in response to meals.
Side effects: Weight gain, hypoglycaemia

Question 18

Thiazolidinedione (pioglitazone, rosiglitazone)

Answer 18

Reduces insulin resistance by activating PPAR-Y receptors.
Reduces hepatic glucose production and enhances peripheral glucose uptake.
Side effect: Weight gain, heart failure, osteoporosis

Question 19

DPP4 inhibitors (sitagliptin and linagliptin)

Answer 19

Enhance incretin effect as DPP$ inactivates GLP-1 as it is released into circulation.
GLP-1 enhances insulin secretion and lowers glucagon secretion.
Effective in early stages of T2DM
Side effects: Nausea, weight loss, diarrhoea
The incretin effect is when insulin response to oral glucose is greater than the response to I.V glucose.

Question 20

GLP1-agonists (exenatide, liraglutide and lixisenatide)

Answer 20

GLP-1 is a gut hormone involved in the incretin effect.

Side effects: Nausea, acute pancreatitis and AKI

Question 21

SLGT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin)

Answer 21

New and expensive
Used when metformin is considered inappropriate
Prevents glucose reabsorption in renal tubules
Side effects: UTIs and weight loss

Question 22

A-glucosidase inhibitors (acarbose)

Answer 22

Inhibits enzymes that release glucose from larger carbs.

Side effects: Major flatulence and diarrhoea

Question 23

Amylin analogue (pramlintide)

Answer 23

Slows gastric emptying promotes satiety

Inhibits glucagon secretion and promotes insulin secretion following a meal

Question 24

Surgical management for T2DM

Answer 24

Bariatic surgery for selected groups.

Question 25

Treatment algorithm for T2DM

Answer 25

Lifestyle changes> +metformin> + other drugs >+ insulin.
If HbA1c is > 48 mmol/mol on lifestyle interventions: metformin aiming for < 48
If HbA1c is > 58 mmol/mol: Metformin + SU/DPP4+ glitazone/SGLT2 aiming for <58. Firs
If HbA1c is > 58 mmol/mol and doesn’t drop 58, triple therapy of metformin + SU + DPP4 inhibitors + glitazone AND insulin based treatment.
HbA1c > 86 mmol/mol: Basal-bolus insuline + lifestly measures

Question 26

Annual review for T2DM

Answer 26

Weight 
Diet 
Exercise review 
Smoking
BP 
Glucose control 
Lipids (cholesterol <5, LDL <3 HDL > 1)  
Urinary albumin : creatinine ration 
eGFR 
Diabetic foot exam 
Screening of eyes, kidneys and feet for complications.