TYPE 2 DIABETES DIAGNOSIS Diagnostic criteria for diabetes Fasting plasma glucose HbA1c 2-hr post-OGTT Pre-diabetes 5.6-6.

9 mmol/L 5.4-6.4% 7.8-11.0 mmol/L Diabetes 7.0 mmol/L+ 6.5%+ 11.1 mmol/L+

Advantages and disadvantages of each test: Fasting plasma glucose Advantages: - Widespread availability - Low cost OGTT Advantages: - Most sensitive - Earliest marker of glucose dysregualtion HbA1c Advantages: - Fasting not required - Marker of long-term hyperglycemia - Global standardization - Close association of results with complications Disadvantages: - Not reliable in patients with certain conditions: - (Hemoglobinopathies, altered RBC turnover, ESKD, transfusion) - Higher cost - Lack of global availability

Disadvantages: - Fasting required - Only reflects current glycaemia - Biological variability - Influence of acute illness

Disadvantages: - Fasting required - Poor reproducibility - Inconvenient - Higher cost - Lack of association with complications

Recommended screening approach: Screen at-risk patients with FPG or HbA1c, or both If normal glucose: Repeat in 1-3 years If pre-diabetes: Lifestyle management o If glycaemia improves, continue lifestyle change and repeat test in 1 year o If glycaemia remains, continue lifestyle change and repeat test in 6 months o If glycaemia worsens, consider metformin If diabetes: Repeat test on a different day. o If still positive, treat with metformin o If improved, treat as pre-diabetes

MEDICATION

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Drug Biguanides (metformin)

Mechanism Decrease hepatic gluconeogenesis

Advantages Weight neutral Modest effect on lipid profile No hypoglycaemia

Disadvantages GI upset in 1/3rd Risk of lactic acidosis

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Sulphonylureas (glibenclamide)

Increase insulin production by beta cells

Risk of hypoglycaemia Weight gain

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Decrease insulin resistance Thiazolidinediones Increase peripheral (pioglitazone) insulin sensitivity by stimulating a nuclear receptor in tissues Meglitinides (repaglinide) Short-acting sulphonylureas

No hypoglycaemia

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DPP4 inhibitors (Sitagliptin)

Stops DPP-4 metabolizing GLP-1 Indirectly stimulates insulin secretion and suppressing glucagon release Stimulate insulin secretion, suppress glucagon release

Used in combination with metformin or sulphonylurea

Water and salt retention C/I in heart failure and IHD Risk of raised LFTs Risk of hypoglycaemia in elderly/liver/renal impairment Long term data lacking Minimal A/E

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GLP-1 agonist (Exenatide)

Weight loss

Subcutaneous injection GI effects Long-term data lacking

STEPWISE MANAGAMENT Step 1: Exercise, lose weight, diet, cease smoking and reduce alcohol Step 2: Metformin Start at 250-500mg daily for one week to look for GI side effects If tolerated/side effects subside, move up to 1g daily Max dose: 2-3g daily (split into 1g BD) If renal clearance impaired, halve the dose Beware of lactic acidosis

Step 3: Metformin + Sulphonylurea May have to reduce metformin dose

Beware of hypoglycaemia, especially in elderly

Step 4: Metformin + Insuline glargine at bedtime +/- Sulphonylurea o o Add a bedtime single dose of long-acting insulin Start with 10U Monitor blood glucose in morning and before and after meals Can consider taking away or reducing the sulphonylurea to avoid hypoglycaemia and reduce medication burden Alternative 1: Metformin + sulpholnyurea + sitagliptin Alternative 2: Metformin + sulphonylurea + thiazolidinedione