Diabetes Flashcards
Notes on MODY 1
- <10% MODY cases
- Hepatic nuclear transcription factor 4a
- Reduced insulin secretion, mild risk microvascular complications
- Can treat with sulphonylureas
Features of MODY 2
- 20-50% MODY cases
- Glucokinase mutation altering the insulin set point
- Isolated mild fasting hyperglycaemia, mild reduced insulin
- Not associated with microvascular complications in absence of glucose lowering medical
- Absence of family history is common
- Only 50% of mothers with GCK mutation will require insulin therapy during pregnancy if foetal growth is increased
Features of MODY3
- 70% MODY cases
- HNF1A mutation → reduced beta cell mass/function
- Elevated post-prandial glucose + marked OGTT excusion, then progressive BSL deterioration
- C peptide positive (still making insulin)
- Sensitive to sulphonylureas
- Also see elevated HDL
Pharmacological notes on human insulin
- Absorbed slowly, reaches peak 60-90 minutes from SC injection
- Action persists too long after meals -> hypoglycaemia
- Stable hexamers - needs to disociate to monomers or dimers before it can enter the circulation -> delayed absorption
Action of glucagon
- Stimulates lipolysis
- Stimulates catecholamine secretion
- Delays gastric emptying
- Reduces pancreatic exocrine secretions
- Stimulates glycogenolysis
- Inhibits glycolysis
- Activates gluconeogenesis
Oral diabetes medication assoicated with two fold increase in foot fractures
SGLT2 inhibitors
What is the main reason for deterioration over time in glycaemic control in patients with Type 2 DM
- Decreased insulin secretion
Progression decrease in insulin action (insulin resistance) following by inability of beta cells to compensate for beta cell dysfunction → decreased insulin secretion
Most important known factor which influences the rate of development of microvascular complications in diabetes
- Hyperglycaemia (not duration of diabetes)
Principles of the incretin effect
- Insulin secretion stimulated to a greater extent by an oral glucose load than intravenous → effect due to release of two peptide hormones in gut - glucagon-like peptide 1 and insulinotropic peptide (GIP) from the L cells in the intestine
Notes on GLP-1 agonists
- Short half-life 1-2 minutes
- Do not cause hypoglycaemia
- Stimulates glucose-dependent insulin release from pancreatic beta cells
- Affect glucose control through several mechanisms:
- Increase glucose dependent insulin secretion
- Decrease gastric emptying
- Decrease weight
- Inhibit inappropriate post-meal glucagon release
- Reduce food intake
- No significant cardiovascular effects (unlike SGLT-2 inhibitors)
- Degraded by enzyme DPP- IV
Incretin effect
- Basis of use of GLP1 agonists
- Insulin release from pancreas is far greater after oral glucose as compared to IV glucose - GLP1 released from gut after a meal → GLP1 stimulation enhances insulin release, decreases glucagon secretion, and delays gastric emptying (appetite suppression)
Adverse effects
- Nausea and vomiting
- Pancreatitis
Most suitable sulphonylurea in elderly patients
Tolbutamide - shortest duration of action
Diagnostic criteria for DM
NZ: HbA1C > 6.7% (> 50mmol) and FPG > 7 or random > 11
HbA1C → cannot be used if abnormal red cell turnover
Target HbA1c during treatment
- <7% (53mmol)
- If old < 8% (64)
Notes on metformin
Suppresses hepatic glucose production
- Inhibition of glycolytic and/or gluconeogenic enzymes
- No effect on B cell function
- Reduction in CVD events
- Does not improve muscle insulin sensitivity in the absence of weight loss
- Reduction in fasting Hba1c though not sustainable
- Adverse effects: Vitamin B12 deficiency, lactic acidosis
- Evidence to reduce malignancy
Notes on DPP4 inhibitors
- Prolong halflife of endogenous GLP1
- Modest reduction in HBA1c
- No concerns re pancreatitis, neutral effect on CVS endpoints
- Increased HF risk with saxagliptin (not sitagliptin)
- Side effects → angioedema, urticaria, skin reactions, joint pains
Notes on Thiazolindinediones
- Enhance insulin action in skeletal, cardiac and adipose tissue
- Seem to preserve insulin secretion and B cells
- Durable, sustainable action
- Pioglitaone reduces end points (MI, CVA, CVS death)
- Contraindicated in HF
- Side effects → bone fractures in post-menopausal women and older men, no longer linked with bladder cancer/;==
