Management of Diabetes Flashcards
(35 cards)
What dietary advice should be given to patients with newly diagnosed type 2 diabetes?
Encourage high fibre, low glycaemic index sources of carbohydrates
Include low-fat dairy products and oily fish
Control the intake of foods containing saturated fats and trans fatty acids
Limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
Discourage the use of foods marketed specifically at people with diabetes
Initial target weight loss in an overweight person is 5-10%
Why is weight management an important aspect of managing diabetic patients?
A high percentage of patients with type 2 diabetes are overweight or obese, and many anti-diabetic drugs including insulin, encourage weight gain.
Obesity, particularly central obesity, with increased waist circumference also predicts insulin resistance and cardiovascular risk.
How should alcohol consumption be approached in diabetic patients?
Alcohol can be consumed in moderation unless there is a co-existing medical problem that requires abstinence.
Alcohol suppresses gluconeogenesis, so it can precipitate or protract hypoglycaemia particularly in patients taking insulin and sulphonylureas.
Patients need to be aware of recommenced limits which are 14 U for both men and women in the UK.
What HbA1c targets should be set for patients with diabetes?
This depends on how the patient is managed.
Lifestyle interventions alone or single drug treatment:
Lifestyle = 48 mmol/mol (6.5%)
Lifestyle + metformin = 48 mmol/mol (6.5%)
Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) = 53 mmol/mol (7.0%)
Already on treatment:
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%) = 53 mmol/mol (7.0%)
At what level of HbA1c should a new drug be added?
58 mmol/mol (but the HbA1c target remains 53)
What is the mechanism of action of the biguinides?
Metformin is the only biguinide available and is widely used first line for type 2 diabetes irrespective of body weight (but it is particularly useful in obese patients).
Its mechanism of action is not precisely known. It has no hypoglycaemic effect in non-diabetic individuals, but in diabetes, insulin sensitivity and peripheral glucose uptake are increased, possibly through inhibition of mitochondrial respiration and activation of AMP regulated kinase in muscle.
There is some evidence that it also impairs glucose absorption by the gut and inhibits hepatic gluconeogenesis.
Does metformin cause hypoglycaemia?
No! Contrary to what many people think, metformin does not cause fasting hypoglcyaemia on its own. When used in conjunction with other oral hypoglycaemic agents it may contribute to hypoglycaemia.
What are the indications for using metformin?
Metformin is weight neutral and it may be beneficial for obese patients.
Glucose lowering effects of metformin are synergistic with sulphonylureas so the two are commonly combined.
It is given with food, usually starting with 500mg 12 hourly, gradually increased as required to a maximum of 1g TDS.
What are the side effects of metformin?
GI disturbance (diarrhoea) is the main side effect. It can also increase susceptibility to lactic acidosis. Because of this, its use is contraindicated in patients with impaired renal or hepatic function and in those who drink alcohol in excess. It is contraindicated if the eGFR is <30.
How should a patient with metformin who develops diarrhoea be managed?
Switch to a modified release preparation in the first instance before trialling another hypoglycaemic agent.
What is the mechanism of action of the sulphonylureas?
These are “insulin secretagogues” that act through a specific receptor which is linked to a K+ channel on the surface of pancreatic beta cells. K+ transport triggers insulin secretion.
What are the indications for using sulphonylureas?
Sulphonylureas are useful in the management of non obese patients with type 2 diabetes who fail to respond to dietary measures alone, or who do not tolerate metformin first line.
Sulphonylureas are not weight neutral, and tend to cause weight gain. For that reason, obese patients with type 2 diabetes should be treated aggressively with dietary measures +/- metformin.
What are the main side effects of sulphonylureas and what are the different types?
The main differences between the individual compounds lie in their potency, duration of action and cost.
Tolbutamide is a first generation sulhonylurea which is well tolerated and has a short duration of action. It is usually administered 8 or 12 horly and is a useful drug in the elderly in whom the risk of hypoglycaemia are greater. Chlorpropamide has a half life of about 36 hours and is taken once daily, but may cause severe and protracted hypoglycaemia and is rarely used.
Of the second generation sulphonylureas, gliclazide and glipizide cause few side effects, but glibenclamide is prone to induce severe hypoglycaemia and shold be avoided in the elderly. New modified release preparations such as glimepiride and gliclazide can be given once per day with no apparent risk of hypoglycaemia.
How should sulphonylureas be dosed? Is there any benefit from increasing doses if patients do not reach their glycaemic targets?
The dose response of all sulphonylureas is steepest at lose dosease, little additional hypoglycaemic benefit is obtained when the dose is increased to maximal levels.
What are some important drug interactions of sulphonylureas?
Several drugs can potentiate the hypoglycaemic effect of sulphonylureas by displacing them from their plasma protein binding sites - e.g. salicylates, phenylbutazone and antifungal agents.
What are the meglitinides?
These insulin secretagogues are called prandial glucose regulators.
Repaglinide directly stimulates endogenous insulin secretion through the sulphonylurea receptor and is taken immediately before food.
Nateglinide has similar mode of action, restores first phase insulin secretion and can be prescribed with metformin.
They are useful for patients with erratic lifestyles.
What are the alpha glucosidase inhibitors?
These agents delay carbohydrate absorption in the gut by selectively inhibiting disaccharidases.
Acarbose and miglitol are available and are taken with each meal. Both lower post-prandial blood glucose and modestly improve glycaemic control. They can be combined with sulphonylureas.
The main side effects are flatulance, abdominal bloating and diarrhoea. They are used very commonly in the Far East but infrequently in the UK.
What are the thiazolidinediones? What is their mechanism of action?
These drugs, also called the glitazones, are PPAR gamma agonists.
They bind and activate peroxisome proliferator-activated receptor gamma, a nuclear receptor prent mainly in adipose tissue that regulates the expression of several genes involved in metabolism.
Gliptins enhance the actions of endogenous insulin, partly directly (in the adipose tissue) and partly indirectly (by altering release of adipokines, such as adiponectin and resistin which alter insulin sensitivity in the liver).
Plasma insulin concentrations are not increased, and hypoglycaemia does not occur.
What are the indications for using the glitazones?
Pioglitazone or rosiglitazone are usually prescribed as second line therapy with metformin, or as third line therapy in combination with sulphonylurea and metformin (known as triple therapy). But they are being used as monotherapy.
They are most likely to be effective in patients with pronounced insulin resistance (e.g. in abdominal obesity) and redistribute fat away from the abdominal stores and subcutaneous deposits. But body weight and total body fat are increased by TZDs so they are not weight neutral.
What are the side effects of the Glitazones?
Glitazones cause significant side effects (common in exams!).
Avoid in liver dysfunction and monitor LFTs.
Sodium and fluid retention mean they are contraindicated in heart failure.
Increase risk of upper limb fractures, mainly in women.
Increased risk of bladder cancer.
(Rosiglitazone was withdrawn in 2010 owing to concerns regarding cardiovascular risk)
What are the SGLT2 inhibitors?
SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion. They all end in “glaflozin”
What are the adverse side effects of the SGLT2 inhibitors?
Urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported
Normoglycaemic ketoacidosis
Increased risk of lower-limb amputation: feet should be closely monitored
What are incretin based therapies?
The secretion of insulin in response to a rise in blood glucose is greater when glucose is given by mouth than by intravenous infusion.
In part, this is caused by secretion of gut hormones, or incretins, which potential glucose induced insulin secretion.
Glucagon like peptide 1, is an incretin hormone which stimulates insulin in a glucose-dependent manner; so hypoglycaemia does not occur.
GLP1 suppresses glucagon secretion, delays gastric emptying, reduces appetite and encourages weight loss.
Two groups of agents are available - DPP4 inhibitors and GLP-1 mimetics
What are the DPP4 inhibitors?
GLP1 is degraded rapidly by the enzyme dipeptidyl peptidase 4. Inhibitors of this enzyme can be used to prolong GLP1’s biological effect.
The DPP4 inhibitors or gliptins (sitagliptin, vildagliptin, saxagliptin) are oral agents. They are weight neutral and have few side effects.
