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Flashcards in Diabetes - Management Deck (37):
1

How many newly diagnosed diabetic patients can be adequately managed on diet alone?

Approximately 50% of new cases of diabetes can be controlled adequately by diet alone, 20-30% will need oral anti-diabetic medication, and 20-30% will require insulin.

The major problem in diabetes is the excess mortality and morbidity due to the long term complications of diabetes. The factors associated with these are:
- duration of diabetes
- early age at onset of disease
- high glycated Hb
- raised BP
- proteinuria, microalbuminuria
- dyslipidaemia
- obesity

2

How should diet composition be changed in patients with diabetes?

Dietary measures are required in the treatment of all people with diabetes. The aims are to improve glycaemic control, manage weight and avoid both acute and long term complications.

Carbohydrate:
People with type 1 diabetes can match the amount of carbohydrate in a meal with a dose of short acting insulin using methods such as DAFNE (dose adjustment for normal eating). This avoids pre and post prandial hypoglycaemia. For patients with type 2 diabetes, avoidance of refined carbohydrate and restriction of carbohydrate to 45-60% of total energy intake is recommended.

Glycaemic index (GI):
Both the amount and source of carbohydrate determine post prandial glucose. Different foods can be ranked by their effect on post prandial glycaemia (GI). Consumption of foods with a low GI is encouraged because they produce a slow, gradual rise in blood glucose - e.g. pasta, rice, lentils. However, GI dose not address the total amount consumed.

Fat:
Intake of fat should be restricted to <35% of energy intake, with <10% as saturated fat, 10-20% monounsaturated fat and <10% from polyunsaturated fat. Omega 3 fatty acids have been shown to assist with secondary cardiovascular prevention.

3

In what groups of diabetic patients is weight management important?

A high percentage of people with type 2 diabetes are overweight or obese, and many anti-diabetic medications and insulin encourage weight gain. Abdominal obesity also predicts insulin resistance and cardiovascular risk. Weight loss is achieved through a reduction in energy intake and an increase in energy expenditure through physical activity. Overweight patients should be encouraged to reduce calorie intake and take regular exercise for approximately 30 mins daily as this improves insulin sensitivity and the lipid profile, and lowers BP.

4

Can patients with diabetes drink alcohol?

Alcohol can be consumed in moderation. As alcohol suppresses gluconeogenesis, it can precipitate or protract hypoglycaemia, particularly in patients taking insulin or sulphonylureas. Drinks containing alcohol can be a substantial source of calories and may have to be reduced to assist weight reduction.

5

Why are most oral anti-diabetic medications used in type 2 diabetes?

Most drugs used to treat type 2 diabetes depend upon a supply of endogenous insulin and therefore have no effect in patients with type 1 diabetes. The sulphonylureas and biguinides have been the mainstay of treatment in the past.

6

What is the mechanism of action of sulphonylureas?

Sulphonylureas stimulate the release of insulin from the pancreatic B cell. They are best used to treat non-obese people with type 2 diabetes who fail to respond to dietary measures, as treatment is often associated with weight gain.

7

Name some sulphonylureas used in clinical practice

Chlorpropamide is rarely used, has a long half life and is taken once daily, but may cause prolonged hypoglycaemia.

Gliclazide and glipizide cause few side effects, but glibenclamide is prone to induce hypoglycaemia and should be avoided in the elderly.

Newer long acting preparations such as glimepiride and modified release gliclazide have no apparent risk of hypoglycaemia.

Sulphonylureas are often used as an add on if metformin fails to produce adequate glycaemic control.

8

What is the term given to patients who fail to respond to initial treatment with sulphonylureas?

These patients are referred to as "primary treatment failures". Patients with "secondary failure" (after a period of satisfactory glycaemic control) include patients with LADA, those with type 2 diabetes and advanced B cell failure, and most commonly, those who are not adhering to the recommended diet Secondary failure affects 3-10% of patients each year.

9

What is the main biguinide used in clinical practice? What is their mechanism of action?

The only biguinide currently used in clinical practice is metformin. Metformin reduces the myocardial infarctions in diabetic patients (UK Prospective Diabetes Study) and is widely used as 1st line treatment for patients with type 2 diabetes.

It improves insulin sensitivity and peripheral glucose uptake, and impairs both glucose absorption by the gut and hepatic gluconeogenesis. Endogenous insulin is required for its glucose lowering action, but it does not increase insulin secretion and seldom causes hypoglycaemia. Metformin does not increase body weight and is therefore suitable in obese patients.

10

What are the side effects of metformin and at what dose is it usually started?

Approximately 25% of patients develop mild gastrointestinal side effects (diarrhoea, abdominal cramps, bloating, and nausea), but only 5% are unable to tolerate it at low doses.

Metform acts synergistically with sulphonylureas so the two can be given together. It is usually given with food 2-3 times daily at an initial starting dose of 500mg BD.

11

Under what conditions is metformin contraindicated?

Alcohol excess
Impaired renal or hepatic function (due to the increased risk of lactic acidosis)

It should be discontinued temporarily if other medical conditions develop (e.g. shock or hypoxaemia).

12

What are the alpha glucosidase inhibitors?

These delay carbohydrate absorption in the gut by selectively inhibiting disaccharidases. Acarbose or miglitol is taken with each meal and lowers post prandial blood glucose. Side effects are flatulence, diarrhoea and bloating.

13

What is the mechanism of action of the thiazolidinediones?

These drugs (TZDs; glitazones) bind and activate peroxisome proliferator activated receptor gamma found in adipose tissue, and work by enhancing the actions of endogenous insulin. Plasma insulin concentrations are not increased and therefore hypoglycaemia is not usually a problem.

14

What are the side effects of the glitazones?

TZDs have been prescribed widely since the 1990s, but recently a number of adverse side effects have become apparent that has limited their use. Rosiglitazone was reported to increase the risk of myocardial infarction and was withdrawn in 2010. The other TZD in common use, pioglitazone, does not appear to increase the risk of MI but does exacerbate cardiac failure by causing fluid retention, and recent data show that it increases the risk of bone fracture and possible bladder cancer.

15

When are the glitazones used?

Pioglitazone can be effective in patients with insulin resistance and also has beneficial effect in reducing fatty liver and non alcohol steatohepatitis (NASH). Pioglitazone is usually added to metformin with or without suphonylurea therapy. It may be given with insulin, when it can be effective, but the combination of TZD and insulin markedly increases fluid retention and risk of cardiac failure, so should be used with caution.

16

What is the incretin effect?

This is the augmentation of insulin secretion seen when glucose is given orally rather than intravenously due to the release of gut peptides (glucagon like peptide 1 (GLP) and gastric inhibitory peptide (GIP)). These are broken down by dipeptidyl peptidase 4 (DPP-4).

17

What are DPP-4 inhibitors?

These drugs prevent the breakdown and therefore increase endogenous GLP-1 and GIP levels. Examples include sitagliptin, vildagliptin, saxagliptin and linagliptin. They are well tolerated and are weight neutral.

18

What are GLP-1 receptor antagonists?

These mimic GLP-1 but are modified to resist DPP-4. They have to be given by sub cut injection but have a key advantage over DPP-4 inhibitors because they decrease the appetite level at the hypothalamus. Thus, GLP-1 analogues lower blood glucose and result in weight loss - a major advantage in obese patients with type 2 diabetes. Examples include exenatide (twice daily) exenatide MR (once weekly) and liraglutide (once daily)

19

What are the different groups of insulin?

These are based on their duration of action:

1) Short acting insulin - (i) soluble insulin and (ii) analogue insulin
2) Intermediate insulin
3) Long acting insulin
4) Mixed preparations

20

What is the typical half life of short acting insulin and give some examples?

Short acting insulin comes in two different forms - soluble and analogue - both have a half life of 3-5 hours (with soluble being slightly longer).

Analogue insulin is recombinant human insulin:
- Aspart/ Novorapid (spart: sounds like sport, implies quick)
- Lispro/ Humalog (pro: like a professional athelete!)

Soluble insulin include animal derived products:
- Actrapid
- Humulin S
- Insuman Rapid

Soluble short acting insulin has a slightly longer onset and lasts longer than analogue types.

21

Name some intermediate acting insulins

The intermediate acting insulins as isophane insulins:
- Humilin I
- Insulatard

They have a duration of action of approximately 12 hours.

22

What is the duration of action of long acting insulins?

Long acting insulin are human insulin analogues and include:
- Detemir
- Glargine/ Lantus
- Degludec/ Tresiba

They have an onset within 3-4hrs and a duration of approximately 24 hours. Degludec has a duration of 42 hours.

23

What types of insulin make up mixed preparations?

Mixed preparations are usually given for BD regimes and include a short acting insulin and an intermediate insulin. They contain a name and a number, with the number representing the proportion of short acting insulin.

Examples include:
- Novomix 30 (30% Aspart/ 70% Aspart protamine)
- Humalog Mix 25 (25% Lispro/ 75% Lispro protamine)

24

How is insulin administered?

Insulin is injected subcutaneously into the anterior abdominal wall, upper arms, outer thighs and buttocks.

25

What affects the rate of absorption of insulin?

The rate of absorption of insulin may be influenced by the insulin formulation, the site, depth and volume of injection, skin temperature (warming), local massage and exercise. Absorption is delayed from areas of lipohypertrophy at injection sites.

26

How is insulin excreted? What are the implications of this?

Excretion is hepatic and renal, so insulin levels are elevated in renal and hepatic failure.

27

What is the advantage of insulin analogues over soluble insulin?

Remember these refer to short acting insulins. Insulin analogues have largely replaced soluble and isophane insulins, especially for type 1 diabetes, because they allow more flexibility and convenience. Unlike soluble insulin, which should be injected 30 mins before eating, rapid acting insulin analogues can be administered immediately before, during or even after meals.

Long acting insulins are better than isophane insulin at maintaining "basal" insulin levels for up to 24hrs, so need only to be injected once daily.

28

What are the complications of insulin therapy?

Hypoglycaemia
Weight gain
Peripheral oedema (insulin treatment causes salt and water retention in the short term)
Insulin antibodies (animal insulins)
Local allergy (rare)
Lipodystrophy at injection sites (includes liphypertrophy and lipoatrophy)

29

What is the "dawn phenomenon"?

A common problem with insulin therapy is fasting hyperglycaemia caused by the release of counter regulatory hormones (e.g. cortisol) during the night which increases the requirement for insulin before waking.

30

What is a basal bolus regime?

This regime aims to mimic normal insulin secretion in a non diabetic patient. It comprises 4 injections per day, 1 long acting insulin at night time (usually before evening meal) followed by a short acting insulin prior to meals.

The long acting insulin provides a basal level for 24 hours, whilst the short acting preparation mimics endogenous insulin release as plasma glucose rises after meals.

31

What is the advantage of a basal-bolus regime?

This regime allows greater freedom with meal times (they can be skipped because the short acting insulin can be omitted) and more variable day to day physical activity.

This can be dangerous in a BD regime because the short acting and intermediate insulins have already been given so meal times cannot be missed due to the risk of hypoglycaemia.

32

What is a twice daily (BD) insulin regime? How do you start the regime?

A short acting and intermediate acting insulin (usually soluble and isophane) are given before breakfast and the evening meal.

Most patients are given 0.5 U times their body weight in kilos (e.g. an 80kg patient requires 40 U insulin). 2/3 of this are given in the morning and the remainder is given in the evening.

33

How is a basal-bolus regime started?

The same principles apply for basal-bolus regimes. Patients are given 0.5 U times their body weight in kilos. 1/2 of these are given as long acting and 1/2 are divided by 3 to give the number of units before each meal.

34

How should insulin be adjusted?

1 unit of insulin reduces serum blood glucose by 3 mmol/l. Insulin regimes may need adjusting if the patient is having hypo's or if there sugars are too high.

If low sugar level (<4 = hit the floor)
- think of which insulin is exerting its influence at that time point (the last insulin injected) and then aim to reduce it by 10-20%
- pre breakfast or overnight hypo: reduce evening dose in bd regime or night dose if qds regime (it is the long acting insulin that is causing the problem in this case)
- pre lunch hypo: reduce breakfast insulin
- pre evening meal hypo: reduce morning long acting insulin in BD regime or lunch dose if qds regime
- pre bed hypo: reduce evening meal insulin

If high sugar level
- use scheme above to decide which insulin to titrate
- increase dose by 20%

35

How should hypoglycaemic events be managed?

For patients that are conscious and able to swallow without danger of aspiration, correct the blood sugar by using refined sugars then follow up with complex sugars about 1 hour later.

Glucagon 1mg IM can also be used when the patient is unconscious to correct hypoglycaemia.

36

What types of sliding scale are there and when should they be used?

FRI: Fixed rate infusion
- this is given in DKA till the patient is out of the DKA state
- it is infused at a rate of 1 unit per 10kg of body weight

VRII: Variable rate insulin infusion
- once DKA resolved; pre-op; intercurrent illness
- 50 units of quick acting insulin in 50ml of normal saline

37

When is transplantation considered in diabetes?

Whole pancreas transplantation presents problems relating to exocrine pancreatic secretions and long term immunosuppression is necessary. At present, the procedure is usually undertaken only in patients with end stage renal failure who require combined pancreas/ kidney transplantation and in whom diabetes control is particularly difficult - e.g. because of recurrent hypoglycaemia.

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