Diabetes Mellitus Flashcards
T2DM - Mx - Updated NICE Guidelines
NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2015. Key points are listed below:
- HbA1c targets have changed. They are now dependent on what antidiabetic drugs a patient is receiving and other factors such as frailty
- There is more flexibility in the second stage of treating patients (i.e. after metformin has been started) - you now have a choice of 4 oral anti diabetic agents
NB: It’s worthwhile thinking of the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)
T2DM - Dietary Advice
Dietary advice:
- 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 use of foods marketed specifically at people with diabetes
- initial target weight loss in an overweight person is 5-10%
T2DM Mx: HbA1c Targets
This is area which has changed in 2015
- individual targets should be agreed with patients to encourage motivation
- HbA1c should be checked every 3-6 months until stable, then 6 monthly
- NICE encourage us to consider relaxing targets on ‘a case-by-case basis, with particular consideration for people who are older or frail, for adults with type 2 diabetes’
- in 2015 the guidelines changed so HbA1c targets are now dependent on treatment:
LIFESTYLE OR DRUG TREATMENT
Lifestyle : HbA1c target 48 mmol/mol (6.5%)
Lifestyle + Metformin: HbA1c target 48 mmol/mol (6.5%)
Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea): HbA1c target 53 mmol/mol (7.0%)
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%): HbA1c target 53 mmol/mol (7.0%)
Practical examples:
A patient is newly diagnosed with HbA1c and wants to try lifestyle treatment first. You agree a target of 48 mmol/mol (6.5%)
You review a patient 6 months after starting metformin. His HbA1c is 51 mmol/mol (6.8%). You increase his metformin from 500mg bd to 500mg tds and reinforce lifestyle factors
T2DM - Drug Treatment
For pt who can tolerate Metformin:
Drug treatment
The 2015 NICE guidelines introduced some changes into the management of type 2 diabetes. There are essentially two pathways, one for patients who can tolerate metformin, and one for those who can’t.
Tolerates metformin:
metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions
if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list:
→ sulfonylurea
→ gliptin (DPP-4 Inhibitors)
→ pioglitazone
→ SGLT-2 inhibitor
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered:
→ metformin + gliptin + sulfonylurea
→ metformin + pioglitazone + sulfonylurea
→ metformin + sulfonylurea + SGLT-2 inhibitor
→ metformin + pioglitazone + SGLT-2 inhibitor
→ OR insulin therapy should be considered
Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)
if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if:
→ BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or
→ BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or
weight loss would benefit other significant obesityrelated comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months
NB Insulin should not be combined with a GLP-1 mimetic.
Practical examples
you review an established type 2 diabetic on maximum dose metformin. Her HbA1c is 55 mmol/mol (7.2%). You do not add another drug as she has not reached the threshold of 58 mmol/mol (7.5%)
a type 2 diabetic is found to have a HbA1c of 62 mmol/mol (7.8%) at annual review. They are currently on maximum dose metformin. You elect to add a sulfonylurea
Example Names:
Sulfonylurea: Gliclazide, Tolbutamide, Glibenclamide, Glipizide, Glimerpiride
SGLT-2 Inhibitors: Dapagliflozin, Canaglifozin, Empagliflozin
Pioglitazone = Only thiazolidinedione licensed for DM
DPP-4 Inhibitors (Gliptins) = Sitagliptin, Linagliptin, Vildagliptin
GLP-1 Mimetic = Exenatide, Liraglutide, Lixisenatide, Dulaglutide
T2DM - Drug Treatment
For pt who cannot tolerate Metformin
The 2015 NICE guidelines introduced some changes into the management of type 2 diabetes. There are essentially two pathways, one for patients who can tolerate metformin, and one for those who can’t.
Cannot tolerate metformin or contraindicated (NB eGFR<30ml/minute/1.73m2 metformin is contraindicated)
If the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions, consider one of the following:
→ sulfonylurea
→ gliptin
→ pioglitazone
if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:
→ gliptin + pioglitazone
→ gliptin + sulfonylurea
→ pioglitazone + sulfonylurea
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy
Starting insulin
metformin should be continued. In terms of other drugs NICE advice: ‘Review the continued need for other blood glucose lowering therapies’
NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at bed-time or twice daily according to need
*this is a bit confusing because isn’t the diagnostic criteria for T2DM HbA1c 48 mmol/mol (6.5%)? So shouldn’t all patients be offered metformin at diagnosis? Our interpretation of this is that some patients upon diagnosis will elect to try lifestyle measures, which may reduce their HbA1c below this level. If it then rises to the diagnostic threshold again metformin should be offered
T2DM - Risk Factor Modification
Risk factor modification
Blood pressure
target is < 140/80 mmHg (or < 130/80 mmHg if end-organ damage is present)
ACE inhibitors are first-line
Antiplatelets
should not be offered unless a patient has existing cardiovascular disease
Lipids
following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on
Insulin Therapy
Insulin therapy
Insulin therapy revolutionised the management of diabetes mellitus when it was developed in the 1920’s. It is still the only available treatment for type 1 diabetes mellitus (T1DM) and is widely used in type 2 diabetes mellitus (T2DM) where oral hypoglycaemic agents fail to gain adequate control.
It can sometimes seem daunting to understand the various types of insulin but it is important you have a basic grasp to avoid potential harm to patients.
Classification of Insulin
Classification of insulin
By manufacturing process
porcine: extracted and purified from pig pancreas
human sequence insulin: either produced by enzyme modification of porcine insulin (emp) or biosynthetically by recombinant DNA using bacteria (crb, prb) or yeast (pyr)
analogues
By duration of action
Onset > Peak > Duration
Rapid-acting insulin analogues:
- 5 mins
- 1 hour
- 3-5 hours
Short-acting insulin
- 30 mins
- 3 hours
- 6-8 hours
Intermediate-acting insulin
- 2 hours
- 5-8 hours
- 12-18 hours
Long-acting insulin analogues
- 1-2 hours
- Flat profile
- Up to 24 hours
Premixed preparations - - -
Patients often require a mixture of preparations (e.g. both short and long acting) to ensure stable glycaemic control throughout the day.
Rapid-acting Insulin
Rapid-acting insulin analogues
the rapid-acting human insulin analogues act faster and have a shorter duration of action than soluble insulin (see below)
may be used as the bolus dose in ‘basal-bolus’ regimes (rapid/short-acting ‘bolus’ insulin before meals with intermediate/long-acting ‘basal’ insulin once or twice daily)
insulin aspart: NovoRapid
insulin lispro: Humalog
Short-acting Insulin
Short-acting insulins
soluble insulin examples: Actrapid (human, pyr), Humulin S (human, prb)
may be used as the bolus dose in ‘basal-bolus’ regimes
Intermediate-acting Insulin
Intermidate-acting insulins
isophane insulin
many patients use isophane insulin in a premixed formulation with
Long-acting Insulin
Long-acting insulins insulin determir (Levemir): given once or twice daily insulin glargine (Lantus): given once daily
Insulin - Pre-mixed Preparations
Premixed preparations
combine intermediate acting insulin with either a rapid-acting insulin analogue or soluble insulin
Novomix 30: 30% insulin aspart (rapid-acting), 70% insulin aspart protamine (intermediate-acting)
Humalog Mix25: 25% insulin lispro (rapid-acting), 75% insulin lispro protamine (intermediate-acting); Humalog Mix50: 50% insulin lispro, 50% insulin lispro protamine
Humulin M3: biphasic isophane insulin (human, prb) - 30% soluble (short-acting), 70% isophane (intermediate-acting)
Insuman Comb 15: biphasic isophane insulin 9human, prb) - 30% soluble (short-acting), 70% isophane (intermediate-acting)
Administration of Insulin
Administration of insulin
The vast majority of patients administer insulin subcutaneously. It is important to rotate injection sites to prevent lipodystrophy. Insulin pumps are available (‘continuous subcutaneous insulin infusions’) which delivers a continuous basal infusion and a patient-activated bolus dose at meal times.
Intravenous insulin is used for patients who are acutely unwell, for example with diabetic ketoacidosis. Inhaled insulin is available but not widely used and oral insulin analogues are in development but have considerable technical hurdles to clear.
Target Blood Sugars - Example Question
A 19-year-old man is reviewed prior to discharge. He presented with vomiting and abdominal pain and was found to have diabetic ketoacidosis. He was managed as an inpatient for five days before being well enough for discharge. He is also diagnosed with type 1 diabetes mellitus on this admission as a cause of the diabetic ketoacidosis. He has been educated by the diabetic nurse on how to manage his diabetes and insulin at home, but he is concerned about what his target plasma glucose should be after eating.
What is the recommended target after eating to be achieved by home monitoring?
3-6mmol/litre 5-10mmol/litre > 5-9mmol/litre 7-12mmol/litre 2-9 mmol/litre
The correct answer is 5-9mmol/litre. NICE recommends that people with type 1 diabetes should aim for 5-7mmol/litre on waking, 4-7mmol/litre before meals and 5-9mmol/litre 90 minutes after eating. Frequent testing is very important in patients starting with insulin therapy to avoid both high and low sugar levels.
Source:
‘Type 1 diabetes in adults: diagnosis and management’ Clinical guideline [NG17]. The National Institute for Health and Care Excellence, August 2015.
DM in Pregnancy
Pregnancy: diabetes mellitus
Diabetes mellitus may be a pre-existing problem or develop during pregnancy, gestational diabetes. It complicates around 1 in 40 pregnancies. NICE updated the guidance in 2015
Risk factors for gestational diabetes
BMI of > 30 kg/m²
previous macrosomic baby weighing 4.5 kg or above
previous gestational diabetes
first-degree relative with diabetes
family origin with a high prevalence of diabetes (South Asian, black Caribbean and Middle Eastern)
Gestational Diabetes - Screening and Diagnosis
Screening for gestational diabetes
women who’ve previously had gestational diabetes: oral glucose tolerance test (OGTT) should be performed as soon as possible after booking and at 24-28 weeks if the first test is normal. NICE also recommend that early self-monitoring of blood glucose is an alternative to the OGTTs
women with any of the other risk factors should be offered an OGTT at 24-28 weeks
Diagnostic thresholds for gestational diabetes
these have recently been updated by NICE, gestational diabetes is diagnosed if either:
fasting glucose is >= 5.6 mmol/l
2-hour glucose is >= 7.8 mmol/l
Mx of Gestational Diabetes and Pre-existing Diabetes in Pregnancy
Management of gestational diabetes:
- Newly diagnosed women should be seen in a joint diabetes and antenatal clinic within a week
- Women should be taught about selfmonitoring of blood glucose
- Advice about diet (including eating foods with a low glycaemic index) and exercise should be given
- If the fasting plasma glucose level is < 7 mmol//l a trial of diet and exercise should be offered
- If glucose targets are not met within 1-2 weeks of altering diet/exercise metformin should be started
- If glucose targets are still not met insulin should be added to diet/exercise/metformin
- If at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be started
- If the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of complications such as macrosomia or hydramnios, insulin should be offered
- Glibenclamide should only be offered for women who cannot tolerate metformin or those who fail to meet the glucose targets with metformin but decline insulin treatment
Management of pre-existing diabetes
- Weight loss for women with BMI of > 27 kg/m^2
- Stop oral hypoglycaemic agents, apart from metformin, and commence insulin
- Folic acid 5 mg/day from pre-conception to 12 weeks gestation
- Detailed anomaly scan at 20 weeks including four-chamber view of the heart and outflow tracts
- Tight glycaemic control reduces complication rates
- Treat retinopathy as can worsen during pregnancy
Targets for self monitoring of pregnant women (pre-existing and gestational diabetes)
Targets for self monitoring of pregnant women (pre-existing and gestational diabetes)
Time Target
Fasting 5.3 mmol/l
1 hour after meals 7.8 mmol/l, or:
2 hour after meals 6.4 mmol/l
Mx of Gestational Diabetes - Example Question
You review a 28-year-old woman who is 26 weeks pregnant. She has just had a routine oral glucose tolerance test as her BMI is 34 kg/m². The following results were obtained:
Time (hours) Blood glucose (mmol/l)
0 7.4
2 11.2
There have been no other antenatal problems and her anomaly scan was normal. What is the most appropriate action?
Repeat oral glucose tolerance test in 4 weeks Start metformin + advice about diet / exercise + self-monitor glucose levels Advice about diet / exercise + self-monitor glucose levels > Start insulin + advice about diet / exercise + self-monitor glucose levels Reassure results within normal limits
NICE have recently changed their gestational diabetes guidelines. Insulin should be started in the fasting glucose is >= 7 mmol/l. Aspirin should also be considered given the increased risk of pre-eclampsia.
Insulin Therapy - Example Question
A 34 year-old woman is seen by her GP for the annual review of her type 1 diabetes. Her most recent HbA1c is 58 mmol/mol and the only problem she has noticed are severe hypoglycaemic episodes during the night around 2-4am, that she noticed she was getting while working night shifts for a local superstore. However, by breakfast time, her blood glucose levels often rise to around 15 mmol/mol. Her insulin regimen is currently a twice daily mixed insulin.
What is the most appropriate change to her current insulin treatment?
> Move to a basal bolus of insulin Take 1 dextrose tablet at 9pm Reduce nocturnal insulin dose Reduce morning insulin dose Add gliclazide
This patient is experiencing severe nocturnal hypoglycaemic episodes followed by rises in blood glucose by breakfast time. The most appropriate change to the insulin treatment regimen is changing to a basal bolus regime, with one daily injection of background long-acting insulin and three short acting injections of insulin.
Diabetes and the New Drugs
Diabetes mellitus: GLP-1 and the new drugs
A number of new drugs to treat diabetes mellitus have become available in recent years. Much research has focused around the role of glucagon-like peptide-1 (GLP-1), a hormone released by the small intestine in response to an oral glucose load
Whilst it is well known that insulin resistance and insufficient B-cell compensation occur other effects are also seen in type 2 diabetes mellitus (T2DM). In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be decreased in T2DM.
Increasing GLP-1 levels, either by the administration of an analogue (glucagon-like peptide-1, GLP-1 mimetics, e.g. exenatide) or inhibiting its breakdown (dipeptidyl peptidase-4 ,DPP-4 inhibitors - the gliptins), is therefore the target of two recent classes of drug.
GLP-1 Mimetics eg Exenatide
Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide)
Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic. These drugs increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss, in contrast to many medications such as insulin, sulfonylureas and thiazolidinediones.
Exenatide must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal.
Liraglutide is the other GLP-1 mimetic currently available. One the main advantages of liraglutide over exenatide is that it only needs to be given once a day.
Both exenatide and liraglutide may be combined with metformin and a sulfonylurea. Standard release exenatide is also licensed to be used with basal insulin alone or with metformin. Please see the BNF for a more complete list of licensed indications.
NICE state the following:
Consider adding exenatide to metformin and a sulfonylurea if:
BMI >= 35 kg/m² in people of European descent and there are problems associated with high weight, or
BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities.
NICE like patients to have achieved a 11 mmol/mol (1%) reduction in HbA1c and 3% weight loss after 6 months to justify the ongoing prescription of GLP-1 mimetics.
The major adverse effect of GLP-1 mimetics is nausea and vomiting. The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that is has been linked to severe pancreatitis in some patients.
DPP-4 Inhibitors eg Vildagliptin
Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
Key points
oral preparation
trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia
do not cause weight gain
NICE guidelines on DPP-4 inhibitors
NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione