Question 146#

A middle-aged man with type 2 diabetes mellitus is reviewed. Despite weight loss, metformin and gliclazide his HbA1c is 8.4%. The patient agrees to start insulin therapy.

According to NICE guidelines which type of insulin should be tried initially?

A. Basal bolus regime

Correct Answer B: Diabetes mellitus: management of type 2

NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2009. Key points are listed below: 

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% 

HbA1c:

• The general target for patients is 48 mmol/mol (DCCT = 6.5%). HbA1c levels below 48 mmol/mol (DCCT = 6.5%) should not be pursued
• However, individual targets should be agreed with patients to encourage motivation
• HbA1c should be checked every 2-6 months until stable, then 6 monthly

Blood pressure:

• Target is < 140/80 mmHg (or < 130/80 mmHg if end-organ damage is present)
• ACE inhibitors are first-line

The NICE treatment algorithm has become much more complicated following the introduction of new therapies for type 2 diabetes. We suggest reviewing this using the link provided. Below is a very selected group of points from the algorithm:

• NICE still suggest a trial of lifestyle interventions first*
• Usually metformin is first-line, followed by a sulfonylurea if the HbA1c remains > 48 mmol/mol (DCCT = 6.5%)
• If the patient is at risk from hypoglycaemia (or the consequences of) then a DPP-4 inhibitor or thiazolidinedione should be considered rather than a sulfonylurea
• Meglitinides (insulin secretagogues) should be considered for patients with an erratic lifestyle
• If HbA1c > 58 mmol/mol (DCCT = 7.5%) then consider human insulin
• Metformin treatment should be continued after starting insulin
• Exenatide should be used only when insulin would otherwise be started, obesity is a problem (BMI > 35 kg/m²) and the need for high dose insulin is likely. Continue only if beneficial response occurs and is maintained (> 1.0 percentage point HbA1c reduction and weight loss > 3% at 6 months)

Starting insulin:

• Usually commenced if HbA1c > HbA1c > 58 mmol/mol (DCCT = 7.5%)
• NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at bedtime or twice daily according to need

Other risk factor modification:

• Current NICE guidelines suggest giving aspirin to all patients > 50 years and to younger patients with other significant risk factors. However, recent evidence does not support this approach. The 2010 SIGN guidelines do not advocate the use of aspirin for primary prevention in diabetics
• The management of blood lipids in T2DM has changed slightly. Previously all patients with T2DM > 40- years-old were prescribed statins. Now patients > 40-years-old who have no obvious cardiovascular risk (e.g. Non-smoker, not obese, normotensive etc) and have a cardiovascular risk < 20%/10 years do not need to be given a statin. We suggest reviewing the NICE T2DM guidelines for further information
• If serum cholesterol target not reach consider increasing simvastatin to 80mg on
• If target still not reached consider using a more effective statin (e.g. Atorvastatin) or adding ezetimibe
• Target total cholesterol is < 4.0 mmol/l
• If serum triglyceride levels are > 4.5 mmol/l prescribe fenofibrate

*many local protocols now recommend starting metformin upon diagnosis.

Question 147#

Which one of the following is least associated with gynaecomastia?

A. Klinefelter's syndrome

Correct Answer E: Gynaecomastia is seen in up to a third of men with thyrotoxicosis, but is not a feature of hypothyroidism.

Gynaecomastia:
Gynaecomastia describes an abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia.

Causes of gynaecomastia:

• Physiological: normal in puberty
• Syndromes with androgen deficiency: Kallman's, Klinefelter's
• Testicular failure: e.g. mumps
• Liver disease
• Testicular cancer e.g. seminoma secreting hCG
• Ectopic tumour secretion
• Hyperthyroidism
• Haemodialysis
• Drugs: see below

Drug causes of gynaecomastia:

• Spironolactone (most common drug cause)
• Cimetidine
• Digoxin
• Cannabis
• Finasteride
• Gonadorelin analogues e.g. Goserelin, buserelin
• Oestrogens, anabolic steroids

Question 148#

A 54-year-old man has a routine medical for work. He is asymptomatic and clinical examination is unremarkable.

Which of the following results establishes a diagnosis of impaired fasting glucose?

A. Fasting glucose 7.1 mmol/L on one occasion

Correct Answer B: Diabetes diagnosis: fasting > 7.0, random > 11.1 - if asymptomatic need two readings.

A 75g oral glucose tolerance test 2 hour value of 8.4 mmol/L would imply impaired glucose tolerance rather than impaired fasting glucose.

Diabetes mellitus: diagnosis:
The following is based on the World Health Organization (WHO) 2006 guidelines. 

Diabetes mellitus

If the patient is symptomatic:

• Fasting glucose greater than or equal to 7.0 mmol/l
• Random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test) 

If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

In 2011 WHO released supplementary guidance on the use of HbA1c on the diagnosis of diabetes:

• A HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus
• A HbA1c value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)
• In patients without symptoms, the test must be repeated to confirm the diagnosis
• It should be remembered that misleading HbA1c results can be caused by increased red cell turnover (for example anaemia, haemoglobinopathies and pregnancy)

Impaired fasting glucose and impaired glucose tolerance:
A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG) Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour.

value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l.

Diabetes UK suggests:

• 'People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes
• A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn't have diabetes but does have IGT.'

Question 149#

A 54-year-old obese man presents with lethargy and polyuria. A fasting blood sugar is requested: Fasting glucose 8.4 mmol/l He is given dietary advice and a decision is made to start metformin.

What is the most appropriate prescription?

A. Metformin 500mg od with food for 5 days then metformin 500mg bd for 5 days then metformin 500mg tds for 20 days then review

Correct Answer C: Metformin should be titrated slowly, leave at least 1 week before increasing dose.

Gastrointestinal side-effects are more likely to occur if metformin is not slowly titrated up. The BNF advises leaving at least 1 week before increasing the dose.

Metformin:
Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves glucose tolerance (see below). Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight.  

Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease.

Mechanism of action:

• Increases insulin sensitivity
• Decreases hepatic gluconeogenesis
• May also reduce gastrointestinal absorption of carbohydrates 

Adverse effects:

• Gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
• Reduced vitamin B12 absorption - rarely a clinical problem
• Lactic acidosis* with severe liver disease or renal failure 

Contraindications**:

• Chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 μmol/l and stopping metformin if > 150 μmol/l
• Do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis)
• Alcohol abuse is a relative contraindication
• Stop 2 days before general anaesthetic, restart when renal function normal
• Stop prior to IV contrast e.g. Angiography, restart when renal function normal 

*it is now increasingly recognized that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams.

**metformin is now sometimes used in pregnancy, for example in women with polycystic ovarian syndrome.

Question 150#

A 56-year-old Muslim man with a history of type 2 diabetes asks for advice. He is due to start fasting for Ramadan soon and is unsure what he should do with regards to his diabetes medications. He currently takes metformin 500mg tds.

What is the most appropriate advice? 

A. Switch to subcutaneous biphasic insulin for the duration of Ramadan

Correct Answer B: Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves glucose tolerance (see below). Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. 

Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease.

Metformin Mechanism of action:

• Increases insulin sensitivity
• Decreases hepatic gluconeogenesis
• May also reduce gastrointestinal absorption of carbohydrates

Adverse effects:

• Gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%
• Reduced vitamin B12 absorption - rarely a clinical problem
• Lactic acidosis* with severe liver disease or renal failure

Contraindications**:

• Chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 μmol/l and stopping metformin if > 150 μmol/l
• Do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis)
• Alcohol abuse is a relative contraindication
• Stop 2 days before general anaesthetic, restart when renal function normal
• Stop prior to IV contrast e.g. Angiography, restart when renal function normal

*it is now increasingly recognized that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams.

**metformin is now sometimes used in pregnancy, for example in women with polycystic ovarian syndrome.