Question 141#

A 50-year-old man who is known to have obesity and hypertension comes for review. His current BMI is 38 kg/m² and blood pressure today is 154/92 mmHg despite ramipril and bendroflumethiazide. Lifestyle and a trial of orlistat have failed to reduce his weight.

Which one of the following is the most suitable intervention?

A. Biliopancreatic diversion with duodenal switch

Correct Answer B: A trial of sibutramine would not be appropriate given his poorly controlled hypertension. Laparoscopic-adjustable gastric banding is the intervention of choice in patients with a BMI < 40 kg/m²

Obesity: bariatric surgery:
The use of bariatric surgery in the management of obesity has developed significantly over the past decade. It is now recognized that for many obese patients who fail to lose weight with lifestyle and drug interventions the risks and expense of long-term obesity outweigh those of surgery.

NICE guidelines on bariatric surgery for adults:

Consider surgery for people with severe obesity if:

• They have a BMI of 40 kg/m^2 or more, or between 35 kg/m² and 40 kg/m² and other significant disease (for example, type 2 diabetes mellitus, hypertension) that could be improved if they lost weight
• All appropriate non-surgical measures have failed to achieve or maintain adequate clinically beneficial weight loss for at least 6 months
• They are receiving or will receive intensive specialist management
• They are generally fit for anaesthesia and surgery
• They commit to the need for long-term follow-up

Consider surgery as a first-line option for adults with a BMI of more than 50 kg/m2 in whom surgical intervention is considered appropriate; consider orlistat before surgery if the waiting time is long.

Types of bariatric surgery:

• Primarily restrictive: laparoscopic-adjustable gastric banding (LAGB) or sleeve gastrectomy
• Primarily malabsorptive: classic biliopancreatic diversion (BPD) has now largely been replaced by biliopancreatic diversion with duodenal switch
• Mixed: Roux-en-Y gastric bypass surgery

Which operation?

• LAGB produces less weight loss than malabsorptive or mixed procedures but as it has fewer complications it is normally the first-line intervention in patients with a BMI of 30-39kg/m²
• Patients with a BMI > 40 kg/m^2 may be considered for a gastric bypass or sleeve gastrectomy. The latter may be done as a sole procedure or as an initial procedure prior to bypass
• Primarily malabsorptive procedures are usually reserved for very obese patients (e.g. BMI > 60 kg/m²)

Question 142#

Which one of the following statements regarding dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes mellitus is correct?

A. Metformin should always be co-prescribed

Correct Answer B: Hypoglycaemia is rare in patients taking dipeptidyl peptidase-4 inhibitors.

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 or inhibiting its breakdown, is therefore the target of two recent classes of drug.

Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide):

• Increase insulin secretion and inhibit glucagon secretion
• Licensed for use in T2DM
• Must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal
• May be combined with metformin, a sulfonylurea or a thiazolidinedione
• Typically results in weight loss
• Major adverse effect is nausea and vomiting

NICE guidelines on the use of 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% in 6 months)

The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide:

• Increased risk of severe pancreatitis
• Increased risk of renal impairment

Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin): 

• 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:

• Continue DPP-4 inhibitor only if there is a reduction of > 0.5 percentage points in HBA1c in 6 months
• 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 

Question 143#

A 4-year-old boy is being investigated for failure to thrive and generalized weakness. His blood pressure is normal. The following blood results are obtained:

• Na+ 137 mmol/l
• K+ 3.0 mmol/l
• Urea 4.5 mmol/l
• Creatinine 65 μmol/l
• Bicarbonate 33 mmol/l

What is the most likely diagnosis? 

A. Conn's syndrome

Correct Answer B: Bartter's syndrome is associated with normotension.

Bartter's syndrome is the most likely diagnosis. Congenital adrenal hyperplasia due to 21- hydroxylase deficiency is associated with precocious puberty rather than failure to thrive in boys. Both Conn's and Cushing's are associated with hypertension and are not common in this age group. 

Liddle's syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.

Bartter's syndrome:
Bartter's syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- co-transporter in the ascending loop of Henle. It should be noted that it is associated with normotension (unlike other endocrine causes of hypokalaemia such as Conn's, Cushing's and Liddle's syndrome which are associated with hypertension).

Features:

• Usually presents in childhood, e.g. Failure to thrive
• Polyuria, polydipsia
• Hypokalaemia
• Normotension
• Weakness

Question 144#

A 29-year-old woman has just found out she is pregnant for the second time. Her first pregnancy was complicated by gestational diabetes. Following her first pregnancy she was told she was no longer diabetic.

What is the most appropriate management?

A. Start insulin

Correct Answer D: Pregnancy: diabetes mellitus:
Diabetes mellitus may be a pre-existing problem or develop during pregnancy, gestational diabetes. It complicates around 1 in 40 pregnancies.

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) 

Screening for gestational diabetes:

• If a women has had gestational diabetes previously an oral glucose tolerance test (OGTT) should be performed at 16-18 weeks and at 28 weeks if the first test is normal
• Women with any of the other risk factors should be offered an OGTT at 24-28 weeks
• Currently the same WHO diagnostic criteria are used as for non-pregnant patients. There is however increasing evidence that a lower threshold should be used as treating borderline patients improves both maternal and neonatal outcomes

NICE issued guidelines on the management of diabetes mellitus in pregnancy in 2008

Management of pre-existing diabetes:

• Weight loss for women with BMI of > 27 kg/m²
• 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 18-20 weeks including four-chamber view of the heart and outflow tracts
• Tight glycaemic control reduces complication rates
• Treat retinopathy as can worsen during pregnancy

Management of gestational diabetes:

• Responds to changes in diet and exercise in around 80% of women
• Oral hypoglycaemic agents (metformin or glibenclamide) or insulin injections are needed if blood glucose control is poor or this is any evidence of complications (e.g. macrosomia)
• There is increasing evidence that oral hypoglycaemic agents are both safe and give similar outcomes to insulin
• Hypoglycaemic medication should be stopped following delivery
• A fasting glucose should be checked at the 6 week postnatal check

Question 145#

A 55-year-old female is reviewed in the diabetes clinic. The following results are obtained:

• Urinalysis protein +
• HbA1c 10.0%

What average blood glucose level for the past 2 months is this most likely to represent?

A. 9

Correct Answer D: Glycosylated haemoglobin (HbA1c) is the most widely used measure of long-term glycaemic control in diabetes mellitus. HbA1c is produced by the glycosylation of haemoglobin at a rate proportional to the glucose concentration. The level of HbA1c therefore is dependent on:

• Red blood cell lifespan
• Average blood glucose concentration 

HbA1c is generally thought to reflect the blood glucose over the previous '2-3 months' although there is some evidence it is weighed more strongly to glucose levels of the past 2-4 weeks.

The relationship between HbA1c and average blood glucose is complex but has been studied by the Diabetes Control and Complications Trial (DCCT). A new internationally standardized method for reporting HbA1c has been developed by the International Federation of Clinical Chemistry (IFCC). 

This will report HbA1c in mmol per mol of haemoglobin without glucose attached.

From the above we can see that average plasma glucose = (2 * HbA1c) - 4.5