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Patient Case Studies

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UK/DIA/00005f Date of preparation: November 2011

The content within this section has been produced with funding from Boehringer Ingelheim and Eli Lilly & Company Ltd. Boehringer Ingelheim and Eli Lilly & Company Ltd have reviewed this content for medical accuracy, and compliance with industry and company regulations only.

• Understanding the management of a patient with newly diagnosed type 2 diabetes

• Understanding the diagnostic approach in diabetes

• Appreciation of the management of other metabolic parameters in diabetes

Learning objectives (Case Study 1)

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A 51 year old traffic police officer presents to clinic accompanied by his wife.

•He is complaining of lethargy and malaise for the past 3 months. •On further questioning, he has been feeling increasingly tired for

approximately 4 years but he ascribed this to the stress of his job. •His weight has increased by 20 kg over this period although his

appetite remains unchanged. •His wife reports that he frequently consumes lots of sugary snacks

when on road duty although he denies this.

Case Study 1

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•Recently he has been complaining of polydipsia and polyuria associated with dysuria and has had a few episodes of penile thrush over the last year or so. •He has noticed a change in vision recently, describing objects as appearing ‘blurred’ but he is reluctant to visit an Optician as he is concerned that having to wear glasses may impact on his driving duties. He suffers from hypertension and gout and takes bendroflumethazide 2.5mg daily and allopurinol 100mg daily. •His mother had type 2 diabetes (T2D) and died from a stroke aged 64. •He has two grown up sons who are healthy. •He drinks 28 units of alcohol a week and smokes 20 cigarettes per day.

Case Study 1 (cont)

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On examination, his BMI is 28 kg /m2 and his blood pressure is 164/98 mmHg. Cardiovascular and respiratory examination is unremarkable although on abdominal examination you note the presence of central adiposity (waist circumference 116cm) and 2cm smooth hepatomegaly, which is not associated with any signs of chronic liver disease.

Neurological examination revealed slightly reduced sensation in both light touch and pinprick sensation and vibration below mid tibia bilaterally. His dorsalis pedis and posterior tibial pulses were palpable. Fundoscopy reveals bilateral capillary microaneurysms and ‘dot and blot’ haemorrhages. You organise some investigations and the results are shown in the following table:

Case Study 1 (Examination)

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FBC Normal

LFT’sALT 102 IU/L (5-35 IU/L), bilirubin 9µmol/L (3-17µmol/L), albumin 41 g/L (35-50 g/L, Alkaline Phosphatase 102 IU/L (30-145 IU/L), gamma-GT 94 IU/L (11-51 IU/L)

Uric acid 190 µmol/L (110-420µmol/L)

U&Es Normal with eGFR >90mls/min/1.73m2

TFTs Normal

Fasting plasma glucose 14.1 mmol/L

HbA1c 8.20%

Fasting Lipid profileTotal cholesterol 6.4mmol/L (<4mmol/L), HDL 0.74mmol/L (0.9-1.9mmol/L), LDL 5.1mmol/L (<4mmol/L), Triglycerides 5.1mmol/L (<1.69mmol/L)

Urine albumin estimation

Urine albumin 107mg/24hr (<30mg/24hr); Albumin:Creatinine =6.1 (<2.5)

Mid-Stream Urine Heavy growth of C.albicans.

Ultrasound AbdomenThe liver appearances are bright with a hyper-echoic echotexture. There are no focal abnormalities. The kidneys, spleen, and aorta all appear structurally normal.

Case Study 1 (Results)

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(Q1) What is the underlying diagnosis and how does this explain his symptoms?

Based on the presence of symptoms coupled with a random plasma glucose >11.1mmol/L, he has a diagnosis of T2DM1. Polyuria, polydipsia and blurred vision are called ‘osmotic symptoms’; these symptoms are a consequence of the osmotic effects of hyperglycaemia with associated fluid shifts. The hyperglycaemia would exceed the renal threshold for renal tubular reabsorption thus causing glycosuria. Glycosuria effectively serves as a culture medium for microbial growth, which would explain the growth of C.albicans in his urine and associated balanitis.

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Reference 1: www.patient.co.uk, glucose tolerance tests, last accessed September 2011


http://www.patient.co.uk/

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(Q2A) What modifiable risk factors does he have for cardiovascular disease?

Modifiable risk factors include: smoking, obesity, hypertension, hyperuricaemia, hyperglycaemia, a mixed hyperlipidaemia, and stress. Note hyperglycaemia, dyslipidaemia, hyperuricaemia, and hypertension are effectively ‘modifiable’ risk factors, as with treatment, a euglycaemic improved lipid profile and normotensive state can be achieved thus modifying the morbidity and mortality risk to that of the background population.

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(Q2B) What non-modifiable risk factors does he have for cardiovascular disease?

Non-modifiable risk factors include a positive family history of T2DM, and having T2DM.

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(Q3) What treatment, if any, is indicated for:

(a) The underlying diagnosis?

1st line treatment for T2DM, in conjunction with NICE Guidelines, would include a combination of lifestyle intervention changes from the outset and commencing metformin if required2. Lifestyle measures should include advice on smoking cessation and reducing alcohol consumption.

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Reference 2: NICE Guidance CG87 May 2009


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(b) His weight?

One should aim for a 10% reduction in target weight3. To attain this he should be given advice on diet and reduced caloric intake, increased exercise and possibly referred onto an X-PERT educational programme to assist with the management of diabetes4.

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Reference 3: National Collaborating Centre for Chronic Conditions. Type 2 diabetes: national clinical guideline for management in primary and secondary care (update). London: Royal College of Physicians, 2008.

Reference 4: X-PERT Educational Programme http://www.xperthealth.org.uk/, last accessed September 2011


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(c) His fasting lipid profile?

He has a typical dyslipidaemic profile of T2DM with high total cholesterol, low HDL and a high triglyceride concentration. Dietary measures would be expected to lower his total cholesterol by only 10%. Therefore, NICE guidelines would advocate the use of a statin in the first instance, as he is over 40 years old with risk factors stratifying him as intermediate-high risk for a cardiac event2.

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(d) His blood pressure?

NICE suggests his target blood pressure should be <140/80mmHg. If lifestyle interventions prove unsuccessful, then antihypertensive therapy should be employed. First line therapy should be an Angiotensin Converting Enzyme Inhibitor (ACE-I), or an Angiotensin Receptor Blocker (ARB) if ACE-I is contraindicated. You will note he is on a thiazide diuretic. There is evidence to suggest that diabetic patients have a salt sensitive hypertension that is responsive to thiazide diuretics2.

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(e) His LFT’s and liver ultrasound report?

Elevated levels of ALT and gamma-GT serve as sensitive biomarkers of hepatic steatosis, when interpreted in the context of his history. This is most likely due to, predominantly T2DM, and to a lesser but significant extent, a high alcohol intake. The attainment of both euglycaemia and a normal lipid profile coupled with reducing his alcohol intake would be expected to partially or even completely reverse this process. Serial monitoring of gamma-GT and ALT may guide this.

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(f) His urinary albumin estimation?

A urinary albumin estimation cannot be interpreted in the context of ongoing urinary contamination. Due to the suspected presence of C.Albicans balanitis, it should be treated with a topical anti-fungal agent. When the contamination has resolved he would need two urinary albumin estimations three months apart in order to be able to diagnose diabetic nephropathy.

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(g) The findings of the neurological examination?

He has evidence of a sensory neuropathy with both small (spinothalamic - pain) and large (dorsal column – light touch, vibration) neuronal fibre involvement. He is at an increased risk of diabetic foot complications and he should be given advice on foot care e.g. regular self-examination of feet, including regular nail trimming and spotting any changes in temperature or swelling5. He should be referred to a Podiatrist where any trauma can be documented. The Podiatrist may wish to carry out a thorough foot examination, to include doppler analysis of pedal pulses and 10g monofilament sensory testing, which should constitute an integral part of his annual review foot examination6. If he has symptoms suggestive of neuropathic pain, these should be investigated and managed appropriately.

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Reference 5: www.thepodiatrist.com, foot problems, diabetes and your feet, care of the diabetic foot, last accessed September 2011

Reference 6: NICE CG10, type 2 diabetes, prevention and management of foot problems, January 2004


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(Q4) What complications of the underlying diagnosis has he developed?

There is evidence of microvascular complications predominantly retinopathy, a neuropathy and microalbuminuria. He does not yet meet diagnostic criteria for nephropathy.

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(Q5) What advice would you offer regarding his reduced visual acuity and his employment?

His visual acuity will improve with the restoration of euglycaemia. As he has background retinopathy it must be noted that restoration of euglycaemia should be attained gradually as rapid attainment could result in a deterioration of retinopathy. However, this is usually a problem in patients on insulin therapy and would be very unlikely in this case it may seem contradictory to a lay person but this is factually correct. It isn't well appreciated that in individuals with diabetes if you improve their control too quickly (particularly with insulin) then their retinopathy may actually deteriorate rather than improve. As he is a serving police officer, he may wish to consider informing his employers of his diagnosis, so that they can discuss whether his condition will affect his day to day duties and if so, what support can be offered to overcome this3.

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Reference 3: National Collaborating Centre for Chronic Conditions. Type 2 diabetes: national clinical guideline for management in primary and secondary care (update). London: Royal College of Physicians, 2008.


• How to manage patients with type 2 diabetes (T2D) and deteriorating glycaemic control on relatively optimal oral hypoglycaemic therapies

• Consideration of the psychological changes of insulin conversion

• Understanding issues of self glucose monitoring

Learning Objectives (Case Study 2)

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A 54 year old teacher, with a 6 year history of type 2 diabetes mellitus (T2DM), presents for annual review.• Over the last year her weight has increased by 6kg• She is feeling more lethargic but denies any osmotic symptoms. • She is conscious of her weight and confesses to feeling depressed

over this. • She monitors her capillary blood glucose five times a week. The

fasting capillary blood glucose average ~9mmol/L and 2hr post-prandial readings average ~14mmol/L. Her HbA1c at her last annual review was 8.3%.

Case Study 2

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•She is taking metformin 1g b.i.d., gliclazide160mg b.i.d., lisinopril 10mg o.d., simvastatin 20mg nocte, and 75mg aspirin o.d. •She is needle phobic and is not keen on any injectable form of therapy.•Her mother had T2D and died from a myocardial infarction aged 74. •She has two grown up sons who are healthy. •She drinks 22 units of alcohol a week and smokes 10 cigarettes per day. She is keen to stop smoking and has tried nicotine replacement therapy with little success.

Case Study 2 (cont)

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On examination, her BMI is 29 kg / m2, resting heart rate is 118bpm, and her blood pressure is 144/95 mmHg in the supine position and 108/70 mmHg erect. There is mild bilateral pitting oedema to the ankles. Respiratory, abdominal and neurological examination is unremarkable. Her annual review results are tabulated on the following slide:

Case Study 2 (Examination)

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FBC Normal

Random plasma glucose 9.4mmol/L

HbA1c 8.1%

Fasting lipid profileTotal cholesterol 5.4mmol/L (<4mmol/L), HDL 0.94mmol/L (0.9-1.9mmol/L), LDL 3.1mmol/L

(<4mmol/L), Triglycerides 3.1mmol/L (<1.69mmol/L).

U&E’s Normal with eGFR >90mls/min/1.73m2

TFT’s Normal

Urine albumin estimation Urine albumin 4mg/24hr (<30mg/24hr); Albumin:Creatinine =1.1 (<2.5)

Retinal Photography Grade ‘R1’

Podiatry assessment Low – intermediate risk

ECG Sinus rhythm with left ventricular hypertrophy

Case Study 2 (Results)

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(Q1) What advice would you offer to improve her overall diabetic control?

To attain a target HbA1c of <7.5%1, her oral hypoglycaemic therapy needs to be escalated (assuming she is compliant with treatment, which should be checked). She is on optimal doses of first and second line therapy in the form of metformin and gliclazide. There is little evidence to suggest that 3g of metformin offers superior glycaemic control compared to 2g and the risks of gastrointestinal adverse effects outweigh any benefits.

(continued on next slide)

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Reference 1: www.patient.co.uk, glucose tolerance tests, last accessed September 2011


http://www.patient.co.uk/

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(Q1 cont.) What advice would you offer to improve her overall diabetic control?

Third line therapy is now indicated. A thiazolidinedione would be contraindicated in view of the features of mild cardiac failure, thus, a DPP-IV inhibitor would be an appropriate third choice agent. However, gliptins are associated with modest HbA1c reductions of ~0.4 – 0.7% and it is likely that in the future she will need either GLP-1 agonist therapy, or insulin. However, she is needle phobic and whilst there is scope to escalate oral therapy with a third line agent then that seems the most appropriate choice.

(continued on next slide)

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(Q1 cont.) What advice would you offer to improve her overall diabetic control?

Similarly, she should be offered advice to assist weight loss with the aim of achieving a 10% weight reduction2. This could also be assisted by encouraging a reduction in alcohol consumption as there are a considerable amount of calories in alcohol. Both exercise and weight loss would assist glycaemic control. She should be encouraged to adhere to a calorie restricted diet of approximately 1500 kCals/d and to also exercise. She may also benefit from a patient education programme such as X-PERT4.

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Reference 2: NICE Guidance CG87 May 2009Reference 4: X-PERT Educational Programme http://www.xperthealth.org.uk/, last accessed September 2011


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(Q2) When would insulin be indicated?

She is not keen on injectable therapy. The increase in HbA1c over the last year suggests that her beta-cell mass is progressively declining and/or she is becoming more insulin resistant. Once triple therapy is initiated she would be on appropriate insulinotropic and insulin sensitising therapy but if her HbA1c continued to decline over the next 6 months, then insulin therapy would be indicated.

She has microvascular complications (retinopathy and neuropathy) and so improved glycaemic control is necessary to reduce the progression of such complications potentially mandating the use of insulin.

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(Q3) What advice would you offer regarding capillary blood glucose monitoring?

Her fasting capillary blood glucose levels should be <7mmol/L and her 2 hour post prandial levels should ideally be 9-11mmol/L. 2 hour-post prandial capillary glucose levels >11mmol/L correlate strongly with progression of microvascular disease and confer a poorer prognosis. However there is little evidence to indicate that self monitoring improves HbA1c, decreases body weight or reduces hypoglycaemic events5.

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Reference 5: www.thepodiatrist.com, foot problems, diabetes and your feet, care of the diabetic foot, last accessed September 2011


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