Diabetes 521/15

Question 1

1. T2DM Inx

Answer 1

In addition to history taking and physical examination, arranging to have blood tests to assess levels of HbA1c would be appropriate steps.

Traditionally, an oral glucose tolerance test (OGTT) was carried out to confirm a diagnosis of diabetes. However, the HbA1c test is much simpler for the patient as it does not require any special preparation and can be done at any time of day.

The HbA1c test is now accepted by clinicians and health authorities in Australia, the US and Europe as an appropriate diagnostic test for diabetes.1 A diagnostic level has been set at ≥48 mmol/mol (6.5%) with the requirement that a second factor confirm the diagnosis (symptoms of type 2 diabetes or a second test, such as fasting blood glucose levels, on a second day).

Question 2

2. T2DM Dx

Answer 2

Elevated HbA1c > 6.5% together with history of eg recurrent thrush, which is a classical symptom of T2DM, is diagnostic of diabetes.

Confirmation of the diagnosis requires two abnormal glycaemic test results on different days, or one abnormal test result and one or more classical symptoms of diabetes.

Question 3

1. Weight gain in recent times

Answer 3

Since the 1980s, there has been a steady increase in the number of Australians who are overweight, and individual Australians, particularly women, gain weight as they age. Eg our grandmother in 1960 and mother in 1990 probably weighed 6 kg and 3.6 kg, respectively, less than someone at the same age.

Over time, higher energy foods and lower activity lifestyles have become part of our lives, and healthy lifestyle choices have become difficult choices.

Apart from the ‘big two’ leading causes of weight gain (high-energy food and low-energy lifestyle), there may be other systematic factors that predispose to weight gain:

• We now sleep less than in the past, and this is associated with weight gain.
• People become heavier as they get older and the population as a whole is getting older. As serial generations become heavier, their children are predisposed to being heavy.
• Women are delaying having children and older mothers seem to have heavier children.
• We are exposed to more chemicals (pharmaceuticals and industrial/agricultural chemicals) and some of these can lead to weight gain.
• Heating and air conditioning have reduced the need for body energy expenditure to keep warm or cool.
• Genetic factors may contribute to weight gain.

Question 4

1. T2DM Risk factors

Answer 4

The major risk factors for developing T2DM are

• having family history of T2DM,
• being overweight or obese, and
• being over the age of 40 years.

Age over 40 is the dominant risk factor. After the age of 40 years, the risk of developing T2DM is considerably higher in men than in women. Eg age (52 years) increases her risk 11-fold. Her positive family history increases her risk by 1.4-fold and a BMI of 28.2 kg/m2 increases her risk about twofold.

In young people, family history and being overweight are more important risk factors.

For a woman aged 25 years, for example, a positive family history increases her risk threefold and BMI ≥30 kg/m2 increases her risk eightfold.

Question 5

1. T2DM Targets

Answer 5

The Australian Diabetes Society has recommended glycaemic targets for different groups with T2DM (Table 1). The principle is that targets will be lower where the benefits (symptomatic relief, reduced microvascular and, possibly, macrovascular risk) exceed the costs (daily inconvenience, more medication, more visits to health professionals, greater risk of hypoglycaemia and weight gain). For example, a lower target is set for a young person with newly diagnosed T2DM, on metformin therapy alone, and
at low risk of hypoglycaemia or weight gain, and no end-organ complications or comorbidities. Higher targets would be set for people with lesser potential to benefit (eg limited life span) and/
or with greater potential for harm (eg existing microvascular or macrovascular complications or multiple comorbidities).

The general target for HbA1c is ≤ 53 mmol/mol (7.0%).

Question 6

1. T2DM Initial Rx- Metformin

Answer 6

Pharmacotherapy may be required to achieve long-term glycaemic control and to prevent complications of diabetes, if lifestyle modifications alone do not achieve glycaemic targets.4 If required, the Royal Australian College of General Practitioners’ (RACGP) diabetes guidelines4 recommend starting with metformin and then adding or substituting other hypoglycaemic medication, depending on the patient’s clinical characteristics. The most common side effects of metformin are gastrointestinal effects.11 It is advisable to start with a low dose and, if tolerated, gradually increase the dose if glycaemic targets are not achieved (eg starting with 250 mg and increasing at weekly intervals to 500 mg twice daily and, finally, 850–1000 mg twice daily).11 The therapeutic effect of metformin is greater at higher doses, but side effects also increase at higher doses.

Metformin Intolerance

Intolerance to metformin requiring cessation of therapy (as opposed to dose reduction) is unusual and occurs in 5% of the patient population.

Gastrointestinal side effects include:

• gastric irritation with upper abdominal discomfort and nausea (sometimes vomiting)
• bloating and flatulence
• frequent bowel actions, sometimes associated with urgency and incontinence.

Gastric irritation can be minimised by taking the metformin with food. The other gastrointestinal effects are usually minor and can be minimised with appropriate dose titration.

It is claimed that the slow-release form of metformin has fewer side effects, but the decrease is not striking.

Co-existing gastrointestinal disease

increases the risk of severe adverse reactions to metformin (especially coeliac disease, inflammatory bowel disease and irritable bowel syndrome).

• If these exist, add appropriate treatment and try re-introducing metformin cautiously.

Question 7

1. T2DM Rx- Sulphonylurea and weight gain

Answer 7

The cause of weight gain is likely to be multifactorial; however sulphonylureas could contribute to weight gain.

Patients usually lose 2–3 kg in the first year on metformin but gain 3–4 kg with a sulphonylurea.

Sulphonylureas predispose to weight gain by two mechanisms:

• Significantly decreasing blood glucose also reduces glycosuria. This would result in a net energy gain. The higher the HbA1c, the greater the glycosuria and the greater the weight gain as glycaemic targets are approached.

Sulphonylureas stimulate the pancreatic beta cells to secrete insulin, irrespective of the prevailing blood glucose. These agents, therefore, are associated with hypoglycaemia, especially when unexpected activity occurs or when carbohydrate intake is inadequate. Minor hypoglycaemia may cause the patient to be hungry (or hungrier) and to eat more than usual.

More severe hypoglycaemia (eg <3 mmol/L) can cause unpleasant symptoms including tachycardia, anxiety, headache, confusion and, rarely, loss of consciousness.

Patients with diabetes learn and/or are taught to always carry quick-acting carbohydrates (ideally a fizzy drink of glucose solution, but non-diet soft drinks or jellybeans are often more practical) that can be taken promptly when such symptoms of hypoglycaemia occur.

There is a tendency for patients to eat until they feel better, by which time they will have eaten large amounts of carbohydrate (this is somewhat like people who drink alcohol until they feel cheerful, but by this time the alcohol already in the body is more than enough to inebriate them).

An accredited dietitian can offer patients advice about the types and amounts of suitable carbohydrate. They could use their BGM to help reduce her hypoglycaemic risk and, if hypoglycaemia occurs, to deal with it more appropriately.

Patients can test blood glucose level when hungry or suspecting hypoglycaemia. If blood glucose is <4 mmol/L, she could take approximately 15 g of some fast-acting carbohydrate (eg half can of non-diet soft drink, half glass of fruit juice, 3 teaspoons of sugar or honey, 6–7 jellybeans, 3 glucose tablets).

After 15 minutes, patients should re-test her blood glucoselevel.
If the blood glucose is still <4 mmol/L, repeat the quick-acting carbohydrate dose as necessary.

If blood glucose has increased to >4 mmol/L, take 15 g of slow-acting carbohydrate (eg a sandwich, a glass of milk or soy milk, one piece of fruit, a few dried apricots, figs or other dried fruit, one tub of natural low-fat yoghurt, six small dry biscuits and cheese) and re-test 1–2 hours later to make sure the blood glucose has remained >4 mmol/L.

This ‘rule of 15’

(15 g quick-acting carbohydrate, 15 minutes, 15 g of slow-acting carbohydrate) should reduce the amount of carbohydrate eaten to relieve hypoglycaemic symptoms.

Question 8

1. T2DM hypoglycaemic agents- weight gain and hypogylcaemia

Answer 8

The classes of available hypoglycaemic medications, in terms of their associated risk of weight gain and hypoglycaemia, include:

• Acarbose is neutral in terms of weight gain and hypoglycaemia, and can be very effective at reducing an excessive prandial glycaemic response. However, it has less effect on 24-hour basal glycaemia. It has the advantage of only requiring doses before any meal associated with excess prandial glycaemia (eg often once daily before the evening meal), but the disadvantage of causing bloating and flatulence if the dose is escalated too fast.
• Dipeptidyl peptidase-4 (DPP4) inhibitors inhibit the enzyme that breaks down glucagon-like peptide (GLP) after it is secreted by the L cells of the intestine. This inhibition increases the levels and physiological effects of GLP1.
• GLP agonists are neutral in terms of hypoglycaemia and the injectable agents (exenatide, liraglutide) are associated with considerable and continuing weight loss. For Margaret, exenatide would be subsidised by the Pharmaceutical Benefits Scheme (PBS) if taken as dual therapy with a sulphonylurea. The main practical disadvantages are the need for twice-daily injection and very significant gastrointestinal side effects.
• Gliflozins are associated with some weight loss associated with the provoked glycosuria and neutral as far as hypoglycaemia is concerned. Their main disadvantage is vulvovaginal thrush and urinary tract infections
• Glitazones are neutral for hypoglycaemia but cause significant weight gain associated with increases in fat mass and increases in the extracellular fluid (usually as peripheral oedema but occasionally with precipitation of heart failure).
• Metformin is the initial hypoglycaemic of choice and is associated with weight loss and is neutral for hypoglycaemia. GI side effects
• Sulphonylureas are usually the second hypoglycaemic agent of choice but, can be associated with weight gain and hypoglycaemia.
• Insulin is very effective in controlling glycaemia but is associated with significant weight gain and hypoglycaemic risk (especially prandial or bolus insulin).

Question 9

2. BMI and Obesity

Answer 9

The risk associated with a given level of BMI varies across different ethnic groups. For example, in the US, Asian populations tend to have higher risk of diabetes at a lower level of BMI than the general population. This has led to suggestion that that the appropriate level for overweight should be >23 kg/m2 rather than >25 kg/m2.

Waist circumference is a good indicator of total body fat and is a useful predictor of visceral fat. Compared with BMI, waist circumference is a better predictor of cardiovascular risk, T2DM in women (but not in men) and metabolic syndrome.

In general, risk of disease is increased at ≥80 cm and high at ≥88 cm for women, and increased at ≥94 cm and high at ≥102 cm for men.

Question 10

2. T2DM and AUSRISK Score

Answer 10

AUSDRISK4 score at 20, indicates that she is at high risk (one in three risk) of developing T2DM.

This risk is equivalent to having impaired glucose tolerance and Carol would benefit from lifestyle intervention to prevent diabetes.

For example, weight loss of 5–10% can prevent or delay the onset of diabetes and cardiovascular disease.

Question 11

2. T2DM and fatigue

Answer 11

Trigger questions to consider include:

• How many hours of sleep do you get at night?
• Do you have any problems with sleep? If so, what disturbs your sleep?

Disturbed sleep may be associated with a variety of problems, including depression and anxiety, sleep apnoea and diabetes.

Question 12

2. T2DM consult room Inx

Answer 12

• Capillary BSL
• Urinalysis
• Foot examination
  • This should include examination of skin, sensation (light touch using a monofilament, vibration using a tuning fork, and peripheral circulation, especially post-tibial and dorsalis pedis). Neuropathy occurs in 10% of men and 9% of women with diabetes. It is associated with poor glucose control, duration of diabetes and age.10
• Eye examination
  
  • This should include visual acuity (with correction) and
  • retinal examination (with pupil dilation and photography).
• Absolute cardiovascular disease (CVD) risk assessment
  
  • This can be performed using the Australian CVD risk calculator, which assesses risk on the basis of
    
    • age,
    • gender,
    • Aboriginal and Torres Strait Islander background,
    • smoking status,
    • diabetes status,
    • blood pressure and
    • high-density lipoprotein (HDL)-to-cholesterol ratio.

Question 13

2. T2DM further Inx

Answer 13

The following investigations should be performed:

• Glycated haemoglobin (HbA1c) can be used to confirm a diagnosis of T2DM and is also a marker of insulin resistance and glucose control over the previous 6 weeks. It should be noted that HbA1c estimates tend to be 1–2% lower in patients with renal failure than in other patients with diabetes. High variability of HbA1c (from one test to another) is itself correlated with renal failure. It may also be influenced by haemoglobinopathies.
• Urinary microalbumin:creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) should be performed to assess for nephropathy.
• Plasma lipids should be assessed as elevations of low-density lipoprotein (LDL) cholesterol and triglyceride levels are common in people with T2DM and impaired glucose tolerance, and are markers of increased risk of macrovascular disease, such as heart disease and stroke.

Question 14

2. T2DM and renal impairment

Answer 14

eGFR results indicate stages of renal disease:

• Stage 1 >90 mL/min/1.73 m2 with microalbuminuria, proteinuria or haematuria
• Stage 2 (mild) 60–89 mL/min/1.73 m2 with microalbuminuria, proteinuria or haematuria
• Stage 3a (mod) 45–59 mL/min/1.73 m2
• Stage 3b (mod) 30–44 mL/min/1.73 m2
• Stage 4 (severe) 15–29 mL/min/1.73 m2
• Stage 5 (end-stage) <15 mL/min/1.73 m2

Kidney disease is associated with increased cardiovascular mortality in patients with T2DM, and kidney function tends to deteriorate with duration of diabetes.

It occurs in 3% of men with diabetes over 45 years of age and in 11% of women with diabetes.

The development of kidney disease is associated with duration of diabetes, poor blood sugar control, high blood pressure, anaemia, genetic susceptibility to diabetic kidney disease and smoking.

Referral criteria for specialist renal care include:

• eGFR <30 mL/min/1.73m2
• persistent significant albuminuria (UACR ≥30 mg/mmol)
• consistent decline in eGFR from a baseline of <60 mL/min/1.73m2 (a decline >5 mL/min/1.73m2 over a 6-month period confirmed on at least three separate readings)
• glomerular haematuria with macroalbuminuria
• chronic kidney disease and hypertension where achieving target blood pressure levels is difficult, despite treatment with at least three antihypertensive agents.

Question 15

2. T2DM management of elevated HbA1c

Answer 15

Diabetes

Non-pharmacological approaches include

• dietary control
  
  • aiming to achieve and maintain a weight reduction of 5–10%.
• physical activity,
  
  • Physical activity should involve at least 30 minutes of moderate physical activity on most days of the week and avoiding sedentary behaviour (>2 hours). Diet should be aimed at achieving a deficit of 2500 KJ (or about a quarter of current energy intake), limiting high saturated fats, increasing fruit and vegetable intake and avoiding drinks with high sugar content. This is unlikely to be achieved with brief advice alone.
  • Patients should be assisted by referral to a dietician and exercise physiologist, for diet and physical activity assessment and education. They should receive follow-up coaching for 6–8 sessions (which may be delivered by telephone) and follow-up in general practice.

Pharmacology

• Metformin is the preferred first-line pharmacological therapy. It may be used with caution when the eGFR is 30–60 mL/min/1.73 m2, but is not generally recommended for eGFR of <30 mL/ min/1.73 m2. If monotherapy is insufficient to control the HbA1c (<7%), other oral hypoglycaemic agents, such as a sulphonylurea, may be added.
• Treatment with a statin may be commenced, aiming to reduce LDL levels to <2.0 mmol/l. A fibrate, such as fenofibrate, may be added if the triglyceride level is >2.3 or if HDL is <0.9 mmol/L.

The PBS criteria for prescription of lipid-lowering medications are available at www.pbs.gov.au/info/healthpro/explanatory-notes/

gs-lipid-lowering-drugs.

These criteria allow prescription of a statin or fibrate after a trial of diet for patients with a total cholesterol > 5.5 mmol/L. For patients at high risk statins or fibrates may be prescribed concurrently with diet management.

Patients identified as being in one of the following very high risk categories may commence drug therapy with statins or fibrates at any cholesterol level:

• coronary heart disease that has become symptomatic
• cerebrovascular disease that has become symptomatic
• peripheral vascular disease that has become symptomatic

• diabetes mellitus with microalbuminuria (defined as urinary albumin excretion rate of >20 μg/min or urinary albumin:creatinine ratio of >2.5 for males, >3.5 for females)
• diabetes mellitus in Aboriginal or Torres Strait Islander patients
• diabetes mellitus in patients aged 60 years or older
• family history of coronary heart disease that has become symptomatic before the age of 55 years in two or more first degree relatives
• family history of coronary heart disease that has become symptomatic before the age of 45 years in one or more first degree relatives.

Question 16

2. T2DM and renal disease targets

Answer 16

Renal disease

The key goals for the management of renal disease are to control blood pressure and blood glucose levels.

Angiotensin converting enzyme inhibitors or angiotensin receptor blockers are reno- protective and should be added to her current amlodipine (or replace it) in order to lower her blood pressure to <130/80 mmHg.

Question 17

2. T2DM and peripheral neuropathy

Answer 17

Peripheral neuropathy

Should be assessed for autonomic neuropathy (orthostatic hypotension, gastrointestinal symptoms) and given advice about glycaemic control (HbA1c <53 [7%]).

Referred to a foot clinic or podiatrist for assessment, including advice about appropriate footwear.

Question 18

2. T2DM and peripheral neuropathy

Answer 18

Peripheral neuropathy

Other investigations that could be performed include electro- diagnostic studies; however, careful assessment of symptoms and physical examination are most important.

The Diabetes Neuropathy Score may be used to confirm diagnosis and assess severity. This includes the following questions that are answered ‘yes’ (positive: 1 point) if a symptom occurred several times a week during the last 2 weeks or ‘no’ (negative: no point) if it did not.

• Are you experiencing unsteadiness in walking (need for visual control, increase in the dark, walk like a drunk man, lack of contact with floor)?
• Do you have a burning, aching pain or tenderness at your legs or feet (occurring at rest or at night, not related to exercise, excluding intermittent claudication)?
• Do you have prickling sensations on your legs and feet (occurring at rest or at night, distal>proximal, stocking glove distribution)?
• Do you have places of numbness on your legs or feet (distal>proximal, stocking glove distribution)?

Maximum score: 4 points; 0 points, PNP absent; 1–4 points, PNP present.

Treatment

Tricyclic antidepressant medication (such as amitriptyline) can be tried as first-line therapy after briefing the patient on possible side effects and success rates.

If this is unsuccessful, treatment with gabapentin or pregabalin may be considered (pregabalin is PBS subsidised when prescribed for neuropathic pain, and gabapentin is subsidised for this indication only under the RPBS). A Cochrane review found that either of these drugs provided pain relief to about half of patients with painful diabetic neuropathy

Question 19

2. T2DM long term management

Answer 19

Education on diabetes, which should be tailored to patients level of understanding and specific goals. This includes:

• lifestyle management, including weight management
• adherence to her medications
• foot care
• self-monitoring of glucose and blood pressure
• detection and monitoring of microvacular complications, including retinopathy, nephropathy and neuropathy as well as symptoms or signs of macrovascular disease.

It is also important they have good continuity of care and regular monitoring of complications as part of a planned approach to care. It is important that care plans are reviewed to see if they have been implemented, and to review their objectives.

Question 20

2. Foot pain in T2DM Inx

Answer 20

2.

Other investigations that could be performed include electro- diagnostic studies; however, careful assessment of symptoms
and physical examination are most important.

The Diabetes Neuropathy Score may be used to confirm diagnosis and assess severity. This includes the following questions that are answered ‘yes’ (positive: 1 point) if a symptom occurred several times a week during the last 2 weeks or ‘no’ (negative: no point) if it did not.

1. Are you experiencing unsteadiness in walking (need for visual control, increase in the dark, walk like a drunk man, lack of contact with floor)?
2. Do you have a burning, aching pain or tenderness at your legs or feet (occurring at rest or at night, not related to exercise, excluding intermittent claudication)?
3. Do you have prickling sensations on your legs and feet (occurring at rest or at night, distal>proximal, stocking glove distribution)?
4. Do you have places of numbness on your legs or feet (distal>proximal, stocking glove distribution)?

Maximum score: 4 points; 0 points, PNP absent; 1–4 points, PNP present.

Question 21

2. T2DM Foot Pain Management

Answer 21

Tricyclic antidepressant medication (such as amitriptyline) can be tried as first-line therapy after briefing the patient on possible side effects and success rates.

If this is unsuccessful, treatment with gabapentin or pregabalin may be considered (pregabalin is PBS subsidised when prescribed for neuropathic pain, and gabapentin is subsidised for this indication only under the RPBS). A Cochrane review found that either of these drugs provided pain relief to about half of patients with painful diabetic neuropathy.

Question 22

3. T1DM vs T2DM

Answer 22

History

• strong family history of T2DM, which significantly increases lifetime risk of developing T2DM.
• the onset of diabetes during adolescence would make type 1 diabetes mellitus (T1DM) the likely diagnosis.
• personal or family history of T1DM and other autoimmune conditions such as autoimmune thyroid disease and coeliac disease.
• Rarer forms of diabetes such as MODY (maturity-onset diabetes of the young), accounting for about 1% of diabetes, might need to be considered.

History/Examination/Inx:

The presentation at diagnosis can offer clues as to the type of diabetes.

• acute onset with polyuria, polydipsia and weight loss would favour T1DM, and admission to hospital with diabetic ketoacidosis is almost pathognomonic of T1DM.
• Conversely, an insidious slowly progressive condition would favour T2DM. Terminology ‘quite some time’ would further stratify the likelihood of this being T1DM or T2DM. If ‘quite some time’ means several years, the more likely diagnosis would be T2DM or, less likely, MODY.
• Evidence of autoantibodies such as GAD (glutamic acid decarboxylase), anti-insulin antibodies, anti-islet antibodies, insulin antibodies and zinc transporter 8 antibodies would be confirmatory of T1DM.
• It should be noted, however, that low-level autoantibodies may occur in T2DM and autoantibodies may be absent in 5–10% of individuals with T1bDM.
• Estimations of insulin or C-peptide are unhelpful as the presence of these fails to differentiate between failing but functioning pancreatic beta cells in T2DM or T1DM (the honeymoon phase of T1DM). MODY can be diagnosed on genetic testing but the testing is not widely available and would generally have to be privately funded at significant personal cost. If the diagnosis remains unclear, referral to a specialist may be required to confirm the diagnosis.

Question 23

3. T2DM and non compliance

Answer 23

History

• clarify where patient is in diabetes trajectory
• BMI
• current medication
• assess understanding of diabetes and their health
• discuss rationale for lifestyle modification and adherance to medications

Question 24

3. T2DM risk assessment

Answer 24

Inx

• HbA1c and fastihng glucose
• Lipid profile
• EUC
• LFT

Assesses

• glycaemic control
• cardio-metabolic risk and
• adherance to medications
• can cross check prescriptions and expected use of medications to assess adherance
• referral to diabetes educator

Behavioural change

• the five ‘A’s (Ask, Assess, Advise, Assist and Arrange) motivational interviewing to progress Sabina along the trans-theoretical model of change from pre-contemplation to contemplation and eventually to taking appropriate action
• formulation of goals such as SMART goals (specific, measurable, attractive, realistic and time framed).
• Consideration should be given to referral to a psychologist skilled in areas of motivational interviewing and goal setting. Consideration should also be given to screening the patient for depression with the Depression Anxiety Stress Scale, and for diabetes distress with the Problem Areas in Diabetes tools

Question 25

4. Peripheral swelling DDx

Answer 25

Possible causes of swelling include:

• trauma
• cellulitis
• deep vein thrombosis (DVT)
• acute gout
• rupture of a Baker’s cyst
• inflammatory arthritis
• Charcot’s neuroarthropathy.

Question 26

4. Peripheral swelling examination

Answer 26

• Identify areas of deep pain by palpation of both limbs. This shouldindicate the extent of the swelling and involvement of heat, pain and erythema of structures of the digits, mid foot, ankle and calf, and behind the knee.
• Check posterior tibial and dorsalis pedal pulses.
• Use a standard tuning fork to sense vibratory perception to the level of tibial tuberosity, and a 10 g monofilament to assess the presence of protective sensation to the level of the tibial tuberosity indicating peripheral neuropathy in both lower limbs. Peripheral sensory neuropathy often renders a personal history concerning antecedent trauma as unreliable.
• Examine feet to check for any breaches in skin integrity, tinea pedis, or possible portals for skin infection. Warmth in the foot indicates increased perfusion, inflammation and possibly cellulitis.
• Check random blood sugar levels, temperature, blood pressure, and ascertain if there is any groin pain, which may indicate infection.
• Check for evidence of varicose veins and hemosiderin deposits in both lower limbs.
• Assess whether walking causes any leg fatigue or shortness of breath.

Physical examination findings,

• warmth in foot, indicate that he may have cellulitis, ? secondary to tinea pedis (in the case).
• However, there was also evidence of peripheral neuropathy.
• Charcot’s neuroarthropathy (vibration absent) must be considered in a patient with diabetes and no pain.

Question 27

4. T2DM Charcot’s Neuroarthropathy

Answer 27

Typical clinical findings include

• a markedly swollen,
• warm and,
• often, erythematous foot with
• only mild-to-modest pain or discomfort.

Acute local inflammation is often the earliest sign of underlying bone and joint injury.

DVT should be investigated with ultrasonography. There is most often a temperature differential between the two feet. The affected population typically has well preserved or even exaggerated arterial blood flow in the foot.

Pedal pulses are characteristically bounding unless obscured by concurrent oedema.

Any trauma is often seen as trivial in light of no pain symptoms.

Question 28

4. T2DM Peripheral swelling Inx

Answer 28

Radiography

• In the absence of pain or recall of trauma, baseline bilateral weight-bearing radiographs (plain X-rays) should be obtained to identify morphology and bone architecture. These images may highlight the presence of arterial calcification (arteriosclerosis) of the posterior tibial and/or the dorsalis pedis arteries. Radiographs are also imperative in determining if there are any fractures, joint subluxation, dislocations and osteopenia. However, a negative radiograph should be repeated if the signs and symptoms continue. Bone changes may not be present until there is 30% pathology evident. Gout is not likely to be evident on radiographs for at least 12 months. Osteomyelitis may be evident in the presence of local infection or ulceration. Narrowing of joint spaces indicates osteoarthritis, whereas significant joint space effusion indicates inflammatory arthritis. The presence of joint effusion, dislocation, subluxations and osteopenia may indicate Charcot’s neuroarthropathy.

Single-photon emission computed tomography (SPECT)

• SPECT, which combines metabolic imaging with anatomical information, can provide valuable information in cases where there are very few of the classically described changes secondary to an occult injury and poorly defined symptoms.

Magnetic resonance imaging (MRI)

• This is often the gold standard for many conditions but waiting times can reduce immediate access unless privately sought.

Ultrasonography

• An ultrasound of the lower limb can identify any DVT or a ruptured Baker’s cyst in the leg.
• Early diagnosis using the above imaging methods and referral to a high-risk foot clinic enables early treatment for the management of Charcot’s neuroarthropathy before deformity occurs. Deformity places the foot at increased risk for ulceration.

Laboratory tests

• Blood tests, including a full blood evaluation, should be ordered to determine serum uric acid levels (to check for gout), C-reactive protein and erythrocyte sedimentary rate to check for inflammatory arthritis, blood glucose levels and vitamin D levels. Low vitamin D has been found in people with diabetes and Charcot’s neuroarthropathy where there is evidence of osteopaenia or related to reduced renal function. Kidney function should also be assessed.

Question 29

4. Charcot’s Neuroarthropathy pathophysiology/Xray

Answer 29

The X-ray shows a plantar flexion of the rear foot and dorsal dislocation of the forefoot.

There is evidence of soft tissue oedema and arterial calcification.

These results confirm the diagnosis of acute Charcot’s neuroarthropathy.

Pathophysiology

The active phase pathogenesis of Charcot’s neuroarthropathy results in:

• elevated pO2 levels
• increased blood volume, swelling and temperature
• synovium proliferation
• bone resorption
• loss of trabecular structure
• cartilaginous debris
• osseous debris.

An occult injury initiates uncontrolled inflammation and release
of proinflammatory cytokines tumour necrosis factor-alpha and interleukin-1 beta.

This results in an increased expression of the polypeptide RANKL (receptor activator of nuclear factor kappa ligand), which stimulates the maturation of osteoclasts and the production of osteoprotegerin from osteoblasts.

Factors that contribute to Charcot’s neuroarthropathy include:

• diabetes duration
• ankle equinus: opposing force of the rear foot and fore foot leads to bone collapse of the midfoot commonly
• retinopathy: increased risk of trauma
• plantar fascia tears/ruptures: midfoot subluxations and dislocation
• nephropathy: reduced vitamin D
• trauma:
  
  • insidious forefoot fractures in type 1 diabetes mellitus (T1DM) and
  • midfoot subluxation/dislocation in T2DM
• previous foot surgery (including amputation) or transplant surgery.

Risk factors for Charcot’s neuroarthropathy include:

• poor glycaemic control
• increased serum concentrates of osteoprotegerin
• increased osteopaenia and arteriovenous shunting
• trauma
• arterial calcification
• renal disease.

Eating disorders can result in poor glycaemic control, and malnutrition and osteopaenia.

Vitamin D deficiency can result in reduced bone mineral density.

Question 30

4. T2DM Charchot’s Neuroarthropathy Rx

Answer 30

Acute Charcot’s neuroarthropathy is considered an emergency and should prompt immediate referral to a dedicated multidisciplinary high-risk foot service.

Early management aims to eliminate further trauma.

The aim of treatment is to prevent progression of the pathological process.

Complications that may arise from inadequate or delayed treatment include foot deformity, chronic ulceration and infection (including osteomyelitis).

Offloading is widely accepted as the most effective treatment for patients with acute Charcot’s neuroarthropathy. Offloading with a total contact cast has been shown to protect the foot, and to reduce foot temperature and bone activity. However, depending on the patient’s circumstances or level of deformity, other offloading such as non- removable negative walkers, controlled ankle movement walkers, or Charcot restraint orthotic walkers, may be fitted.

Management should also consider protection of the contralateral foot.

[Case]

Consider treatment for his fungal infection and cellulits. Amoxycillin and clavulanate 875/125 mg 12 hourly are recommended for mild cellulitis; cephalexin monohydrate 500 mg 6 hourly can be used for those with penicillin allergy.

Martin should be instructed on the use of antifungal agents to treat his current infection. Attention to the use of socks with all footwear, including slippers, will also be helpful in preventing cross-infections.

Martin should also be advised about the need for tighter control of his HbA1c levels.

This will require a review of diet and lifestyle factors and may warrant follow-up with a dietitian and diabetes educator.

Review of his diabetes medication should be implemented.

Vitamin D supplementation could also be considered, given his low levels.

Follow up Management Charcot’s Neuroarthropathy

The Charcot foot in diabetes consensus report has identified
various possible aetiologies, but no randomised controlled trials
have been conducted to date to identify effective treatments. Thus, management and treatment of Charcot foot are based on professional opinion. There is no accepted measure to define the transition from acute to quiescent Charcot’s neuroarthropathy other than follow-up examinations, assessing equalisation of the temperature discrimination between the near lower limbs, and X-rays

Question 31

5. GDM Dx

Answer 31

Current guidelines recommend that pregnant women should have a 75-g GTT at 26–28 weeks gestation to test for GDM.

A normal pregnancy 75 g GTT has

• a fasting plama glucose <5.1 mmol/L,
• a 1-hour value <10 mmol/L and a
• 2-hour value <8.5 mmol/L.*

GDM is currently a controversial area. The diagnostic criteria have changed and the World Health Organization (WHO) has accepted the new criteria.

In some but not all areas, the new criteria will lead to an increase in the number of patients diagnosed in what is already a common problem. The net result of this attention to GDM will almost certainly be a change in the way patients are managed. The screening approach, diagnostic criteria and treatment regimens will be decided locally and run on formal protocols. The role of the GP in share-care protocols is likely to be increased but remain somewhat limited.

Question 32

5. GDM Aetiology

Answer 32

Aetiology

Normal pregnancy induces insulin resistance. All pregnant women are insulin resistant.4 In women with pigmented skin, acanthosis nigricans, a marker of insulin resistance, may be present.5

Women are often relieved when the aetiology of this abnormality (often thought by patient or her partner to be a dirty neck) is explained.

In a pregnancy without GDM, the insulin resistance is overcome
by increased insulin secretion. In most women who develop GDM,
the compensatory increase in insulin secretion does not occur or
is inadequate, resulting in hyperglycaemia. This failure of insulin secretion to increase is usually genetic. It is commonly associated with a family history of type 2 diabetes mellitus (T2DM), which becomes more apparent with subsequent pregnancies as the patient’s parents and grandparents age and develop T2DM. The insulin resistance can result in GDM in those with a genetic predisposition
for T2DM.

This relatively simple explanation helps to alleviate the anxiety and/or guilt felt by a woman who might feel she is somehow responsible for her diabetes.

Question 33

5. GDM Rx

Answer 33

Benefits of treating GDM

–> reduce risks assoicated with GDM to the level of normal pregnancy

DIet

The general public is aware that treatment of diabetes consists of diet and exercise, and it is understood that the diet is one of restriction. However, restriction of foods is inappropriate and potentially harmful in pregnancy, as the diet of a pregnant woman must consist of an appropriate intake of food to ensure normal fetal growth.

This requires adequate carbohydrate intake, although the exact amount during pregnancy is not evidence-based (ie no level 1, 2 or 3 evidence).

Current Australian dietary recommendations for pregnant women include at least 175 g of carbohydrates per day, to be distributed into three meals and three snacks throughout the day. The dietary recommendations also include information for foods with low glycaemic index.

Exercise recommendations will depend on the woman’s previous exercise regimen. At a minimum, 5–10 minutes of activity around the house or with a short walk after each meal should be encouraged. This assumes there are no obstetric contraindications to walking.

The Institute of Medicine (IOM)11 provides recommendations for total weight gain and rates of weight gain during pregnancy. Patients can be advised that the dietitian will provide information for appropriate weight gain, based on the IOM guidelines, for the remainder of her pregnancy.

The two large randomised controlled trials cited above used treatment targets of <5.3 and 5.5 mmol/L for fasting glucose levels, and <6.7 and 7 mmol/L for 2 hour values.

Tighter targets are recommended by some on the basis of the range of plasma glucose excursions in women without GDM and having a uncomplicated pregnancy. However, longer term benefits of these targets have not been established.

Question 34

5. BGL and Glucometers

Answer 34

Almost all the glucometers used in Australia have a bias to read high. This is particularly important as the threshold for initiating insulin therapy to correct fasting hyperglycaemia is low.

If the home-monitored glucose level is higher than the formal fasting glucose at the time of the recent GTT, this tends to confirm the glucometer bias.

However, if concern persists, an urgent formal fasting plasma glucose, compared with a home-monitored glucose measurement and collected at the same time, will probably provide evidence of the bias. This can then be taken into consideration in considering the fasting results.

Question 35

5. GDM and future risks T2DM

Answer 35

Women with a history of GDM are at risk of a recurrent abnormality of glucose tolerance in any subsequent pregnancy, as well as T2DM (including in a subsequent pregnancy) and cardiovascular disease.

The risk of cardiovascular disease relates predominantly, but not exclusively, to the development of diabetes. Very good long-term follow-up data suggest that the average risk of developing T2DM is 1–1.5% per year for at least the next 18 years and almost certainly longer.17 The risk in an individual woman can be stratified according to the severity of GDM. Markers of severity include early diagnosis, higher glucose levels during the GTT and the need for insulin therapy.

The Diabetes Prevention Program (DPP) has shown that lifestyle modification can reduce the risk of progression to type 2 diabetes by 58%, at least over 5 years. Women with a history of GDM would seem an ideal population to benefit from prevention strategies.

They also require follow-up to detect the development of glucose intolerance prior to the next pregnancy.

Metformin was also used in the DPP and was successful in preventing diabetes by 31%. Mangahas et al have summarised the American Diabetes Association recommendations for the use of metformin and provide a table listing doses. However, a recent article in the British Medical Journal notes that, in a post hoc analysis of the DPP, metformin was only effective in the upper quartile of the population at risk of developing T2DM, which, essentially, includes those with prediabetes (impaired fasting glucose or impaired glucose tolerance). This suggests that metformin should not be used in women at lower risk (ie those with normal glucose tolerance following a pregnancy complicated by GDM).

Question 36

5. GDM follow up post pregnancy

Answer 36

The follow-up of women with GDM is an area that is evolving at present. The follow-up will depend in part on whether the woman plans to have future pregnancy or to prevent further pregnancies. For the latter option, advising about suitable methods of contraception should be considered.

All women are advised to have a repeat GTT 6–12 weeks postpartum. Most, but not all, women will have returned to normal glucose tolerance by this stage. The proportion with normal glucose tolerance is higher at 12 weeks than at 6 weeks.

The National Gestational Diabetes Register, which is administered within the National Diabetes Services Scheme (NDSS), is designed as a recall system to notify the woman and her doctor of the need for appropriate follow-up after pregnancy complicated by GDM. One weakness in this system is that women often change their GP postpartum for a variety of reasons.

A logical follow-up plan would be for women to receive lifestyle

advice following their postpartum GTT, with the possibility of metformin treatment for those found to have pre-diabetes. Annual follow-up† could be with a fasting plasma glucose and glycated haemoglobin HbA1c, although a formal oral glucose tolerance test (OGTT) should be arranged if a pregnancy is planned. The thresholds for action with this follow-up program have not yet been defined, but trends in the patient’s fasting plasma glucose and HbA1c will be important. The Australian Diabetes Society has adopted the consensus HbA1c value of 48 mmol/mol (6.5%) to diagnose diabetes, as recommended by the WHO. It has not adopted HbA1c values of 5.7–6.4% to indicate a prediabetes equivalent.

A comment about possible discrepancies between the OGTT and the HbA1c is necessary, as this seems to cause confusion. The WHO document explicitly states that an HbA1c value of <6.5% does not exclude the possibility of diabetes diagnosed by a GTT.

This follow-up program should be integrated with an appropriate assessment of absolute cardiovascular risk and attention to the cardiovascular risk factors if required.

Women with a history of GDM should be offered lifestyle advice to minimise their risk of progression to T2DM. This advice should be based on the advice from the DPP,26 which recommends that women who are overweight or obese should lose 5% of their body weight, should be active for 30 minutes each day and consume a diet containing <30% fat, <10% saturated fat and >15 g of fibre per 1000 kcal consumed.27 Most people would need to see a dietitian to understand this diet.

Other cardiovascular risk factors should be addressed if required.

Metformin therapy has been shown to be successful in preventing, or at least delaying, T2DM for up to 10 years in women with either impaired fasting glucose or impaired glucose tolerance.