What is best practice in managing T2DM and CVD? Expert commentary on management of modifiable risk factors, treatment options and targets are emphasised in clinical cases demonstrating the progressive nature of both conditions
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Case study 1:
First visit: A case for lifestyle modification in pre-diabetes
Patient: Mrs A D, aged 52 years
- History of fatigue and generally not feeling herself
- Menopausal for two years with significant weight gain over a period of time. BMI 34kg/m2
- No known allergies
- Patient’s father had T2DM at the age of 65
- Patient presents with a prior diagnosis of hypertension, hypothyroidism and hyperlipidaemia. She is on treatment with an ACE inhibitor/diuretic combination, levothyroxine and statin therapy, respectively
- No history of renal disease and no CV disease
- Comfortable at rest, becomes short of breath while undressing for the examination.
- Resting pulse rate is 98bpm, sinus rhythm
- Blood pressure: 148/96mmHg
- + oedema of legs
- Grade 1 varicose veins
- Height 1.65m
- Weight 102kg
- Waist circumference 106cm
- No thyromegaly
- No gallop audible, borderline LV hypertrophy on ECG, ECG confirms pulse rate of 98bpm
- Abdominal examination indicates no hepatosplenomegaly; urine test positive for microalbuminuria: 2+ on MICRAL test
- Urea = 9.2mmol/l
- Creatinine = 136mmol/l
- eGFR = 65ml/min/1.73m2
- TSH = 2.4mIU/l
- Normal FBC
- LDLc = 3.6mmol/l
- TG = 4.7mmol/l
- HDLc = 0.8mmol/l
- Uric acid = 3.4mg/dl
- HbA1c: not measured
1. Which of the following results is abnormal for this middle-aged woman?
2. What would the ideal BMI for this patient be?
3. What would the ideal blood pressure and pulse rate for this patient be?
View Expert Comment »
For a middle-aged woman in menopause with multiple risk factors for CV disease and a risk of impaired glucose tolerance, the work-up needs to examine the cause of her fatigue and poor effort tolerance, apart from the obesity. She may have obstructive sleep apnoea and her spouse/partner needs to be brought into the discussion to determine whether there is snoring or any apnoeic episodes at night.
Several metabolic factors will need improvement and stabilisation:1
- Uncontrolled blood pressure and microalbuminuria with impaired renal function
- The hyperlipidaemia with inadequate control on her present statin therapy. Simvastatin 20mg should be increased to atorvastatin 20mg daily and then repeat measurements should be done after 3/12.
- A high BMI with increased waist circumference. Ideally, the BMI for this patient should be 24-26 kg/m2 with a waist circumference of 84cm.
- Investigate for possible hepatic steatosis. Elevated liver enzymes and ultrasound features of fatty infiltration may give an indication.
- Patient requires a fasting blood glucose (FBG) ± oral glucose tolerance test, or HbA1c test.
Second visit: Now, three months later, she is newly diagnosed with T2DM
The patient underwent new blood tests, with a FBG test revealing a level of 9.6mmol/l with no other reason for the elevation: for example, recent surgery, medications such as steroids or recent trauma. In view of her multiple risk factors, as well as her being menopausal, she is at significant risk for CV disease.
The first gold standard choice of treatment for T2DM is metformin, initially at a dose of 500mg bd, to avoid gastrointestinal side effects. The dose should be slowly increased to 850mg bd after seven days and 1g bd if not controlled to a FBG level of <4-6mmol/l. Alternatively, an extended-release metformin formulation can be used to avoid the gastrointestinal side effects. Moreover, this formulation can be increased to a dose of 2g daily. Optimal dose titration of metformin is very important, as early glucose control reduces adverse diabetes outcomes.2, 3
As she has renal dysfunction, metformin can be combined with a sulphonylurea, a DPP4 inhibitor, or a SGLT-2 inhibitor as oral therapy. Of these, the SGLT-2 inhibitor would have compelling evidence to be added, as it does not cause weight gain. In fact, it may cause weight loss. Furthermore, SGLT-2 inhibitors improve or protect against deterioration of renal function, and prevent cardiac failure.
In addition, injectable therapies would include insulin or a GLP-1 RA; liraglutide has compelling evidence in this situation, as it is cardioprotective and improves renal outcomes.4
4. The ideal combination therapy for this patient includes the addition of:
5. This patient requires therapy that is weight neutral or causes weight loss and no hypoglycaemia. Choose the best regimen to achieve this with metformin:
6. In order to evaluate her cardiac risk, what test will she need to undergo?
7. Which of the following treatments is not needed for this patient?
In this typical patient, all aspects of her cardiovascular risk must be addressed as well as her self-image. Motivation should be provided to improve her physical well-being by promoting an exercise programme she can follow, as well as dietary advice to reduce carbohydrate intake, especially of high glycaemic index foods.
She will require aggressive therapy to control her blood pressure to a target level of <130/85mmHg using an ACE inhibitor/CCB combination ± indapamide. If this target is still not achieved, and her pulse rate is elevated, a selective β-blocker like bisoprolol can be added to reduce the pulse rate to <72bpm.
She will require a target LDLc of < 2.5mmol/l initially and if CV disease is found, LDLc < 1.8mmol/l, TG < 1.7mmol/l, and HDLc > 1.2mmol/l. Her ideal HbA1c level is < 7% without causing hypoglycaemia, with a FBG < 6mmol/l and a two-hour postprandial level of <7.8mmol/l.
This patient can really improve her quality of life, as well as her life expectancy, by addressing these risk factors.
Case study 2:
A T2DM patient with atherosclerotic CV disease, chronic kidney disease or heart failure, who presents at a three-monthly visit with poor glycaemic control while receiving metformin and gliclazide MR
Patient: Mr G K, aged 64 years
- Presents with a history of T2DM, treated for the last eight years on metformin 1g bd and gliclazide MR 60mg bd
- HbA1c level is 8.4% on this treatment
- Heart failure symptoms with LV dysfunction present
- Ejection fraction of 35%
- NYHA class 3 symptoms on diuretics, ARB, β-blocker (bisoprolol), statin therapy and aspirin
- Blood pressure 102/56mmHg
- Resting pulse rate of 62bpm, with atrial fibrillation
- LDLc 1.8mmol/l
- HDLc 1.1mmol/l
- TG 1.6mmol/l
- Retinopathy currently controlled following bevacizumab injections
- Impaired renal function with an eGFR: 44ml/min/1.73m2
- Normal Na+ and K+ levels
What do you do now?
8. The additional choice of diabetic medication for this patient should include:
9. Choose the INCORRECT answer: As the heart failure may be associated with worsening renal function, the patient should avoid the following:
10. As the patient will require regular follow-up, which of the following blood tests must be done at least every six months?
11. The patient visits the rooms and now presents with worsening fatigue and dizziness. What should be considered?
View Expert Comment »
The patient with diabetes and ischaemic heart disease must be seen regularly and all comorbidities must be considered and managed carefully. Diabetic control must be set at a level with a low risk of hypoglycaemia, as the patient will be at increased risk of arrhythmias. It would be better to aim for a HbA1c of 7.5-8%, using medication with a low hypoglycaemia risk, such as a DPP4 inhibitor, SGLT-2 inhibitor or GLP-1 RA.
Heart failure may require an ACE inhibitor/ARB combined with prudent diuretic use, such as spironolactone with careful K+ monitoring and a β-blocker. A target pulse rate of < 72bpm should ideally be achieved.
Lipid therapy should aim for a target LDLc of < 1.8mmol/l in this setting. Again, a SGLT-2 inhibitor would be an ideal add-on therapy to metformin, provided the eGFR is not <30ml/min/1.73m2.
At visit nine months later, after telephonic communication on progress – adjustment of therapy is required.
12. Once the patient is on metformin/ DPP4 inhibitor, combined with SGLT-2 inhibitor, and HbA1c is still not controlled, you can do the following:
View Expert Comment »
*Additional options will be available soon with the launch of dulaglutide. Dulaglutide is a GLP-1 RA with a once-weekly dosing regimen. Insulin degludec/liraglutide is an insulin/GLP-1 RA combination.
13. If the patient develops postural hypotension, it could be due to?
14. Choose the INCORRECT answer: The ideal HbA1c level in this patient will be influenced by:
15. Choose the INCORRECT answer: Insulin choices for the complex patient may include:
View Expert Comment »
Metformin should be continued in a patient with CV disease and uncontrolled T2DM. The addition of a SGLT-2 inhibitor or GLP-1 RA gives significant benefits in this type of patient as well as improving or preserving renal function. These agents improve cardiac function, improve LV function, protect renal function and at the same time improve glycaemic control safely.
Insulin must be used with care and careful consideration as to the best insulin preparation available; for example, improved long-acting insulin formulations such as degludec and glargine 300U/ml, or a GLP-1 RA/insulin combination, such as degludec and liraglutide. Pre-mixed insulin formulations have also improved, with the advent of IDegAsp, and these agents should be considered preferred alternatives in complex patients where hypoglycaemia and weight gain must be avoided.5