A detailed review of the management of diabetes was published as SIGN Guideline 116, which is available at SIGN.
Diabetes and cardiovascular disease (CVD) develop in concert with metabolic abnormalities mirroring and causing changes in vasculature. More than half the mortality and the vast amount of morbidity in people with diabetes is related to CVD; with rates that are between two to five times higher than in the non-diabetic population. Importantly, women with diabetes have a higher relative risk than men, and an increased mortality is evident in all age groups, especially young people with type 1 diabetes, and is exacerbated by social deprivation.
Management of cardiovascular risk factors in diabetes assumes that each individual has been offered the appropriate life style advice to improve cardiovascular risk factors including;
- All individuals should be advised to stop smoking
- All individuals should be encouraged to increase their level of physical activity to achieve current physical activity recommendations
- Obese adults with diabetes should be offered individualised interventions (lifestyle, pharmacological or surgical) to encourage weight loss. Options include simple caloric restriction, reducing fat intake, consumption of carbohydrates with low rather than high glycaemic index, and restricting total daily carbohydrate.
- Dietary fibre intake should be >40g/day (or >20g/1000Kcal/day) about half of which should be soluble. Daily consumption of ≥5 servings of fibre-rich vegetables or fruit and ≥4 of legumes per week can provide minimum requirements. Cereal foods should be whole grain and high in fibre.
- Alcohol intake should be within the range recommended for people without diabetes
- Coffee drinking: >4 cups/day is associated with a lower risk if CVD in people with T2D, but boiled coffee without filtering raises LDL-C and should be avoided.
Antiplatelet Therapy
- Low-dose aspirin is not recommended for primary prevention of vascular disease in patients with diabetes
- Aspirin (75 – 160 mg mg daily) should be given routinely and continued long-term in patients with diabetes and coronary artery disease.
- Clopidogrel is recommended as an alternative antiplatelet therapy in case of aspirin intolerance.
- A P2Y12 receptor blocker is recommended in patients with DM and ACS for 1 year and in those subjected to PCI (duration depending on stent type). In patients with PCI for ACS preferably prasugrel or ticagrelor should be given.
Lipids
- The characteristic dyslipidaemia of Type 2 diabetes is the combination of elevated triglycerides, low HDL and small dense LDL.
- In Type 1 patients, normal or high HDL-cholesterol concentrations are often seen. However an elevated HDL-cholesterol is not associated with the same cardio-protective effect as in non-diabetic individuals.
- Triglyceride concentrations are elevated by poor diabetic control. Triglycerides may normalise with good diabetic control, attention to diet and increasing exercise. Otherwise drug treatment may be indicated.
- In type 2 diabetes these is a comprehensive and consistent data on the mechanism of action and efficacy of statins in the prevention of CVD events. The benefits of statin therapy in lowering LDL-C and reducing CVD events are seen in all subgroup analyses of major RCTs.
- In type 1 diabetes, no trial data exist on the efficacy of statin therapy in a younger population (
Screening for Dyslipidaemia
- Check annually as part of the “Annual Review”.
- Total cholesterol, HDL-cholesterol and triglycerides should be requested. For ease, non-fasting estimation is usually adequate.
Management of Lipids: Primary Prevention
- Statin therapy is recommended in all patients with Type 1 or Type 2 Diabetes aged>40 years.
- Treatment, initially with atorvastatin 20mg (in preference to Simvastatin 40mg), is recommended for primary prevention regardless of baseline cholesterol.
- Reports from major RCTs demonstrate that statins are safe and well-tolerated. The frequency of adverse events, except for muscle symptoms, is rare. In the majority of cases of myopathy or rhabdomyolysis there are drug interactions with a higher-than-standard dose of statin.
- For those individuals reporting mild intolerance with Simvastatin or Atorvastatin despite a reduction in dose (e.g myalgia without a rise in CK), then an alternate lipid soluble statin (e.g. pravastatin) may be tried.
- Cholesterol Testing: Serum Cholesterol should be tested prior to commencement of a statin and then repeated three months after starting, to ensure a 40% reduction in non-HDLCholesterol has been achieved. Thereafter there is no need for further testing. Ongoing routine annual cholesterol testing is NOT required.
Management of Lipids: Secondary Prevention
- Higher doseStatin therapy (e.g. atorvastatin 80 mg) is recommended in patients with T1DM and T2DM at very high-risk (i.e. if combined with documented CVD, severe CKD or with one or more CV risk factors and/or target organ damage) with a cholesterol target of 4.0 mmol/L or at least ≥50% LDL-C reduction if this target goal cannot be reached.
- Intensification of statin therapy should be considered before combination therapy with addition of ezetemibe.
- The use of drugs that increase HDL-C to prevent CVD in T2DM is not recommended.
Note:
Patients who are intolerant of atorvastatin and simvastatin should be offered an alternative agent.
In patients with persistently raised Triglyceride concentrations, checkfasting sample (Total-cholesterol, HDL-cholesterol & Triglycerides), optimise glycaemic control, and exclude co-existing pathology e.g. alcohol-related liver disease. If TG consistently >4.5 mmol/l fenofibrate may be prescribed.
** October 2012 Updated advice for patients with diabetes on simvastatin: drug interactions and contraindications
The Medicines and Healthcare products Regulatory Agency (MHRA) has issued advice via Drug Safety Update, Volume 6, Issue 1, August2012 on prescribing of simvastatin with some other medicines associated with an increased risk of myopathy and/or rhabdomyolysis. Key points to note in the management of patients with diabetes are that:
- Simvastatin is now contraindicated with ciclosporin, danazol and gemfibrozil.
- The maximum recommended dose for simvastatin in conjunction with amlodipine or diltiazem is now 20mg daily.
- There is an increased risk of myopathy associated with high dose (80mg) simvastatin. Prescribers are reminded that simvastatin 80mg is non-formulary and should not be routinely used.
The NHS Tayside Guidance for patients with diabetes on a combination of simvastatin 40mg and amlodipine, diltiazem, verapamil or amiodarone is that such patients should be reviewed with consideration given to changing to atorvastatin 20mg.
This advice differs slightly from the generic guidance given in Tayside Prescriber Issue 125 – September 2012, because:
- Patients with diabetes are at significantly heightened risk of cardiovascular disease
- Atorvastatin 20mg has the closest dose equivalence to simvastatin 40mg
Hypertension
Recent evidence suggests that aggressive lowering of BP in the majority of patients with diabetes in older age groups is not as beneficial as previously thought. In view of this we have revised our local guidance as follows:
- In patients with type 2 diabetes aged >55 years achieving a BP in the range of 130-140/80-85 is sufficient. This target is also valid for many patients with type 1 diabetes aged >55 years.
- If there is associated diabetic nephropathy, guidance on appropriate BP targets will be communicated by the specialist service on an individual basis, as tighter BP control may be required depending on disease progression.
- In frail elderly patients with both types of diabetes, higher targets than this may be appropriate and so an individual assessment is needed. In general a range of SBP 130-160mmHg strikes a balance between favourable cardiovascular outcomes and reduced hospitalisations.
- In younger patients (ie aged < 55 years) with both types of diabetes, more aggressive blood pressure targets ie <130/80mmHg may still be appropriate, especially if there is either micro- or macroalbuminuria present. Such patients should be referred to specialist services ie the hospital-based Diabetes Clinic or Diabetes-Renal Clinic respectively, if they are not attending at present.
- Patients with micro- or macroalbuminuria should usually receive an ACEI or ARB, unless other contraindications exist. However dual blockade using ACEI and ARB in combination is not recommended routinely except under the direction of the specialist diabetes or renal services. The decision to use this drug combination should be reviewed at least annually and patients should receive advice about how to manage intercurrent dehydrating illness to minimise the risks of hospitalisation due to acute kidney injury
- Hypertension in people with diabetes should be treated with lifestyle modification (including salt restriction and weight loss) and drug therapy.
- Target diastolic blood pressure in most people with diabetes is <=80-85mmHg.
- Target systolic blood pressure in people with diabetes is between 130-140 mmHg.
Management
1. Confirm the Diagnosis
- If hypertension is severe (DBP >110mmHg) and there is evidence of Grade III-IV retinopathy, start anti-hypertensive therapy immediately.
- If hypertension is sustained or severe (DBP >110mmHg), there is target organ damage (retinopathy, nephropathy, LVH) present, or there are multiple cardiovascular factors, institute therapy within 1 - 2 weeks.
- In uncomplicated patients (no target organ damage, BP <150/90mmHg), delay pharmacological intervention and reassess after 12 weeks of lifestyle measures.
- All patients with Hypertension should receive lifestyle advice
- British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. Br Med J 2004; 328; 634-640. Free fulltext at British Hypertension Society.
2. Treatment
- The British Hypertension Society A/CD alogorithm has been accepted as a reasonable approach of defining combination therapy.
- However, on balance current evidence appears to support ACE-I (or ARB) use in patients with T2D at particularly high risk if CVD and/or who have microalbuminuria.
- In addition, RCTs such as (ACCOMPLISH) indicated that calcium channel antagonists (amlodipine) was superior to hydrochlorothiazide in combination with ACE-I in T2D.
- Dual blockade of RAAS with ACEI and ARB has not shown any evidence of additional benefit and should not be prescribed unless specifically instructed by the specialist team.
- Beta-blockers and alpha-blockers should not usually be used in the initial management of blood pressure in patients with diabetes.
- Follow the A/CD algorithm unless there is a specific indication for a different agent (e.g. ACE in individuals
- Expect most patients to require more than one agent.
- Patients with diabetes tend to have blood pressure through the night and if so indicated by ABPM prescription of anti-hypertensives at bedtime should be considered.
- Summary Recommendation for antihypertensive therapy in diabetes:
- ACEI/ARB
- CCB
- Thiazide
- Other: alpha- /beta-blocker, spironolactone etc
3. Treatment in presence of Microalbuminuria or Proteinuria
- Anti-hypertensive therapy reduces urinary albumin excretion and delays progressive loss of glomerular function. The greatest renal benefits have been observed in trials with ACE inhibitors in type 1 diabetes and ARBs in type 2 diabetes.
- Other classes of drugs may be added as required to achieve target BP.
- Short acting dihydropyridine calcium channel blockers (e.g. nifedipine), are not as effective in limiting protein excretion and should be avoided.
4. Indications for Hospital Referral
- Evidence of nephropathy (persistent microalbuminuria, overt proteinuria or falling eGFR (see Screening and Management of Kidney complications and Guidelines for the Combined Diabetes Renal Clinic)
- Presence of cardiac failure or retinopathy.
- Clinical suspicion of renovascular disease or other secondary cause of hypertension.
- BP difficult to control despite prescription of three agents.
- Rise in serum creatinine (>20% from baseline) after ACE inhibitor or ARB started.
- If in doubt, discuss with or refer to secondary care physician.
5. Use of ACE Inhibitors/Angiotensin Receptor Blockers: safety
- Consider the presence of renal artery stenosis in patients with type 2 diabetes.
- Suspect underlying renovascular disease if widespread atheroma present (e.g. carotid or abdominal bruits, aortic aneurysm, absent peripheral pulses).
- Before starting ACE inhibitor or ARB, measure baseline urea, creatinine and electrolytes.
- Repeat after 4 - 7 days, again after 1 month and thereafter annually.
- Stop drug if significant hypotension or a significant rise in creatinine occurs (>20% from baseline).
- ARBs should NOT usually be used in combination with ACE inhibitor therapy except in certain specialist settings (e.g. renal or renal diabetes clinic).
- Renin inhibitors may be suitable for patients intolerant of ACE inhibitors and ARBs, but should not be used in combination therapy with ACE inhibitors and ARBs (monitor potassium for hyperkalaemia).
N.B Ambulatory Blood Pressure Monitoring (ABPM)
BHS guidelines now recommend ABPM is used to confirm the diagnosis of primary hypertension in individuals with clinic BP >140/90 mmHg.
When ABPM is used, mean daytime BP and not over the whole 24 hours should be used to make treatment decisions
BP measured by ABPM is systematically lower than surgery or clinic measurements in hypertension patients; the average difference in techniques is 12/7 mmHg
Useful Links
Management of Diabetes and Acute Coronary Syndrome – see SIGN 116
Management of Diabetes and Heart Failure – see SIGN 116
Management of Acute Stroke – see SIGN 118
Management of Peripheral Arterial Disease - see SIGN 89