In the UK, cardiovascular (CV) disease accounts for almost 198 000 deaths each year. Around half of these are caused by coronary heart disease (CHD) and over one-quarter by stroke. CHD itself is the most common single cause of death, with around one in five men and one in seven women dying from the disease (Allender et al, 2008).
Diabetes significantly increases the risk of CHD. Men with type 2 diabetes have a two- to four-fold greater annual risk, and women with type 2 diabetes have a three- to five-fold greater annual risk, than those without the condition (Allender et al, 2008). The INTERHEART case-control study estimated that around 9% of heart attacks in Central and Eastern Europe, and 15% of heart attacks in Western Europe, are due to diagnosed diabetes (Yusef et al, 2004). Dyslipidaemia is an important CV risk factor in people with diabetes. Around 35% of heart attacks in Central and Eastern Europe, and 45% of heart attacks in Western Europe, are due to abnormal blood lipids, and people with abnormal lipids are at over three times the risk of having a heart attack than those with normal lipids (Yusef et al, 2004).
Although overall CV risk is determined by a number of factors, in the context of lipids it is principally determined by concentrations of low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol (inversely) and, to a lesser extent, triglyceride concentrations (British Cardiac Society [BCS] et al, 2005).
Cholesterol is an essential component of the cell’s external membrane and intracellular contents. The balance of the various lipid fractions and membrane proteins determines the integrity of the cell membrane. LDL provides cholesterol to the tissues but is only required at low levels, for example levels of <1 mmol/L are present in infants during their period of rapid growth. HDL is the reverse cholesterol transporter. It can carry cholesterol from cholesterol-satisfied cells back to the liver or supply to other lipoproteins.
Triglycerides are essential for the structural integrity of the cell and are the essential energy source for the body tissues. They are derived either from the diet or synthesized in the liver from other available metabolites such as carbohydrates. Once absorbed from the gut they are carried on chylomicrons to the peripheral tissues where they are hydrolysed for energy supply or stored in excess. The excess storage of triglycerides in the peripheral tissues, liver and abdomen leads to insulin resistance.
People with diabetes tend to have similar LDL-cholesterol levels, but higher triglyceride and lower HDL-cholesterol levels than people without the condition (Table 1). However, people with diabetes also tend to have a greater concentration of small, dense LDL particles, and this combination appears to be more atherogenic than non-diabetic dyslipidaemia (Taskinen, 2002; Moon and Kashyap, 2004). The excess risk of CV disease (CVD) in people with diabetes is attributed to the combination of this type of dyslipidaemia together with hyperglycaemia and high blood pressure (National Collaborating Centre for Chronic Conditions [NCCCC], 2008). The typical lipid profile results from a sedentary lifestyle combined with excess calorie intake and weight gain leading to insulin resistance. People of south Asian origin are more vulnerable to these changes.
A low level of HDL-cholesterol confers an additional risk of CVD irrespective of total cholesterol levels. A 12-year follow-up of the Framingham Heart Study showed that individuals with high HDL-cholesterol (in the 80th percentile) were at 50% less risk of CHD than those with low HDL-cholesterol (20th percentile) (Castelli et al, 1986).
While the term “hyperlipidaemia” is used to describe raised serum levels of one or more of total cholesterol, LDL-cholesterol, triglycerides or total cholesterol and triglycerides combined (combined hyperlipidaemia), the term “dyslipidaemia” also includes low levels of HDL-cholesterol (Gross and Reese, 2005).
Between 2003 and 2009, angina was the most common complication resulting in hospital admission in people with type 2 diabetes in England, and its prevalence increased steadily over this time period (NHS Information Centre, 2010).
Modifying cholesterol levels with diet, drugs or other means, reduces the risk of CVD (BCS et al, 2005).
Evidence for lipid-modifying drugs
Trials using statins, with non-fatal and fatal clinical events as endpoints, have provided the most compelling evidence for cholesterol lowering (Shepherd et al, 1995; Pedersen et al, 1998; Downs et al, 1998; Lewis et al, 1998; LIPID [Long-term Intervention with Pravastatin in Ischaemic Disease] Study Group, 1998). Subsequent trials have extended the evidence base for this drug class in people with diabetes (Heart Protection Study Collaborative Group, 2002; Colhoun et al, 2004; Shepherd et al, 2006).
The Cholesterol Treatment Trialists conducted a meta-analysis of 14 randomised trials of statins including data from over 90000 participants. They found that statin therapy safely reduced the 5-year risk of major coronary events, coronary revascularisation and stroke by about one-fifth per mmol/L reduction in LDL-cholesterol, irrespective of age, sex, blood pressure, pre-existing diabetes or history of previous vascular event. This meant that 48 fewer participants had major vascular events per 1000 among those with pre-existing CHD at baseline (95% confidence interval [CI], 39–57), compared with 25 per 1000 among those with no such history (95% CI, 19–31) (Baigent et al, 2005).
Several trials have reviewed the safety and efficacy of statins specifically in people with type 2 diabetes. The TNT (Treating to New Targets) study (Shepherd et al, 2006) involved 1501 participants with type 2 diabetes, CHD and LDL-cholesterol levels <130.0 mg/dL (<3.36 mmol/L), who were randomised to therapy with atorvastatin 10 mg or 80 mg per day. Follow-up continued for a median of 4.9 years. By study end, LDL-cholesterol levels were 98.6 mg/dL (2.55 mmol/L) with atorvastatin 10 mg versus 77.0 mg/dL (1.99 mmol/L) with atorvastatin 80 mg. Although the risk of a major CV event was significantly lower in those receiving the 80 mg dose, representing a 25% risk reduction in favour of the high-dose group (P>0.026), there were no differences between the groups in terms of treatment-related adverse events and persistent liver enzymes (Shepherd et al, 2006).
The URANUS (Use of Rosuvastatin Versus Atorvastatin in Type 2 Diabetes Mellitus; Berne et al, 2005) study compared the results of statin treatment for the reduction of LDL-cholesterol in people with type 2 diabetes and LDL-cholesterol levels ≥3.3 mmol/L. Treatment was titrated up from 10 mg/day to a maximum of rosuvastatin 40 mg/day or atorvastatin 80 mg/day over 12 weeks, to achieve an LDL-cholesterol target of <3 mmol/L. After 16 weeks of treatment, significantly more participants (94% vs 88%; P<0.05) achieved their LDL-cholesterol goal with rosuvastatin and fewer participants taking this drug required dose titration. Again, both treatments were similarly well tolerated (Berne et al, 2005).
Miller et al (2004) investigated the efficacy of simvastatin (40 and 80 mg) for raising HDL-cholesterol in participants with stable type 2 diabetes (HbA1c <9% [<75 mmol/mol]). At the end of the study, both doses had significantly increased HDL-cholesterol from baseline (mean increases of 5% and 8% respectively) compared with placebo (Miller et al, 2004).
Three other studies involving people with type 2 diabetes were post hoc analyses of large trials. ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm; Sever et al, 2005) examined the effect of atorvastatin 10 mg/day on total CV outcomes in 2532 participants with hypertension and type 2 diabetes. At a median follow-up of 3.3 years, total and LDL-cholesterol levels were around 1 mmol/L lower in those randomised to atorvastatin than placebo, and 9.2% of participants had major CV events or procedures with atorvastatin versus 11.9% with placebo (P=0.036). Atorvastatin prevented around nine people with diabetes from suffering a first major event or procedure for every 1000 treated for 1 year (Sever et al, 2005).
The DALI (Diabetes Atorvastatin Lipid Intervention; van Venrooij et al, 2002) investigated the effect of 30 weeks atorvastatin therapy (10 and 80 mg) on endothelial function in 133 people with type 2 diabetes and dyslipidaemia, but no history of CVD. These people were found to have considerable endothelial dysfunction, and although aggressive lipid lowering with atorvastatin substantially lowered all atherogenic lipid parameters, it did not reverse endothelial dysfunction (van Venrooij et al, 2002).
The CARDS (Collaborative Atorvastatin Diabetes Study; Charlton-Menys et al, 2009) analysed the time between the initiation of atorvastatin 10 mg and the appearance of significant differences in the incidence of CV events when compared with placebo in 2350 people with type 2 diabetes and no prior history of CVD. By 6 months the effect of atorvastatin on CV events was already apparent and at 1 year it was similar to the 37% relative risk reduction observed at trial closure (Charlton-Menys et al, 2009).
Statins can reduce LDL-cholesterol by between 18% and 55%, and triglycerides by between 5% and 15% (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001). In addition to these benefits, statins can also increase HDL-cholesterol by between 3% and 10% (BCS et al, 2005). Although changes in lipid levels explain most of the observed benefits of statins (Simes et al, 2002), some treatment effects may be mediated through non-lipid mechanisms that modify endothelial dysfunction, inflammatory responses, atherosclerotic plaque stability and thrombus formation (Rosenson and Tangney, 1998).
The FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study compared fenofibrate therapy with placebo in 9795 people with type 2 diabetes (2131 of which had previous CVD), who were not taking statin therapy at study entry, over 5 years (Keech et al, 2005). There were significant reductions in total cholesterol, LDL-cholesterol and triglyceride levels, and increases in HDL-cholesterol levels with fenofibrate versus placebo.
Although fenofibrate did not significantly reduce the risk of the primary outcome of coronary events, it did reduce total CV events and was also associated with less retinopathy needing laser treatment (3.6% vs 5.2% with placebo). There were slight increases in pancreatitis associated with fenofibrate treatment compared with placebo (0.8% vs 0.5%) and pulmonary embolism (1.1% vs 0.7%) respectively, but no other significant adverse effects. Gastrointestinal events were the most frequently reported adverse event (Keech et al, 2005).
Although some studies involving people with type 2 diabetes have found additional benefits on lipid profile from combining statin therapy with fenofibrate as compared with monotherapy with either (Athyros et al, 2002; Derosa et al, 2004), the more recent ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial suggests that the addition of fenofibrate to ongoing statin therapy offers only limited benefit (Toth, 2010).
An early study of 13 participants with type 2 diabetes found that nicotinic acid 1.5g three times daily reduced total cholesterol by 24%, plasma triglycerides by 45%, very-LDL (VLDL)-cholesterol by 58% and LDL-cholesterol by 15%, and increased HDL-cholesterol by 34% (Garg and Grundy, 1990). However, it also resulted in a deterioration of glycaemic control, as demonstrated by a 16% increase in mean plasma glucose, a 21% increase in HbA1c levels, and the induction of marked glycosuria in some participants. Flushing was considered a minor complaint. Flushing can now be reduced with the combination of nicotinic acid with laropiprant.
The later ADMIT (Arterial Disease Multiple Intervention Trial) investigated efficacy and safety of nicotinic acid 3000 mg/day versus placebo, in 125 people with diabetes and a diagnosis of peripheral arterial disease, for up to 60 weeks. Nicotinic acid significantly increased HDL-cholesterol by 29% and reduced triglycerides and LDL-cholesterol by 23% and 8%, respectively. Nicotinic acid also caused small but significant increases in average glucose levels and increased uric acid levels over baseline values. Mean plasma alanine aminotransferase level was not significantly changed (Elam et al, 2000).
Omega-3 polyunsaturated fatty acids
The effect of omega-3 polyunsaturated fatty acids (omega-3 PUFA) on serum lipoproteins was investigated in a comprehensive review of the published literature. In total, 36 crossover and 29 parallel design studies using doses of around 4 g/day from fish oil were included in the analysis, a small number of which included people with diabetes. Although total cholesterol was not materially affected by long-chain omega-3 PUFA, LDL-cholesterol and HDL-cholesterol tended to increase by 5–10% and 1–3%, respectively, while serum triglyceride concentrations decreased by 25–30% (Harris, 1997).
A more recent study investigated the effects of omega-3 PUFA ethyl esters (4 g/day) in atorvastatin-treated (10, 20 and 40 mg/day) people with raised non-HDL-cholesterol and triglyceride levels. Omega-3 PUFA plus atorvastatin reduced median total cholesterol, LDL-cholesterol and triglyceride levels, and increased HDL-cholesterol levels, to a significantly greater degree than placebo plus atorvastatin (Bays et al, 2010).
However, while some trials have shown a reduction in CV risk with increased omega-3 PUFA intake (Burr et al, 1989; Siscovick et al, 1995; Gillum et al, 1996; GISSI [Gruppo Itlaiano per lo Studio della Sopravvivenza nell’Infarto miocardi] Prevenzione Trial Group, 1999; Albert et al, 2002), others have not (Morris et al, 1995; Oriencia et al, 1996; Nilsen et al, 2001; Burr et al, 2003). NICE (2007) recommends giving consideration to providing at least 1 g/day of omega-3 PUFA esters licensed for the secondary prevention of myocardial infarction (MI) for up to 4 years. It is not recommended for primary prevention by NICE, however advising people to eat two to three portions of oily fish a week seems a sensible approach.
Guidance on lipid levels in type 2 diabetes
Several guidelines have included recommendations on lipid modification for the prevention of CVD (BCS et al, 2005; SIGN, 2007; NICE, 2008a). However, the NICE guideline on type 2 diabetes (NCCCC, 2008) provides management recommendations specific to this patient group and the following sections of this module are based primarily on this guidance. In 2010, SIGN guideline 116 (SIGN, 2010) on the management of diabetes was published.
CVD risk estimation in people with type 2 diabetes
Risk equations are not generally used for people with diabetes since they are already considered to be at high risk of CVD (BCS et al, 2005; NICE, 2008a). A person with type 2 diabetes should be considered at high premature CV risk for their age, unless they (NCCCC, 2008):
- Are not overweight (according to risk associated with ethnic group).
- Are normotensive (<140/80 mmHg).
- Do not have microalbuminuria.
- Do not smoke.
- Do not have a high-risk lipid profile.
- Have no prior or family history of CVD.
If, on the basis of the above findings, a person is not considered to be at high CV risk, their risk should be estimated annually using the UK Prospective Diabetes Study risk engine (www.dtu.ox.ac.uk/riskengine). A full lipid profile, including triglyceride and HDL-cholesterol estimation, should be performed as part of this annual assessment and prior to initiating lipid-modifying therapy (NCCCC, 2008). This should be a fasting sample to allow for the accurate estimation of triglycerides and LDL-cholesterol.
People with type 2 diabetes should be supported to try and achieve and maintain a lipid and lipoprotein profile that reduces the risk of vascular disease, through combination of pharmacotherapy and dietary modification (NICE, 2008a).
Lifestyle measures for lipid lowering
In addition to pharmacotherapy, lifestyle changes have also been shown to play an important role in managing dyslipidaemia, by reducing both total and LDL-cholesterol levels and hence atherogenesis (Gross and Reese, 2005). For preventing CVD in high-risk individuals, management strategies are likely to require a combination of pharmacological and lifestyle interventions. NICE provides lifestyle recommendations based on review of the available evidence (NCCCC, 2008; NICE, 2008a; Table 2).
The benefits of structured exercise interventions also include reductions in HbA1c and improvements in glycaemic control, independent of weight loss (Boulé et al, 2001). Although exercise alone – without dietary calorific restriction – tends to produce only modest weight loss of around 2 kg (Sigal et al, 2006), research has shown that 1 hour/day of moderate intensity exercise produced as much fat loss as the equivalent degree of caloric restriction, with greater resulting improvements in insulin sensitivity (Ross et al, 2000).
The amount of exercise required to achieve sustained major weight loss is probably much greater than that needed to achieve improved glycaemic control and CV health (Sigal et al, 2006). All people should be encouraged to exercise for 20–30 minutes twice a day and to combine this with a healthy diet, because the most successful programmes for long-term weight control have involved combinations of diet, exercise and behaviour modification (Wing et al, 2002).
There are now clear dietary guidelines for intakes of omega 3 for different populations in the UK. For primary prevention of CVD in the general population, the Food Standards Agency (FSA, 2004) recommends eating two portions of fish per week, one of which should be oily. Diabetes UK (2009) recommends that all people with diabetes, who are at increased risk of CV disease, should be encouraged to oily fish at least twice per week.
The cholesterol-lowering efficacy and safety of plant sterols and stanols was investigated in a meta-analysis of 41 randomised, double-blind trials, of which 16 used plant sterols, 20 used plant stanols and five used both. The doses ranged from 0.7–3.3 g daily and were administered for an average of 7 weeks. The mean reductions in LDL-cholesterol were 9.7% for plant sterol 2.3 g/day, and 10.1% for plant stanol 2.5 g/day (Katan et al, 2003).
Furthermore, trials in people taking statins have shown that consuming plant sterol or stanol esters can reduce LDL-cholesterol by a further 7–11%, a greater effect than can be expected from doubling the statin dose (Thompson, 2005). However, to achieve this effect a sufficient quantity of the food supplement needs to be taken on a daily basis, which is expensive and adherence is poor as a result.
For people with type 2 diabetes aged ≥40 years, unless the CV risk from non-hyperglycaemia-related factors is low, statin therapy should be initiated with generic simvastatin (to 40 mg) or an alternative of similar efficacy and cost. If their risk from non-hyperglycaemia related factors is low, statin therapy should be initiated only if their CV risk exceeds 20% over 10 years (NCCCC, 2008). SIGN (2010) recommends lipid-lowering therapy with simvastatin 40 mg or atorvastatin 10 mg for primary prevention in people with type 2 diabetes aged >40 years regardless of baseline cholesterol.
For people with type 2 diabetes ≤40 years of age, statin therapy should be considered if their CV risk profile appears particularly poor, for example including multiple features of the metabolic syndrome, the presence of conventional risk factors, microalbuminuria, a strong family history of premature CVD or an at-risk ethic group (NCCCC, 2008).
Once initiated, statin dose may be increased to 80 mg daily in people with total cholesterol <4.0 mmol/L or LDL-cholesterol <2.0 mmol/L. In those with existing or newly diagnosed CVD, or an increased albumin excretion rate, therapy can be intensified with a more effective statin or ezetimibe, to achieve total cholesterol <4.0 mmol/L or LDL-cholesterol <2.0 mmol/L (NCCCC, 2008). However, a recent safety warning from the Medicines and Healthcare products Regulatory Agency (MHRA, 2010) about intensive therapy with simvastatin 80 mg, based on evidence from the SEARCH (Study of the Effectiveness of Additional Medications in Cholesterol and Homocysteine) trial, has led to alternative high-potency statins being used (SEARCH Collaborative Group et al, 2007).
Regarding arterial risk reduction in type 1 diabetes, NICE (2004) provides helpful advice. Arterial risk factors should be assessed annually. Arterial risk tables, equations or engines for calculation of arterial risk should not be used because they underestimate risk in adults with type 1 diabetes.
The combination of a statin with ezetimibe – the only cholesterol absorption inhibitor – can have a particular role to maximise LDL-cholesterol lowering and is recommended by NICE (NCCCC, 2008) when lipid targets are not met. It is useful when statins are not tolerated and can be effective when combined with low doses of statins when they cause side-effects. As yet there is no convincing outcome data to support this approach.
People with a history of elevated serum triglycerides should have a full fasting lipid profile, including triglyceride and HDL-cholesterol, performed as part of their annual CV risk estimation. Possible secondary causes of hypertriglyceridaemia, for example hypothyroidism, renal impairment and liver inflammation, should be investigated and managed if found.
Fibrate therapy, and fenofibrate first-line, is recommended if triglyceride levels remain >4.5 mmol/L. Where CV risk is high and triglyceride levels remain between 2.3–4.5 mmol/L despite statin therapy, a fibrate may be added (NCCCC, 2008), but this recommendation was made before the results of the ACCORD trial were available.
The ACCORD study published this year showed that combination therapy with fenofibrate and simvastatin failed to reduce the risk of fatal CV events, non-fatal MI or non-fatal stroke in high-risk people with diabetes. However, subgroup analysis suggested that those with higher baseline triglycerides and lower HDL-cholesterol levels benefited from the combination more than the overall cohort (ACCORD Study Group et al, 2010).
Although NICE does not recommend routine use of nicotinic acid in people with type 2 diabetes, it may have a role in a small number of people with more extreme disorders of blood lipid metabolism and intolerance to other therapies, but only when managed by specialists in this area (NCCCC, 2008). If nicotinic acid is used in people with diabetes, their antidiabetes medication may need to be titrated up.
Omega-3 fish oils
Fish oil preparations are not recommended for the primary prevention of CVD in people with type 2 diabetes, unless prescribed by a healthcare professional with expertise in blood lipid management for hypertriglyceridaemia. A trial of a highly concentrated licensed product may be considered for people with refractory hypertriglyceridaemia if fibrate therapy and lifestyle measures have failed (NCCCC, 2008).
After initiating lipid-lowering therapy in a person with type 2 diabetes, assess their lipid profile, modifiable risk factors and any new diagnosis of CVD within 1–3 months after starting treatment, then annually thereafter (NCCCC, 2008). It is appropriate to check hepatic, renal, thyroid function and creatinine kinase (CK) prior to starting statins, as a baseline. Routine measurement of CK in the absence of symptoms is unlikely to be helpful and may be confusing because of day-to-day variability.
It is reasonable to check alanine transaminase (ALT) levels at 1–3 months when the first follow-up lipid level is checked. In asymptomatic patients a rise of ALT up to three times and a CK up to five times the upper limit can be acceptable but would need to be monitored more regularly.
Statins and risk of incident diabetes
JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin; Ridker et al, 2008) reported an increased risk for diabetes in patients assigned to the rosuvastatin arm, and the PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease; Shepherd et al, 2002) trial reported similar findings with pravastatin.
A recent meta-analysis (Sattar et al, 2010) investigated this relationship via 13 statin trials conducted between 1999 and 2009 that involved 91140 participants, of whom 4278 (2226 assigned statins versus 2052 assigned control treatment) developed diabetes over a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio, 1.09; 95% CI, 1.02–1.17), with little heterogeneity between trials.
The risk of developing diabetes with statin therapy was highest in trials involving older participants. To put it into perspective, treating 255 people with statins for 4 years resulted in one extra case of diabetes. The authors concluded that although statin therapy is associated with a slightly increased risk of developing diabetes, the risk is low in both absolute terms and when compared with the reduction in coronary events (Sattar et al, 2010).
Statins in older people, children and women
Statins have been underused in older people due to limited evidence that they reduce mortality (Golomb, 2005; Afilalo et al, 2008) and concerns that their adverse effects (such as muscle and cognitive problems) may be amplified in this group (Golomb, 2005).
The PROSPER trial found that pravastatin given for 3 years reduced the risk of coronary disease in people aged 70–82 years with or at high risk of CVD, and had no significant effect on cognitive function or disability (Shepherd et al, 2002). A more recent meta-analysis, including data from 19569 participants with CHD aged between 65 and 85 years, estimated a relative risk reduction of 22% over 5 years. Statins reduced CHD mortality by 30%, non-fatal MI risk by 26%, need for revascularisation by 30% and risk of stroke by 25%. The number needed to treat to save one life was estimated at 28. Conclusions were that statins reduce all-cause mortality in older people with a substantially larger effect that previously estimated (Afilalo et al, 2008).
All people aged over 75 years should be assumed to be at increased risk of CVD – particularly if they have raised blood pressure or smoke – and are considered likely to benefit from statin therapy. However, the decision to initiate lipid modification therapy should be guided by informed individual preference, comorbidites, and the likely benefits and risks (NICE, 2008a). When initiating statin therapy for older people, dose adjustment is not generally necessary. Because this population has an increased risk of rhabdomyolysis, a reference CK level should be measured before starting treatment.
A number of statins are licensed for use in children aged 10 years and over for the treatment of primary hypercholesterolaemia (Electronic Medicines Compendium, 2010a; 2010b; 2010c; 2010d).
Statin therapy in pregnancy is contraindicated. Maternal treatment with a statin may reduce fetal levels of mevalonate, which is a precursor of biosynthesis. Because atherosclerosis is a chronic process, and discontinuation of lipid-lowering agents while trying to conceive and during pregnancy is likely to have little effect on long-term CV risk, the licence holders recommend that these drugs are not used in these circumstances (Electronic Medicines Compendium, 2010a; 2010b; 2010c; 2010d; 2010e).
In women with type 2 diabetes who may become pregnant, NICE does not recommend statins unless the issues have been discussed and agreed (NCCCC, 2008). NICE (2008b) guidance on the management of individuals with familial hyperlipidaemia recommends that women wishing to become pregnant should be advised to stop statins three months prior to attempting to conceive. Bile acid sequestrants can be used with caution, but may cause fat-soluble vitamin deficiency on prolonged use and may need supplementation.
Current management of dyslipidaemia in people with diabetes
The National Diabetes Audit showed that between 2008 and 2009 in England, 78% of people with type 1 diabetes and 94% of people with type 2 diabetes had their cholesterol checked. The NICE target of <5 mmol/L was achieved by 56% of people with type 1 diabetes and 73% of people with type 2 diabetes. The tighter <4 mmol/L target introduced in 2008 was achieved in only 24% of people with type 1 diabetes and 37% of people with type 2 diabetes. The <5 mmol/L target was achieved less often in those under the age of 40, possibly due to this age being a common clinical threshold for preventative treatment with statins (NHS Information Centre, 2010). Table 3 details the current QOF indicators for lipid modification in people with diabetes.
Significant improvements have been made in lipid management in primary care. In people with type 2 diabetes, use of lipid-lowering drugs increased from 8% in 1997 to 85% in 2007, compared with 3–29% in matched individuals without diabetes (Figure 1). Between 2001 and 2007, people with type 2 diabetes treated with insulin experienced a mean reduction in total cholesterol of 1.4 mmol/L, from 5.6 to 4.2 mmol/L. This 25% relative improvement in total cholesterol was significantly greater than the relative improvements in HbA1c level (1% in people with type 1 diabetes), and systolic and diastolic blood pressure (5%), over the same time-frame (Currie et al, 2010).
Boxes 1 and 2 contain two case studies that highlight some of the practical issues encountered in the management of people with diabetes and dyslipidaemia.
To prevent CVD in people with diabetes, “total” CV risk management is required to maximise risk reduction, with the modification of lipids being one essential component.
Medication adherence is the key to achieving benefits from drug therapy for the prevention of CVD, and to gain maximum benefits individuals probably need to take the drugs at the recommended doses for the rest of their lives. However, Bandolier (2007) found that the majority of people prescribed statins had either stopped taking the drug altogether or were taking less than the recommended dose within 12 months, and women showed poorer adherence than men.
To improve adherence we need to ensure regular follow-up and good communication, simple drug regimens that are tailored to suit the individual, education about the condition and reasons for therapy, and the provision of dedicated CVD and diabetes clinics to monitor progress and improve motivation.
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