David Levy, MD, FRCP
Dyslipidemia in diabetes is usually the simplest cardiovascular risk factor to control. There are few patients whose lipid profile cannot be optimized, or at least markedly improved, with a combination of lifestyle interventions and single or combination drug therapy. The increasingly stringent targets recommended for high-risk patients, usually with pre-existing cardiovascular disease, proteinuria or both, are also attainable, but judicious combination therapy will be needed in some. There is persuasive evidence that low LDL levels maintained in the long term are associated with stabilization or even reversal of carotid and coronary atheroma, though we have yet to see the impressive intravascular ultrasound images correlate with event reduction in RCTs.
The difficulty lies not so much in achieving targets, but deciding which patients or groups of patients are likely to gain the most benefit from treatment. Statins do not consistently reduce total mortality, even in patients with diabetes, and although absolute event risk reduc- tions in the early studies (e.g. 4S, 1994) were large (about 25–30%), in current trials they are much lower, about 3% over 5 years. Even with the most stringent LDL lowering, residual risk is still high; factors other than LDL must be important, and relatively modest lipid- lowering in the Steno type 2 study (2008) was associated with a very impressive absolute risk reduction, so long as it was accompanied by reasonable glycemic and blood pressure control, lifestyle and aspirin treatment.
Lipids in type 1 diabetes
Type 1 patients without microvascular complications (especially microalbuminuria) and in good glycemic control have a good lipid profile, similar to that of non-diabetic people of the same age. For example, baseline lipids in DCCT patients during the 1980s were as follows:
- total cholesterol 4.6 mmol/L (180 mg/dL)
- HDL-cholesterol 1.3 mmol/L (51 mg/dL)
- LDL-cholesterol 2.8 mmol/L (110 mg/dL)
- triglycerides 0.9 mmol/L (80 mg/dL).
Despite these impressive numbers, there are subtle lipoprotein abnormalities, for example slight increases in small atherogenic particles and minor differences in HDL subfractions, though total atherogenic particles are no different. Accordingly, the management of lipids in uncomplicated type 1 diabetes is quite different from that in type 2 diabetes, though the distinction is not sufficiently recognized in guidelines a.
There is an intriguing association between exceedingly high HDL-cholesterol levels and long survival (50 years or more) in type 1 diabetes with a relatively low burden of vascular disease. In the UK and USA alike, these golden cohort patients have mean HDL-cholesterol levels of 1.7–1.9 mmol/L (66–74 mg/dL), with correspondingly low triglycerides (0.8–1.0 mmol/L, 70–90 mg/dL). Males comprised half the cohorts, which itself is remarkable, and hints at a causal link between lipid profiles and long survival. Contributing factors to the high HDL levels in these groups (mean age 70) might include current (and therefore probably long-standing) exercise and moderate alcohol intake, but other factors operate, for example familial longevity (see Chapter 4). Although the HDL in some people with numerically high levels may not be ‘good,’ at least in this situation it appears to be benign.
Lipids in type 2 diabetes
Type 2 patients are usually considered to have similar or slightly higher total and LDL cholesterol levels compared with non-diabetic subjects, but contemporary studies, for example the Heart Protection Study (HPS), found slightly lower mean baseline total cholesterol levels (about 0.2 mmol/L, 8 mg/dL), possibly as a result of greater awareness of dyslipidemia among people with type 2 diabetes. Even though LDL levels are not significantly elevated, at any LDL level coronary risk is higher than in non-diabetic subjects, though the studies from which these data come are now old (e.g. MRFIT, mid-1970s), and the current risk difference is likely to be considerably lower. Interestingly, there was also no difference in HDL-cholesterol levels in the HPS (mean 1.08 mmol/ L, 42 mg/dL). However, whatever the mean levels, individual type 2 patients and those with the insulin resistance syndrome tend towards a characteristic profile, with increased triglycerides and depressed HDL-cholesterol.
Non-traditional lipid measurements that increase atherogenicity in type 2 diabetes include:
- increased apolipoprotein (apo)B, reflecting the total number of atherogenic particles, even though LDL may be normal;
- increased small, dense, atherogenic LDL particles that are prone to oxidation and glycation;
- possibly increased lipoprotein(a);
- altered HDL subfractions (HDL2 is the most powerful anti-atherogenic fraction, and is reduced in diabetes; the antioxidant activity of the small dense HDL3 fraction is reduced);
- increased non-HDL-cholesterol (easily calculated from the standard
- lipid profile).
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David Levy, MD, FRCP, Consultant Physician, Gillian Hanson Centre, Whipps Cross University Hospital; Honorary Senior Lecturer
Queen Mary University of London London, UK
This edition first published 2011, © 2011 by David Levy. 1st edition 1998 (Greenwich Medical Media/Cambridge University Press) 2nd edition 2006 (Altman Publications)