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Practical Diabetes Care, 3rd Ed., Excerpt #32: Lipids Part 2 of 6

David Levy, MD, FRCP

altIncreased cardiac risk in type 2 diabetes, and a re-evaluation of the ‘coronary equivalent’ concept

These subtle differences together may account for some of the increased cardiovascular risk in type 2 diabetes. The level of increased risk is the subject of much academic discussion. In large diabetic populations studied in the past, coronary risks were often found to be approximately doubled compared with non-diabetic groups, and the concept of diabetes as a coronary risk equivalent is almost embedded – type 2 patients who have not yet suffered a coronary event have a similar coronary risk as non- diabetic patients who have already had an event. The therapeutic corollary of this view is that all patients require equally intensive secondary prevention treatment.

More recent studies find a much lower coronary event rate in type 2 patients, and meta-analysis estimates the risk not as twofold increased but about half that of the non-diabetic population with a previous event. This may reflect the gradual but cumulatively important improvements in multimodal management resulting in better cardiovascular outcomes in type 2 diabetes. However, the statistic that is invariant across old and recent studies alike is the extremely high risk of type 2 patients who have had an event (e.g. 10% annual risk, compared with about 2% in those without an event) [1]. Guidelines do not yet reflect this revised view that implies we should individualize risk management with a strong emphasis on the highest risk patients.

Lipid profiles in poorly controlled diabetes and effects of intensive glycemic treatment

In poorly controlled type 1 and 2 diabetes, insulin deficiency increases hepatic VLDL secretion leading to elevated serum triglycerides, sometimes massively so, resulting in lipemic serum, difficulties in measuring many other serum components (including amylase), and an increased risk of acute pancreatitis. In large clinical studies improvement in glycemic control from moderately poor levels primarily reduces triglycerides, with lesser falls in total and HDL cholesterol, but these would not usually be detectable in the individual patient (Table 12.1). Intensified glycemic control in type 1 diabetes often causes weight gain, and intensively treated patients in the DCCT with the greatest weight gain (BMI 34 vs. 24) also showed a global deterioration in lipid profiles, with increased total and LDL cholesterol, increased triglycerides and lower HDL levels [2]. Systolic and diastolic blood pressure and high-sensitivity CRP all increased as well. There must be concern that worsening cardiovascular risk profiles in intensively treated type 2 diabetes may outweigh the limited advantages of tight glycemic control as shown in the recent trials.

PDCChapt12Table12.1
Click to expand.

There is little point in requesting lipid profiles in severely hyperglycemic newly diagnosed or very poorly controlled patients; leave until control has been stabilized for at least a month (Box 12.1).

PDCChapt12Box12.1
Click to expand.

Familial hypercholesterolemia may coexist with diabetes; suspect where there is high cholesterol (> 8.0 mmol/L, 310 mg/dL) and normal triglycerides. Clinical characteristics include:

  • premature arcus senilis (in the 30–40 year age group);
  • tendon xanthomata, xanthelasmata;
  • family history of premature coronary artery disease (< 50 years of age) in non-diabetic first-degree relatives.

Familial combined hyperlipidemia is an important, common (1 in 250) but complex polygenic disorder that shares many of the features of the insulin resistance syndrome, and is the most common familial form of hyperlipidemia in young survivors of myocardial infarction. Definitions are not standardized but a typical lipid profile would show total cholesterol 7.0 mmol/L, HDL-cholesterol 0.9 mmol/L and triglycerides 3.0 mmol/L.

 

References:

  1.  Bulugahapitiya U, Siyambalapitiya S, Sithole J, Idris I. Is diabetes a coronary risk equivalent? Systematic review and meta-analysis. Diabetic Med 2009;26:142–8. PMID: 19236616.
  2. Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD. Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. JAMA 1998;280:140–6. PMID: 9669786.
  3. Duntas LH, Wartofsky L. Cardiovascular risks and subclinical hypothyroidism: focus on lipids and new emerging risk factors. What is the evidence? Thyroid 2007;17:1075–84. PMID: 17900236.
  4. Feher MD, Winocour PH, on behalf of the Association of British Clinical Diabetologists. ABCD position statement on lipid modifying drug therapy in diabetes. Practical Diabetes International 2007;24:458–62.
  5. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy of cholesterol- lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117–25. PMID: 18191683.
  6. Wiviott SD, Cannon CP, Morrow DA, Ray KK, Pfeffer MA, Braunwald E. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE-IT TIMI 22 substudy. J Am Coll Cardiol 2005;46:1411–16. PMID: 16226163.
  7. LaRosa JC, Deedwania PC, Shepherd J et al. Comparison of 80 versus 10 mg of atorvastatin on occurrence of cardiovascular events after the first event (from the Treating to New Targets [TNT] trial). Am J Cardiol 2010;105:283–7. PMID: 20102935.
  8. Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004;109(23 Suppl. 1):III50–III57. PMID: 15198967.
  9. Landray M, Baigent C, Leaper C et al. The second United Kingdom Heart and Renal Protection (UK-HARP-II) Study: a randomized controlled study of the bio- chemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis 2006;47:385–95. PMID: 16490616.
  10. Cannon CP, Giugliano RP, Blazing MA etal. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008;156:826–32. PMID: 19061694.
  11. Rajamani K, Colman PG, Li LP et al. Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet 2009;373:1780–8. PMID: 19465233.
  12. Ginsberg HN, Elam MB, Lovato LC et al. Effects of combination lipid therapy in type 2 diabetes mellitus. ACCORD Study Group. N Engl J Med 2010;362:1563– 74. PMID: 20228404.
  13. Belalcazar LM, Reboussin DM, Haffner SM et al. Marine omega-3 fatty acid intake: associations with cardiometabolic risk and response to weight loss intervention in the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care 2010;33:197–9. PMID: 19841042.
  14. Zhao XQ, Krasuski RA, Baer J et al. Effects of combination lipid therapy on coronary stenosis progression and clinical cardiovascular events in coronary disease patients with metabolic syndrome: a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL-Atherosclerosis Treatment Study (HATS), and the Armed Forces Regression Study (AFREGS). Am J Cardiol 2009;104:1457–64. PMID: 19932775.
  15. Fazio S, Guyton JR, Polis AB et al. Long-term safety and efficacy of triple combination ezetimibe/simvastatin plus extended-release niacin in patients with hyperlipidemia. Am J Cardiol 2010;105:487–94. PMID: 20152243.

 

For more information and to purchase this book, just follow this link:

http://www.wiley.com/WileyCDA/WileyTitle/productCd-1444333852.html

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)