Diabetic dyslipidaemia

It is indicated as an adjunct to diet to reduce elevated total cholesterol, LDL-cholesterol and TG levels in patients with primary hypercholesterolemia, diabetic dyslipidaemia or mixed hyperlipidemia, hypertriglyceridemia, dysbetalipo-proteinemia and familial hypercholesterolemia. 

In this chapter, the pathophysiology of diabetic dyslipidaemia and its relation to CVD are described. RCTs, which provide the basis for clinical practice, are discussed together with new information pointing to benefits from more intensive therapy. As a result of this evidence more stringent goals of therapy have been advocated by national and international bodies. 

Taskinen MR. Diabetic dyslipidaemia from basic research to clinical practice. Diabetologia. 2003 46 733-749. 

In a related study, streptozotocin-induced diabetic rats were treated with pyridox-amine, vitamin E, and enalapril (7V-(l-[ethoxycarbonyl -3-phcny I propyl)-Ala-Pro), an AGE/ALE inhibitor, an antioxidant, and an ACE-inhibitor, respectively.598 Diabetic hyperglycaemia was accompanied by severe dyslipidaemia. Treatment with pyridoxamine was the most effective in reducing lipid abnormalities and in retarding nephropathy, retinopathy, and protein modification. Vitamin E was the next most effective treatment in retarding nephropathy, but did not affect retinopathy or AGE/ALE formation. Enalapril normalised blood pressure and retarded nephropathy and the accumulation of CML in the kidney, but did not affect dyslipidaemia and retinopathy. Thus pyridoxamine is the most effective therapy overall. 

Body weight and metabolism are regulated by the hypothalamus. In experimental animals diabetes, insulin resistance and dyslipidaemia can be corrected by weight loss (Brownell etal., 1986 Brindley and Russell, 1995), and this has recendy been demonstrated in humans (Benotti and Forse, 1995). Increased activity of the hypothalamic NPY system may contribute to the development of obesity in animals. The abnormalities seen in genetically obese rodents can be mimicked by central injection of NPY (Zarjevski etal., 1993). 

Type 2 diabetes (T2D) is a fast-growing disease with an increase in prevalence of some 5% per year. This increase may, however, in part, be explained by a reduction in mortality indicating that the investment in better treatment has been fruitful [1]. Especially, treatment of arterial hypertension and dyslipidaemia may have had an impact, whereas severe hyperglycaemia still seems to present a serious problem in T2D subjects and therefore needs more attention. The UKPDS clearly showed the existence of a close correlation between blood glucose values and diabetic complications, as also seen in type 1 diabetes [2] (Fig. 1). In fact, the epidemiological calculation based on the UKPDS data showed a redaction of abont 20% in both mortality rate and in the risk of developing myocardial infarct per 1% rednction in HbAlc [2]. Conseqnently, we mnst aim to normalise HbAlc valnes in these snbjects. 

During recent years numerous prospective studies have identified several modifiable risk factors for CVD in patients with type 2 diabetes. On top of hyperglycaemia these factors include hypertension, dyslipidaemia, microalbuminuria, a pro-thrombotic state, visceral fat accumulation, and associated chronic low-grade inflammation, smoking, diets... 

Two different pills plus insulin for control of blood glucose, one or two for dyslipidaemia, then three or four for hypertension and on top of this a low-dose aspirin a day. Upwards of eight or more drugs a day for each intensively treated type 2 diabetic patient and that is even before we consider the drug treatment of concomitant diseases. No wonder that patients exposed to life-long intensive treatment of type 2 diabetes to be motivated, need continued and personalized education about indications, mechanisms of actions, and potential side effects of the prescribed medications. Whether... 

Cardiovascular disease (CVD) remains the most important cause of morbidity and mortality in people with diabetes [1], This high-risk population is more likely to suffer a fatal event as the first manifestation of myocardial infarction (MI) or stroke, making primary prevention a priority. The pathogenesis of atherosclerosis-related disease is multifactorial but dyslipidaemia is a common and important risk predictor and is open to therapeutic intervention. Pharmacological intervention is supported by major randomised, controlled clinical trials (RCTs) of primary and secondary CVD prevention. RCTs with statin drugs have demonstrated unequivocal benefit in reducing major coronary events and stroke. 

Dyslipidaemia is strongly correlated to insulin resistance and hyperinsulinaemia. It is present at the time of diagnosis of diabetes as part of the insulin-resistance syndrome and persists despite treatment of glycaemia. It should be treated in its own right indeed, given the evidence of benefit from RCTs, effective management of dyslipidaemia needs to move centrestage in the prevention of CVD. 

Factors leading to characteristic dyslipidaemia are complex and not fully understood. Insulin resistance is associated with the failure of normal suppression of hormone-sensitive lipase in adipose tissue and increased lipolysis leading to increased flux of non-esterified fatty acids (NEFAs) to the liver this is partly responsible for increased hepatic output of very low-density lipoprotein (VLDL) [6]. Central obesity is common in insulin resistance and type 2 diabetes and visceral fat is increasingly recognised as an important paracrine and endocrine organ [7]. Adiponectin, an important adipose-specific adipokine, is reduced in insulin resistance and type 2 diabetes [8]. This would favour increased lipolysis as the action of a further important cytokine, TNF-alpha in stimulating lipolysis is unopposed. 

Ginsberg HN, Illingworth DG. Postprandial dyslipidaemia an atherogenic disorder common in patients with diabetes mellitus. Am J Cardiol. 2001 88(Suppl9) 9H-15H. 

Sniderman AD, Scantlebury T, Cianflone K. Hypertriglyceridaemic hyper apoB the unappreciated atherogenic dyslipidaemia in type 2 diabetes mellitus. Ann Intern Med. 2001 135 447 59. 

Lehto S, Ronnemaa T, Haffner SM, et al. Dyslipidaemia and hyperglycaemia predict coronary heart disease in middle-aged patients with NIDDM. Diabetes. 1997 46 1354-1359. 

Babaei-Jadidi, R., Karachalias, N., Kupich, C., Ahmed, N., and Thornalley, P.J., 2004. High-dose thiamine therapy counters dyslipidaemia in strepto-zotocin-induced diabetic rats. Diabetologia. 47 2235-2246. 

Bhandari, U., Kanojia, R., and Pillai, K.K. 2005. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J. Ethnopharmacol 97 227-230. 

LR-90 was derived from LR-16, a compound that is able to lowers cholesterol levels in rats. In our apoE KO model, no effects on lipid profile by LR-90 were detected, possibly as the effects of genetic deficiency of the lipoprotein profile overwhelms and drug associated actions. However, in the Zucker model of diabetes and dyslipidaemia lipid lowering effects have been propertied with LR-90... 

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