Lipid disorders in diabetes

Type 2 diabetes is a major, and largely reversible, cardiovascular risk factor. About one third of patients will have the classic diabetic dyslipidaemia consisting of raised plasma triglycerides, low HDL cholesterol and only moderately, if at all, raised LDL cholesterol. This dyslipidaemia also includes qualitative changes to the lipoprotein particles in that both HDL and LDL are composed of cholesterol-depleted and smaller than normal lipoprotein particles. Beyond the overburdening of the lipid transport system imposed by an overall excess of lipids stored in the human body (obesity), relative insulin deficiency plays a role in creating the features of diabetic dyslipidaemia. The first line of treatment of diabetic dysglycaemia is to improve metabolic control, following which treatment follows the same lines as in non-diabetic dyslipidaemia.

Background

Insulin plays important regulatory roles in adipose tissue and in the liver in terms of determining release, storage and transport of either fatty acids or triglyceride-rich lipoproteins. The metabolic background to diabetic dyslipidaemia is explained within Overview of lipid transport

In the absence of direct evidence, it is assumed that the components of diabetic dyslipidaemia contribute to the increased cardiovascular risk seen in type 2 diabetes. Furthermore, there is unequivocal evidence that aggressive lipid-lowering therapy improves the prognosis of these patients.

It has to be recognized that type 2 diabetes is now so common that it may well coincide with other primary and secondary hyperlipoproteinaemias. In the first instance, nonetheless, it is reasonable to assume that hyperlipidaemia in type 2 diabetes is secondary to the diabetes.

Management

It is therefore important to focus on optimization of glycaemic control before considering other lipid lowering therapies. There is no specific treatment for diabetic dyslipidaemia, but it is well established that patients with type 2 diabetes respond equally well to conventional lipid-lowering therapies as do non-diabetics, both in terms of lipid lowering effect and reduction of cardiovascular risk. In fact, most guidelines suggest that type 2 diabetes is a cardiovascular high risk syndrome that should be treated in par with secondary prevention in non-diabetic patients.

Pathogenesis

Poorly controlled diabetes will inevitably involve a relative state of insulin deficiency. Due to insulin’s critical role as an antilipolytic hormone, this will create a state of unopposed lipolysis with a significant flux of free fatty acids from adipose tissue to the liver.

Meanwhile, insulin is also critical for the up-regulation of lipoprotein lipase (LPL) in adipose tissue, which enables storage of fatty acids from triglyceride-rich lipoproteins. A particularly severe consequence of the increased flux of fatty acids to the liver and the reduction of adipose tissue LPL is seen in patients with an underlying genetic vulnerability, often understood to involve mutations in genes critical to plasma triglyceride extraction. This may lead to extreme hypertriglyceridaemia which is a risk factor for acute pancreatitis.

In contrast to type 2 diabetes, lipid management in patients with type 1 diabetes is an area in need of further clinical evidence.

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