Diabetic dyslipidaemia

doi:10.1053/beem.1999.0019

Best Practice & Research Clinical Endocrinology & Metabolism

Volume 13, Issue 2, July 1999, Pages 265-278

https://doi.org/10.1053/beem.1999.0019 Get rights and content

Abstract

The risk of coronary heart disease and atherosclerosis is increased in both Type 2 and Type 1 diabetes mellitus. The dyslipidaemia of Type 2 diabetes consists of hypertriglyceridaemia and low levels of high-density lipoprotein (HDL) cholesterol. In Type 1 diabetes, hypertriglyceridaemia is also present, but when glycaemic control is good, HDL cholesterol levels may be normal or even increased. In both types of diabetes, nephropathy is associated with an exacerbation of hypertriglyceridaemia, a decline in HDL cholesterol level and an increase in serum cholesterol. In the absence of nephropathy, serum cholesterol levels are typically similar to those of the background non-diabetic population. The risk of coronary heart disease (CHD) associated with serum cholesterol is, however, considerably higher in diabetics than in non-diabetic people, and is much less in diabetic populations living in countries where the average cholesterol level is low, even when hypertension is present. Currently, the strongest evidence that lipid-lowering drug therapy will decrease the risk of CHD, particularly in secondary prevention, comes from trials of statins that lower cholesterol. There is growing experimental and observational evidence that hypertriglyceridaemia, because of its effects on cholesteryl ester transfer, leading to the formation of a small low-density lipoprotein susceptible to oxidation, compounds the risk of serum cholesterol in diabetes. Both fibrates and statins can decrease this cholesteryl ester transfer. Further studies of fibrates with clinical end-points should clarify their role in the prevention of CHD. In the meantime, statins should be part of routine diabetic clinical practice, fibrates having a more limited role when hypertriglyceridaemia is extreme.

References (84)

MF Oliver
It is more important to increase the intake of unsaturated fats than to decrease the intake of saturated fats: evidence from clinical trials relating to ischaemic heart disease
American Journal of Clinical Nutrition
(1997)
FJ Tames et al.
Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects
Atherosclerosis
(1992)
EA Nikkila et al.
Plasma triglyceride transport kinetics in diabetes mellitus
Metabolism
(1973)
MR Taskinen
Hyperlipidaemia in diabetes
Baillière's Clinical Endocrinology and Metabolism
(1990)
PN Durrington
Triglycerides are more important in atherosclerosis than epidemiology has suggested
Atherosclerosis
(1998)
AN Phillips et al.
How independent are ‘independent’ effects? Relative risk estimation when correlated exposures are measured imprecisely
Journal of Clinical Epidemiology
(1991)
M Egger et al.
Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error
Atherosclerosis
(1999)
SH Gianturco et al.
Cellular binding site and membrane binding proteins for triglyceride-rich lipoproteins in human monocyte-macrophages and THP-1 monocytic cells
Journal of Lipid Research
(1994)
A Chait et al.
Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B
American Journal of Medicine
(1993)
S Dejager et al.
Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidaemia
Journal of Lipid Research
(1993)

K CB Tan et al.

Fasting and postprandial determinants for the occurrence of small dense LDL species in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia: the involvement of insulin, insulin precursor species and insulin resistance

Atherosclerosis

(1995)

A Gaw et al.

Effects of ciprofibrate on LDL metabolism in man

Atherosclerosis

(1994)

CJ Fielding et al.

Molecular physiology of reverse cholesterol transport

Journal of Lipid Research

(1995)

KM Channon et al.

Investigation of lipid transfer in human serum leading to the development of an isotopic method for the determination of endogenous cholesterol esterification and transfer

Atherosclerosis

(1990)

D Bhatnagar et al.

Effects of treatment of hypertriglyceridaemia with gemfibrozil on serum lipoprotein and the transfer of cholesteryl ester from high density lipoproteins to low density lipoproteins

Atherosclerosis

(1992)

M Farrer et al.

Patients undergoing coronary artery bypass surgery are at a high risk of impaired glucose tolerance and diabetes mellitus during the first post-operative year

Metabolism

(1995)

D Bhatnagar et al.

Increased transfer of cholesteryl esters from high density lipoproteins to low density and very low density lipoproteins in patients with angiographic evidence of coronary artery disease

Atherosclerosis

(1993)

JD Bagdade et al.

Accelerated cholesteryl ester transfer in non-insulin dependent diabetes mellitus

Atherosclerosis

(1993)

M Elchebly et al.

Alterations in composition and concentration of lipoproteins and elevated cholesteryl ester transfer in non-insulin-dependent diabetes mellitus

Atherosclerosis

(1996)

WH Sutherland et al.

Plasma cholesteryl ester transfer in patients with non-insulin dependent diabetes mellitus

Clinical Chimica Acta

(1994)

S Riemens et al.

Elevated plasma cholesteryl ester transfer in NIDDM: relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein

Atherosclerosis

(1998)

PN Durrington et al.

Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia

Atherosclerosis

(1998)

PN Durrington

Serum high density lipoprotein cholesterol in diabetes mellitus: an analysis of factors which influence its concentration

Clinica Chimica Acta

(1980)

PN Durrington

Serum high density lipoprotein subfractions in type 1 insulin-dependent diabetes mellitus

Clinica Chimica Acta

(1982)

PN Durrington et al.

Indications for cholesterol-lowering medication: comparison of risk-assessment methods

Lancet

(1999)

M Bliss

The Discovery of Insulin

(1983)

M Laakso et al.

Epidemiology of risk factors for cardiovascular disease in diabetes and impaired glucose tolerance

Atherosclerosis

(1998)

J Jarrett

Diabetes and the heart: coronary heart disease

Clinical Endocrinology and Metabolism

(1978)

J Charlton et al.

Trends in diet 1841–1994

AO Pietri et al.

The effect of continuous subcutaneous insulin infusion on very-low-density lipoprotein triglyceride metabolism in type 1 diabetes mellitus

Diabetes

(1983)

UP Steinbrecher et al.

Glucosylation of LDL to an extent comparable to that seen in diabetes slows their catabolism

Diabetes

(1984)

T Mazzone et al.

In vivo stimulation of low-density lipoprotein degradation by insulin

Diabetes

(1984)

American Journal of Cardiology

(1995)

Lancet

(1998)

K Mahlberg

Prospective randomised study of intensive insulin treatment on long-term survival after acute myocardial infarction in patients with diabetes mellitus

British Medical Journal

(1997)

PN Durrington

Secondary hyperlipidaemia

Hyperlipidaemia Diagnosis and Management

(1995)

W Dong et al.

Blood Analytes

J Stamler et al.

Diabetes, other risk factors and 12 year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial

Diabetes Care

(1993)

Lancet

(1994)

FM Sacks et al.

The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels

New England Journal of Medicine

(1996)

New England Journal of Medicine

(1998)

Cited by (35)

Impact of migration on coronary heart disease risk factors: Comparison of Gujaratis in Britain and their contemporaries in villages of origin in India
2006, Atherosclerosis
Citation Excerpt :
The increased BMI would also have led to the increases in serum cholesterol, triglycerides and apo B [31], an effect further compounded by the increase in dietary saturated fat [32]. The apparent small increase in HDL cholesterol associated with migration might at first sight be unanticipated, because HDL cholesterol decreases with obesity [33], insulin resistance [34] and type 2 diabetes [35]. It is, however, likely to be a genuine finding because it was supported by the increased serum apo AI in British Gujaratis.
The causes of the excess coronary heart disease (CHD) risk in South Asian migrants from the Indian subcontinent remain unclear. Comparisons of CHD risk factors amongst South Asian migrants living in Britain with those of the general UK population provide only a partial explanation. We compared Gujaratis in Britain with similar, non-migrant Gujaratis in India, to test the hypothesis that differences in CHD risk factors associated with migration would be more informative. Randomly sampled Gujaratis aged 25–79 years living in Sandwell (n = 242) were compared with age-, gender- and caste-matched contemporaries remaining in their villages of origin in Navsari, India (n = 295). Lifestyle indices, food intake and physical activity, were assessed with standardised questionnaires and energy expenditure and metabolic parameters measured.
British Gujaratis had higher, mean body mass indices by 6 (4.5–7.4) kg/m² mean (95% CI), and greater dietary energy intake, fat intake, blood pressure, fasting serum cholesterol, apolipoprotein B, triglycerides, non-esterified fatty acid (NEFA) and C-reative protein concentrations than Gujaratis in India. Dietary folate and serum folate and Vitamin B₁₂ were lower and plasma homocysteine was higher in India. Smoking was less prevalent and high-density lipoprotein cholesterol tended to be higher in Britain. Diabetes prevalence was high in both populations and impaired fasting or 2 h post-glucose challenge plasma glucose was even more prevalent in Gujarat. In India, however, where insulin secretion and NEFA were lower diabetes and impaired glucose tolerance were less frequently accompanied by excess metabolic CVD risk factors.
In conclusion, exposure to increased fat intake and obesity related to migration is likely to explain the disproportionate combination of established and emerging CHD risk factors prevalent in Gujaratis in Britain. Strategies to improve nutrition and to identify and treat cardiovascular risk factors such as dyslipidaemia and hypertension are urgently required.
Rosuvastatin and fenofibrate alone and in combination in type 2 diabetes patients with combined hyperlipidaemia
2004, Diabetes Research and Clinical Practice
The aim of this study was to evaluate the effects of rosuvastatin and fenofibrate alone and in combination in type 2 diabetes associated with combined hyperlipidaemia. A total of 216 patients with total cholesterol ≥200 mg/dl (≥5.17 mmol/l) and triglycerides ≥200 and <800 mg/dl (≥2.26 and <9.03 mmol/l) were randomised to one of two placebo groups, rosuvastatin 5 mg or rosuvastatin 10 mg for 6 weeks (fixed-dose phase). During the subsequent 18-week dose-titration phase, one placebo group received titrated rosuvastatin 10, 20 and 40 mg (placebo/rosuvastatin); one placebo group received titrated fenofibrate 67 mg once, twice and three times daily (placebo/fenofibrate); and patients receiving 5 or 10 mg rosuvastatin received titrated fenofibrate as above (rosuvastatin 5 mg/fenofibrate and rosuvastatin 10 mg/fenofibrate groups). Doses were increased at 6-week intervals if low-density lipoprotein (LDL) cholesterol remained >50 mg/dl (>1.3 mmol/l). At 24 weeks, the placebo/rosuvastatin group and placebo per fenofibrate group had triglyceride reductions of 30.3% versus 33.6%, respectively (P=NS), and LDL cholesterol was reduced by 46.7% in the rosuvastatin group and increased by 0.7% in the fenofibrate group (P<0.001). The triglyceride reduction in the rosuvastatin 10 mg/fenofibrate group (47.1%) was significantly greater than in the placebo/rosuvastatin group (P=0.001), with no significant differences in other lipid measures found between these two groups. No significant differences in effect on high-density lipoprotein (HDL) were observed among treatment groups. In the fixed-dose phase, rosuvastatin 5 and 10 mg reduced triglycerides by 24.5 and 29.5%, respectively, and decreased LDL cholesterol by 40.7 and 45.8%, respectively. All treatments were well tolerated. These results indicated that rosuvastatin produces marked reductions in triglycerides and LDL cholesterol when used alone or in combination with fenofibrate in type 2 diabetes patients with elevated cholesterol and triglyceride levels and may constitute a valuable treatment option in the diabetic population.
Dyslipidaemia
2003, Lancet
Citation Excerpt :
The dominant hyperlipidaemia in diabetes is hypertriglyceridaemia,12,132 which is most likely to be associated with hypercholesterolaemia and with decreased HDL cholesterol in type 2 diabetes.133 The hypertriglyceridaemia is associated not simply with an increase in VLDL, but also in intermediate-density lipoprotein and small dense LDL.134,135 Since neither of these lipoproteins contribute greatly to a rise in lipid concentrations, the term dyslipoproteinaemia is particularly aptly applied in diabetes.
The lowering of serum cholesterol is increasingly recognised as essential in the prevention of coronary heart disease and other atherosclerotic disease. The success of statin trials and the need to deploy these drugs effectively in the population has led increasingly to the identification of many people whose serum cholesterol, triglycerides, and HDL-cholesterol require clinical assessment, and frequently treatment. Lipid disorders are mainly straightforward, but some are complex or resistant to simple treatment strategies. I have reviewed the clinical manifestations of disordered lipid metabolism (dyslipidaemia) and its management.
Effect of ergotamine on plasma metabolite and insulin-like growth factor-1 concentrations in cows
2003, Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
Bovine plasma was assayed to determine if ergotamine affected plasma metabolite and insulin-like growth factor-1 (IGF-1) concentrations. In Experiment 1, four cows received a single bolus intravenous injection of ergotamine tartrate (19 μg/kg body wt.) or saline vehicle in a crossover design 2 days after prostaglandin-induced luteolysis. Treatment×time affected plasma glucose, triglyceride, total cholesterol and IGF-1 concentrations. Glucose and cholesterol were increased after ergotamine. Triglycerides were elevated within 1 h after ergotamine, but were decreased 3 h after ergotamine treatment. Plasma IGF-1 decreased in response to ergotamine. Blood constituents were unchanged after treatment with saline. In Experiment 2, six cows received a single bolus intravenous injection of ergotamine (20 μg/kg body wt.) or saline vehicle in a crossover design 10 days after receiving norgestomet (6 mg) via subcutaneous ear implant. Treatment×time affected glucose, triglycerides, total cholesterol and IGF-1 concentrations. Glucose and cholesterol were increased after ergotamine. Triglycerides were elevated 1 h after ergotamine and decreased 3–7 h after ergotamine. Plasma IGF-1 decreased after ergotamine treatment. Blood constituents were unresponsive to the saline vehicle. Results indicated ergotamine altered plasma metabolite and IGF-1 concentrations in cows.
Sex difference impacts on the relationship between paraoxonase-1 (Pon1) and type 2 diabetes
2020, Antioxidants
Antihyperlipidemic activity of Commiphora mukul against atherogenic diet-induced hyperlipidemia in experimental rats
2018, Asian Journal of Pharmaceutical and Clinical Research

View all citing articles on Scopus

View full text

Regular ArticleDiabetic dyslipidaemia

Abstract

American Journal of Clinical Nutrition

Atherosclerosis

Metabolism

Baillière's Clinical Endocrinology and Metabolism

Atherosclerosis

Journal of Clinical Epidemiology

Atherosclerosis

Journal of Lipid Research

American Journal of Medicine

Journal of Lipid Research

Atherosclerosis

Atherosclerosis

Journal of Lipid Research

Atherosclerosis

Atherosclerosis

Metabolism

Atherosclerosis

Atherosclerosis

Atherosclerosis

Clinical Chimica Acta

Atherosclerosis

Atherosclerosis

Clinica Chimica Acta

Clinica Chimica Acta

Lancet

The Discovery of Insulin

Epidemiology of risk factors for cardiovascular disease in diabetes and impaired glucose tolerance

Atherosclerosis

Diabetes and the heart: coronary heart disease

Clinical Endocrinology and Metabolism

Trends in diet 1841–1994

The effect of continuous subcutaneous insulin infusion on very-low-density lipoprotein triglyceride metabolism in type 1 diabetes mellitus

Diabetes

Glucosylation of LDL to an extent comparable to that seen in diabetes slows their catabolism

Diabetes

In vivo stimulation of low-density lipoprotein degradation by insulin

Diabetes

American Journal of Cardiology

Lancet

Prospective randomised study of intensive insulin treatment on long-term survival after acute myocardial infarction in patients with diabetes mellitus

British Medical Journal

Secondary hyperlipidaemia

Hyperlipidaemia Diagnosis and Management

Blood Analytes

Diabetes, other risk factors and 12 year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial

Diabetes Care

Lancet

The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels

New England Journal of Medicine

New England Journal of Medicine

Regular Article
Diabetic dyslipidaemia