Atherosclerosis. 2015 Apr;239(2):483-95.

doi:
10.1016/j.atherosclerosis.2015.01.039. Epub 2015 Feb 7.
New insights into the pathophysiology of dyslipidemia in type 2 diabetes.
Taskinen MR1, Born J2.
Author information
Abstract
Cardiovascular disease (CVD) remains the leading cause of morbidity and
mortality for patients with type 2 diabetes, despite recent significant advances
in management strategies to lessen CVD risk factors. A major cause is the
atherogenic dyslipidemia, which consists of elevated plasma concentrations of
both fasting and postprandial triglyceride-rich lipoproteins (TRLs), small dense
low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) cholesterol.
The different components of diabetic dyslipidemia are not isolated
abnormalities but closely linked to each other metabolically. The underlying
disturbances are hepatic overproduction and delayed clearance of TRLs. Recent
results have unequivocally shown that triglyceride-rich lipoproteins and their
remnants are atherogenic. To develop novel strategies for the prevention and
treatment of dyslipidaemia, it is essential to understand the pathophysiology of
dyslipoproteinaemia in humans. Here, we review recent advances in our
understanding of the pathophysiology of diabetic dyslipidemia.

Copyright 2015 Elsevier Ireland Ltd. All rights reserved.

Diabetes Care. 1997 Nov;20(11):1683-7.

U.K. Prospective Diabetes Study 27. Plasma lipids and lipoproteins at diagnosis
of NIDDM by age and sex.
[No authors listed]
Abstract
OBJECTIVE:
To compare fasting plasma lipids and lipoproteins in male and female patients
at diagnosis of NIDDM and to examine age and sex differences in lipid
concentrations.
RESEARCH DESIGN AND METHODS:
Cross-sectional study of fasting plasma total cholesterol, LDL cholesterol, HDL
cholesterol, and triglyceride in 2,139 male and 1,574 female white patients,
aged 25-65 years, at diagnosis of NIDDM.
RESULTS:
At diagnosis of NIDDM, the mean age +/- SD for men was 52 +/- 9 and 53 +/- 9
years for women; BMI was 28.3 +/- 4.9 and 30.8 +/- 6.7 kg/m2, and fasting
plasma glucose was 11.6 +/- 3.6 and 12.4 +/- 3.8 mmol/l, respectively. The
mean total and LDL cholesterol were higher in female than in male NIDDM
patients, 5.8 +/- 1.2 vs. 5.5 +/- 1.1 and 3.9 +/- 1.1 vs. 3.6 +/- 1.0 mmol/l (both
P < 0.001), respectively, while triglyceride levels were similar: geometric mean
(1 SD interval) for men and women was 1.8 (1.1-3.1) vs. 1.8 (1.1-2.9) mmol/l.
HDL cholesterol was higher in female than in male NIDDM patients, 1.09 +/- 0.2
vs. 1.01 +/- 0.24 mmol/l (P < 0.001); the sex differential for HDL cholesterol
was 7% in NIDDM patients compared with 22% in the general population. Data
analysis by 5-year age bands showed a significant trend toward lower total
cholesterol and triglyceride and higher HDL cholesterol in men diagnosed
above the age of 50 years. In female NIDDM patients, lipid concentrations
increased with age of diagnosis but reached a plateau above the age of 50
years.
CONCLUSIONS:
The effect of NIDDM, observed at diagnosis, on plasma lipid and lipoprotein
levels is more pronounced in women than in men. This may explain in part why
the cardiovascular risk is proportionally higher in female patients.

Diabetologia. 1991 Dec;34(12):877-90.

UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and
performance.
[No authors listed]
Abstract
The UK Prospective Diabetes Study (UKPDS) is a multi-centre, prospective,
randomised, intervention trial of 5100 newly-diagnosed patients with Type 2
(non-insulin-dependent) diabetes mellitus which aims to determine whether
improved blood glucose control will prevent complications and reduce the
associated morbidity and mortality. Newly presenting Type 2 diabetic patients
aged 25-65 years inclusive, median age 53 years, median body mass index 28
kg/m2 and median fasting plasma glucose 11.3 mmol/l, were recruited and
treated initially by diet. Ninety five percent remained hyperglycaemic (fasting
plasma glucose greater than 6 mmol/l) and were randomly allocated to
different therapies. In the main randomisation, those who were asymptomatic
and had fasting plasma glucose under 15 mmol/l were allocated either to diet
policy, or to active policy with either insulin or sulphonylurea aiming to reduce
the fasting plasma glucose to under 6 mmol/l. Over 3 years, the median fasting
plasma glucose in those allocated to diet policy was 8.9 mmol/l compared with
7.0 mmol/l in those allocated to active policy. The Hypertension in Diabetes
Study has been included in a factorial design to assess whether improved blood
pressure control will be advantageous. Patients with blood pressure greater
than or equal to 160/90 mm Hg were randomly allocated to tight control aiming
for less than 150/85 mm Hg with either an angiotensin-converting enzyme
inhibitor or a Beta-blocker or to less tight control aiming for less than 200/105
mm Hg. The endpoints of the studies are major clinical events which affect the
life and well-being of patients, such as heart attacks, angina, strokes,
amputations, blindness and renal failure. To date, 728 patients have had at
least one clinical endpoint. Surrogate endpoints include indices of
macrovascular and microvascular disease detected by ECG with Minnesota
Coding, retinal colour photography and microalbuminuria. The studies also aim
to evaluate potential risk factors for the development of diabetic complications
such as smoking, obesity, central adiposity, plasma LDL- and HDL-cholesterol,
triglyceride, insulin, urate and other biochemical variables. The studies are
planned to terminate in 1994, with a median follow-up of 9 years (range 3-16
years) for the glucose study and 5 years (range 2-6 years) for the hypertension
study.

Am Heart J. 1985 Nov; 110(5):1100-7.

Lipids, diabetes, and coronary heart disease: insights from the Framingham
Study.
Kannel WB.
Abstract
Both risk factors and the incidence of cardiovascular disease are higher in
diabetic patients. Total serum cholesterol has the same impact on coronary
heart disease (CHD) incidence in diabetic patients as in nondiabetic individuals.
Abnormal blood lipids in diabetic patients include elevated very low-density
lipoproteins (VLDL) and triglyceride and reduced levels of high-density
lipoproteins (HDL). These are associated with obesity and precede the onset of
diabetes. Diabetes increases the risk of all clinical manifestations of CHD, has a
greater impact in women, and predisposes to cardiac failure and fatal outcome.
In men, it predisposes to silent myocardial infarctions. CHD risk reduction in the
diabetic patient requires multifactorial control. In evaluating the lipid-induced
CHD risk, the level of low-density lipoprotein (LDL) cholesterol is not as
valuable as the LDL/HDL cholesterol ratio, which is the most reliable criterion.
Triglyceride levels make no independent contribution. Most CHD preventive
measures, including weight control, exercise, avoidance of cigarettes, and
improvement of glucose tolerance also increase HDL cholesterol, reduced
levels of which are chiefly responsible for the poor LDL/HDL ratio in diabetics.
Weight control merits a high priority because of its favorable influence on the
lipid profile, glucose tolerance, and blood pressure.

Nat Clin Pract Endocrinol Metab. 2009 Mar;5(3):150-9. doi:

10.1038/ncpendmet1066.
Dyslipidemia in type 2 diabetes mellitus.
Mooradian AD1.
Author information
Abstract
Dyslipidemia is one of the major risk factors for cardiovascular disease in
diabetes mellitus. The characteristic features of diabetic dyslipidemia are a
high plasma triglyceride concentration, low HDL cholesterol concentration and
increased concentration of small dense LDL-cholesterol particles. The lipid
changes associated with diabetes mellitus are attributed to increased free fatty
acid flux secondary to insulin resistance. The availability of multiple lipidlowering drugs and supplements provides new opportunities for patients to
achieve target lipid levels. However, the variety of therapeutic options poses a
challenge in the prioritization of drug therapy. The prevalence of
hypercholesterolemia is not increased in patients with diabetes mellitus, but
mortality from coronary heart disease increases exponentially as a function of
serum cholesterol levels, and lowering of cholesterol with statins reduces
diabetic patients' relative cardiovascular risk. Although drug therapy for
dyslipidemia must be individualized, most people with diabetes mellitus are

candidates for statin therapy, and often need treatment with multiple agents to
achieve therapeutic goals.

Atheroscler Suppl. 2002 May;3(1):47-51.

Diabetic dyslipidemia.
Taskinen MR1.
Author information
Abstract
By the year 2025, there will be more than 300 million type 2 diabetes sufferers
worldwide. This epidemic will be followed by a wave of cardiovascular disease.
Diabetes is in fact a serious vascular disease with poor prognosis, and not only
a disease characterized by elevated blood glucose. If adequate attention were
paid to this, it would be much easier to relieve the burden of cardiovascular
disease in type 2 diabetes patients. One important cardiovascular risk factor in
type 2 diabetic people is dyslipidemia. This is characterized by low HDLcholesterol, high serum VLDL-triglycerides, and a preponderance of small,
dense LDL. Even slight elevations of LDL-cholesterol in type 2 diabetic patients
are associated with a substantial increase in cardiovascular risk. The
composition of lipid particles in diabetic dyslipidemia is more atherogenic than

in dyslipidemia in general. This means in turn that normal lipid concentrations

are more atherogenic in diabetic than in non-diabetic patients. Retrospective
analyses show that, in terms of protection from cardiovascular endpoints, the
benefit of lipid lowering in type 2 diabetic patients is at least as great as in the
non-diabetic population. Lowering of LDL-cholesterol is a very attractive target
for the reduction of coronary heart disease in type 2 diabetic people.