Pathophysiology/Complications

B R I E F R E P O R T

Triglyceride–to–HDL Cholesterol Ratio in

the Dyslipidemic Classification of Type 2
Diabetes
ANA MARÍA WÄGNER, MD, PHD1 JOSE LUIS SÁNCHEZ-QUESADA, PHD2 SP3– 07. Its cutoff point (0.97 g/l) was
ANTONIO PÉREZ, MD, PHD1 JORDI ORDÓÑEZ-LLANOS, MD, PHD2,3 defined as the equivalent to an LDL cho-
lesterol of 3.36 mmol/l (7) in a previously
described nondiabetic normolipidemic
control group (8). LDL size was deter-
mined by polyacrylamide gradient (2–

A
lthough LDL cholesterol is the main [3.7–16]) were consecutively included in
target in the treatment of diabetic the study. None of the patients were tak- 16%) gel electrophoresis (3), and LDL
dyslipidemia, it does not fully ac- ing drugs or were in situations (not re- phenotype B was defined by a predomi-
count for the cardiovascular risk associ- lated to diabetes) known to affect nant LDL diameter ⬍25.5 nm.
ated with diabetes, neither alone nor in lipoprotein metabolism. Patients were classified according to
combination with triglycerides and HDL Total cholesterol and triglycerides their triglyceride and apoB concentra-
cholesterol. On the other hand, diabetic were measured by enzymatic methods tions as well as according to their triglyc-
dyslipidemia also includes an overall in- and HDL cholesterol by a direct method erides, triglyceride–to–HDL cholesterol
crease in atherogenic particles identifi- (Roche Diagnostics, Basel, Switzerland). ratio, and their non-HDL cholesterol.
able, by measuring apolipoprotein B Hypertriglyceridemia was defined by trig- Statistical analysis was performed us-
(apoB), and a predominance of small, lycerides ⬎2.25 mmol/l (4,5). LDL cho- ing the SPSS 10.0 statistical package for
dense LDL particles (phenotype B). The lat- lesterol was obtained by Friedewald’s Windows (SPSS, Chicago, IL). Results are
ter, although associated with increased car- formula (if triglycerides ⬍3.39 mmol/l) expressed as means ⫾ SD (Gaussian dis-
diovascular risk, is not routinely assessed or by ultracentrifugation. Non-HDL cho- tribution), median and ranges (non-
because its measurement is not available to lesterol was calculated by subtracting Gaussian distribution), or as percentages.
most clinical laboratories. Therefore, easily HDL cholesterol from total cholesterol. Nonparametric, bivariate correlations
measurable predictors of LDL size, such as High non-HDL cholesterol was defined (Spearman) were performed between
triglycerides or LDL cholesterol/apoB and by the equivalent to an LDL cholesterol ⬎ LDL size and other parameters. Concor-
triglyceride–to–HDL cholesterol ratios, 3.36 mmol/l, when pharmacological in- dance between the dyslipidemic pheno-
have been proposed, with the latter being tervention is recommended, i.e., non- typic classifications was assessed using
suggested as the best surrogate (1,2,3). HDL cholesterol ⬎4.13 mmol/l (4). The the kappa index (␬). Values between 0.21
However, no study has been conducted that triglyceride–to–HDL cholesterol ratio and 0.40, 0.41 and 0.60, 0.61 and 0.80,
compares all of these predictors. was expressed in mmol/l over mmol/l. and 0.81 and 1.0 showed fair, moderate,
The aim of the present study is to Previously described cutoff points were good, and very good concordance, re-
evaluate the triglyceride–to–HDL choles- used (1,2,6), as well as that calculated spectively (9).
terol ratio, non-HDL cholesterol, and from the regression equation obtained
apoB to predict LDL phenotype and to from the samples included in the present RESULTS — The patients showed the
assess them in the risk classification of pa- study: triglyceride–to–HDL cholesterol following lipoprotein concentrations (in
tients with type 2 diabetes. ratio ⫽ 42.122 ⫺ 1.576 ⫻ LDL size (R ⫽ mmol/l unless otherwise indicated): trig-
0.625) for an LDL size of 25.5 nm. ApoB lycerides 1.38 (0.56 –9.25), LDL choles-
RESEARCH DESIGN AND was measured by an immunoturbidimet- terol 3.58 (0.94), HDL cholesterol 1.20
METHODS — A total of 107 type 2 di- ric method (Tina-quant, Roche Diagnos- (0.29), non-HDL cholesterol 4.42 (1.18),
abetic patients (68% male, age 59 ⫾ 10 tics) calibrated against the World Health apoB 1.16 (0.25) g/l, and LDL size 25.8
years [means ⫾ SD], time since diagnosis Organization/International Federation of (24.4 –27.0) nm. When comparing pa-
8.5 years [range 0 –37], HbA1c 7.35% Clinical Chemistry reference standard tients with phenotypes A and B, the
former showed lower triglyceride–to–
● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● HDL cholesterol ratios (0.88 [0.30 –3.17]
From the 1Endocrinology Department, Hospital Sant Pau, Barcelona, Spain; the 2Biochemistry Department, vs. 2.33 [0.53], P ⬍ 0.0005). LDL size
Hospital Sant Pau, Barcelona, Spain; and the 3Biochemistry Department, Universitat Autònoma de Barce- showed a direct correlation with HDL
lona, Barcelona, Spain. cholesterol (R ⫽ 0.439) and LDL choles-
Address correspondence and reprint requests to Ana Ma Wägner, Steno Diabetes Center, Niels Steensens
vej 2. 2820 Gentofte, Denmark. E-mail: awgn@steno.dk. terol/apoB (R ⫽ 0.583) and an inverse
Received for publication 24 February 2005 and accepted in revised form 28 March 2005. correlation with triglycerides (R ⫽
Abbreviations: apoB, apolipoprotein B. ⫺0.626) and the triglyceride–to–HDL
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion cholesterol ratio (R ⫽ ⫺0.643, P ⬍ 0.0005
factors for many substances.
© 2005 by the American Diabetes Association.
for all). No correlation was found with
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby non-HDL cholesterol or apoB. When pa-
marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. tients were classified according to previ-

1798 DIABETES CARE, VOLUME 28, NUMBER 7, JULY 2005


Figure 1—Distribution of the patients into apoB-dependent dyslipidemic phenotypes according to
their triglyceride–to–HDL cholesterol ratio (A) and their non-HDL cholesterol (B). Tg, triglyc-
eride; HDLc, HDL cholesterol.
ously proposed cutoff points for
triglycerides–to–HDL cholesterol, the
concordance with their classification into
LDL phenotypes A and B was fair (␬ ⫽
0.390 for a cutoff point of 0.9) to moder-
ate (␬ ⫽ 0.478 for a cutoff point of 1.33
and ␬ ⫽ 0.545 for a cutoff point of 1.64).
When using the regression equation trig-
lycerides/HDL cholesterol ⫽ 42.122 ⫺
1.576 ⫻ LDL size (R ⫽ 0.625), for an LDL
size of 25.5 nm, a triglyceride/HDL cho-
lesterol cutoff point of 1.93 was obtained.
When this cutoff point was used, the con-
cordance of the patients’ classification
with LDL phenotype was also moderate,
though slightly better than with the other
cutoff points (␬ ⫽ 0.554). It showed a
sensitivity of 60% and a specificity of 92%
to predict LDL phenotype B. We used
1.93 as the cutoff point to classify the pa-
tients (normal-high triglyceride–to–HDL
cholesterol ratio) and compare their dis-
tribution with when the classification was
DIABETES CARE, VOLUME 28, NUMBER 7, JULY 2005
performed using apoB and triglycerides
(Fig. 1). Using these cutoff points, the
concordance between hyperapoB and the
hypertriglyceride–to–HDL cholesterol ra-
tio was poor (␬ ⫽ 0.175), whereas the
concordance between hyperapoB and hy-
per–non-HDL cholesterol was moderate
(␬ ⫽ 0.522). Results were similar when
cutoff points equivalent to LDL choles-
terol of 2.59 mmol/l were used for non-
HDL cholesterol and apoB, as well as
when men and women were analyzed
separately (data not shown).
CONCLUSIONS — T h e p r e s e n t
study shows that the triglyceride–to–HDL
cholesterol ratio is not superior to non-
HDL cholesterol in classifying patients
with type 2 diabetes into dyslipidemic
phenotypes. The triglyceride–to–HDL
cholesterol ratio is cheap and easy to cal-
culate and is a good predictor of LDL size.
However, it does not identify most of the
Wägner and Associates
patients with hyperapoB, has a high bio-
logical variability that is inherent to trig-
lycerides (10), as reflected by the wide
range of recommended cutoff points, and
its determination should be made in the
fasting state. On the other hand, non-
HDL cholesterol is as cheap and easy to
measure as the triglyceride–to–HDL cho-
lesterol ratio, with the additional advan-
tage that its biologic variability is much
lower and fasting samples are not needed.
ApoB reflects the total number of athero-
genic particles and is superior to non-
HDL cholesterol both as a cardiovascular
risk predictor and as a predictor of the
risk reduction following treatment of dys-
lipidemia (11). Its determination can also
be made in the nonfasting state (12), its
biological variability is lower than for
other lipidic components, and the intro-
duction of an international standard has
made results from different labs compara-
ble (13).
We have previously shown that in hy-
pertriglyceridemic patients, apoB and
non-HDL cholesterol are equivalent in
classifying them into dyslipidemic phe-
notypes (14). This is also true for the tri-
glyceride–to–HDL cholesterol ratio. In
normotriglyceridemic subjects, however,
non-HDL cholesterol identifies around
half of the individuals with hyperapoB
(14), whereas the triglyceride–to–HDL
cholesterol ratio identifies ⬍10% (Fig. 1).
Therefore, based on current and pre-
vious results and the cost-effectiveness of
the different components, a strategy con-
sisting of the estimation of non-HDL cho-
lesterol (as a surrogate of apoB) in all of
the subjects and the measurement of apoB
itself in the normotriglyceridemic sub-
jects with normal non-HDL cholesterol is
proposed for dyslipidemic risk classifica-
tion of patients with type 2 diabetes. The
triglyceride–to–HDL cholesterol ratio
does not add useful information to the
previously mentioned strategy.
Acknowledgments — The study was partially
funded by grants from Fondo de Investigacio-
nes Sanitarias (no. C03/01 and C03/08).
References
1. Boizel R, Benhamou PY, Lardy B, Laporte
F, Foulon T, Halimi S: Ratio of triglycer-
ide to HDL cholesterol is an indicator of
LDL particle size in patients with type 2
diabetes and normal HDL cholesterol lev-
els. Diabetes Care 23:1679 –1685, 2000
1799
Triglyceride–to–HDL cholesterol ratio vs. apoB
2. Hanak V, Muñoz J, Teague J, Stanley A,
Bittner V: Accuracy of the triglyceride to
high-density lipoprotein cholesterol ratio
for prediction of the low-density lipopro-
tein phenotype B. Am J Cardiol 94:219 –
222, 2004
3. Wägner AM, Jorba O, Rigla M, Alonso E,
Ordoñez-Llanos J, Pérez A: LDL-choles-
terol/apolipoprotein B ratio is a good pre-
dictor of LDL phenotype B in type 2
diabetes. Acta Diabetol 39:215–220, 2002
4. Expert Panel on Detection, Evaluation
and Treatment of High Blood Cholesterol
in Adults: Executive summary of the third
report of the National Cholesterol Educa-
tion Program (NCEP) expert panel on de-
tection, evaluation and treatment of high
blood cholesterol in adults (Adult Treat-
ment Panel III). JAMA 285:2486 –2496,
2001
5. American Diabetes Association: Manage-
ment of dyslipidemia in adults with
diabetes. Diabetes Care 27 (Suppl. 1):
S68 –S71, 2004
6. Maruyama C, Imamura K, Teramoto T:
Assessment of LDL particle size by triglyc-
eride/HDL-cholesterol ratio in non-dia-
1800
betic, healthy subjects without prominent
hyperlipidemia. J Atheroscler Thromb 10:
186 –191, 2003
7. Contois JH, McNamara JR, Lammi-Keefe
CJ, Wilson PW, Massov T, Schaeffer E:
Reference intervals for plasma apoli-
poprotein B determined with a standard-
ized commercial immunoturbidimetric
assay: results from the Framingham Off-
spring Study. Clin Chem 42:515–523,
1996
8. Wägner AM, Pérez A, Calvo F, Bonet R,
Castellvı́ A, Ordóñez J: Apolipoprotein B
identifies dyslipidemic phenotypes asso-
ciated with cardiovascular risk in normo-
cholesterolemic type 2 diabetic patients.
Diabetes Care 22:812– 817, 1999
9. Altman DG. Some common problems in
medical research. In Practical Statistics for
Medical Research. Altman DG, Ed. New
York, Chapman and Hall, 1991, p. 396 –
439
10. Ortolá J, Castineiras MJ, Fuentes-Arderiu
X: Biological variation data applied to the
selection of serum lipid ratios used as risk
markers of coronary heart disease. Clin
Chem 38:56 –59, 1992
11. Sniderman AD, Furberg CD, Keech A,
Roeters van Lennep JE, Frohlich J, Jung-
ner I, Walldius G: Apolipoproteins versus
lipids as indices of coronary risk and as
targets for statin treatment. Lancet 361:
777–780, 2003
12. Walldius G, Jungner I, Holme I, Aastveit
AH, Kolar W, Steiner E: High apolipopro-
tein B, low apolipoprotein A-I, and im-
provement in the prediction of fatal
myocardial infarction (AMORIS study): a
prospective study. Lancet 358:2026 –2033,
2001
13. Marcovina SM, Albers JJ, Kennedy H, Mei
JV, Henderson LO, Hannon WH: Interna-
tional Federation of Clinical Chemistry
standardization project for measurement
of apolipoproteins A-I and B: comparabil-
ity of apolipoprotein B values by use of
International Reference Material. Clin
Chem 40:586 –592, 1994
14. Wägner AM, Pérez A, Zapico E, Ordóñez-
Llanos J: Non-HDL cholesterol and
apolipoprotein B in the dyslipidemic clas-
sification of type 2 diabetic patients. Dia-
betes Care 26:2048 –2051, 2003
DIABETES CARE, VOLUME 28, NUMBER 7, JULY 2005