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Insulin resistance and enhanced protein

glycation in men with prehypertension

Article in Clinical Chemistry and Laboratory Medicine · February 2006

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 Article in press - uncorrected proof
Clin Chem Lab Med 2006;44(12):1457–1461
2006 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2006.264 2006/272

Insulin resistance and enhanced protein glycation

in men with prehypertension

Viswanathan Sathiyapriya1,a, Hanumanthappa Introduction

Nandeesha1,a, Zachariah Bobby1,*,
Purushothaman Pavithran2, Nambiar Selvaraj1 Hypertension is a common cardiovascular disorder
and Nadaradjan Rattina Dasse1 accounting for approximately 6% of all deaths, defin-
1 ing the risk factor as a major problem globally (1). Epi-
Department of Biochemistry,
2 demiologic studies in urban and rural regions of India
Department of Physiology,
in the last decade have shown an increase in the over-
Jawaharlal Institute of Postgraduate Medical
all prevalence of hypertension from 1.24% in 1949 to
Education and Research, Pondicherry, India
36.4% in 2003 in urban populations and from 1.99%
in 1958 to 21.2% in 1994 in rural populations (2).
Insulin resistance and hyperinsulinemia are two
Abstract metabolic disorders that have been demonstrated
to be frequently associated with both human and ex-
Background: Insulin resistance and hyperinsulinemia perimental hypertension (3, 4). This observed associ-
have been reported among patients with hyperten- ation between hypertension and hyperinsulinemia is
sion. However, little is known about insulin sensitivity progressively assuming greater significance because
in subjects with prehypertension. The aim of this of the putative atherogenic effect of hyperinsulinemia
study was to assess whether the metabolic character- (5, 6).
istics of insulin resistance syndrome are present in It has been reported that insulin-resistant subjects
prehypertensive subjects. are at risk of developing a cluster of abnormalities,
Methods: Plasma fasting glucose, lipid profile, glyca- including high plasma concentrations of triglyceride
ted hemoglobin, fructosamine and insulin concentra- (TG), a decrease in plasma high-density lipoprotein
tions were evaluated in 35 prehypertensive subjects cholesterol (HDL-C) concentrations, and hypertension
and in 30 healthy controls. (6). This cluster of cardiovascular risk factors has been
Results: Prehypertensive subjects had significantly referred to as insulin resistance syndrome or the met-
higher levels of plasma insulin and triglycerides com- abolic syndrome and can lead to an increased risk of
pared with normotensive subjects. The level of high- coronary heart disease (7).
density lipoprotein cholesterol was significantly lower Apart from hyperinsulinemia and dyslipidemia, ele-
in prehypertensive subjects compared with controls. vated glycated protein levels represent another para-
There was no significant difference in total cholesterol meter known to have pathological consequences,
and low-density lipoprotein cholesterol levels. The including vascular complications (8, 9). Glycation of
levels of glycated hemoglobin and fructosamine were hemoglobin and serum proteins is reported to be pro-
also significantly higher in prehypertensive subjects portional to the ambient glucose concentration (8).
compared with controls. Plasma insulin levels were However, there is convincing evidence that non-enzy-
positively correlated with systolic and diastolic blood matically glycated protein concentrations are also
pressure in prehypertensive subjects. Similarly, plas- higher in many non-diabetic pathological states,
ma insulin was significantly positively correlated with including hypertension and gestational hypertension
triglyceride and negatively correlated with high-den- (10–13).
sity lipoprotein cholesterol. In contrast to the huge amount of experimental and
Conclusions: The present study indicates that prehy- clinical data available on the association of insulin
pertensive non-diabetic subjects have higher insulin resistance with hypertension, few clinical data sup-
resistance and protein glycation compared to nor- port such an association in prehypertensive subjects
motensive subjects, which may contribute to the (14, 15) and no such association has been reported
pathogenesis of prehypertension. among Indian prehypertensive subjects. Moreover,
Clin Chem Lab Med 2006;44:1457–61. there are no reports in the literature indicating the lev-
els of glycated proteins among prehypertensive
Keywords: hyperinsulinemia; hypertension; insulin subjects.
resistance; prehypertension; protein glycation. According to the Joint National Committee 7 (JNC
7) report, prehypertension (PHT) has been recently
a
These authors contributed equally to this study. described as an independent category of blood pres-
*Corresponding author: Dr. Zachariah Bobby, Assistant sure (BP) (16). It has been estimated that prehyper-
Professor, Department of Biochemistry, Jawaharlal Institute tensive subjects have twice the risk of developing
of Postgraduate Medical Education and Research (JIPMER), hypertension compared to normotensive individuals
Pondicherry-605 006, India
Phone: q91-413-2273078, Fax: q91-413-2372067, (17). Das et al. reported that PHT is present in approx-
E-mail: zacbobby@yahoo.com imately 58.7% of adults in urban India (18).
 Article in press - uncorrected proof
1458 Sathiyapriya et al.: Insulin resistance and protein glycation in prehypertension

As there is a drastic rise in the prevalence of hyper- lated by dividing the TG concentration by 2.2 (19). Low-den-
tension in India, it was deemed pertinent to study the sity lipoprotein cholesterol (LDL-C) levels were calculated
indicators of insulin resistance in PHT subjects. In using Friedewald’s formula. The homeostasis model assess-
addition, glycated hemoglobin and fructosamine lev- ment insulin resistance index (HOMA-IR) was calculated
according to the formula: fasting plasma insulin (mU/mL)
els were also measured in these individuals.
=fasting plasma glucose (mmol/L)/22.5 (20).

Statistical analysis
Materials and methods
All results except for plasma TG are presented as mean"SD.
Subjects Plasma TG levels are presented as median (interquartile
range), as they did not follow a normal Gaussian distribu-
The current study was conducted in the Department of Bio- tion. Student’s unpaired t-test and the Mann-Whitney U-test
chemistry and the Department of Physiology, JIPMER, Pon- were used to assess the significance of differences between
dicherry. Our subjects included the non-teaching staff of our the groups. Correlation analysis was assessed using Pear-
institute and outpatients who visited our laboratory for BP son’s test. A p-value of less than 0.05 was considered statis-
check-up. BP was measured using a mercury sphygmoma- tically significant.
nometer according to standardized procedures. BP was
measured three times over a 3-week period. At each visit,
the average of three readings was recorded to stage the
patients as having normal BP or PHT. Results
Subjects were classified as normotensive or prehyperten-
sive according to the recommendation of the JNC 7 report The general characteristics and clinical profiles of
(16). A total of 35 prehypertensive wsystolic BP (SBP) the prehypertensive and normotensive subjects are
120–139 mm Hg or diastolic BP (DBP) 80–89 mm Hgx and 30 shown in Table 1. There was no significant difference
normotensive (SBP -120 mm Hg and DBP -80 mm Hg) in age and BMI between the two groups. In the PHT
men in the age group 25–50 years were enrolled for this group, plasma insulin and HOMA-IR were significant-
study. Subjects with a history of diabetes, renal disease, ly higher compared to normotensive subjects (p-
endocrine dysfunction, coronary heart disease, or infection,
0.05). Levels of glycated hemoglobin and fructos-
smokers, alcoholics and those on any type of medication
amine were both significantly higher in prehyperten-
were excluded from the study. Written informed consent
was obtained from each subject. The study was approved by
sive subjects (p-0.05). TG and VLDL-C levels were
the institutional research and Ethics Committee. significantly higher and HDL-C levels were signifi-
cantly lower in prehypertensive compared to normo-
Anthropometric measurements tensive subjects. No significant difference in concen-
trations of total cholesterol and LDL-C was observed
Height and weight were measured using a standardized pro- between the two groups.
tocol, and body mass index (BMI) was calculated as weight Table 2 shows the correlation of age, BMI, BP, and
in kilograms divided by square of height in meters. Only sub- lipid profile with plasma insulin and HOMA-IR in PHT
jects with BMI-30 kg/m2 were included in the study.
subjects. Univariate analysis showed that both SBP
and DBP was significantly associated with HOMA-IR
Blood sample collection and fasting plasma insulin in PHT subjects. A signifi-
On the day of the study, subjects reported to our laboratory cant positive correlation was observed between plas-
in the morning after an overnight fast of 12 h. Venous blood ma TG and both fasting plasma insulin and HOMA-IR.
(5 mL) was collected from subjects in bottles containing Similarly, a negative correlation was observed be-
EDTA. An aliquot of 1 mL of the whole blood was used for tween both fasting plasma insulin and HOMA-IR with
estimation of glycated hemoglobin. The remainder of the HDL-C. A significant positive correlation was also
sample was centrifuged at 2500=g for 5 min, and the plasma observed between plasma TG/HDL-C and TC/HDL-C
samples obtained were used for assay of glucose, insulin, ratios and both fasting insulin and HOMA-IR.
fructosamine and lipid profile. Plasma glucose was estimat-
ed immediately and the rest of the sample was stored at
y708C until analysis.
Discussion
Analytical methods
It has become increasingly clear that hypertension is
Plasma glucose levels were determined by the glucose associated with abnormalities of glucose and lipid
oxidase method using a commercially available kit (Agappe metabolism (21). Patients with hypertension com-
Diagnostics, Kerala, India) adapted to a 550 analyzer (Ciba monly exhibit hyperinsulinemia and dyslipidemia,
Corning Diagnostics, Oberlin, OH, USA). Plasma insulin lev- which in turn can lead to increased cardiovascular risk
els were measured using a radio-immunoassay kit (BARC, (4, 21). To the best of our knowledge, this is the first
Mumbai, India). Glycated hemoglobin levels were measured
study to investigate the associations of hyperinsulin-
by ion-exchange chromatography (Biocon Diagnostik, Vöhl-
emia and insulin resistance with BP and dyslipidemia
Marienhagen, Germany). Plasma fructosamine was deter-
mined by p-indonitrotetrazolium violet assay with a in non-obese, middle-aged male prehypertensive sub-
RAICHEM kit (Hemagen Diagnostics, San Diego, CA, USA) jects in India.
adapted to a 550 express plus autoanalyzer. TG, TC and HDL- In the present study, significantly higher levels of
C were also measured using an automated blood analyzer. fasting plasma insulin and HOMA-IR were observed
Very low-density lipoprotein (VLDL)-C (mmol/L) was calcu- in prehypertensive subjects compared to normoten-
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Sathiyapriya et al.: Insulin resistance and protein glycation in prehypertension 1459

Table 1 Mean"SD for age, BMI, blood pressure, insulin, HOMA-IR, lipid profile and glycated proteins in prehypertension
and control subjects.

Parameter Control (ns30) Prehypertension (ns35)

Age, years 37"10 39"8

BMI, kg/m2 24.61"2.53 25.26"3.05
Waist-to-hip ratio 0.91"0.06 0.93"0.03
SBP, mm Hg 114"5 122"8*
DBP, mm Hg 72"4 81"4*
Plasma glucose, mmol/L 4.79"1.02 5.08"0.98
Plasma insulin, pmol/L 157.8"74.4 272.87"166.2*
HOMA-IR 4.90"2.80 9.02"6.66*
Total cholesterol, mmol/L 4.66"0.98 4.84"0.85
Triglycerides, mmol/L 4.83 (3.66–5.8) 5.23 (4.29–5.8)*
HDL-C, mmol/L 1.29"0.28 1.13"0.3*
LDL-C, mmol/L 2.8"1.01 2.93"0.86
VLDL-C, mmol/L 0.58"0.28 0.78"0.42*
Triglycerides/HDL-C 1.11"0.73 1.88"1.77*
Total cholesterol/HDL-C 3.86"1.5 4.6"1.77
Glycated hemoglobin, % 5.52"1.18 6.21"1.30*
Fructosamine, mmol/L 1.41"0.57 1.74"0.69*
Triglycerides are reported as median (interquartile range). *p-0.05 compared to control subjects.

sive subjects. Previous studies on hypertension re- The HOMA-IR and plasma insulin levels in prehy-
vealed that hypertension per se, even in the absence pertensive subjects were significantly associated with
of obesity and/or diabetes mellitus, is associated with higher TG and lower HDL-C. Haffner et al. reported a
insulin resistance, which supports our findings (22– significant association between hyperinsulinemia and
24). the development of dyslipidemia in normoglycemic
We also found a significant association between subjects (28). They also proposed that this association
HOMA-IR and plasma insulin levels and both SBP and is independent of obesity and body fat distribution.
DBP in prehypertensive subjects. Salonen et al. sug- Similarly, many previous studies have demonstrated
gested that fasting insulin concentrations predict the that fasting hypertriglyceridemia and lower HDL-C
incidence of hypertension (4). In addition, a direct cor- concentrations are associated with insulin resistance
relation has been reported between plasma insulin (29, 30). In the present study, we also found signifi-
concentration and severity of hypertension (21). This cant positive correlations between plasma TG/HDL-C
relationship was found to be independent of other and TC/HDL-C ratios and both fasting plasma insulin
confounding factors such as obesity and lipid abnor- and HOMA-IR. These relationships observed in the
malities (4). present study indicate an association with the devel-
In the present study, while prehypertensive sub- opment of atherosclerosis and coronary heart dis-
jects had significantly higher levels of TG and VLDL- ease. In a recent longitudinal, population-based, US
C, their plasma HDL-C levels were significantly lower. cohort study, it was also shown that PHT is associated
Prehypertensive subjects in the present study had a with increased risk of major cardiovascular events
higher plasma TG/HDL-C ratio, which is considered a (31).
better surrogate marker of insulin resistance and car- A number of plausible pathophysiological mecha-
diovascular events (25–27). nisms support the causality of the associations obser-

Table 2 Correlation of age, BMI, blood pressure, glycated proteins and lipid profile with plasma insulin and HOMA-IR in
prehypertension.

Parameter Plasma insulin HOMA-IR

r p r p

SBP 0.415 0.013 0.422 0.012

DBP 0.401 0.017 0.444 0.007
Age y0.018 0.917 0.054 0.760
BMI 0.215 0.215 0.322 0.060
Total cholesterol 0.127 0.467 0.102 0.560
Triglycerides 0.391 0.020 0.366 0.031
VLDL-C 0.385 0.022 0.367 0.03
HDL-C y0.451 0.007 y0.432 0.009
LDL-C 0.096 0.582 0.074 0.672
TG/HDL 0.466 0.005 0.443 0.008
TC/HDL 0.5 0.002 0.48 0.004
Glycated hemoglobin 0.321 0.06 0.325 0.057
Fructosamine 0.101 0.563 0.155 0.374
 Article in press - uncorrected proof
1460 Sathiyapriya et al.: Insulin resistance and protein glycation in prehypertension

ved in the present study. Insulin resistance has been 2. Gupta R. Meta analysis of prevalence of hypertension in
proposed to: 1) elevate serum TG by increasing the India. Indian Heart J 1997;49:43–8.
3. DeFronzo RA, Ferrannini E. Insulin resistance: a multi-
rate of production and reducing the catabolism of
faceted syndrome responsible for NIDDM, obesity,
VLDL through low lipoprotein lipase activity; and to hypertension, dyslipidemia and atherosclerotic cardio-
2) lower serum HDL-C by decreasing the synthesis of vascular disease. Diabetes Care 1991;14:173–94.
HDL-C from LDL TGs due to low lipoprotein lipase 4. Salonen JT, Lakka JA, Lakka HM, Valkonen VP, Everson
activity, increasing the fractional catabolic rate of apo- SA, Kaplan GA. Hyperinsulinemia is associated with the
lipoprotein A-1 (the major apolipoprotein for HDL-C), incidence of hypertension and dyslipidemia in middle
elevating hepatic lipase concentrations, and increas- aged men. Diabetes 1998;47:270–5.
5. Stolar MW. Atherosclerosis in diabetes: the role of hy-
ing cholesteryl ester transferase activity (30). It has
perinsulinemia. Metabolism 1988;37:1–9.
been suggested that insulin resistance and/or subse- 6. Reaven GM. Insulin resistance, the insulin resistance
quent hyperinsulinemia chronically elevate BP by syndrome, and cardiovascular disease. Panminerva Med
enhancing sympathetic nervous system activity, in- 2005;47:201–10.
creasing renal tubular sodium reabsorption, modulat- 7. Sheu WH, Jeng CY, Shieh SM, Fuh MM, Shen DD, Chen
ing cation transport, and inducing vascular smooth- YD, et al. Insulin resistance and abnormal electrocardio-
grams in patients with high blood pressure. Am J Hyper-
muscle cell hypertrophy (32), and by decreasing basal
tens 1992;5:444–8.
production of nitric oxide by the vascular endotheli- 8. Wolff SP, Jiang ZY, Hunt JV. Protein glycation and oxi-
um (33). It has also been observed that insulin resis- dative stress in diabetes mellitus and ageing. Free Radic
tance is associated with increased carotid wall Biol Med 1991;10:339–52.
thickness and carotid artery plaques (34). 9. Zhoa R, Shen GX. Functional modulation of antioxidant
In the present study we found higher levels of both enzymes in vascular endothelial cells by glycated LDL.
fructosamine and glycated hemoglobin in prehyper- Atherosclerosis 2005;179:277–84.
10. Chowdhury TA, Lasker SS. Elevated glycated haemoglo-
tensive compared to normotensive subjects. Incre-
bin in non-diabetic patients is associated with an
ased glycated hemoglobin levels have been reported increased mortality in myocardial infarction. Postgrad
in both non-diabetic essential hypertensive and ges- Med J 1998;74:480–1.
tational hypertensive subjects (12, 13). Glycation of 11. Sabater J, Quereda C, Herrera I, Pascual J, Villafruella
proteins, enzymes, and insulin can reduce insulin sen- JJ, Ortuno J. Nonenzymatic glycosylation of hemoglo-
sitivity and increase oxidative susceptibility, and is bin and total plasmatic proteins in end-stage renal dis-
considered as a risk factor in the development of vas- ease. Am J Nephrol 1991;11:37–43.
12. Nilsson PM, Lind L, Pollare T, Berne C, Lithell HO.
cular disease in diabetes (8, 9, 35). The mechanisms
Increased level of hemoglobin A1C, but not impaired
for higher fructosamine and glycated hemoglobin in insulin sensitivity, found in hypertensive and normoten-
prehypertensive subjects are not clear. We and Jain sive smokers. Metabolism 1995;44:557–61.
et al. have identified that lipid peroxides and reduced 13. Roberts RN, Traub AI, Kennedy AL, Hadden DR. Glyco-
glutathione can per se influence the glycation of pro- sylated haemoglobin and hypertension arising in preg-
teins (36, 37). nancy. Br J Obest Gynaecol 1998;105:1122–4.
In conclusion, the findings from the present study 14. Kanauchi M, Kanauchi K, Hashimoto T, Saito Y. Meta-
bolic syndrome and new category ‘‘pre-hypertension’’ in
suggest that hyperinsulinemia and insulin resistance
a Japanese population. Curr Med Res Opin 2004;20:
in prehypertensive subjects are associated with high- 1365–70.
er plasma TG, lower HDL-C concentrations and an 15. Cordero A, Laclaustra M, León M, Grima A, Casasnovas
increase in both systolic and diastolic BP. Higher gly- JA, Luengo E, et al. Prehypertension is associated with
cated protein levels in these subjects with normal glu- insulin resistance state and not with an initial renal func-
cose levels may also have important pathophysio- tion impairment. A Metabolic Syndrome in Active Sub-
logical implications. All of these changes have been jects in Spain (MESYAS) Registry substudy. Am J
Hypertens 2006;19:189–96.
shown to increase the risk of coronary heart disease.
16. Chobanian AV, Bakris GR, Black HR, Cushman WC,
Moreover, the present findings should also have ther- Green LA, Izzo JL Jr, et al. Seventh report of the Joint
apeutic implications when choosing pharmacological National Committee on prevention, detection, evaluation
tools to ameliorate the development of hypertension and treatment of high blood pressure: the JNC 7 report.
in this highly susceptible section of the population. J Am Med Assoc 2003;289:2560–72.
17. Vasan RS, Larson MG, Leip EP, Kannel WB, Levy D.
Acknowledgements Assessment of frequency of progression to hypertension
in non-hypertensive participants in the Framingham
This work was supported by a grant from the Department of Heart study: a cohort study. Lancet 2001;358:1682–6.
Science, Technology and Environment, Pondicherry, India, 18. Das SK, Sanyal K, Basu A. Study of urban community
and by the Council of Scientific and Industrial Research, New survey in India: growing trend of high prevalence of
Delhi, India, in the form of a Senior Research Fellowship to hypertension in a developing country. Int J Med Sci
Ms. V. Sathiyapriya. We thank Mr. R. Balakrishnan, Technical 2005;2:70–8.
Supervisor and Mr. A. Venkatraman, Laboratory Technician 19. Friedewald WT, Levy RI, Fredrickson DS. Estimation of
for their technical support during this study. the concentration of low-density lipoprotein cholesterol
in plasma, without use of the preparative ultracentrifuge.
Clin Chem 1972;18:499–502.
20. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Trea-
References cher DF, Turner RC. Homeostasis model assessment:
insulin resistance and b-cell function from fasting plas-
1. Reddy KS. Hypertension control in developing countries: ma glucose and insulin concentration in man. Diabeto-
generic issues. J Hum Hypertens 1996;10:S33–8. logia 1985;28:412–9.
 Article in press - uncorrected proof
Sathiyapriya et al.: Insulin resistance and protein glycation in prehypertension 1461

21. Grunfeld BM, Balzareti M, Romo M, Gimenez M, Gutman 30. Laakso M. The possible pathophysiology of insulin resis-
R. Hyperinsulinemia in normotensive offspring of hyper- tance syndrome. Cardiovasc Risk Factors 1993;3:55–66.
tensive patients. Hypertension 1994;3:112–5. 31. Kshirsagar AV, Carpenter M, Bang H, Wyatt SB,
22. Cubeddu LX, Hoffmann IS. Insulin resistance and upper- Colindres RE. Blood pressure usually considered normal
normal glucose levels in hypertension: a review. J Hum is associated with an elevated risk of cardiovascular
Hypertens 2002;16:S52–5. events. Am J Med 2006;119:133–41.
23. Capaldo B, Lembo G, Napoli R, Rendina V, Albano G, 32. Sowers JR, Standley PR, Ram JL, Jacober S, Simpson
Sacca L, et al. Skeletal muscle is primary site of insulin L, Rose K. Hyperinsulinemia, insulin resistance, and
resistance in essential hypertension. Metabolism 1991; hyperglycemia: contributing factors in the pathogenesis
40:1320–2. of hypertension and atherosclerosis. Am J Hypertens
24. Ferrannini E. Insulin resistance in essential hypertension. 1993;6:S260–70.
N Engl J Med 1987;317:350–7. 33. Scherrer U, Randin D, Vollenweider P, Vollenweider L,
25. McLaughlin T, Abbasi F, Cheal K, Chu J, Lamendola C, Nicod P. Nitric oxide accounts for insulin’s vascular
Reaven G. Use of metabolic markers to identify over- effects in humans. J Clin Invest 1994;94:2511–5.
weight individuals who are insulin resistant. Ann Intern 34. Suzuki M, Shinozaki K, Kanazawa A, Hara Y, Hattori Y,
Med 2003;139:802–9. Tsushima M, et al. Insulin resistance as an independent
26. McLaughlin T, Reaven G, Abbasi F, Lamendola C, Saad risk factor for carotid wall thickening. Hypertension
M, Waters D, et al. Is there a simple way to identify insu- 1996;28:593–8.
lin-resistant individuals at increased risk of cardiovas- 35. Lapolla A, Tessari P, Poli T, Valerio A, Duner E, Iori E, et
cular disease? Am J Cardiol 2005;96:399–404. al. Reduced in vivo activity of in vitro glycosylated insu-
27. Lemieux I, Lamarche B, Couillard C, Pascot A, Cantin B, lin. Diabetes 1988;37:787–91.
Bergeron J, et al. Total cholesterol/HDL cholesterol ratio 36. Jain SK, Palmer M. The effect of oxygen radicals metab-
vs. LDL cholesterol/HDL cholesterol ratio as indices of olites and vitamin E on glycosylation of proteins. Free
ischemic heart disease risk in men: the Quebec Cardio- Radic Biol Med 1997;22:593–6.
vascular Study. Arch Intern Med 2001;61:2685–92. 37. Selvaraj N, Bobby Z, Sathiyapriya V. Effect of lipid per-
28. Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales oxides and antioxidants on glycation of hemoglobin: an
PA, Stern MP. Prospective analysis of the insulin resis- in vitro study on human erythrocytes. Clin Chim Acta
tance syndrome (syndrome X). Diabetes 1992;41:715–22. 2006;366:190–5.
29. Garg A. Insulin resistance in the pathogenesis of dys-
lipidemia. Diabetes Care 1996;19:387–9. Received July 14, 2006, accepted August 31, 2006

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