Blood Vessels
Increased Arterial Stiffness in Normoglycemic Normotensive
Offspring of Type 2 Diabetic Parents
Cristina Giannattasio, Monica Failla, Anna Capra, Elisabetta Scanziani, Maria Amigoni, Lucia Boffi,
Christine Whistock, Pierluigi Gamba, Felice Paleari, Giuseppe Mancia
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Abstract—Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether
or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring
of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic
diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by
echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the
brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and
large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid
diameters at diastole and a reduced increase in carotid diameter at systole (⫺16%), a reduced carotid artery distensibility
(⫺30%), and an increased pulse pressure (⫹21.8%), all differences being statistically significant (P⬍0.05) and
persisting in subgroups with elevated or normal body mass index values (⬍25 and ⱖ25 kg/m2). Carotid artery wall
thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery
stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism,
body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical
properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.
(Hypertension. 2008;51:182-187.)
Key Words: diabetes mellitus 䡲 arterial distensibility 䡲 atherosclerosis 䡲 blood pressure
D
iabetes mellitus is associated with an increase in large
artery wall thickness and a reduction in large artery
distensibility.1–10 These alterations are not late consequences
of the disease, because recent studies have shown that arterial
distensibility and wall thickness are altered also in subjects
with glucose intolerance who do not have but are predisposed
to diabetes11,12 and individuals aged ⬍40 years with a type 1
diabetes not accompanied by microvascular or macrovascular
complications.13
Except for a small study in which an increase in pulse wave
velocity was reported in very young subjects with a familial
background for diabetes,14 no information exists on arterial
structure and function in normoglycemic subjects with a
predisposition to type 2 diabetes. This is of clinical relevance,
because arterial stiffening and thickening are independent
predictors of an increase in cardiovascular risk.15,16 Furthermore, arterial stiffening has been associated with increased
atherogenesis, because its occurrence enhances the traumatic
effect of intravascular pressure on the endothelium, triggering
the cascade of events that leads to atherosclerosis.17
The present study addressed the impact of a familial
diabetic background on large artery function and structure by
measuring carotid artery distensibility and wall thickness in a
group of normoglycemic healthy offspring of 2 parents with
type 2 diabetes mellitus, ie, nondiabetic subjects with a high
probability of developing diabetes later in life.18
Materials and Methods
Subjects
We investigated a total of 109 subjects of either sex. Fifty-four
subjects (16 males and 38 females; age: 37.8⫾0.8 years, mean⫾SE)
were selected on a consecutive basis if the following were true: (1)
their age was in the 30- to 45-year range; (2) both parents had a type
2 diabetes mellitus under treatment in the outpatient clinic of our
hospital; (3) there was no evidence of clinical or subclinical
atherosclerotic disease at history, physical examination and laboratory examinations such as a chest x-ray, a standard and an exercise
ECG, or an echocardiogram and an echocolor-Doppler of the carotid
arteries, the femoral arteries, and the abdominal aorta; (4) fasting
blood glucose was ⬍110 mg/dL; (5) there was no history or evidence
of major noncardiovascular diseases; (6) blood pressure was ⬍140/
90 mm Hg; and (7) serum cholesterol was ⬍200 mg/dL. The
remaining 55 subjects (17 males and 38 females) were normotensive
healthy individuals without diabetic parents in the age range of 30 to
Received July 9, 2007; first decision July 23, 2007; revision accepted December 8, 2007.
From the Clinica Medica (C.G., M.F., A.C., E.S., M.A., L.B., C.W., P.G., F.P., G.M.), Milano-Bicocca University and S. Gerardo Hospital, Monza,
Italy; Instituto DiRicovero e Cura a Carattere Scientifico (G.M.), Istituto Auxologico Italiano, Milan, Italy.
Correspondence to Cristina Giannattasio, Clinica Medica, Università di Milano-Bicocca, Ospedale S. Gerardo dei Tintori, Via Pergolesi 33, Monza,
Italy. E-mail [email protected]
© 2008 American Heart Association, Inc.
Hypertension is available at http://hypertension.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.107.097535
182
Giannattasio et al
45 years (mean: 38.2⫾0.9 years) recruited among the administrative
personnel of our hospital and used as control subjects. Five subjects
in the group with diabetic parents and 7 subjects in the control group
were smokers. Both offspring of diabetic parents and control subjects
were further classified according to their body mass index (BMI), ie,
⬍25 kg/m2 or ⱖ25 kg/m2. All of the subjects agreed to participate in
the study after being informed of its nature and purpose. The ethics
committees of the institutions involved approved the protocol of
the study.
Carotid Artery Distensibility and Wall Thickness
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
With the subject supine and the neck in partial extension, the
diameter and wall motion of the right common carotid artery (CA)
were measured 2 cm below the carotid bifurcation by a B-M mode
echo-tracking device based on Doppler shift (Wall Track System,
PIE Medical) and on a transducer operating at a frequency of 7.5
MHz.19,20 The transducer was manually oriented perpendicularly to
the longitudinal axis of the vessel under B-mode guidance. After
switching to A-mode, the backscattered echoes from the anterior and
posterior CA walls were visualized on a screen, and the corresponding radiofrequency signal was tracked by electronic tracers to allow
the digitalized signal of the internal diameter variations to be derived
at 50 Hz. The spatial resolution was 300 ␮m.19 Blood pressure was
measured from the brachial artery at the same time of the ultrasound
evaluation via a semiautomatic device (Dinamap 1846 SX/SXP,
Critikon), and CA distensibility was derived according to the
following formula19:
Dist ⫽ [(2 ⌬D ⫻ Dd) ⫹ ⌬D2]/⌬P ⫻ Dd2
where Dist was distensibility, Dd was the diastolic diameter of the
vessel, ⌬D was the systodiastolic diameter change, and ⌬P was the
corresponding pulse pressure.
CA intima-media wall thickness (IMT) was measured at a posterior wall site located 2 cm below bifurcation through an ultrasonographic device (Philips Sonos 5500). Measurements were obtained
by first scanning the artery in B-mode, then freezing the digitized
image in M-mode, and finally tracking the inner ipoechogenic and
the middle anechogenic layers.21
Measurements were made by 2 operators unaware of the subject’s
clinical status. The within-operator and interoperator variability of
CA diameter measurements at diastole (ie, the coefficient of variation of the mean values of 2 measurements performed at 2 different
times) in our laboratory were 2.5% and 3.5%, respectively. The
within-operator and interoperator variability for CA wall thickness
were 3.0% and 4.0%, respectively.
Additional Measurements
Blood pressure was measured not only by the Dinamap device (see
above) but also, with the patient supine, by a mercury sphygmomanometer, taking the first and fifth Korotkoff sounds to identify
systolic and diastolic values, respectively. Heart rate was obtained by
palpatory method over 30 seconds. Abdominal circumference was
measured in centimeters with the subject in the standing position,
and BMI was derived from the formula: weight (kilograms)/height
(meters squared). Blood glucose, total serum cholesterol, highdensity lipoprotein (HDL) serum cholesterol, and serum triglycerides
were measured from a venous blood sample within the week
preceding the study (see below). In both offspring of diabetic parents
and in control subjects, glycohemoglobin and homeostasis model
assessment (HOMA) index values (derived by the formula: fasting
plasma insulin⫻fasting plasma glucose)22 were also measured. In
our laboratory, normal glycohemoglobin and HOMA index values
are ⬍6% and ⬍2.5 U, respectively.
Protocol and Data Analysis
Each patient was asked to come to the outpatient clinic of the San
Gerardo Hospital in the afternoon, after a 24-hour abstinence from
alcohol, caffeine consumption, and cigarette smoking, to undergo the
Arterial Stiffness in Offspring of Diabetics
183
Table 1. Baseline Demographic, Metabolic, and Hemodynamic
Values in Offspring of Diabetic Parents and in Control Subjects
Variable
No. (male)
Age, y
BMI, kg/m2
Offspring of Diabetic
Parents
Control
Subjects
54 (16)
55 (17)
37.8⫾5.8
38.2⫾6.6
26.18⫾5.10*
24.2⫾4.4
Abdominal circumference, cm
92.0⫾3.1*
80.0⫾23.6
Fasting blood glucose, mg/dL
89.0⫾8.7
91.1⫾9.6
Serum total cholesterol, mg/dL
181.2⫾30.6
172.3⫾26.6
HDL cholesterol, mg/dL
40.2⫾27.0
39.9⫾28.1
Serum triglycerides, mg/dL
123.2⫾29.2*
92.4⫾25.1
Glycated hemoglobin, %
5.300⫾0.029
4.70⫾0.04
2.00⫾0.73
1.85⫾1.40
HOMA index, U
Systolic BP, mm Hg
115.7⫾14.6
110.3⫾7.4
Diastolic BP, mm Hg
64.8⫾8.7*
69.00⫾8.14
Heart rate, bpm
70.3⫾10.5
71.3⫾6.4
BP indicates blood pressure. Data are shown as mean⫾SD unless otherwise
specified.
*P⬍0.05 vs control subjects.
evaluation of CA structure and function. The protocol of the study
was as follows: (1) blood pressure was measured 3 times by a
mercury sphygmomanometer with the patient in the sitting position;
(2) the subject was placed in the supine position and fitted with the
semiautomatic blood pressure measuring device on the brachial
artery and the probe for CA evaluation on the neck; (3) five 6-second
acquisitions of carotid diameter throughout the cardiac cycle were
obtained during a 10-minute period together with semiautomatic
blood pressure measurements; and (4) carotid IMT was measured by
echocolor Doppler.
The 3 sphygmomanometric blood pressure values were averaged.
CA diastolic diameter and distensibility were obtained by averaging
the data derived from the five 6-second acquisition periods. Carotid
IMT was measured on the screen image of the vessel over a
30-second period. Results from individual subjects were averaged.
The statistical significance of the differences in mean values was
assessed by 2-way ANOVA. The 2-tailed t test for unpaired
observations was used to locate differences between control subjects
and subjects with 2 diabetic parents, as well as between groups with
higher or lower BMI. The Bonferroni correction was used when
multiple comparisons were made. Data were also analyzed by the
univariate regression of Spearman. A P⬍0.05 was taken as the level
of statistical significance. Throughout the text the symbol⫾refers to
the SD (tables) or the SE (figure) of the mean.
Results
As shown in Table 1, abdominal circumference, BMI, and
serum triglycerides, while being in the reference range, were
significantly greater in subjects with 2 diabetic parents than in
control subjects, whereas age, fasting blood glucose, and total
and HDL serum cholesterol were similar in the 2 groups.
Heart rate and systolic blood pressure also did not show
between-group differences, whereas diastolic blood pressure
was significantly lower in offspring of diabetic parents than
in control subjects. Offspring of diabetic parents also showed
normal glycohemoglobin and HOMA index values with no
significant differences with respect to control subjects.
As shown in Figure 1, CA diameter at diastole was
similar in the 2 groups. Compared with control subjects,
184
Hypertension
February 2008
Figure 1. Pulse pressure, CA diastolic
diameter, CA distension from diastole to
systole, calculated CA distensibility, and
IMT in healthy subjects with 2 diabetic
parents and in control subjects. For other
symbols, see text. Data are shown as
mean⫾SE.
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
however, in offspring of diabetic parents, the increase in
CA diameter with systole (CA distension) was less pronounced, with a reduction in calculated CA distensibility.
Pulse pressure was significantly greater in the offspring of
diabetic parents compared with control subjects, whereas
carotid IMT was somewhat smaller in offspring of diabetic
parents, the difference failing to reach statistical significance. There was no significant correlation between BMI
and the baseline variables shown in Table 1 (r always
⬍0.15; P not significant).
Table 2 shows the baseline values of offspring of diabetic
parents and control subjects with a BMI ⬍25 kg/m2 and ⱖ25
kg/m2. Most values did not differ significantly between the
lower and higher BMI groups except for the abdominal
circumference, which was less at the lower BMI both in the
offspring of diabetic parents and in control, and the plasma
glucose and HOMA index values, which were less at the
lower BMI in the offspring of diabetic parents only. As
shown in Figure 2, with 1 exception (pulse pressure in
offspring of diabetic parents) CA diameter at diastole, CA
Table 2. Baseline, Demographic, Metabolic, and Hemodynamic Values in Offspring of
Diabetic Parents and Control Subjects Divided According to a BMI <25 kg/m2 or >25 kg/m2
Offspring of Diabetic Parents
Variable
No. (male)
Control Subjects
BMI ⬍25
BMI ⱖ25
BMI ⬍25
BMI ⱖ25
18 (6)
36 (10)
31 (9)
24 (7)
Age, y
36.5⫾4.6
40.0⫾6.0
36.7⫾7.1
39.4⫾9.6
BMI, kg/m2
22.0⫾1.7
28.9⫾5.8*
21.4⫾1.6
27.09⫾0.90*
Abdominal circumference, cm
87.0⫾10.0
96.0⫾19.2*
76.0⫾11.5
84.0⫾16.3*
Fasting blood glucose, mg/dL
84.3⫾5.8
93.7⫾39.0
89.2⫾12.6
92.3⫾27.3
Serum total cholesterol, mg/dL
176.5⫾21.4
185.2⫾36.4
170.4⫾23.6
175.2⫾24.0
41.4⫾16.3
39.4⫾24.6
38.2⫾10.8
41.2⫾25.0
122.0⫾17.2†
124.0⫾23.5†
91.3⫾24.5
93.4⫾20.0
5.10⫾0.02
5.40⫾0.03
4.60⫾0.04
4.8⫾0.03
HDL cholesterol, mg/dL
Serum triglycerides, mg/dL
Glycated hemoglobin, %
HOMA index, U
1.81⫾0.60
2.2⫾2.4
Systolic BP, mm Hg
111.7⫾11.7
118.2⫾15.6
Diastolic BP, mm Hg
61.50⫾0.67†
66.5⫾9.0
68.8⫾8.2
69.2⫾7.6
70.7⫾11.3
70.0⫾10.8
72.3⫾18.7
69.8⫾12.9
Heart rate, bpm
Data are shown as means⫾SD. BP indicates blood pressure.
*P⬍0.05 for BMI ⬍25 kg/m2 vs ⬎25 kg/m2.
†P⬍0.05 offspring vs their respective control group.
1.84⫾1.60
110.0⫾1.8
1.86⫾1.90
110.7⫾6.7
Giannattasio et al
Arterial Stiffness in Offspring of Diabetics
185
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Figure 2. Pulse pressure, CA diastolic diameter, CA distension from diastole to systole, calculated CA distensibility, and IMT in subjects of Figure 1 divided according to a BMI ⱖ25 kg/m2 or ⬍25 kg/m2. Symbols as in Figure 1.
distension at systole, pulse pressure, calculated CA distensibility, and carotid IMT were not significantly different in the
group with a lower and a greater BMI. For all of the above
variables, the differences between offspring of diabetic parents and control subjects remained statistically significant
regardless of the BMI value.
Discussion
In our normoglycemic healthy offspring of 2 diabetic parents,
CA diameter at diastole was similar to that of control
individuals, ie, age-matched healthy subjects with no parental
diabetes. However, compared with control subjects, in subjects with 2 diabetic parents, pulse pressure was greater, the
ability of the CA to distend in response to an increase in
pressure from diastole to systole was less, and the calculated
value of arterial distensibility was markedly reduced. This
was the case both in subjects with an elevated BMI and in
those with a normal BMI, the value of which bore no
significant relationship to the CA values. Thus, subjects with
a pronounced familial background for and, thus, a high
probability of developing diabetes18 show arterial stiffening
already at a stage in which blood glucose is normal. This has
clinical implications, because arterial stiffening is an important cardiovascular risk factor.15 That is, its occurrence
increases the risk of cardiac and vascular morbid or fatal
events presumably because a reduction in the ability of the
arteries to distend when blood pressure increases is associated
with an increase in arterial impedance and, thus, in the
afterload to the heart, an increase in systolic blood pressure,
and endothelial damage because a reduced distensibility
enhances the traumatic effect of the intravascular pressure on
the vessel wall.20
The mechanisms responsible for the early arterial stiffening of normoglycemic offspring of diabetic parents are not
clarified by our study. However, our data allow some considerations to be made. First, the offspring of diabetic parents
had greater triglyceride values compared with control subjects, but to date there is no evidence that low triglyceride
values exert any substantial modulating role on large artery
mechanical properties. Second, because glucose values were
normal and similar between the offspring of diabetic parents
and control subjects, the arterial stiffening cannot be ascribed
to any adverse effect of this substance on the functional
characteristics of the vessel wall.23,24 Third, although an
increase in body weight and/or a state of insulin resistance
reduce large artery distensibility (via a sympathetic activation25–30 and possibly also via trophic influences that may
alter the tissue composition of the vessel wall), it is also
unlikely that these factors played a major role. This is because
there was no relationship between BMI and carotid distensibility, which, in offspring of diabetic parents, was reduced
also when BMI was normal. Furthermore, HOMA index
values were within the reference range and slightly and
nonsignificantly greater in the offspring of diabetic parents
than in control subjects. Finally, taking into account that
arterial distensibility decreases as blood pressure increases,20
186
Hypertension
February 2008
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
it is unlikely that a blood pressure factor was involved,
because although systolic blood pressure was 5 mm Hg
greater in the offspring of diabetic parents than in control
subjects (a difference that was not statistically significant),
diastolic blood pressure was lower in the former than in the
latter group and so was mean blood pressure, although the
difference was negligible (81.5 versus 82.7 mm Hg). We
may, thus, suggest that the arterial stiffening seen so early in
subjects with a strong familial background and predisposition
to diabetes depends to only a little degree on initial and
inconsistent alterations in glucose metabolism and body
weight, does not depend on blood pressure modifications, and
that genetic influences operating through other mechanisms
may be responsible in the majority. In this context, it is
interesting to note that, although diabetes is accompanied by
an increased wall thickness even in the absence of microvascular and macrovascular complications,13 in our normoglycemic offspring of diabetic parents, CA IMT was similar to the
value seen in control subjects. This suggests that arterial
stiffening may precede arterial thickening and that, if involved, genetic influences do not operate through an increase
in the amount of wall tissue.
In the subjects of our study we did not measure pulse
pressure at the level of the CA nor did we calculate the central
pulse pressure value by subtracting the amplification factor
from the peripheral artery signal.20 The possibility thus exists
that the reduced excursion of CA diameter from diastole to
systole seen in the offspring of diabetic parents compared
with control subjects was because of a reduced distending
stimulus, ie, to the fact that central (and, thus, carotid) pulse
pressure was less in the offspring of diabetic parents than in
control subjects. Although this possibility cannot be excluded, it seems to be hardly compatible with the opposite
phenomenon seen in the periphery, ie, a greater pulse pressure value in the offspring of diabetic parents than in control
subjects (50 versus 41.3 mm Hg).
Perspectives
In summary, subjects with a pronounced familial background for and, thus, a high probability of developing
diabetes show arterial stiffening already at a stage in which
blood glucose is normal. In our normoglycemic offspring
of diabetic parents, CA IMT was similar to the value seen
in control subjects, thus suggesting that arterial stiffening
may precede arterial thickening and that, if involved,
genetic influences do not operate through an increase in
the amount of wall tissue. No relationship between BMI
and carotid distensibility was seen, and arterial distensibility in offspring of diabetic parents was reduced also
when BMI was normal.
This has clinical implications, because arterial stiffening
is an important cardiovascular risk factor. Genetic influences operating through a mechanism different from IMT,
BMI, and glucose metabolism may be responsible in the
majority.
Disclosures
None.
References
1. Wahlqvist ML, Relf IRN, Myers KA, Lo C. Diabetes and macrovascular
disease: risk factors for atherogenesis and non-invasive investigation of
arterial disease. Hum Nutr Clin Nutr. 1984;38c:175–184.
2. Lo CS, Relf IRN, Myers KA, Wahlqvist ML. Doppler ultrasound
recognition of preclinical changes in the arterial wall in diabetic
subjects: compliance and pulse-wave damping. Diabetes Care. 1986;
9:27–31.
3. Fujiwara S, Emoto M, Komatsu M, Motoyama K, Morioka T, Koyama H,
Shoji T, Inaba M, Nishizawa Y. Arterial wall thickness is associated with
insulin resistance in type 2 diabetic patients. Atheroscler Thromb. 2003;
10:246 –252.
4. Lehman Ed Hopkins KD, Gosling RG. Increased aortic stiffness in
women with NIDDM. Diabetologia. 1996;39:870 – 871.
5. Salomaa V, Riley W, Kark J, Nardo C, Folson AR. Non-insulin
dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes. The ARIC Study.
Circulation. 1995;91: 1432–1433.
6. Lambert J, Pijpers R, van Ittersum FJ, Comans EF, Aarsen M, Pieper EJ,
Donker AJ, Stehouwer CD. Sodium, blood pressure and arterial distensibility in insulin-dependent diabetes mellitus. Hypertension. 1997;30:
1162–1168.
7. Kool MJF, Lambert J, Stehauwer CDA, Hoeks APG, Struijker Bandier
HAJ, Van Basten LMAB. Vessel wall properties of large arteries in
uncomplicated insulin-dependent diabetes mellitus (IDDM). Diabetes
Care. 1995;18:618 – 624.
8. Rema M, Mohan V, Deepa R, Ravikumar R. Chennai Urban Rural
Epidemiology Study-2. Association of carotid intima-media thickness
and arterial stiffness with diabetic retinopathy: the Chennai Urban
Rural Epidemiology Study (CURES-2). Diabetes Care. 2004;27:
1962–1967.
9. Christianssen T, Neubauer B. Arterial wall stiffness in insulin-dependent
diabetes mellitus. Acta Radiol. 1987;28:207–209.
10. Henry RM, Kostense PJ, Dekker JM, Nijpels G, Heine RJ, Kamp O,
Bouter LM, Stehouwer CD. Carotid arterial remodelling : a maladaptive
phenomenon in type 2 diabetes but not in impaired glucose metabolism:
the Hoorn study. Stroke. 2004;35:671– 676.
11. Henry RM, Kostense PJ, Spijkerman AM, Dekker JM, Nijpels G, Heine
RJ, Kamp O, Westerhof N, Bouter LM, Stehouwer CD. Arterial stiffness
increases with deteriorating glucose tolerance status: the Hoorn Study.
Circulation. 2003;107:2089 –2095.
12. Cruickshank K. Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG.
Aortic pulse-wave velocity and its relationship to mortality in diabetes
and glucose intolerance: an integrated index or vascular function? Circulation 2002;106:2085–2090.
13. Giannattasio C, Failla M, Piperno A, Grappiolo A, Gamba P, Paleari F,
Mancia G. Early impairment of large artery structure and function in type
I diabetes mellitus. Diabetologia. 1999;42:987–994.
14. McEleavy OD, McCallum RW, Petrie JR. Higher carotid-radial pulse
wave velocity in healthy offspring of patients with type 2 diabetes.
Diabetic Med. 2004;21:262–266.
15. Blacher J, Safar ME, Guerin AP, Pannier B, Marchais SJ, London GM.
Aortic pulse wave velocity index and mortality in end-stage renal disease.
Kidney Int. 2003;63:1852–1860.
16. Roman MJ, Naqvi TZ, Gardin JM, Gerhard-Herman M, Jaff M, Mohler
E. American society of echocardiography report. Clinical application of
non-invasive vascular ultrasound in cardiovascular risk stratification: a
report from the American Society of Echocardiography and the Society
for Vascular Medicine and Biology. Vasc Med. 2006;11:201–211.
17. Booth RFG, Martin JF, Honey AC, Hassal DG, Beesley JE, Moncada S.
Rapid development of atherosclerotic lesions in the rabbit carotid artery
induced by perivascular manipulation. Atherosclerosis. 1989;76:
257–268.
18. Polonsky KS, Sturis J, Belle GI. Non-insulin-dependent diabetes mellitusa genetically programmed failure of the beta cell to compensate for
insulin resistance. N Engl J Med. 1996;334:777–783.
19. Kool MJF, Van Merode T, Reneman RS, Hoeks APG, Struyker Boudier
H, Van Bortel LMAB. Evaluation of reproducibility of a vessel wall
movement detector system for assessment of large artery properties.
Cardiovasc Res. 1994;28:610 – 614.
20. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C,
Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H;
European Network for Noninvasive Investigation of Large Arteries.
Methodological issues and clinical applications. Eur Heart J. 2006;27:
2588 –2605.
Giannattasio et al
21. Salonen R, Haapdnen A, Salonen JT. Measurement of intima-media
thickness of common carotid arteries with high-resolution B-mode ultrasonography: inter and intra-observer variability. Ultrasound Med Biol.
1991;17:225–230.
22. Matthews DR, Hosker JP, Rudenski AS, Treacher DF, Turner RC.
Homeostasis model assessment: insulin resistance and beta-cell
function from fasting plasma glucose and insulin concentrations in
man.Diabetologia. 1985;28:412– 419.
23. Tropeano AI, Boutouyrie P, Katsahian S, Laloux B, Laurent S. Glucose
level is a major determinant of carotid intima-media thickness in patients
with hypertension and hyperglycemia. J Hypertens. 2004;22:2153–2160.
24. Mentik CJ, Hendriks M, Levels AA, Wolffenbuttel BH. Glucosemediated cross-linking of collagen in rat tendon and skin. Clin Chim Acta.
2002;321:69 –76.
25. Grassi G, Dell’Oro R, Facchini A, Quarti Trevano F, Bolla GB, Mancia
G. Effect of central and peripheral body fat distribution on sympathetic
and baroreflex function in obese normotensives. J Hypertens. 2004;22:
2363–2369.
Arterial Stiffness in Offspring of Diabetics
187
26. Li S, Chen W, Srinivasan SR, Berenson GS. Influence of metabolic
syndrome on arterial stiffness and its age-related change in young adults:
the Bogalusa Heart Study. Atherosclerosis. 2005;180:349 –354.
27. Ferreira I, Henry RM, Twisk JW, van Mechelen W, Kemper HC,
Stehouwer CD. Amsterdam Growth and Health Longitudinal Study. The
metabolic syndrome, cardiopulmonary fitness, and subcutaneous trunk fat
as independent determinants of arterial stiffness: the Amsterdam Growth
and Health Longitudinal Study. Arch Intern Med. 2005;25:875– 882.
28. Tomiyama H, Koji Y, Yambe M, Motobe K, Shiina K, Gulnisa Z,
Yamamoto Y, Yamashina A. Elevated C-reactive protein augments
increased arterial stiffness in subjects with the metabolic syndrome.
Hypertension. 2005;45:997–1003.
29. Giannattasio C, Failla M, Lucchina S, Zazzeron C, Scotti V, Capra A,
Viscardi L, Bianchi F, Vitale G, Lanzetta M, Mancia G. Arterial
stiffening influence of sympathetic nerve activity: evidence from hand
transplantation in man. Hypertension. 2005;45:608 – 611.
30. Mircoli L, Mangoni AA, Giannattasio C, Mancia G, Ferrari AU. Heart
rate-dependent stiffening of large arteries in intact and sympathectomized
rats. Hypertension. 1999;34:598 – 602.
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Increased Arterial Stiffness in Normoglycemic Normotensive Offspring of Type 2 Diabetic
Parents
Cristina Giannattasio, Monica Failla, Anna Capra, Elisabetta Scanziani, Maria Amigoni, Lucia
Boffi, Christine Whistock, Pierluigi Gamba, Felice Paleari and Giuseppe Mancia
Downloaded from http://hyper.ahajournals.org/ by guest on June 16, 2017
Hypertension. 2008;51:182-187; originally published online January 14, 2008;
doi: 10.1161/HYPERTENSIONAHA.107.097535
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2008 American Heart Association, Inc. All rights reserved.
Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://hyper.ahajournals.org/content/51/2/182
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial
Office. Once the online version of the published article for which permission is being requested is located,
click Request Permissions in the middle column of the Web page under Services. Further information about
this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Hypertension is online at:
http://hyper.ahajournals.org//subscriptions/