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Endothelial Dysfunction & Insulin Resistance in Normoglycemic Offsprings
particularly in skeletal muscle [10]. Insulin stimulates
bulk flow as an endothelium-dependent vasodilator
via nitric oxide production [11]. Impaired
endothelial function in type 2 diabetics is documented
by reduced effect of endothelial-dependent
vasodilators such as acetylcholine (ACH) [12].
Insulin resistance is defined as a state of reduced
responsiveness to normal circulating levels of
insulin. This condition is a feature of various
disorders, such as type 2 diabetes, is also implicated
in impaired glucose tolerance (IGT) or impaired
fasting glucose (IFG), both considered as ''prediabetes''
by the Expert Committee on the Diagnosis
and Classification of Diabetes Mellitus, as well as
in obesity, hypertension, dyslipidaemia [13], the
possibility of existence of earlier in life metabolic
effect in genetically predisposed persons as offspring
of type 2 diabetics was thought as another
face of the coin.
Whether family history for diabetes predispose
to alteration in vascular function through an unknown
''genetic susceptibility'' or through higher
prevalence of insulin resistance has not yet been
fully investigated. The aim of the present study
was to investigate endothelial function in normotensive
normoglycemic offspring of diabetic subjects
and to explore its relationship with the insulin
resistance.
Patients and Methods
The study population consisted of 57 subjects:
NOPD group: 36 healthy subjects, with one or
both parents having type 2 diabetes mellitus.
Control group: 21 healthy normotensive normoglycemic
subjects with no family history of
type 2 diabetes mellitus.
Exclusion criteria: Tobacco smoking, history
or clinical evidence of cardiac diseases or systemic
diseases, obesity [body mass index (BMI) ≥30kg/
m 2 and/or Waist-to-hip ratio (WHR) >0.9m in
males and >0.85m in females], hypertension, diabetes,
or dyslipidemia. All women were premenopausal
and their investigations were undertaken
during the first week of their menstrual cycles.
None of them were taking oral contraceptives.
Anthropometric, metabolic characteristics and
laboratory measurements:
Height, weight and waist circumference were
determined for all participants. BMI was determined
as body weight (kg)/height (m) 2. Total and
20
HDL cholesterol, triglycerides and routine chemistry
were measured by standard laboratory techniques.
Oral glucose tolerance test (OGTT):
A standard OGTT was done after an overnight
10- to 12-h fast. Blood samples were obtained
before and 2h after 75g of glucose administration.
Homeostasis model assessment (HOMA):
Serum insulin was determined by an electrochemiluminescense
assay. Insulin resistance [14]
was calculated as follows:
HOMA-IR=fasting glucose (mmol/L) x insulin (mIu/mL)
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22.5
Endothelial function:
Endothelial function was measured 1h before
the OGTT was started. All studies were performed
in the morning in a quiet room. Brachial artery
reactivity was measured by colored Doppler ultrasound,
using a 7.5MHz linear array transducer
ultrasound system. The mean right brachial artery
antero-posterior diameter was measured 3-5cm
above the elbow, between media and adventitia
from 4 cycles synchronized with the end-diastole
at the R wave peaks [15]. The ECG was monitored
continuously throughout the study.
• A basic scan of the brachial artery diameter and
flow was taken.
• 2 nd scan was taken after applying a pneumatic
tourniquet of 250-300mmHg. (Using mercurial
sphygmomanometer) for about 5 minutes. The
scan was taken to measure brachial artery diameter,
60 seconds after releasing the tourniquet
measuring the maximum FMD (index of endothelium-dependent
vasodilation).
• 3 rd scan was taken after 15 minutes of rest to
allow recovery of the artery after FMD and considered
the basic scan of GTN-MD reading.
• 4 th scan was taken 4 minutes after administration
of 400mg of GTN spray sublingually to assess
non-endothelium dependent dilation. GTN serves
as an exogenous source of Nitric Oxide (NO),
bypassing the need for endogenous endothelial
NO production.
o FMD percentage was calculated by the following
equation:
2 nd scan – 1 st scan
FMD% = ––––––––––––––––– x 100
1 st scan