the egyptian society of cardiology board of ... - Cardioegypt.com

Endothelial Dysfunction & Insulin Resistance in Normoglycemic Offsprings
2.5
2
1.5
1
0.5
0
HOMA-IR
HOMA-IR
p=0.013
Control NOPD
Figure 3: HOMA-IR in NOPD and Controls.
Discussion
The present study showed that: (a) normotensive
normoglycemic offsprings of type 2 diabetic subjects
present insulin resistance and early endothelial
dysfunction, as they had impaired FMD, while the
direct vasodilator capacity induced by GTN was
not impaired. (b) FMD was impaired more in
offsprings of diabetics with more insulin resistance.
Our findings are in agreement with Caballero
et al [16] who showed decreased FMD and decreased
microvascular reactivity in first degree
relatives of type 2 diabetic subjects as compared
to controls.
Balletshofer et al [17] found impaired FMD in
normoglycemic offspring of diabetic parents, but
this was significant only in insulin resistant normoglycemic
offspring of diabetic parents compared
to controls. There was no significant difference in
GTN-MD between all the studied groups. Of note,
that study included only 10 control subjects to
compare with 53 subjects with diabetic parents
and smokers were not excluded from study. This
may attenuate the difference between offspring of
diabetic parents and controls as regard FMD.
Furthermore, Chen et al [18], McSorley et al
[19] and Iellamo et al [20] found a significantly
reduced forearm vasodilation, indicating endothelial
dysfunction in normoglycemic first degree relatives
of type 2 diabetic subjects. However, McSorley et
al [19] did not find significant difference in HOMA-
IR, an index of insulin resistance, between NOPD
and controls, nonetheless, several findings from
that study suggested the presence of hyperinsulinemic
state in the NOPD group. These include higher
22
values of HbA1c and higher values for blood glucose
120 minutes after OGTT concomitant with
higher insulin levels, reflecting a relative hyperinsulinemic
state. In addition, the area under glucose
curve (AUCs) for glucose and insulin during OGTT
were inversely correlated with FMD.
Goldfine et al [21] found that FMD was reduced
in normoglycemic offsprings of type 2 diabetic
subjects (even the most insulin-sensitive), with no
difference in GTN-MD. This significant attenuation
of endothelial dysfunction even in insulin sensitive
offsprings could be due to enriched familiar difference
in that study as both parents were diabetic.
Moreover, the studied subjects had non significantly
higher BMI compared to our subjects (23.98±2.95
Vs 22.89±2.71).
Tesauro et al [22] found that normoglycemic
offsprings of type 2 diabetic subjects were more
insulin resistant on average than the control group,
and had significantly lower both FMD and GTN-
MD compared with the control group. They suggested
that in addition to decreased insulin sensitivity;
otherwise healthy subjects with a family
history of type 2 diabetes mellitus have impairment
in vascular responsiveness to NO that may be
endothelium dependent and/or independent.
In concordance of our results, Amudha et al
[23] found that NOPD had significantly impaired
FMD and higher HOMA-IR, reflecting endothelial
dysfunction and insulin resistance.
Frequent presence of vascular pathology at the
time of diagnosis of diabetes suggests importance
for identification of prediabetic persons with diminished
endothelial function and early atherosclerotic
disease and family history of diabetes is a
recognized risk for development of diabetes [21].
In normoglycemic offspring of patients with
type 2 diabetes mellitus, significant endothelial
dysfunction and insulin resistance are detectable
even in the absence of frank diabetes. This suggests
that genetic factors contributing to insulin resistance
and diabetes may also influence development of
cardiovascular diseases including atherosclerosis
and coronary heart disease that are related to endothelial
dysfunction [22].
From data of our study and other studies, we
can speculate that NOPD present a blunted endothelial
function in relation to a primary inherited
genetic susceptibility yet to be identified, or in
relation to the metabolic alteration detectable even