Jackson wrote:
>
> Hey, dear all,
>
> I am a Ph.D. student working on diabetes research using
> mouse model, this is my first time being here in this
> forum, this is great place. I have now a problem in
> calculating the insulin sensitivity index, any help from
> you is highly appreciated:
>
> A: There are many ways to calculate the insulin
> sensitivity index, which way is mostly authorized and
> accepted?
"Measurements of insulin sensitivity index, glucose
effectiveness, and acute insulin response and C-
peptide response.
Each subject underwent an intravenous glucose tolerance test
(IVGTT) after the overnight fasting period of 12 h. After
insertion of a cannula into the antecubital vein each
subject rested in a quiet room for at least 20 min. Baseline
values of serum insulin, serum C-peptide, and plasma glucose
were taken in duplicate with 5-min intervals. Glucose was
injected intravenously in the contralateral antecubital vein
over a period of 60 s (0.3 grams/kg body weight of 50%
glucose). At 20 min after the end of the glucose injection,
a bolus of 3 mg tolbutamide/kg body weight (Rastinon,
Hoechst, Germany) was injected during 5 s to elicit a
secondary pancreatic -cell response. Venous blood was
sampled at 2, 4, 8, 19, 22, 30, 40, 50, 70, 90, and 180 min,
timed from the end of the glucose injection for measurements
of plasma glucose, serum insulin and serum C-peptide. All
the IVGTTs were done by the same investigator. Insulin
sensitivity index and glucose effectiveness were calculated
using the Bergman MINIMOD computer program developed
specifically for the combined intravenous glucose and
tolbutamide tolerance test (26, 27, 28, 29, 30). The insulin
sensitivity index represents the increase in net fractional
glucose clearance rate per unit change in serum insulin
concentration after the intravenous glucose load. Glucose
effectiveness represents the net fractional glucose
clearance rate due to the increase in glucose itself without
any increase in circulating insulin concentration above
baseline. Furthermore, glucose effectiveness includes a
lesser contribution mediated by the preexisting basal
insulin status. Importantly, both the insulin sensitivity
index and glucose effectiveness involve an inhibition of
hepatic glucose output (26, 27). Acute phase insulin and C-
peptide responses (0-8 min) were calculated by means of the
trapezoidal rule as the incremental values (areas under the
curve when expressed above basal values). Glucose
disappearance constant (Kg) was calculated as the slope of
the line relating the natural logarithm of the glucose
concentration to the time between 8 and 19 min after the
glucose bolus administered as a part of the IVGTT (31). The
disposition index was calculated as the product of insulin
sensitivity index and first phase insulin responses (0-8
min) (32, 33).
Validation of the IVGTT with reduced sampling for
measurements of insulin sensitivity index and glucose
effectiveness.
The tolbutamide-boosted protocol for frequently sampled
IVGTT with minimal model analysis has been validated
previously against the euglycemic, hyperinsulinemic clamp in
normal subjects (34, 35). To validate the reduced sampling
protocol of the tolbutamide-modified IVGTT, 18 of the study
participants volunteered for a study to compare the
frequently sampled protocol (33 samples) with the present
protocol (12 samples). Highly significant correlations
considering insulin sensitivity index (r = 0.98, 95%
confidence interval 0.95-0.99) and considering glucose
effectiveness (r = 0.93, 95% confidence interval .82- 0.97)
were found between the IVGTT method using 33 samples and the
present method using 12 samples. The difference between the
two IVGTT methods was plotted against the average of the two
methods for each participant to give an estimate of the
agreement between the two methods (Bland-Altman plot) (36).
Limits of agreement were calculated as mean difference±1.96
× SD of the difference. Limits of agreement between the
method using 33 samples and the method using 12 samples were
from 3.2 to
2.1 × 105 (min × pmol/liter)1 considering insulin
sensitivity index and from 0.7 to 0.6 × 102 × min1
considering glucose effectiveness. Thus, the 12-sample
protocol may estimate insulin sensitivity index 3.2 × 105
(min × pmol/liter)1 below or 2.1 × 105 (min × pmol/liter)1
above the values obtained with the 33-sample schedule. As
the limits of agreement are narrower than the variation of
both insulin sensitivity index (mean value = 15.3 × 105
(min × pmol/liter)1 and SD = 9.3) and glucose
effectiveness (mean value = 2.1 × 102 × min1 and SD =
0.6), the reduced sampling schedule during the IVGTT as
applied here provides an acceptable estimate of both the
insulin sensitivity index and the glucose effectiveness in
population studies. Similar results have been obtained in
a recent comparative study (27)." Source: Insulin
Sensitivity Index, Acute Insulin Response, and Glucose
Effectiveness in a Population-based Sample of 380 Young
Healthy Caucasians
http://www.jci.org/cgi/content/full/98/5/1195
Assessment of insulin sensitivity with minimal model: role
of model assumptions
http://ajpendo.physiology.org/cgi/cont-
ent/abstract/272/5/E925
A Google search using "Measurement of insulin sensitivity
index" -
http://tinyurl.com/34a5s
The following is an old article. If you have access to the
full article, you may find more recent citations that have
reference to this article.: Quantitative estimation of
insulin sensitivity
http://ajpgi.physiology.org/cgi/content/abstract/236/6/G667
The following are two High-Wire search across multiple
journals: The first using search terms "insulin sensitivity
index"+definition -
http://tinyurl.com/2qyot The second
using the search terms "insulin sensitivity"+definition -
http://tinyurl.com/2u558
This group has a few professional MDs and scientist. I am
not one of them.
Frank
>
> B: In details, we have two groups of mice A and B(all
> fully diabetic with 18-hour fasting glucose >210 mg/dl
> ), which are fully equivalent. Same strain, same
> food... After overnight fasting we did the GTT (glucose
> tolerance test)in timepoints of 0, 30,60, and 120
> minutes. The group A has significantly higher glucose
> level in all time points of GTT; In terms of insulin
> level, group A is significantly higher than B in 0
> minute (before injection glucoe); However, in the
> timepoints of 30,60,120 (after glucose injection),
> Group B has significantly higher level of insulin.
>
> C: Based on above situation, can we make any decision
> to say that which group has higher insulin
> sensitivity? why?
>
> I do not know if any of you have met the same situation,
> any of your ideas, suggestion and help are highly
> appreciated!!! In all the literatures I read do not
> release any situation like we have: In GTT, one group is
> significantly higher in glucose level (p<0.001), while
> significantly lower (P<0.001) in insulin level (except in
> 0 minute significant higher).
