25 Settembre 2007 Presentazione progetto Edificio Eco-Compatibile.
2007 15th eco
32
RELATIONSHIP OF SGPT (ALT) LEVELS WITH INSULIN RESISTANCE IN OVERWEIGHT AND OBESE PERSONS Kapantais E, Chala E. Department of Diabetes-Obesity-Metabolism, Metropolitan Hospital, Neo Faliro, Athens, Greece ECO 2007 Budapest Hungary
Transcript of 2007 15th eco
RELATIONSHIP OF SGPT (ALT) LEVELS WITH INSULIN RESISTANCE IN
OVERWEIGHT AND OBESE PERSONS
Kapantais E, Chala E.
Department of Diabetes-Obesity-Metabolism,
Metropolitan Hospital, Neo Faliro, Athens, Greece
ECO 2007
Budapest
Hungary
INTRODUCTIONA number of studies have shown relationship
between gamma-GT or SGPT/ALT levels and insulin
resistance, suggesting that these parameters can be
used as markers for the insulin resistance state.
Gamma-GT and SGPT/ALT levels, even within the
normal range, correlate with increasing intrahepatic
fat. It has been suggested that the elevation of the
hepatic enzymes could be the expression of excess
deposition of fat in the liver, which is closely related
to obesity and other metabolic disturbances such as
dyslipidaemia or diabetes mellitus.
AIMof our study was to investigate the relationship
between SGPT/ALT levels and insulin resistance
indices in overweight and obese persons who are
invariably insulin resistant.
SUBJECTS-METHODSWe studied retrospectively 219 male and 382 female (total 601) overweight and
obese persons who attended the outpatient clinic of Diabetes-Obesity-Metabolism
Department of our Hospital, in order to reveal any trend between ALT and insulin
resistance.
Subjects with overt liver disease were excluded from the study.
Subjects were also classified as “non-diabetic” and “diabetic” according to
reported personal history or considering HbA1c (cutoff point: 6.2%) and fasting
plasma glucose levels (cutoff point: 110mg/dl).
Fasting glucose and insulin levels as well as ferritin, SGOT, SGPT, ALP and gamma-
GT levels were measured after overnight fasting.
Anthropometric measurements were performed: BMI, waist circumference, WHR,
sagittal abdominal diameter, % total body fat (BIA method).
Insulin resistance (HOMA model) and insulin sensitivity (Quicki) were calculated as
well as “Insulinogenic” Index which was defined as the ratio of fasting insulin to
fasting glucose.
Subjects were divided in HOMA, Quicki and Insulinogenic Index quartiles and SGPT
comparisons were made within these quartiles. Statistic analysis included ANOVA,
multiple regression analysis, Man-Whitney test and non parametric (Spearman)
correlation.
SUBJECTS-METHODSMales(n=218)
Females(n=382)
p
Age (years) 46.0 ± 13.9 42.2 ± 13.7 0.001
BMI (kg/m2) 35.1 ±6.2 34.3 ±6.2 NS
Waist Circumference (cm) 115.6 ± 14.5 104.0 ± 13.6 0.000
% Total Body Fat 35.9 ± 5.9 44.4 ± 6.1 0.000
Glucose (mg/dl) 122.1 ± 49.3 102.9 ± 33.7 0.000
Insulin (μU/ml) 16.9 ± 11.6 13.3 ± 9.8 0.000
SGOT (U/l) 25.8 ± 13.2 20.7 ± 8.3 0.000
SGPT (U/l) 38.9 ± 24.3 25.7 ± 15.2 0.000
Gamma-GT (U/l) 38.1 ± 26.9 23.4 ± 19.8 0.000
HOMA 5.06 ± 3.86 3.45 ± 2.82 0.000
Quicki 0.318 ± 0.046 0.331 ± 0.0319 0.000
Insulinogenic Index 0.154 ± 0.117 0.135 ± 0.101 0.043
Type 2 Diabetes (Yes/No) 94 / 124 64 / 318 0.000
RESULTS
382218N =
sex
femalemale
SG
PT
150
125
100
75
50
25
0
382571435626429574
621620628257
563496
631453
595
622362
772072129821619442
33193
131
106
SG
PT
Male Female
Males had higher SGPT levels than females
(38.9U/l 24.3U/l vs. 25.7U/l 15.2U/l, p= 0.000)
RESULTS (Males)
SGPT differed within HOMA, Quicki
and Insulinogenic Index quartiles.
RESULTS (Males)
54545555N =
Homa quartiles according to males
4321
SG
PT
150
125
100
75
50
25
0
33
131
106
138
7720798
215
7223
193
54545555N =
Homa quartiles according to males
4321
SG
PT
150
125
100
75
50
25
0
33
131
106
138
7720798
215
7223
193
Homa quartiles
SG
PT
F= 3.798, p= 0.011
RESULTS (Males)
54555356N =
quicki quartiles according to males
4321
SG
PT
150
125
100
75
50
25
0
215
7223
193
138
77207
33
131
106
Quicki quartiles
SG
PT
F= 4.440, p= 0.005
RESULTS (Males)
54545654N =
insulinogenic index quartiles (males)
4321
SG
PT
150
125
100
75
50
25
0
106
98
33
131
214
77
7223
193
Insulinogenic index quartiles
SG
PT
F= 5.215, p= 0.002
RESULTS (Males)
fasting insulin
9080706050403020100
SG
PT
150
125
100
75
50
25
0
SG
PT
fasting insulin
r= 0.351, p= 0.000
RESULTS (Males)
Insulin Resistance (HOMA)
302520151050
SG
PT
150
125
100
75
50
25
0
SG
PT
Insulin resistance (HOMA)
r= 0.248, p= 0.000
RESULTS (Males)
Quicki
,8,7,6,5,4,3,2
SG
PT
150
125
100
75
50
25
0
SG
PT
Quicki
r= -0.248, p=0.000
RESULTS (Males)
"insulinogenic" index
1,0,8,6,4,20,0
SG
PT
150
125
100
75
50
25
0
SG
PT
Insulinogenic index
r= 0.340, p= 0.000
RESULTS (Males)
R R square F p
0.401 0.161 15.24 0.000
Beta t p
Insulinogenic
Index0.319 4.39 0.000
Ferritin 0.230 3.16 0.002
Multiple regression analysis
Age, BMI, WHR and Waist circumference
were not significant in the model
RESULTS (Males)
ferritin
7006005004003002001000
SG
PT
150
125
100
75
50
25
0
SG
PT
Ferritin
r= 0.230, p= 0.003 (r= 0.2015, p= 0.01 after controlling for Insulin Resistance)
On the other side, the relationship between SGPT and Insulin Resistance
remains after controlling for ferritin (r= 0.1706, p= 0.03)
RESULTS (Males)
r= 0.265, p= 0.001
SEX: 0 male
Insulin Resistance (HOMA)
2520151050
ferr
itin
700
600
500
400
300
200
100
0
Ferr
itin
Insulin resistance (HOMA)
RESULTS (Females)
SGPT differed within HOMA, Quicki
and Insulinogenic Index quartiles.
RESULTS (Females)
95959696N =
Homa quartiles according to females
4321
SG
PT
150
125
100
75
50
25
0
621628257
563
595
622
620
496
631
611557
453
405
435626
362
Homa quartiles
SG
PT
F= 10.830, p= 0.000
RESULTS (Females)
95979595N =
Quicki quartiles according to females
4321
SG
PT
150
125
100
75
50
25
0
405
435626
362
611557
453
620
496
631
621628257
563
595
622
Quicki quartiles
SG
PT
F= 10.800, p= 0.000
RESULTS (Females)
95959696N =
insulinogenic index quartiles (females)
4321
SG
PT
150
125
100
75
50
25
0
621620
563
595
622
364557
496
628257
631453
362
405611239
435626574
Insulinogenic index quartiles
SG
PT
F= 4.836, p= 0.003
RESULTS (Females)
fasting insulin
9080706050403020100
SG
PT
150
125
100
75
50
25
0
SG
PT
fasting insulin
r= 0.278, p= 0.000
RESULTS (Females)
Insulin Resistance (HOMA)
302520151050
SG
PT
150
125
100
75
50
25
0
SG
PT
Insulin resistance (HOMA)
r= 0.309, p= 0.000
RESULTS (Females)
Quicki
,5,4,3,2
SG
PT
150
125
100
75
50
25
0
SG
PT
Quicki
r= -0.309, p= 0.000
RESULTS (Females)
"insulinogenic" index
1,41,21,0,8,6,4,20,0
SG
PT
150
125
100
75
50
25
0
SG
PT
Insulinogenic index
r= 0.180, p= 0.000
RESULTS (Females)
R R square F p
0.361 0.130 25.57 0.000
Beta t p
HOMA-IR 0.226 4.40 0.000
Ferritin 0.243 4.75 0.000
Multiple regression analysis
Age, BMI, WHR and Waist circumference
were not significant in the model
RESULTS (Females)
ferritin
5004003002001000
SG
PT
150
125
100
75
50
25
0
SG
PT
Ferritinr= 0.240, p= 0.000
(r= 0.2485, p=0.000 after controlling for Insulin Resistance)
On the other side, the relationship between SGPT and Insulin Resistance
remains after controlling for ferritin (r= 0.2314, p= 0.000)
RESULTS (Females)
r= 0.126, p= 0.019
SEX: 1 female
Insulin Resistance (HOMA)
302520151050
ferr
itin
500
400
300
200
100
0
Insulin resistance (HOMA)
Ferr
itin
Conclusions
1. SGPT/ALT levels are positively related to insulin
resistance not only in the general population, but
also among the overweight and obese persons, in
both sexes, irrespectively of age, BMI, ferritin
levels, body fat distribution or presence of type-2
diabetes.
2. In overweight and obese persons SGPT/ALT levels
are also positively related to serum ferritin levels,
in both sexes.
3. Moreover, our findings document a strong and
positive association between serum ferritin levels
and Insulin resistance.
DiscussionPossible links between SGPT/ALT levels and insulin resistance:
1. ALT has been associated with fatty liver disease, and fatty liver disease has
been associated with insulin resistance.
2. Moreover, because insulin suppresses genes encoding gluconeogenic
enzymes, and ALT is a gluconeogenic enzyme, it is also possible that ALT is
an indicator or impaired insulin signaling not necessarily associated with
liver injury.
3. Finally, inflammation may impair insulin signaling both in the liver and
systemically. Our observation that a high ALT is associated with high ferritin
levels independent of obesity and insulin resistance is consistent with the
hypothesis that raised ALT levels may reflect inflammation which may lead
to insulin resistance. (That, if we consider ferritin to be not only a marker of
insulin resistance, but also an independent inflammatory marker)
One way or another, SGPT/ALT is a simple measurement, available in routine
clinical practice, which, according to our findings, may help identify individuals
likely to have insulin resistance.
Suggested Bibliography
1. Sasiwarang Goya Wannamethee et al. Hepatic Enzymes, the
Metabolic Syndrome and the Risk of Type 2 Diabetes in Older Men.
Diabetes Care 2005; 28: 2913-2918
2. Barbora Vozarova et al. High Alanine Aminotransferase Is Associated
With Decreased Hepatic Insulin Sensitivity and Predicts the
Development of Type 2 Diabetes. Diabetes 2002; 51: 1889-1895
3. Jose Manuel Fernandez-Real et al. Cross-Talk Between Iron
Metabolism and Diabetes. Diabetes 2002; 51: 2348-2354
4. Claudia Bozzini et al. Prevalence of Body Iron Excess in the
Metabolic Syndrome. Diabetes Care 2005; 28: 2061-2063
5. Jose Manuel Fernandez-Real et al. Serum Ferritin as a Component of
the Insulin Resistance Syndrome. Diabetes Care 1998; 21: 62-68
