2007 15th eco

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2007 15th eco

  1. 1. 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
  2. 2. INTRODUCTION A number of studies have shown relationship between gamma-GT or SGPT/ALT levels and insulinresistance, suggesting that these parameters can be used as markers for the insulin resistance state. Gamma-GT and SGPT/ALT levels, even within thenormal range, correlate with increasing intrahepatic fat. It has been suggested that the elevation of the hepatic enzymes could be the expression of excessdeposition of fat in the liver, which is closely relatedto obesity and other metabolic disturbances such as dyslipidaemia or diabetes mellitus.
  3. 3. AIM of our study was to investigate the relationship between SGPT/ALT levels and insulin resistanceindices in overweight and obese persons who are invariably insulin resistant.
  4. 4. SUBJECTS-METHODSWe studied retrospectively 219 male and 382 female (total 601) overweight andobese persons who attended the outpatient clinic of Diabetes-Obesity-MetabolismDepartment of our Hospital, in order to reveal any trend between ALT and insulinresistance.Subjects with overt liver disease were excluded from the study.Subjects were also classified as “non-diabetic” and “diabetic” according toreported personal history or considering HbA1c (cutoff point: 6.2%) and fastingplasma 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 aswell as “Insulinogenic” Index which was defined as the ratio of fasting insulin tofasting glucose.Subjects were divided in HOMA, Quicki and Insulinogenic Index quartiles and SGPTcomparisons were made within these quartiles. Statistic analysis included ANOVA,multiple regression analysis, Man-Whitney test and non parametric (Spearman)correlation.
  5. 5. SUBJECTS-METHODS Males Females p (n=218) (n=382)Age (years) 46.0 ± 13.9 42.2 ± 13.7 0.001BMI (kg/m2) 35.1 ±6.2 34.3 ±6.2 NSWaist Circumference (cm) 115.6 ± 14.5 104.0 ± 13.6 0.000% Total Body Fat 35.9 ± 5.9 44.4 ± 6.1 0.000Glucose (mg/dl) 122.1 ± 49.3 102.9 ± 33.7 0.000Insulin (μU/ml) 16.9 ± 11.6 13.3 ± 9.8 0.000SGOT (U/l) 25.8 ± 13.2 20.7 ± 8.3 0.000SGPT (U/l) 38.9 ± 24.3 25.7 ± 15.2 0.000Gamma-GT (U/l) 38.1 ± 26.9 23.4 ± 19.8 0.000HOMA 5.06 ± 3.86 3.45 ± 2.82 0.000Quicki 0.318 ± 0.046 0.331 ± 0.0319 0.000Insulinogenic Index 0.154 ± 0.117 0.135 ± 0.101 0.043Type 2 Diabetes (Yes/No) 94 / 124 64 / 318 0.000
  6. 6. RESULTS 150 106 125 131 362 193 622 33 595 100 42 194 216 98 SGPT 212 207 77 SGPT 453 631 496 563 75 257 628 620 621 574 429 626 435 571 382 50 25 0 N= 218 382 male Male female Female sex Males had higher SGPT levels than females(38.9U/l 24.3U/l vs. 25.7U/l 15.2U/l, p= 0.000)
  7. 7. RESULTS (Males)SGPT differed within HOMA, Quicki and Insulinogenic Index quartiles.
  8. 8. RESULTS (Males) 150 150 106 125 131 106 193 125 33 131 100 193 33 100 98 207 77SGPT 98 SGPT 207 77 223 SGPT 7 223 75 75 7 138 138 215 215 50 50 25 25 0 N= 55 55 54 54 0 1 2 3 4 N= 55 55 54 54 1 Homa 2 quartiles according to males 3 4 Homa quartiles Homa quartiles according to males F= 3.798, p= 0.011
  9. 9. RESULTS (Males) 150 106 125 131 193 33 100 SGPT 207 77SGPT 223 7 75 138 215 50 25 0 N= 56 53 55 54 1 2 3 4 Quicki quartiles quicki quartiles according to males F= 4.440, p= 0.005
  10. 10. RESULTS (Males) 150 106 125 131 193 33 100 SGPT 98 77SGPT 223 7 75 214 50 25 0 N= 54 56 54 54 1 2 3 4 Insulinogenic index quartiles insulinogenic index quartiles (males) F= 5.215, p= 0.002
  11. 11. RESULTS (Males) 150 125 100 SGPTSGPT 75 50 25 0 0 10 20 30 40 50 60 70 80 90 fasting insulin fasting insulin r= 0.351, p= 0.000
  12. 12. RESULTS (Males) 150 125 100 SGPTSGPT 75 50 25 0 0 5 10 15 20 25 30 Insulin resistance (HOMA) Insulin Resistance (HOMA) r= 0.248, p= 0.000
  13. 13. RESULTS (Males) 150 125 100 SGPTSGPT 75 50 25 0 ,2 ,3 ,4 ,5 ,6 ,7 ,8 Quicki Quicki r= -0.248, p=0.000
  14. 14. RESULTS (Males) 150 125 100 SGPTSGPT 75 50 25 0 0,0 ,2 ,4 ,6 ,8 1,0 "insulinogenic" index Insulinogenic index r= 0.340, p= 0.000
  15. 15. RESULTS (Males) Multiple regression analysis R R square F p 0.401 0.161 15.24 0.000 Beta t pInsulinogenic 0.319 4.39 0.000 Index Ferritin 0.230 3.16 0.002 Age, BMI, WHR and Waist circumference were not significant in the model
  16. 16. RESULTS (Males) 150 125 100 SGPT SGPT 75 50 25 0 0 100 200 300 400 500 600 700 Ferritin 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)
  17. 17. RESULTS (Males) SEX: 0 male 700 600 Ferritin 500 400ferritin 300 200 100 0 0 5 10 15 20 25 Insulin Resistance (HOMA) Insulin resistance (HOMA) r= 0.265, p= 0.001
  18. 18. RESULTS (Females)SGPT differed within HOMA, Quicki and Insulinogenic Index quartiles.
  19. 19. RESULTS (Females) 150 125 362 622 595 100 SGPTSGPT 453 631 496 563 75 257 628 620 621 626 435 557 50 405 611 25 0 N= 96 96 95 95 1 2 3 4 Homa quartiles Homa quartiles according to females F= 10.830, p= 0.000
  20. 20. RESULTS (Females) 150 125 362 622 595 100 SGPTSGPT 631 453 563 496 75 257 628 621 620 626 435 557 50 611 405 25 0 N= 95 95 97 95 1 2 3 4 Quicki quartiles Quicki quartiles according to females F= 10.800, p= 0.000
  21. 21. RESULTS (Females) 150 125 362 622 595 100 SGPTSGPT 453 631 496 563 75 257 628 620 621 574 626 435 557 50 239 611 405 364 25 0 N= 96 96 95 95 1 2 3 4 Insulinogenic index quartiles insulinogenic index quartiles (females) F= 4.836, p= 0.003
  22. 22. RESULTS (Females) 150 125 100 SGPTSGPT 75 50 25 0 0 10 20 30 40 50 60 70 80 90 fasting insulin fasting insulin r= 0.278, p= 0.000
  23. 23. RESULTS (Females) 150 125 100 SGPTSGPT 75 50 25 0 0 5 10 15 20 25 30 Insulin Resistance (HOMA) Insulin resistance (HOMA) r= 0.309, p= 0.000
  24. 24. RESULTS (Females) 150 125 100 SGPTSGPT 75 50 25 0 ,2 ,3 ,4 ,5 Quicki Quicki r= -0.309, p= 0.000
  25. 25. RESULTS (Females) 150 125 100 SGPTSGPT 75 50 25 0 0,0 ,2 ,4 ,6 ,8 1,0 1,2 1,4 "insulinogenic" index Insulinogenic index r= 0.180, p= 0.000
  26. 26. RESULTS (Females) Multiple regression analysis R R square F p 0.361 0.130 25.57 0.000 Beta t pHOMA-IR 0.226 4.40 0.000Ferritin 0.243 4.75 0.000 Age, BMI, WHR and Waist circumference were not significant in the model
  27. 27. RESULTS (Females) 150 125 100 SGPT SGPT 75 50 25 0 0 100 200 300 400 500 Ferritin ferritin r= 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)
  28. 28. RESULTS (Females) SEX: 1 female 500 Ferritin 400 300ferritin 200 100 0 0 5 10 15 20 25 30 Insulin Resistance (HOMA) Insulin resistance (HOMA) r= 0.126, p= 0.019
  29. 29. Conclusions1. 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.
  30. 30. 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 routineclinical practice, which, according to our findings, may help identify individualslikely to have insulin resistance.
  31. 31. Suggested Bibliography1. Sasiwarang Goya Wannamethee et al. Hepatic Enzymes, the Metabolic Syndrome and the Risk of Type 2 Diabetes in Older Men. Diabetes Care 2005; 28: 2913-29182. 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: 1889-18953. Jose Manuel Fernandez-Real et al. Cross-Talk Between Iron Metabolism and Diabetes. Diabetes 2002; 51: 2348-23544. Claudia Bozzini et al. Prevalence of Body Iron Excess in the Metabolic Syndrome. Diabetes Care 2005; 28: 2061-20635. Jose Manuel Fernandez-Real et al. Serum Ferritin as a Component of the Insulin Resistance Syndrome. Diabetes Care 1998; 21: 62-68
  32. 32. Correspondence:Eftychia Chala, email: echala@metropolitan-hospital.gr

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