- Email: [email protected]
Comparison of short insulin tolerance test with HOMA
diabetes research and clinical practice 82 (2008) e9–e12
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/diabres
Brief report
Comparison of short insulin tolerance test with HOMA Method for assessment of insulin sensitivity in Asian Indians in north India Rajeev Sharma a, Naval K. Vikram a, Anoop Misra a,b,* a b
Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi 110029, India Department of Diabetes and Metabolic Diseases, Fortis Flt. Lt. Rajan Dhall Hospital, Vasant Kunj, New Delhi 110070, India
article info
abstract
Article history:
Background: Cost-effective method to assess insulin resistance is needed for Asian Indians.
Received 20 June 2008
Methods: We compared HOMA with SITT methods in 40 subjects.
Received in revised form
Results: Values obtained from both methods did not show any correlation.
20 June 2008
Conclusions: Both methods should be evaluated against hyperinsulinemic clamp to deter-
Accepted 1 July 2008
mine suitability in Asian Indians.
Published on line 15 August 2008
# 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: Asian Indians Metabolic syndrome Insulin resistance
1.
Introduction
Asians Indians have an abnormally high tendency to develop type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [1]. Insulin resistance (IR) is an important determinant of both these diseases [2,3]. Body composition of Asian Indians is favorable for the development of the metabolic syndrome; they have high percentage of body fat [4,5] and abdominal adiposity including high-subcutaneous and intra-abdominal fat [4,6]. Non-alcoholic fatty liver disease (NAFLD) is now considered to be a key component of the metabolic syndrome [7] and is present in nearly one-fourth of Asian Indians living in India [8,9]. Currently, insulin sensitivity needs to be assessed in experimental and clinical studies. It is desirable to have a
cost-effective field-based method for measurement of insulin sensitivity in developing countries. Various methods used to assess IR are; ‘‘gold standard’’ euglycemic hyperinsulinemic clamp technique [10], frequently sampled intravenous glucose tolerance test (FSIGT), homeostasis model assessment for IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), glucose/insulin ratio (G/I ratio) and insulin tolerance test (ITT) [11]. Homeostatic models like HOMA-IR, which require determination of serum insulin and glucose has been used in many studies [12]. SITT is another, less frequently used method of measurement of insulin sensitivity and has been validated against clamp studies [13,14]. In this study, we planned to compare SITT and HOMA-IR for measuring IR in patients with Asian Indians with NAFLD.
* Corresponding author at: Department of Diabetes and Metabolic Diseases, Fortis Flt. Lt. Rajan Dhall Hospital, Vasant Kunj, New Delhi 110070, India. Tel.: +91 11 4277 6222x5030; fax: +91 11 4277 6221. E-mail addresses: [email protected], [email protected] (A. Misra). 0168-8227/$ – see front matter # 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2008.07.010
e10
diabetes research and clinical practice 82 (2008) e9–e12
2.
Methods
2.1.
Subjects
Forty male subjects were enrolled (from June 2004 to April 2006) after informed consent and institution’s ethical committee approval. Inclusion criteria were: age >18 years, normoglycemia, alcohol intake less than 20 g/day, ultrasound documented hyperechoic liver and negative tests for viral and other known liver diseases. This test sample was compared with 20 age-matched healthy controls with normal values of body mass index (BMI), waist circumference, serum aminotransferases, fasting plasma glucose and normal liver ultrasound.
2.2.
Experimental protocol
Anthropometric measurements, fasting blood glucose, serum insulin and lipids were measured as previously described [15,16]. Insulin sensitivity was calculated by the HOMA-IR [17] and ITT [13]. For ITT blood samples were taken for measurement of plasma glucose and fasting serum insulin after an overnight fast. Subsequently rapid acting insulin (Huminsulin R, Eli Lilly, Indianapolis, IN) was given at an intravenous bolus dose of 0.05 U/kg body weight and the blood samples were collected at the time of injection and at 3, 6, 9, 12 and 15 min. The test was terminated by injection of 25 ml 50% dextrose. Rate constant for ITT (KITT) was calculated using formula KITT (%/min) = 0.693/t1/2, where t1/2 was calculated from the slope of the plasma glucose concentration during the period from 3 to 15 min after insulin injection, using the least square analysis. Lower insulin-sensitivity index (KITT) scores mean higher degrees of insulin resistance. HOMA-IR was calculated as the product of fasting serum insulin (mU/L) and fasting plasma glucose (mg/dl) divided by 405. Since there are no accepted cut off values of HOMA to define IR, we used 2.29 as abnormal value in our study [18].
The metabolic syndrome was defined by the presence of three or more modified adult treatment panel III criteria out of five criteria (abnormal waist circumference, high-fasting plasma glucose, high-blood pressure, high-serum TG, and low-serum HDL) [19]. The statistical analysis was conducted by SPSS package for Windows (SPSS, Chicago, IL). Spearman’s correlation was used to explore the relationship between ITT and HOMA-IR.
3.
Results (Table 1)
The mean age of the patients was 35 years (21–54) Twenty patients (50%) had BMI 25 kg/m2. The mean ALT values in patient group were 72 IU/L (range = 19–232 IU/L). Twenty-eight percent of subjects in the study group had the metabolic syndrome according to NCEP, ATP III criteria [19]. In comparison to healthy controls, patients with NAFLD showed more insulin resistance with both the methods. Patients with NAFLD had significantly lower mean KITT value (1.91%/min [range = 0.47–5.47]) than healthy controls (2.48 [0.74–3.62]). Also, they had higher mean HOMA-IR values (2.08 [0.50–12.42]) than the healthy controls (1.47 [0.40–3.52]). There was no correlation between KITT and HOMA-IR values in the NAFLD patients (r = 0.18 and p = 0.2) (Fig. 1).
4.
Discussion
This study shows that SITT does not correlate with HOMA-IR values for determining insulin sensitivity in patients with non-diabetic Asian Indians with NAFLD. These findings are in contrast to those of Duseja et al. [20] who showed fair correlation between these two methods on 22 Asian Indian patients with NAFLD (r = 0.55 and p = 0.03). The ‘gold standard’, euglycemic hyperinsulinemic clamp technique [10], is cumbersome, expensive and requires a great
Table 1 – Demographic, anthropometric and biochemical data Parameters Age (years) Body mass index, BMI (kg/m2) Waist circumference (cm) Waist-hip ratio Body fat (%) AST (IU/L) ALT (IU/L) Fasting blood glucose (mg/dl) The metabolic syndrome (according to ATP III criteria) Fasting serum insulin (mIU/ml) HOMA-IR Kitt Total cholesterol (mg/dl) Serum triglycerides (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl)
NAFLD group (40) 35.6 9.1 25.3 3.1 92.3 10.3 0.97 0.07 28.6 6.4 47.8 24.3 72.8 56.6 94.3 11.1 11 (28%) 11.8 10.1 2.08 2.49 1.9 1.3 198.7 56.8 190.9 84.2 47.1 4.2 113.0 57.4
Control group (20) 34.1 6.8 21.9 2.5 82.0 11.3 0.89 0.07 22.9 6.2 33.2 8.1 33.9 9.7 103.0 41.9 1 (5%) 2.5 0.7 1.47 0.78 88.0 9.5 6.8 3.6 176.7 42.7 138.7 59.7 46.6 3.3
All values are in mean standard deviation. ALT: alanine aminotransferase, AST: aspartate aminotransferase; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Kitt: insulin-induced glucose disposal rate calculated from the slope of the regression line of the logarithm of blood glucose against time; HOMA-IR: homeostasis model assessment-insulin resistance; ATP III: National Cholesterol Education Program, Adult Treatment Panel III.
diabetes research and clinical practice 82 (2008) e9–e12
Fig. 1 – Graph showing correlation between rate constant for insulin tolerance test (KITT) (Y-axis) and homeostasis model assessment for insulin resistance (HOMA) (X-axis) in patients with NAFLD (r = S0.18 and p = 0.2).
deal of expertise and is not an ideal method for epidemiological studies. Both HOMA and SITT methods could be useful for developing country like India. HOMA is probably the easiest method to perform although but it involves measurement of serum insulin which may not be available and is expensive in resource-constrained settings in India. SITT is a safe, inexpensive and easy-to-perform test [21]. However, the limitations of SITT are frequent sampling, possibility of hypoglycemia, and confounding due to secretion of counter-regulatory hormones like cortisol and epinephrine in response to insulin-induced hypoglycemia. However, these responses appear 15–20 min after insulin injection [22]. In our study, the test was completed at 15 min thus avoiding the counter-regulatory hormone response interfering with the rate of glucose fall. To conclude, based on this study, it is not possible to choose between two easy methods of measurement of insulin sensitivity, HOMA and SITT for Asian Indians. These methods need evaluation against hyperinsulinemic euglycemic insulin clamp method.
Conflict of interest There are no conflicts of interest.
Acknowledgement None.
references
[1] K.S. Reddy, S. Yusuf, Emerging epidemic of cardiovascular disease in developing countries, Circulation 97 (1998) 596–601.
e11
[2] R.A. DeFronzo, E. Ferrannini, Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease, Diab. Care 14 (1991) 173–194. [3] S.M. Haffner, L. Mykkanen, A. Festa, J.P. Burke, M.P. Stern, Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state, Circulation 101 (2000) 975–980. [4] A. Misra, Body composition and the metabolic syndrome in Asian Indians: a saga of multiple adversities, Natl. Med. J. India 16 (2003) 3–7. [5] P. Deurenberg, M. Yap, W.A. van Staveren, Body mass index and percent body fat: a meta analysis among different ethnic groups, Int. J. Obes. Relat. Metab. Disord. 22 (1998) 1164–1171. [6] A. Misra, D. Athiko, R. Sharma, R.M. Pandey, N. Khanna, Non-obese hyperlipidemic Asian northern Indian males have adverse anthropometric profile, Nutr. Metab. Cardiovasc. Dis. 12 (2002) 178–183. [7] J.B. Dixon, P.S. Bhathal, P.E.O. Brien, Nonalcoholic fatty liver disease: predictors of non-alcoholic steatohepatitis and liver fibrosis in severely obese, Gastroenterology 121 (2001) 91–100. [8] A. Misra, N.K. Vikram, Metabolic syndrome in children and adolescents: problems in definition, and ethnicity-related determinants, Diab. Metab. Synd. Clin. Res. Rev. 1 (2007) 121–126. [9] A. Luthra, P. Nigam, A. Misra, Metabolic correlation and management strategies of non-alcoholic fatty liver disease: an Asian Indian perspective, Diab. Metab. Synd. Clin. Res. Rev. 1 (2007) 279–285. [10] R.A. DeFronzo, J.D. Tobin, R. Andres, Glucose clamp technique: a method for quantifying insulin secretion and resistance, Am. J. Physiol. 237 (1979) E214–E223. [11] K.A. McAuley, S.M. Williams, J.I. Mann, R.J. Walker, N.J. Lewis-Barned, L.A. Temple, et al., Diagnosing insulin resistance in the general population, Diab. Care 24 (2001) 460–464. [12] M. Jensterle, M. Weber, M. Pfeifer, J. Prezelj, A. Pfutzner, A. Janez, Assessment of insulin resistance in young women with polycystic ovary syndrome, Int. J. Gynaecol. Obstet. 102 (2008) 137–140. [13] E. Bonora, P. Moghetti, C. Zancanaro, M. Cigolini, M. Querena, V. Cacciatori, et al., Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies, J. Clin. Endocrinol. Metab. 68 (1989) 374–378. [14] S.V. Gelding, S. Robinson, S. Lowe, R. Niththyananthan, D.G. Johnston, Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity, Clin. Endocrinol. (Oxf.) 40 (1994) 611–615. [15] V. Dudeja, A. Misra, R.M. Pandey, G. Devina, G. Kumar, N.K. Vikram, BMI does not accurately predict overweight in Asian Indians in northern India, Br. J. Nutr. 86 (2001) 105–112. [16] A. Misra, R.M. Pandey, J.R. Devi, R. Sharma, N.K. Vikram, N. Khanna, High prevalence of diabetes, obesity and dyslipidaemia in urban slum population in northern India, Int. J. Obes. Relat. Metab. Disord. 25 (2001) 1722–1729. [17] D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man, Diabetologia 28 (1985) 412–419. [18] Z. Radikova, J. Koska, M. Huckova, L. Ksinantova, R. Imrich, M. Vigas, et al., Insulin sensitivity indices: a proposal of cutoff points for simple identification of insulin-resistant subjects, Exp. Clin. Endocrinol. Diab. 114 (2006) 249–256.
e12
diabetes research and clinical practice 82 (2008) e9–e12
[19] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), JAMA 285 (2001) 2486–2497. [20] A. Duseja, K.K. Thumburu, A. Das, R.K. Dhiman, Y.K. Chawla, S. Bhadada, et al., Insulin tolerance test is comparable to homeostasis model assessment for insulin resistance in patients with nonalcoholic fatty liver disease, Indian J. Gastroenterol. 26 (2007) 170–173.
[21] S. Graci, R. Baratta, C. Degano, A. Luppa, R. Vigneri, L. Frittitta, et al., The intravenous insulin tolerance test is an accurate method for screening a general population for insulin resistance and related abnormalities, J. Endocrinol. Invest. 22 (1999) 472–475. [22] R.A. Rizza, P.E. Cryer, J.E. Gerich, Role of glucagon, catecholamines and growth hormone in glucose counterregulation, Effects of somatostatin and combined alfa and beta adrenergic blockade on plasma glucose recovery and glucose flux rates after insulin-induced hypoglycemia, J. Clin. Invest. 64 (1979) 62–72.
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/diabres
Brief report
Comparison of short insulin tolerance test with HOMA Method for assessment of insulin sensitivity in Asian Indians in north India Rajeev Sharma a, Naval K. Vikram a, Anoop Misra a,b,* a b
Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi 110029, India Department of Diabetes and Metabolic Diseases, Fortis Flt. Lt. Rajan Dhall Hospital, Vasant Kunj, New Delhi 110070, India
article info
abstract
Article history:
Background: Cost-effective method to assess insulin resistance is needed for Asian Indians.
Received 20 June 2008
Methods: We compared HOMA with SITT methods in 40 subjects.
Received in revised form
Results: Values obtained from both methods did not show any correlation.
20 June 2008
Conclusions: Both methods should be evaluated against hyperinsulinemic clamp to deter-
Accepted 1 July 2008
mine suitability in Asian Indians.
Published on line 15 August 2008
# 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: Asian Indians Metabolic syndrome Insulin resistance
1.
Introduction
Asians Indians have an abnormally high tendency to develop type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [1]. Insulin resistance (IR) is an important determinant of both these diseases [2,3]. Body composition of Asian Indians is favorable for the development of the metabolic syndrome; they have high percentage of body fat [4,5] and abdominal adiposity including high-subcutaneous and intra-abdominal fat [4,6]. Non-alcoholic fatty liver disease (NAFLD) is now considered to be a key component of the metabolic syndrome [7] and is present in nearly one-fourth of Asian Indians living in India [8,9]. Currently, insulin sensitivity needs to be assessed in experimental and clinical studies. It is desirable to have a
cost-effective field-based method for measurement of insulin sensitivity in developing countries. Various methods used to assess IR are; ‘‘gold standard’’ euglycemic hyperinsulinemic clamp technique [10], frequently sampled intravenous glucose tolerance test (FSIGT), homeostasis model assessment for IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), glucose/insulin ratio (G/I ratio) and insulin tolerance test (ITT) [11]. Homeostatic models like HOMA-IR, which require determination of serum insulin and glucose has been used in many studies [12]. SITT is another, less frequently used method of measurement of insulin sensitivity and has been validated against clamp studies [13,14]. In this study, we planned to compare SITT and HOMA-IR for measuring IR in patients with Asian Indians with NAFLD.
* Corresponding author at: Department of Diabetes and Metabolic Diseases, Fortis Flt. Lt. Rajan Dhall Hospital, Vasant Kunj, New Delhi 110070, India. Tel.: +91 11 4277 6222x5030; fax: +91 11 4277 6221. E-mail addresses: [email protected], [email protected] (A. Misra). 0168-8227/$ – see front matter # 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2008.07.010
e10
diabetes research and clinical practice 82 (2008) e9–e12
2.
Methods
2.1.
Subjects
Forty male subjects were enrolled (from June 2004 to April 2006) after informed consent and institution’s ethical committee approval. Inclusion criteria were: age >18 years, normoglycemia, alcohol intake less than 20 g/day, ultrasound documented hyperechoic liver and negative tests for viral and other known liver diseases. This test sample was compared with 20 age-matched healthy controls with normal values of body mass index (BMI), waist circumference, serum aminotransferases, fasting plasma glucose and normal liver ultrasound.
2.2.
Experimental protocol
Anthropometric measurements, fasting blood glucose, serum insulin and lipids were measured as previously described [15,16]. Insulin sensitivity was calculated by the HOMA-IR [17] and ITT [13]. For ITT blood samples were taken for measurement of plasma glucose and fasting serum insulin after an overnight fast. Subsequently rapid acting insulin (Huminsulin R, Eli Lilly, Indianapolis, IN) was given at an intravenous bolus dose of 0.05 U/kg body weight and the blood samples were collected at the time of injection and at 3, 6, 9, 12 and 15 min. The test was terminated by injection of 25 ml 50% dextrose. Rate constant for ITT (KITT) was calculated using formula KITT (%/min) = 0.693/t1/2, where t1/2 was calculated from the slope of the plasma glucose concentration during the period from 3 to 15 min after insulin injection, using the least square analysis. Lower insulin-sensitivity index (KITT) scores mean higher degrees of insulin resistance. HOMA-IR was calculated as the product of fasting serum insulin (mU/L) and fasting plasma glucose (mg/dl) divided by 405. Since there are no accepted cut off values of HOMA to define IR, we used 2.29 as abnormal value in our study [18].
The metabolic syndrome was defined by the presence of three or more modified adult treatment panel III criteria out of five criteria (abnormal waist circumference, high-fasting plasma glucose, high-blood pressure, high-serum TG, and low-serum HDL) [19]. The statistical analysis was conducted by SPSS package for Windows (SPSS, Chicago, IL). Spearman’s correlation was used to explore the relationship between ITT and HOMA-IR.
3.
Results (Table 1)
The mean age of the patients was 35 years (21–54) Twenty patients (50%) had BMI 25 kg/m2. The mean ALT values in patient group were 72 IU/L (range = 19–232 IU/L). Twenty-eight percent of subjects in the study group had the metabolic syndrome according to NCEP, ATP III criteria [19]. In comparison to healthy controls, patients with NAFLD showed more insulin resistance with both the methods. Patients with NAFLD had significantly lower mean KITT value (1.91%/min [range = 0.47–5.47]) than healthy controls (2.48 [0.74–3.62]). Also, they had higher mean HOMA-IR values (2.08 [0.50–12.42]) than the healthy controls (1.47 [0.40–3.52]). There was no correlation between KITT and HOMA-IR values in the NAFLD patients (r = 0.18 and p = 0.2) (Fig. 1).
4.
Discussion
This study shows that SITT does not correlate with HOMA-IR values for determining insulin sensitivity in patients with non-diabetic Asian Indians with NAFLD. These findings are in contrast to those of Duseja et al. [20] who showed fair correlation between these two methods on 22 Asian Indian patients with NAFLD (r = 0.55 and p = 0.03). The ‘gold standard’, euglycemic hyperinsulinemic clamp technique [10], is cumbersome, expensive and requires a great
Table 1 – Demographic, anthropometric and biochemical data Parameters Age (years) Body mass index, BMI (kg/m2) Waist circumference (cm) Waist-hip ratio Body fat (%) AST (IU/L) ALT (IU/L) Fasting blood glucose (mg/dl) The metabolic syndrome (according to ATP III criteria) Fasting serum insulin (mIU/ml) HOMA-IR Kitt Total cholesterol (mg/dl) Serum triglycerides (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl)
NAFLD group (40) 35.6 9.1 25.3 3.1 92.3 10.3 0.97 0.07 28.6 6.4 47.8 24.3 72.8 56.6 94.3 11.1 11 (28%) 11.8 10.1 2.08 2.49 1.9 1.3 198.7 56.8 190.9 84.2 47.1 4.2 113.0 57.4
Control group (20) 34.1 6.8 21.9 2.5 82.0 11.3 0.89 0.07 22.9 6.2 33.2 8.1 33.9 9.7 103.0 41.9 1 (5%) 2.5 0.7 1.47 0.78 88.0 9.5 6.8 3.6 176.7 42.7 138.7 59.7 46.6 3.3
All values are in mean standard deviation. ALT: alanine aminotransferase, AST: aspartate aminotransferase; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Kitt: insulin-induced glucose disposal rate calculated from the slope of the regression line of the logarithm of blood glucose against time; HOMA-IR: homeostasis model assessment-insulin resistance; ATP III: National Cholesterol Education Program, Adult Treatment Panel III.
diabetes research and clinical practice 82 (2008) e9–e12
Fig. 1 – Graph showing correlation between rate constant for insulin tolerance test (KITT) (Y-axis) and homeostasis model assessment for insulin resistance (HOMA) (X-axis) in patients with NAFLD (r = S0.18 and p = 0.2).
deal of expertise and is not an ideal method for epidemiological studies. Both HOMA and SITT methods could be useful for developing country like India. HOMA is probably the easiest method to perform although but it involves measurement of serum insulin which may not be available and is expensive in resource-constrained settings in India. SITT is a safe, inexpensive and easy-to-perform test [21]. However, the limitations of SITT are frequent sampling, possibility of hypoglycemia, and confounding due to secretion of counter-regulatory hormones like cortisol and epinephrine in response to insulin-induced hypoglycemia. However, these responses appear 15–20 min after insulin injection [22]. In our study, the test was completed at 15 min thus avoiding the counter-regulatory hormone response interfering with the rate of glucose fall. To conclude, based on this study, it is not possible to choose between two easy methods of measurement of insulin sensitivity, HOMA and SITT for Asian Indians. These methods need evaluation against hyperinsulinemic euglycemic insulin clamp method.
Conflict of interest There are no conflicts of interest.
Acknowledgement None.
references
[1] K.S. Reddy, S. Yusuf, Emerging epidemic of cardiovascular disease in developing countries, Circulation 97 (1998) 596–601.
e11
[2] R.A. DeFronzo, E. Ferrannini, Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease, Diab. Care 14 (1991) 173–194. [3] S.M. Haffner, L. Mykkanen, A. Festa, J.P. Burke, M.P. Stern, Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state, Circulation 101 (2000) 975–980. [4] A. Misra, Body composition and the metabolic syndrome in Asian Indians: a saga of multiple adversities, Natl. Med. J. India 16 (2003) 3–7. [5] P. Deurenberg, M. Yap, W.A. van Staveren, Body mass index and percent body fat: a meta analysis among different ethnic groups, Int. J. Obes. Relat. Metab. Disord. 22 (1998) 1164–1171. [6] A. Misra, D. Athiko, R. Sharma, R.M. Pandey, N. Khanna, Non-obese hyperlipidemic Asian northern Indian males have adverse anthropometric profile, Nutr. Metab. Cardiovasc. Dis. 12 (2002) 178–183. [7] J.B. Dixon, P.S. Bhathal, P.E.O. Brien, Nonalcoholic fatty liver disease: predictors of non-alcoholic steatohepatitis and liver fibrosis in severely obese, Gastroenterology 121 (2001) 91–100. [8] A. Misra, N.K. Vikram, Metabolic syndrome in children and adolescents: problems in definition, and ethnicity-related determinants, Diab. Metab. Synd. Clin. Res. Rev. 1 (2007) 121–126. [9] A. Luthra, P. Nigam, A. Misra, Metabolic correlation and management strategies of non-alcoholic fatty liver disease: an Asian Indian perspective, Diab. Metab. Synd. Clin. Res. Rev. 1 (2007) 279–285. [10] R.A. DeFronzo, J.D. Tobin, R. Andres, Glucose clamp technique: a method for quantifying insulin secretion and resistance, Am. J. Physiol. 237 (1979) E214–E223. [11] K.A. McAuley, S.M. Williams, J.I. Mann, R.J. Walker, N.J. Lewis-Barned, L.A. Temple, et al., Diagnosing insulin resistance in the general population, Diab. Care 24 (2001) 460–464. [12] M. Jensterle, M. Weber, M. Pfeifer, J. Prezelj, A. Pfutzner, A. Janez, Assessment of insulin resistance in young women with polycystic ovary syndrome, Int. J. Gynaecol. Obstet. 102 (2008) 137–140. [13] E. Bonora, P. Moghetti, C. Zancanaro, M. Cigolini, M. Querena, V. Cacciatori, et al., Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies, J. Clin. Endocrinol. Metab. 68 (1989) 374–378. [14] S.V. Gelding, S. Robinson, S. Lowe, R. Niththyananthan, D.G. Johnston, Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity, Clin. Endocrinol. (Oxf.) 40 (1994) 611–615. [15] V. Dudeja, A. Misra, R.M. Pandey, G. Devina, G. Kumar, N.K. Vikram, BMI does not accurately predict overweight in Asian Indians in northern India, Br. J. Nutr. 86 (2001) 105–112. [16] A. Misra, R.M. Pandey, J.R. Devi, R. Sharma, N.K. Vikram, N. Khanna, High prevalence of diabetes, obesity and dyslipidaemia in urban slum population in northern India, Int. J. Obes. Relat. Metab. Disord. 25 (2001) 1722–1729. [17] D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man, Diabetologia 28 (1985) 412–419. [18] Z. Radikova, J. Koska, M. Huckova, L. Ksinantova, R. Imrich, M. Vigas, et al., Insulin sensitivity indices: a proposal of cutoff points for simple identification of insulin-resistant subjects, Exp. Clin. Endocrinol. Diab. 114 (2006) 249–256.
e12
diabetes research and clinical practice 82 (2008) e9–e12
[19] Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), JAMA 285 (2001) 2486–2497. [20] A. Duseja, K.K. Thumburu, A. Das, R.K. Dhiman, Y.K. Chawla, S. Bhadada, et al., Insulin tolerance test is comparable to homeostasis model assessment for insulin resistance in patients with nonalcoholic fatty liver disease, Indian J. Gastroenterol. 26 (2007) 170–173.
[21] S. Graci, R. Baratta, C. Degano, A. Luppa, R. Vigneri, L. Frittitta, et al., The intravenous insulin tolerance test is an accurate method for screening a general population for insulin resistance and related abnormalities, J. Endocrinol. Invest. 22 (1999) 472–475. [22] R.A. Rizza, P.E. Cryer, J.E. Gerich, Role of glucagon, catecholamines and growth hormone in glucose counterregulation, Effects of somatostatin and combined alfa and beta adrenergic blockade on plasma glucose recovery and glucose flux rates after insulin-induced hypoglycemia, J. Clin. Invest. 64 (1979) 62–72.