Abstract
Introduction: Changes in food consumption and health habits that have developed over the last three decades, the prevalence of obesity in children and adolescents has increased in both developed and developing countries. This has led to a striking worldwide increase in the rate of type 2 diabetes mellitus in the adolescent age group.
Materials and Methods: In the present study, a total of sixty seven subjects were studied comprising of 36 obese adolescents (15 males, 21 females) and 31 (16 males, 15 females) apparently healthy normal weight adolescents of age group between 17-19 years. In all the subjects BMI, waist circumference, hip circumference was measured, GTT was done, and the serum concentrations of fasting glucose, 2 hr glucose and fasting insulin were estimated. Further HOMA-IR, GF/IF, QUICKI, HOMA%B were calculated.
Results: Increased insulin concentrations was observed in obese individuals (18.18±1.29) when compared to non obese individuals (9.41±3.19). Significantly higher HOMA-IR (3.97±2.61 vs 1.97±0.69) (p<0.001) and HOMA%B (269.32±147.02 vs 173.07±92.94) (P<0.01) were observed in obese individuals when compared to non obese individuals. GF/IF (6.31±3.25 vs 10.26±4.18) (p<0.001) and QUICKI (0.32±0.02 vs 0.35±0.02) (p<0.001) were significantly lower in cases when compared to controls. BMI was positively correlated with insulin resistance (r= 0.536, p<0.001) and negatively correlated with insulin sensitivity (r=-0.545, p<0.001) and both were found to be statistically significant. The odds of developing insulin resistance and impaired insulin sensitivity is 6.86 and 5.33 times respectively more in obese when compared to non obese individuals.
Conclusion: The results demonstrate that both insulin resistance and insulin sensitivity predict conversion to diabetes in obese adolescents. Improving insulin resistance may be crucial for the prevention of both type 2 diabetes and premature cardiovascular diseases in this young population at risk. Lifestyle measures have to be taken to improve IR.
Keywords: Beta cell dysfunction, type 2 DM, obesity, insulin resistance, impaired insulin sensitivity.
References
- Deckelbaum RJ, Williams CL. Childhood obesity: the health issue. Obes Rev 2001; 9 (Suppl 4): 239s–243s.
- Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends in overweight among US children and adolescents, 1999–2000. JAMA 2002; 288: 1728–1732.
- Kopelman PG. Obesity as a medical problem. Nature 2000; 404: 635–643.
- Anderson, J.W., Kendall, C.W., and Jenkins, D.J. 2003. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. Am. Coll. Nutr. 22:331–339.
- Pinhas-Hamiel O, Dolan LM, Daniels SR. Increased incidence of non-insulin dependentdiabetes mellitus among adolescents. J Pediatr 1996; 128: 608–615.
- Arslanian SA. Type 2 diabetes mellitus in children: pathophysiology and risk factors. J Pediatr Endocrinol Metab 2000; 13 (suppl 6): 1385–1394.
- American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000; 23: 381–389.
- Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004;291: 2847-50.
- Wang L, Kong L, Wu F, Bai Y, Burton R. Preventing chronic Diseases in China. Lancet 2005; 366: 1821-4.
- Dabelea D, Bell RA, D’Agostino RB Jr, et al;Writing Group for the SEARCH for Diabetes in Youth Study Group. Incidence of diabetes in youth in the United States. 297:2716–27243.
- Chatterjee P. India sees parallel rise in malnutrition and obesity. Lancet. 2002; 360:1948.
- Ramachandran A, Snehalatha C, Vinitha R, Thayyil M,Kumar CK, Sheeba L, et al. Prevalence of overweight in urban Indian adolescent school children. Diabetes Res ClinPract. 2002; 57:185-90.
- Mohan B, Kumar N, Aslam N, Rangbulla A, Kumbkarni S,Sood NK, et al. Prevalence of sustained hypertension and obesity in urban and rural school going children in Ludhiana. Indian Heart J. 2004; 56:310-4.
- Khadilkar VV, Khadilkar AV. Prevalence of obesity in affluent school boys in Pune. Indian Pediatr. 2004; 41:857-8.
- Marwaha RK, Tandon N, Singh Y, Aggarwal R, Grewal K,Mani K. A study of growth parameters and prevalence of overweight and obesity in school children from Delhi.Indian Pediatr. 2006; 43:943-52.
- Sharma A, Sharma K, Mathur KP. Growth pattern and prevalence of obesity in affluent schoolchildren of Delhi. Public Health Nutr. 2007; 10:485-91.
- Kotian MS, S GK, Kotian SS. Prevalence and determinants of overweight and obesity among adolescent school children of South Karnataka, India. Indian J Community Med. 2010; 35:176-8.
- Khadilkar VV, Khadilkar AV, Cole TJ, Chiplonkar SA,Pandit D. Overweight and obesity prevalence and body mass index trends in Indian children. Int J Pediatr Obes.2011; 6:216-24.
- Chakraborty P, Dey S, Pal R, Kar S, Zaman FA, Pal S.Obesity in Kolkata children: Magnitude in relationship to hypertension. J Natural Sci Bio Med. 2012;2:101-6
- Midha T, Nath B, Kumari R, Rao YK, Pandey U.Childhood obesity in India: a meta-analysis. Indian J Pediatr. 2012; 79:945-8.
- Polonsky KS, Sturis J, Bell GI. Non-insulin-dependent diabetes mellitus a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med 1996; 334:777-83.
- Edelstein SL, Knowler WC, Bain RP, Andres R, Barrett-Connor EL, Dowse GK, Haffner SM, Pettitt DJ, Sorkin JD, Muller DC, Collins VR, Hamman RF: Predictors of progression from impaired glucose tolerance to NIDDM: An analysis of six prospective studies. Diabetes 46:701–710,1997
- Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK. Cardiovascular risk factors in confirmed prediabetic individuals: does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA 1990; 263:2893-9.
- Tuomilehto J, Knowler WC, Zimmet P. Primary prevention of noninsulin- dependent diabetes mellitus. Diabetes Metab Rev 1992; 8:339-53.
- Tuomilehto J, Lindström J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344:1343-50.
- Weiss R, Taksali S, Tamborlane W, Burgert T, Savoye M, Caprio S: Predictors of changes in glucose tolerance status in obese youth. Diabetes Care 28:902–909, 2005
- American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care27 (Suppl. 1) :S5 –S10,2004
- Alberti K.G.M.M. Zimmet.P and Shaw J.,Metabolic syndrome a new world –wide definition. A consensus statement from International Diabetes Federation, Diabetic Medicine 2006:23; 469-480.
- National cholesterol Education program. Executive summary of the third report of the national cholesterol Education program expert panel on detection, evaluation and treatment of high cholesterol in adults(Adult treatment Panel III).JAMA 2001;285:2486-97
- WHO expert consultation. Appropriate BMI for Asian populations and its implication for policy and intervention strategies. Lancet 2004;363:156-63
- Sacks DB. Carbohydrates. In: Burtis C, Ashwood E, Bruns D, eds. Tietz textbook of clinical chemistry and molecular diagnostics, 4th ed. St. Louis: Saunders, 2006:837-902
- Carson, Ray J, Konje, Justin C, Expert review of obstetrics &gynecology, March 2010, vol-5,203-213
- National committee for clinical laboratory standards procedure for the collection of diagnostic blood specimens by venipuncture : approved standards H3- A-4 . 4th ed . Wayne P A : National committee for clinical laboratory standards , 1998.
- Warnik-GR,WoodPD.National.cholesterol Education Programme recommendations for measurement of high density Lipo-protein Cholestrol :Executive summary, clinical chemistry 1995;41:1427-1433.
- Kunst A, Draeger, B Ziegenhorn J.UV-methods with hexokinase and glucose -6-phosphate dehydrogenase. Methods of Enzymatic Analysis, Vol VI, Bergmeyer, HU, ED, Verlag Chemie, Deerfield, FL 1983, pp 163-172.
- De Fronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistence. Am J Physiol 1979; 237: E214–E223.
- Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA. Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care 2002; 25: 2081–2087.
- Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity. Diabetes Care 2000; 23: 57–63.
- Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and b-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.
- Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative Insulin Sensitivity Check Index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402–2410.
- Hrebicek J, Janout V, Malincikova J, Horakova D, Cizek L. Detection of insulin resistance by simple Quantitative Insulin Sensitivity Check Index (QUICKI) for epidemiological assessment and preven-tion J Clin Endocrinol Metab 2002; 87:144-1.
- Bonadonna RC, Groop L, Kraemer N, Ferrannini E, Del Prato S, DeFronzo RA. Obesity and insulin resistance in humans: a dose response study. Metabolism 1990; 39: 452–459.
- Rexrode KM, Manson JE, Hennekens CH. Obesity and cardiovascular disease. Curr Opin Cardiol 1996; 11: 490–495.
- Yip J, Facchini F, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab 1998; 83: 2773–2776.
- Vanhala M, Vanhala P, Kumpusalo E. Relation between obesity from childhood to adulthood and the metabolic syndrome: population based study. BMJ 1998; 317: 319.
- K.Garg, M.K.Dutta, Namita Mahalle. Study of beta cell function (by HOMA model) in metabolic syndrome. Indian Journal of Endocrinology and Metabolism/ 2011/vol 15/Supplement1.
- S Shalitin, M Abrahami, P Lilos and M Phillip. Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary care center in Israel. International Journal of Obesity (2005) 29, 571–578.
- Ranjana sinha, M.D., Gene fisch, PH.D., Barbara teague, R.N., William V. Tamborlane, M.D.,Bruna Banyas, R.N., Karin Allen, R.N., Mary Savoye, R.D., Vera Rieger, M.D., Sara Taksali, M.P.H.,Gina Barbetta, R.D., Robert S. Sherwin, M.D.,and Sonia Caprio, M.D..Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med, Vol. 346, No. 11· March 14, 2002·
- Abu Kholdun Al-Mahmood, Aziz Al-Safi Ismail*, Faridah Abdul Rashid, **Wan Mohamad WanBebakar, . Insulin sensitivity and secretory status of a healthy malay population.Malaysian Journal of Medical Sciences, Vol. 13, No. 2, July 2006 (37-44).
- Carlos lorenzo, md, Lynne e. wagenknecht, drph, Ralph b. d’agostino, jr., phd, Marian j. rewers, md, Andrew j. karter, phd, Steven m. haffner, md. Insulin Resistance, β-Cell Dysfunction, and Conversion to Type 2 Diabetes in a Multiethnic Population. Diabetes Care 2010; 33:67–72.
- Fida bacha, md,Sojung lee, phd, Neslihan gungor, md, Silva a. arslanian, md. From Pre-Diabetes to Type 2 Diabetes in Obese Youth.Diabetes care, volume 33, number 10, october 2010.
- Hui-Qi Qu1, Quan Li2, Anne R. Rentfro3, Susan P. Fisher-Hoch1, Joseph B. Mc Cormick. The Definition of Insulin Resistance Using HOMA-IR for Ameri-cans of Mexican Descent Using Machine Learning. PLoS ONE 6(6): e21041. doi:10.1371/journal.pone.0021041.
- Otto Tschritter, MD, Fausto Machicao, MD, PHD, Andreas Fritsche, MD, Hans Haring, MD , Fatemeh Shirkavand, MD, Michael Stumvoll, MD. Assessing the Shape of the Glucose Curve During an Oral Glucose Tolerance Test.Diabetes Care 26:1026–1033, 2003.
- Yiqing Song, MD, SCD, JoAnn E. Manson, MD, DRPH, Lesley Tinker, PHD, RD, Barbara V. Howard, PHD, Lewis H. Kuller, MD, DRPH, Lauren Nathan, MD, Nader Rifai, PHD, and Simin Liu, MD, SCD. Insulin Sensitivity and Insulin Secretion Determined by Homeostasis Model Assessment (HOMA) and Risk of Diabetes in a Multiethnic Cohort of Women: The Women’s Health Initiative Observational Study. Diabetes Care. 2007 July; 30(7): 1747–1752.
Corresponding Author
Dakshayani Patlolla
Department of Biochemistry,
Mediciti Institute of Medical Sciences