Abstract               Background: The American Diabetes Association included hemoglobin A1c (HbA1c) as adiagnostic test for diabetes in their 2010 clinical practice recommendations Aims and Objectives: To study Fasting insulin and insulin resistance in a meta analysis using western countries data. Methodology: This meta-analysis involves non diabetic individual with fasting insulin level in western population form 44 years i.e. 1973 to 2017 published studies related to western world. In total 23222 population was studied; for selecting these article various search engines like PubMed, Medline, Mendlay Library, Cochrane Library, Embase search, Google Scholar, Index Copernicus, Science Direct with key words Hyperinsulinemia, Syndrome X, Type II Diabetes. Statistical analysis done by Comprehensive Metanalysis software. Result: There was statistically significant co-relation between Fasting plasma insulin level and insulin resistance in the western population the overall fixed effect result of our study was with co-relation of (95% CI) was -0.044 (-0.057 to -0.031) with Z=-6.74, p<0.000 Conclusion: It can be concluded from our study that there was statistically significant co-relation between Fasting plasma insulin level and insulin resistance in the western population so this criteria can be used to diagnose insulin resistance and early diagnosis of insulin resistance.

Key Words: Insulin resistance, Hyperinsulinemia, Syndrome X, Type II Diabetes.

INTRODUCTION

The American Diabetes Association included hemoglobin A1c (HbA1c) as a diagnostic test for diabetes in their 2010 clinical practice recommendations¹. In addition to being tightly associated with diabetes, HbA1c predicts cardiovascular events among non-diabetic individuals and it may outperform fasting plasma glucose for predicting cardiovascular disease². In contrast, serum insulin measurement is not used as often, despite the fact that it can identify insulinresistant subjects, which is a strong marker of future diabetes³. The metabolic syndrome defines a group of cardiovascular risk factors that appear together and are strongly associated with the development of ischemic heart disease and diabetes⁴. The metabolic syndrome is tightly linked to insulin resistance⁵, which is considered one of its essential characteristics and it was initially required for diagnosis of the syndrome⁶. Still, the clinical criteria that are currently used for diagnosis face numerous limitations⁷ so we are considering this could be beneficial component for the early diagnosis of insulin resistance. Berson and Yalow⁸ defined insulin resistance (IR) as a state (of a cell, tissue, system, or body) in which greater than normal amount of insulin is required to elicit a quantitatively normal response. Insulin is a key regulator of glucose homeostasis and insulin resistance is determined by both genetic and environmental factors and plays an important pathophysiological role in diabetes.⁹ The abnormalities initially associated with insulin resistance in nondiabetic individuals included hyperinsulinemia, borderline glucose tolerance, dyslipidemia (in the form of increased triglycerides and decreased HDL cholesterol) and hypertension.¹⁰ so this metanalysis was done with aim of asses correlation between fating insulin level and insulin resistance in the western population.

MATERIAL AND METHODS

This meta-analysis study involves non diabetic individual with fasting insulin level in western population form 44 years i.e. 1973 to 2017 published studies involving the western world. In total 23222 population was studied ; for selecting these article various search engines like PubMed, Medline, Mendlay Library, Cochrane Library, Embasesearch, Google Scholar, Index Copernicus, Science Direct etc. to study the Articles with Key Words like insulin resistance, Hyperinsulinemia, Syndrome X, Type II Diabetes in Western Population there was 1,71,00,000 articles were there by using various filters like insulin resistance Western Population there was near about 250 studies were there in the study period again these 250 studies was studied by a Team of Expert for the inclusion and exclusion of studies at the end 14 studied selected ^11-24 Into the study, statistical analysis done by Comprehensive Metanalysis software. The flow chart as per the PRISMA 2009 guideline is as follows.

RESULT

From below table of Meta analysis it is clear that there was statistically significant co-relation between Fasting plasma insulin level and insulin resistance in the western population the over all fixed effect result of our study was with co-relation of (95% CI) was -0.044 (-0.057 to -0.031) with Z=-6.74, P<0.000

Table 1: Metanalysis Showing the correlation of Fasting insulin and Insulin resistance

DISCUSSION

Fasting insulin is one of the most commonly studied surrogate marker of insulin resistance. Yeni - Komshian et al²⁵ studied 490 healthy non-diabetic volunteers. They derived steady state plasma glucose (SSPG) from insulin suppression test and correlated it with various surrogate measures. They reported significant correlations of SSPG with fasting insulin, 120 min insulin, insulin area under the curve, fasting glucose/ insulin ratio and HOMA-IR. Although they described total insulin response during an OGTT as the best surrogate measure, they also suggested that determination of fasting insulin can provide a qualitative estimate of insulin resistance. Similarly Markku Laakso²⁶ measured insulin response to an oral glucose load and quantitated insulin resistance using the euglycemic hyperinsulinemic clamp technique to evaluate the correlation between fasting and postprandial insulin levels, and the degree of insulin resistance in individuals with varying degrees of glucose tolerance They reported that although correlations of direct estimates of insulin resistance with fasting or post-glucose load insulin levels were consistent in subjects with normoglycemia, in subjects with impaired glucose tolerance and diabetes, only the fasting insulin correlated significantly with insulin resistance. They suggested that in population studies, only the fasting insulin level should be used as a marker of insulin resistance. Similarly Hanson RL et al²⁷ achieved high degree of correlation of fasting and post-glucose load insulin with direct measure of insulin resistance as determined by hyperinsulinemia euglycemic clamp. They reported that although correlations of direct estimates of insulin resistance with fasting or post-glucose load insulin levels were consistent in subjects with normoglycemia, in subjects with impaired glucose tolerance and diabetes, only the fasting insulin correlated significantly with insulin resistance. They suggested that in population studies, only the fasting insulin level should be used as a marker of insulin resistance. Similarly Hanson RL et al²⁷ achieved high degree of correlation of fasting and post-glucose load insulin with direct measure of insulin resistance as determined by hyperinsulinemia euglycemic clamp. In our study there was statistically significant co-relation between Fasting plasma insulin level and insulin resistance in the western population the overall fixed effect result of our study was with co-relation of (95% CI) was -0.044 (-0.057 to -0.031) with Z=-6.74, P<0.000 except in the study by Jerrold Olefsky all other studies shown the negative co-relation of Fasting insulin and insulin resistance syndrome the difference in the study may be because in the prediabetic individual reacts with complex mechanism of insulin secretion in the fasting either hyperinsulinemia or hyperinsulinemia probably this complex mechanism might be responsible in their study.

CONCLUSION

It can be concluded from our study that there was statistically significant co-relation between Fasting plasma insulin level and insulin resistance in the western population so this criteria can be used to diagnose insulin resistance and early diagnosis of insulin resistance.

REFERENCES

1. Standards of medical care in diabetes—2013. Diabetes Care. 2013; 36 Suppl 1: S11–66. doi: 10.2337/ dc13-S011 PMID: 23264422
2. Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med. 2010; 362: 800–811. doi: 10. 1056/NEJMoa0908359 PMID: 20200384
3. Hanson RL, Pratley RE, Bogardus C, Narayan KM, Roumain JM, Imperatore G, et al. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. Am J Epidemiol. 2000; 151: 190–198. PMID: 10645822
4. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009; 120: 1640–1645. doi: 10.1161/CIRCULATIONAHA.109.192644 PMID: 19805654
5. Laclaustra M, Corella D, Ordovas JM. Metabolic syndrome pathophysiology: the role of adipose tissue. NutrMetab Cardiovasc Dis. 2007; 17: 125–139. doi: 10.1016/j.numecd.2006.10.005 PMID: 17270403
6. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998; 15: 539–553. doi: 10.1002/(SICI)1096-9136(199807)15:73.0. CO;2-S PMID: 9686693
7. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005; 28: 2289–2304. PMID: 16123508
8. Berson SA, Yalow RS. In: Ellenberg M, Rifkin H (eds) Diabetes Mellitus: Theory and Practice, New York: McGraw-Hill, 1970; 388-423.
9. DeFronzo RA, Bonadanna RC, Ferrannini F. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992;15:318- 68.
10. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988;37:1595-1607
11. Kensuke Yoshida, Takao Kimura,Tomoyuki Aoki. Fasting serum insulin levels and insulin resistance are associated with blood rheology in Japanese young adults without diabetes. Journal of International Medical Research 2016, Vol. 44(3) 496–507
12. Christian Weyer, Robert L. Hanson, P. Antonio Tataranni et al. A High Fasting Plasma Insulin Concentration Predicts Type 2 Diabetes Independent of Insulin Resistance. Diabetes 2000;49:2094–2101.
13. KIRSTEN A. MCAULEY, MBCHB, SHEILA M. WILLIAMS, JIM I. MANN. Diagnosing Insulin Resistance in the General Population. Diabetes Care 24:460–464, 2001
14. Jerrold Olefsky, John W Farquhar, Gerald Reaven,Yeni - KomShian H, Carantoni M, Abbasi F, Reaven GM. Relationship Between Fasting Plasma Insulin Level and Resistance to Insulin-Mediated Glucose Uptake in Normal and Diabetic Subjects. Diabetes 1973 Jul; 22(7): 507-513.
15. Terra G Arnason, Matthew W Bowen. Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. World J Diabetes 2017 April 15; 8(4): 154-164
16. Jerri Chiu Yun Ling, Mohd Nahar Azmi Mohamed. Determinants of High Fasting Insulin and Insulin Resistance Among Overweight/Obese Adolescents. Scientific Reports | 6:36270 | DOI: 10.1038/srep36270 2
17. AK Gupta, SK Jain. A Study to Evaluate Surrogate Markers of Insulin Resistance in Forty Euglycemic Healthy Subjects. JAPI. • JULY 2004; VOL. 52: 559-553.
18. StudyZ. Patakya, A. Golay, M. Laville.articleFasting insulin at baseline influences the number of cardiometabolic riskfactors and R-R interval at 3 years in a healthy population: The RISC Study Diabetesand Metabolism 39 (2013) 330–336.
19. Nicole M.Wedick,1 Elizabeth J. Mayer-Davis,2 Deborah L. Wingard. Insulin Resistance Precedes Weight Loss in Adults without Diabetes-The Rancho Bernardo Study. American Journal of Epidemiology. 2001; 153(12): 1199-1205.
20. John A Morrison, Charles J Glueck, Paul S Horn. Pre-teen insulin resistance predicts weight gain, impaired fasting glucose, and type 2 diabetes at age 18–19 y: a 10-y prospective study of black and white girls. Am J ClinNutr2008; 88:778–88.
21. Cristina Geroldi, Giovanni B. Frisoni, Giuseppe Paolisso. Insulin Resistance in Cognitive Impairment. Arch Neurol. 2005;62:1067-1072
22. EunHeeKim, Hong-Kyu Kim, Sung Jin Bae. Fasting serum insulin levels and insulin resistance are associated with colorectal adenoma in Koreans. J Diabetes Invest 2014; 5: 297–304
23. Gabriela Saravia, Fernando Civeira, Yamilee Hurtado-Roca. Glycated Hemoglobin, Fasting Insulin and the Metabolic Syndrome in Males. Cross- Sectional Analyses of the Aragon Workers’ Health Study Baseline. PLoS ONE 10(8): e0132244. doi:10.1371/journal.pone.0132244
24. Pa¨iviLempia¨inen, LeenaMykka¨nen, ; KaleviPyo¨ra¨la. nsulin Resistance Syndrome Predicts Coronary Heart Disease Events in Elderly Nondiabetic Men. Circulation. 1999; 100:123-128.
25. Laakso M. How good a marker is insulin level for insulin resistance? Am J Epidemiol 1993; 137: 959-65.
26. Hanson RL, Pratley RE, Bogardus C, et al. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. Am J Epidemiol2000; 151:190-8.
27. Hanson RL, Pratley RE, Bogardus C, et al. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. Am J Epidemiol2000; 151:190-8.