Artikel.docx

Waist Circumference and Triglyceride Glucose Index As A Marker for Prediabetes Prediction for Healthy Population Erlina Purnamayani1, Iche A. Liberty2 1

Medical Education Study Program, Faculty of Medicine, Universitas Sriwijaya Bagian Ilmu Kesehatan Masyarakat-Ilmu Kedokteran Komunitas, Fakultas Kedokteran, Universitas Sriwijaya Jl. Dr. Mohammad Ali Komplek RSMH Km. 3,5, Palembang, 30126, Indonesia

2

E-mail: [email protected]

Abstract Occurance rate of type 2 diabetes mellitus (T2DM) is quite worrying worldwide, of which is a major risk factor for cardiovascular disease and even premature mortality1. Thus, it is not easy to early identify and treat patients with high risk of developing T2DM, though the unclear etiologies and pathological process of it. Previous literature indicated that several effective and inexpensive variables, ranging from simple anthropometric measures to more complex models, are closely related to insulin resistance or diabetes. So far, not many studies involving waist circumference and triglyceride glucose index as a marker for prediabetes prediction for healthy population. This study is a diagnostic test. Data is obtained from primary data. The population and sample of this study were all healthy people, that was taken by consecutive sampling. This study was conducted from June 2018 until December 2018. The inclusion criteria of this study were all healthy people who want to be our subject. The test variables in this study are waist circumference and triglyceride glucose index, while the standard variable used is glucose state. After data is collected, it is presented in a narrative form and in tables. The data is then analyzed analytically in narrative form. Data was analyzed Medcalc, Statcalc, and Epicalc. Majority of prediabetes patient were aged 45-55 years old. Waist circumference cutoff for prediabetes male and female patients were 81.5 cm and 83.4 cm, respectively. Waist circumference can’t be a marker for prediabetes caused AUC for both male and female is not good enough. Cutoff triglyceride gluce index for prediabetes is 4.82, with sensitivity 90.1% and specificity 82.4%, with AUC 0.941 and p<0.0001. Triglyceride glucose index can be used as prediabetes predictor. This examination is simpler and cheaper because NLR used data form routine hematology examination that was done on preeclampsia patients. Keywords: Prediabetes, Waist Circumference, Triglyceride Glucose Index

1.

Introduction

The occurance rate of type 2 diabetes mellitus (T2DM) is quite worrying worldwide, of which is a major risk factor for cardiovascular disease and even premature mortality1. Thus, it is not easy to early identify and treat patients with high risk of developing T2DM, though the unclear etiologies and pathological process of it. Previous literature indicated that several effective and inexpensive variables, ranging from simple anthropometric measures to more complex models, are closely related to insulin resistance or diabetes. Body mass index (BMI) and waist circumference (WC), two clinical indices for

body fat assessment, are commonly used for detecting prediabetes and diabetes risk2-4. Moreover, visceral adiposity index (VAI), a mathematical model based on BMI, WC, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), is a more effective tool for prediabetes diabetes prediction5,6. In addition, indicators waist circumference with triglyceride glucose index has been reported as excellent marker of insulin resistance, which is deemed to be the vital pathological mechanism of T2DM7,8. Insulin resistance refers to a decreased sensitivity and responsiveness to the metabolic actions of insulin. Insulin resistance predisposes to several disorders such as hyperglycemia hypertension, and

dyslipidemia, all of which are strongly associated with atherosclerosis9. In addition, insulin resistance contributes to vasoconstriction, inflammation, and thrombosis, leading to accelerated atherosclerosis. In diabetic subjects, insulin resistance is associated with the thickening of the carotid artery intima media and incident CVD (Cardiovascular Disease). This study based on measuring the product of fasting triglyceride and glucose10,11. So far, not many studies involving waist circumference and triglyceride glucose index as a marker for prediabetes prediction for healthy population. Therefore, it is necessary to do a study about waist circumference and triglyceride glucose index as a marker for prediabetes prediction for healthy population. 2.

Methods

This study is a diagnostic test. Data is obtained from primary data. The population and sample of this study were all healthy people, that was taken by consecutive sampling. This study was conducted from June 2018 until December 2018. The inclusion criteria of this study were all healthy people who want to be our subject. The test variables in this study are waist circumference and triglyceride glucose index, while the standard variable used is glucose state. After data is collected, it is presented in a narrative form and in tables. The data is then analyzed analytically in narrative form. Data was analyzed Medcalc and Epicalc.

3.

Results

This study has 2036 patients in the inclusion criteria. Observed variables were age, gender, waist circumference, and triglyceride glucose index.

Subject Distribution Based on Gender Table 1 shows the distribution of based on the gender. Percentage of male subjects is 50,54% (1029 subjects) and 49,46% female (1007 subjects). Table 1. Subjects Distribution Based on Gender Gender Prediabetes Male 278 Female 298

Total 1029 1007

% 27.0 29.5

Subject Distribution Based on Age Table 2 shows the distribution of subjects based on age. The results showed that prediabetes was more common in age 46-55 years, with 158 subjects. The average age subjects in this study was 49 years. The youngest age was 14 years while the oldest age was 96 years. Table 2. Subjects Distribution Based on Age Age (Year Old) <=15 16-25 26-35 36-45 46-55 56-65 >65

Prediabetes Yes No 2 3 7 99 79 232 138 248 158 353 117 322 75 203

Subject Distribution Based on Waist Circumference Subject distribution based on waist circumference can be seen in Table 3. In both male or female patients with or without prediabetes, there are more subjects with waist circumference ≤81,5cm and ≤83,4 respectively.

Prediabet es Yes No

Male ≤81.5 cm >81.5 cm 97 181 447 304

Female ≤83.4 cm >83.4 cm 83 215 459 250

Subject Distribution Based Triglyceride Glucose Index

on

In this study we found a cutoff value triglyceride glucose index >4.82 for patients with prediabetes. The cutoff value is determined using Medcalc program. Table 4 shows triglyceride glucose index from 2036 samples. Most prediabetes patientshastriglyceride glucose index above cutoff, with a percentage of 66.9% (519 subjects). Table 4. Subjects Distribution Based on Triglyceride Glucose Index

Chart 1. Diagnostic Test of Waist Circumference for Prediabetes Patients in Healthy Population (Male) LP 100 80

Sensitivity

Table 3. Subjects Distribution Based on Waist Circumference

waist circumference of ≤81,5 cm. There are 215 female patients has prediabetes status and waist circumference of >83,4 cm, while 83 patients has prediabetes but waist circumference ≤83,4 cm. The sensitivity and specificity for male are 70.6% and 52.1%, respectively. With positive predictive value is 65.1% and 4.4%, respectively. And likelihood ratio + is 2.09 and likelihood ratio – is 0.76. Sensitivity and specificity for female patients are 70.1% and 67.1%, respectively. With positive predictive value is 7.21% and 3.52%, respectively. And likelihood ratio + is 3.01 and likelihood ratio – is 0.63.

Sensitivity: 70.6 Specificity: 52.1 Criterion : >81.5241

60 40 20

Prediabet es Yes No Total

Triglycerida Glucose Index >4.82 ≤4.82 519 256 57 1204 576 1460

Total 0 0

775 1261 2036

20

40 60 80 100-Specificity

100

Chart 2. Diagnostic Test of Waist Circumference for Prediabetes Patients in Healthy Population (Female)

Diagnostic Test of Waist Circumference for Prediabetes Patients in Healthy Population

LP 100

The result of waist circumference for prediabetes in healthy population can be seen in chart 1 for male and chart 2 for female. Area Under Curve of 0.683 is obtained for male and 0.757 for female, both has p<0.0001. Cutoff value that is obtained is >81.5 cm and >83.4 cm, respectively. It is found that 181 male patients has prediabetes status and waist circumference of >81.5 cm, while 97 male patients has prediabetes but

Sensitivity

80 Sensitivity: 70.1 Specificity: 67.1 Criterion : >83.4458

60 40 20 0 0

20

40 60 80 100-Specificity

100

Diagnostic Test of Triglyceride Glucose Index for Prediabetes Patients in Healthy Population The result of of triglyceride glucose index for prediabetes in healthy population can be seen in chart 3. Cutoff value that is obtained is >4.82. It is found that 519 patients has prediabetes status and waist circumference of >4.82, while 256 patients has prediabetes but waist circumference of ≤4.82. The sensitivity and specificity for male are 90.1% and 82.4%, respectively with Area Under Curve (AUC) is 0.941 with p<0.0001. The positive and negative predictive values are 66.9% and 4.52%, respectively. Meanwhile, the likelihood ratio + and likelihood ratio - are 5.18 and 0.11, respectively. Chart 3. Subject Distribution Based on Triglyceride Glucose Index TyG 100 Sensitivity: 90.1 Specificity: 82.4 Criterion : >4.82

Sensitivity

80

appear more prevalent in those with prediabetes compared with their normoglycemic peers12. Hence, there is growing consensus that normoglycemia should be the treatment goal for people with prediabetes13. Subject Distribution Based on Age The age group with the highest frequency of prediabetes status is 46-55 years. This result doesn’t match the theory stating that people at age 45 years, risk of prediabetes starts to rise, and after age 65 years, risk increases exponentially. Increased incidence of prediabetes at age >45 years can caused by insulin resistance. Insulin resistance is already well established when impaired glucose tolerance is present and the increase in glucose, even across the normal range, is due to a continuous declin in β cell function accounts for the evolving natural history of the disease from impaired glucose tolerance to T2DM14. Diagnostic Test of Waist Circumference for Prediabetes Patients in Healthy Population

60 40 20 0 0

4.

20

40 60 80 100-Specificity

100

Discussion Subject Gender

Distribution

Based

on

In this study, percentage of prediabetes in female more than male patients. But it is not significant. However, no previous study was found about gender related risk and treatment for reverting prediabetes to normal glucose regulation. In fact, even if diabetes could be delayed or prevented, both microvascular and macrovascular disease

Based on International Diabetes Federation (IDF)’s recommendation, WC cut-off values for clinical practice should be determined in different ethnicities. Although IDF has suggested WC greater than 90 and 80 cm, respectively for Asian male and female15. The result of this study has cut-off point waist circumference for male and female are 81.5 cm and 83.4 cm, respectively. Waist circumference directly associated with the incidence risk of prediabetes. It is found waist circumference for male has 70.6% sensitivity and 52.1% specificity. Area Under Curve (AUC) obtained in this study is 0.683 with p<0.0001 and cutoff

point 81.5 cm. AUC 0.683 indicate that waist circumference is an poor diagnostic value. The positive predictive value of waist circumference for male that is obtained in this study is 65.1%. Positive predictive value indicates that if a patient has waist circumference of >81.5, the probability of the patient actually experience prediabetes is 65.1%. Negative predictive value obtained in this study is 4.04%. This value indicates that if a patient has waist circumference of ≤81.5 cm, the probability of the patient not experiencing prediabetes is 4.04%. The likelihood ratio + that is obtained in this study is 2.09. This value indicates that the ratio of waist circumference >81.5 cm in patients with prediabetes and waist circumference >81.5 cm in patients without prediabetes is 2.09. The likelihood ratio value obtained is 0.76. This value indicates that the ratio of waist circumference ≤83.4 cm in patients with prediabetes and waist circumference ≤83.4 cm in patients without prediabetes is 0.76. Waist circumference for female has 70.1% sensitivity and 67.1 specificity. AUC obtained in this study is 0.757 with p<0.0001 and cutoff point 83.4 cm. AUC 0.757 indicate that waist circumference is an fair diagnostic value. The positive and negative predictive value of waist circumference for female that is obtained in this study is 7.21% and 3.52%, respectively. The likelihood ratio + and likelihood ratio – that is obtained in this study is 3.01 and 0.63, respectively. Diagnostic Test of Triglyceride Glucose Index for Prediabetes Patients in Healthy Population Triglyceride Glucose Index used to predict incident T2DM used it as a surrogate for insulin resistance, and reported that its

predictive ability s better than that of the homeostasis model of assessment15,16. Triglyceride Glucose Index is a practical measure for use in T2DM prediction because of its cost-efficiency. Moreover, the use of HbA1c has been recommended for diagnosis and screening of patients17,18. It is found triglyceride glucose index has 90.1% sensitivity and 82.4% specificity. Area Under Curve (AUC) obtained in this study is 0.941 with p<0.0001 and cutoff point 4.82. 90.1% sensitivity and 82.4% specificity indicate that triglyceride glucose index is an excellent diagnostic value. Triglyceride glucose index can be used as a consideration to establish the diagnosis of prediabetes. The positive predictive value of triglyceride glucose index that is obtained in this study is 66.9%. Positive predictive value indicates that if a patient has triglyceride glucose index of >4.82, the probability of the patient actually experience prediabetes is 66.9%. Negative predictive value obtained in this study is 4.52%. This value indicates that if a patient has triglyceride glucose index of ≤4.82, the probability of the patient not experiencing prediabetes is 4.52%. The likelihood ratio + that is obtained in this study is 5.18. This value indicates that the ratio of triglyceride glucose index >4.82 in patients with prediabetes and triglyceride glucose index >4.82 in patients without prediabetes is 5.18. The likelihood ratio value obtained is 0.11. This value indicates that the ratio of triglyceride glucose index ≤4.82 in patients with prediabetes and triglyceride glucose index ≤4.82 in patients without prediabetes is 0.11. 5.

Conclusion

The cutoff value of waist circumference for male and female patients with prediabetes is >81.5 cm and >83.4, respectively. Area Under Curve (AUC) for

male is 0.683 and female 0.757. With sensitivity and specificity for male are 70.6% and 52.1%. sensitivity and specificity for female are 70.1% and 67.1%. Triglyceride glucose index has AUC 0.941 with sensitivity and specificity are 90.1% and 82.4%. Triglyceride and glucose index can be use for prediabetes marker. References 1. Keating, S. et al. 2016. Epigenetic Changes in Diabetes and Cardiovascular Risk. Journal of Circulation Research. 118 (11): 1706 – 22. 2. Hunter, G., Paula, C., David, B., Cristina, L., and Jose, R. 2010. Fat Distribution, Aerobic Fitness, Blood Lipids, and Insulin Sensitivity in African-American and EuropeanAmerican Women. Journal of Wiley Online Library. 18 (2): 874 – 82. 3. Nan, H., Ji, A., Hyunjoo, C., Ji, H., Hye, J., Sin, G., et al. 2016. Risk of the Development of Diabetes and Cardiovascular Disease in Metabolically Healthy Obese People. The Korean Genome and Epidemiology Study. 95 (15): 650 – 8. 4. Amato, M., Giordano, C., Galia, M., Criscimanna, A., Vitabile, S., Midiri, M., et al. 2010. Visceral adiposity index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 33 (4): 920–2. 5. Oti, S., Agyemang, C., Kyobutungi, C. 2013. The Magnitude of Diabetes and Its Association with Obesity in the Slums of Nairobi, Kenya: Results from a Cross sectional Survey. Trop Med Int Health. 18 (12): 1520 – 30. 6. Chen, C., Yan, X., Zhi, R., Jie, Y., Ming, W., and Xiao, S. 2014. The Application of Visceral Adiposity Index in Identifying Type 2 Diabetes Risks

Based on a Prospective Cohort in China. Lipids in Health and Disease. 13: 108. 7. Sun, D., Huo, R., and Yu, X. 2014. Visceral Adiposity Index, Hypertriglyeridemic Waist and Risk of Diabetes: The China Health and Nutrition Survey 2009. 38 (6): 840 – 7. 8. Guerrero, F., Luis, E., Manuel, G., Esperanza, M.,Maria, G., Sandra, O., et al. 2010. The Product of Triglycerides and Glucose, A Simple Measure of Insulin Sensitivity. Comparison with the Euglycemic-Hyperinsulinemic Clamp. The Journal of Clinical Endocrinology & Metabolism. 95 (7): 3347 – 51. 9. Kiaw, L., Semon, W., Hsin, H., Lung, A., Ming, S., and Yu, S. 2016. Triglyceride Glucose-Body Mass Index is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals. 11(3):e0149731. 10. Alberti, K., Zimmet, P. 2018. 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. 15(7): 539– 53. 11. Eun, Y., Hae, K., Joonyub, L., Borami, K., Yeoree, Y., Seung, H. et al. 2016. Triglyceride Glucose Index, a marker of Insulin Resistance, is Associated with Coronary Artery Stenosis in Asymptomatic Subjects with Type 2 Diabetes. 15: 155. 12. Song, X., Miaoyan, Q., Zhang, X., Haiyan, W., Wenxin, T., Liping, J., et al. 2016. Gender-Related Affecting Factors of Prediabetes on its 10-year Outcome. 4(1): 1011 – 36. 13. Perreault, L. 2014 Approaching PreDiabetes. J Diabetes Complication. 22633.

14. Steven, K., Mark, C., and Stefano, D. 2014. Pathophysiology and Treatment of Type 2 Diabetes: Perspectives on the Past, Present and Future. 383(9922): 1068 – 83. 15. Fahimeh, H., Masoud, A., Awat, F., and Bijan, I. 2017. Are Body Mass Index and Waist Circumference Significant Predictor of Diabetes and Prediabetes Risk: Result from a Population Based Cohort Study. 8(7): 365 – 73. 16. Nor, M., Lee, S., Bacha, F., Tfayli, H., Arslanian, S. 2016. Triglyceride Glucose Index as a Surrogate Measure of Insulin Sensitivity in Obese Adolescents with Normoglycemia, Prediabetes, and Type 2 Diabetes Mellitus: Comparison with the Hyperinsulinemic-Euglycemic Clamp. 17 (6): 458 – 65. 17. Joung, W., Nam, K., and Hyun, K. 2018 The Product of Fasting Plasma Glucose and Triglycerides Improves Risk Prediction of Type 2 Diabetes in Middle-Aged Koreans. 18. Juan, S., Valmore, B., Maria, C., Luis, C., and Eliana, L. 2018. Optimal Cutoff for the Evaluation of Insulin Resistance Through Triglyceride-Glucose Index: A Cross Sectional Study in a Venezuelan Population.