Document Type : Original Article

Authors

1 Doctoral program of Medical Science, Faculty of Medicine Universitas Brawijaya, Indonesia

2 Saiful Anwar Hospital, Malang, Indonesia

3 Pediatric Department, Faculty of Medicine Universitas Brawijaya, Malang, Indonesia

4 Nutrition Science Program, Medical Faculty, Universitas Brawijaya, Malang, Indonesia

5 Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia

10.48305/arya.2024.11581.2125

Abstract

BACKGROUND: Type 1 diabetes (T1D) carries a significant risk of atherosclerosis as the main driver for cardiovascular events. Atherosclerosis is initiated by the activation of the endothelium by various risk factors through the inflammation process. The anti-inflammatory cytokine TGF-β1 may inhibit the development of atherosclerosis.
METHODS: In a cross-sectional study, a total of 40 patients aged 14.5±3.16 years old with T1D and 40 healthy controls aged 14.7±0.99 years old were involved. Common carotid artery IMT (cIMT) was measured by real-time M-echocardiography mode (Affinity 50G Philips) and Flow Mediated Dilatation (FMD), using high-resolution ultrasonography and Doppler flow characteristics. The TGF-β1 level was measured by indirect ELISA at Saiful Anwar Hospital Laboratory.
RESULTS: There were no differences in age, gender, Body Mass Index (BMI), duration of diabetes, renal function, or nutritional status between the T1D and healthy groups (p>0.05). A significant difference in cIMT was observed between the T1D group and the healthy group (0.567 ± 0.87 mm vs. 0.387 ± 0.57 mm, p = 0.000), FMD (7.17 ± 3.98 mm vs. 11.22 ± 5.48 mm, p = 0.000), and the level of TGF-β1 cytokine (39.83±13.51 vs. 73.67±15.34 pg/ml, p = 0.000). A significantly negative correlation between TGF-β1 and cIMT (p = 0.000; r = -0.685) and a significantly positive correlation between TGF-β1 and FMD (p = 0.000; r = +0.55) were found.
CONCLUSION: Atherosclerosis is an inflammatory disease accelerated by diabetes. The inflammation process is more prominent in T1D patients. T1D patients show a decreased level of TGF-β1, increased measurement of cIMT (>0.5 mm), and a decreased measurement of FMD.

Keywords

1. Soedamah-Muthu SS, Fuller JH, Mulnier HE, Raleigh VS, Lawrenson RA, Colhoun HM. All-cause mortality rates in patients with type 1 diabetes mellitus compared with a non-diabetic population from the UK general practice research database, 1992-1999. Diabetologia. 2006 Apr;49(4):660-6. https://doi.org/10.1007/s00125-005-0120-4
2. Redondo S, Navarro-Dorado J, Ramajo M, Medina Ú, Tejerina T. The complex regulation of TGF-β in cardiovascular disease. Vasc Health Risk Manag. 2012;8:533-9. https://doi.org/10.2147%2FVHRM.S28041
3. Fusaro MF, Zanini JL, Silva IN. Increased carotid intima-media thickness in Brazilian adolescents with type 1 diabetes mellitus. Diabetol Metab Syndr. 2016 Nov 11;8:74. https://doi.org/10.1186/s13098-016-0190-0
4. Järvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, Laine S, Lehtimäki T, Rönnemaa T, Viikari J, Raitakari OT. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004 Apr 13;109(14):1750-5. https://doi.org/10.1161/01.cir.0000124725.46165.2c
5. Urbina EM, Williams RV, Alpert BS, Collins RT, Daniels SR, Hayman L, et al. Noninvasive assessment of subclinical atherosclerosis in children and adolescents: recommendations for standard assessment for clinical research: a scientific statement from the American Heart Association. Hypertension. 2009 Nov;54(5):919-50. https://doi.org/10.1161/hypertensionaha.109.192639
6. de Ferranti SD, de Boer IH, Fonseca V, Fox CS, Golden SH, Lavie CJ, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care. 2014 Oct;37(10):2843-63. https://doi.org/10.2337/dc14-1720
7. Pezeshki Rad M, Farrokh D, Vakili R, Omidbakhsh M, Mohammadi M. The Association between Carotid Intima-Media Thickness and the Duration of Type 1 Diabetes in Children. Iran J Pediatr. 2014 Jun;24(3):249-54.
8. Pillay S, Anderson J, Couper J, Maftei O, Gent R, Peña AS. Children With Type 1 Diabetes Have Delayed Flow-Mediated Dilation. Can J Diabetes. 2018 Jun;42(3):276-280. https://doi.org/10.1016/j.jcjd.2017.06.011
9. Toma I, McCaffrey TA. Transforming growth factor-β and atherosclerosis: interwoven atherogenic and atheroprotective aspects. Cell Tissue Res. 2012 Jan;347(1):155-75. https://doi.org/10.1007%2Fs00441-011-1189-3
10. Fusaro MF, Zanini JL, Silva IN. Increased carotid intima-media thickness in Brazilian adolescents with type 1 diabetes mellitus. Diabetol Metab Syndr. 2016 Nov 11;8:74. https://doi.org/10.1186/s13098-016-0190-0