Elevated high-sensitivity C-reactive protein among apparently healthy adults with concomitant prediabetes and latent tuberculosis infection in Nigeria

Benson O. Akinshipe, Edirin O. Yusuf, Alfred F. Ehiaghe, Tunde O. Egunjobi, Opeoluwa A. Yusuf


Background: The increasing prevalence and convergence of type 2 diabetes mellitus (DM) and active tuberculosis (TB) comorbidity, especially in adults in the lower-and middle-income countries, demand new approaches to control the ‘syndemic’. Consequently, we set out to investigate the possibility of early detection of prediabetes mellitus and/or latent tuberculosis infection using novel method.

Methods: This was a case-control study of 105 adults classified into 4 groups: Healthy Community Controls (HCC, n=30); Prediabetes mellitus (PDM, n=25); Latent Tuberculosis Infection (LTBI, n=23); Individuals with Prediabetes mellitus+Latent Tuberculosis Infection (PDM+LTBI, n=27). Sera collected were assayed for high-sensitivity C-reactive protein (hs-CRP) using the ultra-sensitive Human high sensitivity C-reactive protein ELISA Kit (Melsin Medical Co., Ltd, China). Other ancillary tests and measurements done include Erythrocyte Sedimentation Rate, serum Glycated-hemoglobin (HbA1c), Interferon-gamma (INF-ϒ) and Waist circumference.

Results: A total of 88 (83.8%) of the enrolled participants had full complement of results and were included in the analysis of four study groups: HCC (n=25), PDM (n=21), LTBI (n=19) and PDM+ LTBI (n=23). With respect to the serum biomarkers, isolated PDM and LTBI cases recorded significantly higher HbA1c (%) and INF-ϒ positivity respectively. Predictors of PDM+LTBI show statistically significant higher tertile (T3), representing elevated hs-CRP levels, (OR=6.50, 95% CI=4.83-22.39, p=0.0037).

Conclusions: This study revealed that persons harboring the two associated asymptomatic conditions, PDM + LTBI have higher inflammatory state detectable by assaying the biomarker, hs-CRP, which could be used for ‘one-time bi-directional targeted screening’ for PDM in LTBI and vice versa.


Adults, Biomarker, Highly-Sensitive C-reactive protein, Latent tuberculosis infection, Prediabetes

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Al-Rifai RH, Pearson FG, Critchley JA, Abu-Rhadad LJ. Association between diabetes mellitus and active TB. A systematic review and meta-analysis. PLoS ONE 2017;12:eo187967.

Firanescu AG, Popa A, Sandu MM, Protasiewicz DA, Popa SG, Mota M. The global prevalence and incidence of diabetes mellitus and pulmonary tuberculosis. Roma J Diabetes Nutr Meta Dis. 2016;23(3):319-26.

Global Tuberculosis Control 2018, WHO, Geneva. Use of high burden country list for TB by WHO in post-2015 era. Available at https// /tb/publications/global_report/en/.2018. Accessed on 04 March 2020.

Adeloye D, Ige JO, Aderemi AV, Adeleye N, Amoo EO, Auta A, Oni G . Estimating the prevalence, hospitalization and mortality from type 2 diabetes mellitus in Nigeria: a systematic review and meta-analysis. BMJ Open.

Chatterjee R, Narayan KMV, Lipscomb J and Phillips LS. Screening for diabetes and pre-diabetes should be cost-saving in patients at high risk. Diabetes Care. 2013;36(7):1981-7.

Baumeister D, Akhtar R, Ciufulini S, Pariante CM, Modelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour-necrosis factor-α. Mol Psychiatry. 2016;21:642-9.

Rekeneire N, Pelia R, Ding J, Colbert LH, Visser M, Shorr R et al. Diabetes, hyperglycemia,and inflammation in older individuals. The Health, Aging and body composition study. Diabetes Care. 2006;29:1902-8.

Pepys MB, Hirschfied GM. C-reactive protein. A critical update. J Clin Invest. 2003;111:180512

Meier-Ewert HK, Ridker P, Rifai N, Prick N, Dinger D, Mullington J. Absence of diurnal variation of C-reactive protein levels in healthy human subjects. Clin Chem. 2001:47:426-30.

Ehiaghe FA, Akinshipe BO, Ehiaghe IJ, Josiah S, Agbonlahor ED, Etikerentse M. The levels of C-reactive protein, malondialdehyde and absolute lymphocyte counts in pre and post-acute exercise. J Sports Med Doping Studies. 2017;7:188.

Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol. 2005;45:1563-9.

Azam M, Lestari S, Rahayu SR, Fibriana AI, Setianto B, Widyyastiti NS. et al. Baseline and post-exercise high-sensitivity c-reactive protein levels in endurance cyclists: The Indonesian north coast and Tour de Borobudur 2017. Study. Indones Biomed J. 2019;11(1):91-9.

Ockene IS, Matthews CE, Rifai N, Ridker PM, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem. 2001:47:444-50.

Ledue TB, Rifai N. High sensitivity immunoassays for C-Reactive protein: promises and pitfalls. clinical chemistry and laboratory Med. 2005;39(11):185

American Diabetic Association. Classification and diagnosis of diabetes: Standard medical care in diabetes. Diabetes Care. 2018;41:S13-S27.

Shin SH, Lee YJ, Lee YA, Kim JH, Lee SY, Shin CH. High-sensitivity C-Reactive protein is associated with prediabetes and adiposity in Korean Youth. Metabolic Syn Related Dis. 2020;18(1):47-55.

Dodig S, Galez D, Zoricic LI, Kristic KB, Kovac K, Nogalo B. C-Reactive protein and complement components C3 and C4 in children with latent tuberculosis infection. Biochemia Medica. 2008;1:52-8.

Effoe VS, Correa A, Chen A, Lacy ME and Bertoni AG. High-sensitivity c-reactive protein is associated with incident type 2 diabetes among African Americans: The Jackson Heart Study. Diabetes Care. 2015;38(9):1694-1700.

Sabanayagam C, Shankar A, Lim SC, Lee J, Tai ES, Wong TY. Serum C-reactive protein level and prediabetes in two Asian populations. Diabetologia. 2011;54:767-75.

Akinshipe BO, Ezeani PC, Digban KA, Ehiaghe FA, Adedeji EB, Ehiaghe JI. Immunodiagnostic potential of an in-vitro interferon-gamma release assay for latent tuberculosis infection among apparently healthy individuals in Okada Community, Nigeria. Int J Immunol. 2017;5(3):41-8.

Akinshipe BO, Yusuf EO, Akinshipe FO, Moronkeji MA, Nwaobi AC. Prevalence and determinants of pre-diabetes and latent tuberculosis infection among apparently healthy adults in three Communities in Southern Nigeria. Int J Immunol. 2019:7(2):23-32.

Ayah R, Joshi MD, Mutai KK, Wanjiru R. A population-based survey of prevalence of diabetes and correlates in an urban slum in Nairobi, Kenya. BMC Public Health. 2013;13:371.

Meme N, Amwayi S, Nganga Z, Buregyeya E. Prevalence of undiagnosed diabetes and pre-diabetes among hypertensive patients attending Kiambu district Hospital, Kenya: A cross-sectional study. Pan African Medi J. 2015;22:286.

Roche Cobas c111 User Manual. Available at https// c111-user-Manual. Accessed on 24 March 2020

Nigeria diabetes association guidelines 2018. Published by the Diabetes Association of Nigeria. Available at https// /regions-members/Africa. Accessed on 4 March 2020.

Nigeria National tuberculosis and leprosy and Buruli Ulcer control Program (NTLCP) National Strategic Plan-TB 2015-2020.

Quantiferon-TB Gold (in-tube method).Package insert.2013.Retrieved from Cellestis website. Available at /company/show page.aspx (cpin-1171) Accessed on 19 December 2019

Human high sensitivity C-Reactive Protein (hs-CRP) ELISA KIT.CAT.NO: EKHU-1155’Package insert. May 2019. Melsin Medical Co, Limited, China.

Luna JM, Moon YP, Liu KM, Spitalnik S, Paik MC, Cheung K. High Sensitivity C-reactive protein and interleukin-6 dominant inflammation and ischemic stroke risk: The Northern Manhattan Study. Stroke. 2014;45(4):979-87.

Pfutzner A, Forst T. High-sensitivity C-reactive protein as cardiovascular risk marker in patients with diabetes mellitus. Diabetes Technol Ther. 2006:8(1):28-36.

Ehiaghe FA. Some physicochemical changes associated with type2 diabetes mellitus in Benin City, Nigeria.Int J Biol Chem Sci. 2015;9:2582-8.

Sarrinapakorn V, Wanicagool W. Association between hs-CRP and HbA1c in overweight type-2 diabetic female patients. J Med Assoc Thai. 2013;96(3):54-8.

Danesh J, Wheeler JG, Hirschfield GM, Eda S. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease, N Engl J Med. 2004;350:1387-97.