Exploring Interleukin-10 Levels in Diabetes Patients with and without Oral Diseases: A Systematic Review

Figures & data

Figure 1 The PRISMA flow diagram of the article search and selection process.

Table 1 Characteristics of the Reviewed Studies

No	Researcher	Country	Aim	Population	Type of DM	Oral Diseases	Sample	Method of Measurement	Result	Conclusion
1	Andriankaja et al, 2023^Citation34	USA	To study the associations between serum or GCF endothelial and inflammatory mediators and chronic PD among T2D Hispanic	248 Puerto Rican residents with T2D aged 40–65 years	T2D	Periodontitis	Blood & GCF	ELISA (Luminex^®200 TM)	Increased serum IL-10, sICAM-1, and elevated serum IL-1β were statistically significant or close to being significantly associated with a percent of sites with PPD ≥ 4 mm.	There is an association between elevated serum IL-10 and higher periodontal incidence in individuals with T2D.
2	Ikbal et al, 2023^Citation35	India	To estimate serum IL‑10 and its association with glycemic status in T2D and chronic periodontitis and to evaluate the influence of periodontal inflammatory state on glycemic status	80 patients were divided into four groups consisting of 20 patients in each group. Group 1: healthy control, Group 2: T2D without chronic periodontitis, Group 3: CPD only, Group 4: T2D with CPD	T2D	Periodontitis	Blood	ELISA (Diaclone, France)	IL 10 was detected lowest in Group 3 followed by Group 4. Highest level of IL 10 was found in the healthy group then in Group 2.	The lowest level of IL-10 in CPD is associated with periodontal inflammation itself, which influences regulating serum IL-10 levels and poor glycemic control.
3	Halimi et al, 2022^Citation36	Iran	To correlate serum IL-10 and IFN-γ with oral candidiasis in T2D	122 participants consist of 81 patients with T2D and 41 non-diabetic individuals aged 30 to 70 years	T2D	Oral candidiasis	Blood	ELISA (Biolegend, CA, USA)	An increase in IL-10 by 40% and a decrease in IFN-γ by 6% can increase oral candidiasis prevalence among diabetic patients.	An elevated risk of oral candidiasis may be linked to an increase in IL-10 in the diabetic population.
4	Liu et al, 2022^Citation37	China	To investigate the expression of single-stranded microRNAs (miRNAs) in serum and GCF of patients with T2D complicated by PD and its correlation with inflammatory factors	A total of 26 periodontitis patients without DM, 24 patients with T2D, 22 patients with both T2D and PD, and 25 healthy individuals without a history of PD	T2D	Periodontal disease	Blood & GCF	ELISA (Quanzhou Ruixin Biotechnology Co., Ltd.)	Compared with the healthy group, the other three groups showed a decreased level of IL-10 in the GCF (all p<0.05)	The periodontal group had lower levels of IL-10 compared to the healthy group, and the periodontal patient’s comorbidity with T2D had lower levels of IL-10 compared to the periodontal group, indicating a trend towards a decrease in IL-10.
5	Zhang H. et al, 2021^Citation38	China	To analyze the effect of statins on cytokines levels in GCF and saliva and on clinical periodontal parameters of middle-aged and elderly patients with T2D	143 subjects were classified into three groups: healthy controls (C group, n= 62), T2D patients not taking statins (D group, n= 57), T2D patients taking statins (S group, n= 24)	T2D	Gingivitis, Periodontitis	Saliva & GCF	The Luminex fluorescent technique, utilizing Milliplex Magnetic Beads (Merck Millipore, BA, USA)	The IFN-γ, IL-6 and IL-10 levels were lower in the Dp group than those in the Cp group (p<0.05).	The levels of IL-10 were lower in the diabetic group with periodontitis than those in the control group with periodontitis.
6	Elazazy et al, 2021^Citation39	Egypt	To investigate the role of specific miRNAs (miR-223, miR-203, and miR-200b) in periodontal disease and diabetes and to check their levels in blood and gingiva, exploring their connection to inflammation markers (TNF-α, IL-10).	60 subjects were recruited and divided into three groups; chronic periodontitis (n=20), T2D chronic periodontitis (n=20), and healthy control (n=20).	T2D	Periodontal disease	Blood & GCF	ELISA (using IDK^®, Immun-diagnostik, K9610 and SinoGeneClon Biotech, SG-10271)	A significant increase in the relative quantification levels of miR-223 and miR-200b were detected in patient groups along with a positive correlation with TNF-α.	A significant decrease in IL-10 levels in both experimental groups (periodontitis patients with and without T2D) was observed when compared to the control group (healthy patients without periodontitis).
7	Rangel et al, 2021^Citation40	Brazil	To examine the levels of LTA and LPS in the gingiva of DM and to see the relationship between cytokines and MMPs in the gingiva of DM compared to non-DM	30 subjects were allocated to 15 T2D with periodontitis and 15 non-DM with periodontitis.	T2D	Periodontitis	GCF	Luminex/ MAGpix technology	Non-diabetic subjects presented a lower IL-10 concentration (p<0.05).	Higher levels of IL-10 were found in the DM group.
8	Kassab et al, 2021^Citation41	Tunisia	To analyze the correlation between HbA1c and the prevalence of gingival pathogens and circulating interleukin levels in T2D Tunisian subjects.	120 subjects divided into 4 groups.	T2D	Periodontal disease	Saliva	ELISA cytokine multiplex kits (R&D Systems, Inc. Minneapolis, MN, USA)	The lowest level of IL-10 was seen in individuals with ITIID & CP, whereas the highest mean level was seen in healthy individuals.	ITIID&CP showed the lowest level of IL-10.
9	Rabelo et al, 2021^Citation42	Brazil	To evaluate in GP subjects with or without hyperglycemia the short-term effects of non-surgical periodontal therapy on levels of serum, saliva, and GCF inflammatory markers.	60 subjects divided into four groups of equal size were selected to participate: T2D + GP, pre-diabetics with GP, NG+ GP, and healthy controls.	T2D	Periodontal disease	Blood, saliva and GCF	Multiplex fluorescent bead-based immunoassay system (Bio-Plex MAGPIX Multiplex Reader, Bio-Rad, Hercules, CA, USA)	NG + GP and T2D + GP had significantly higher GCF and salivary levels of IL-10 when compared to the control group. The highest IL-10 level was in the serum control group.	Serum IL-10 levels were lowest in the pre-diabetic and diabetic groups with periodontitis.
10	Kumar et al, 2020^Citation43	USA	To understand host-microbiome interactions and to measure a set of cytokines to gauge inflammation using graph theory, explore connections between these two areas.	54 subjects consist of 17 T2D with periodontitis, 17 non-T2D with periodontitis, and 20 periodontally healthy subjects.	T2D	Periodontitis	Sub-gingival biofilm and GCF	The High Sensitivity Human Cytokine-08 plex (Millipore Corporation) at Luminex/ MAGpix platform	IL-10 levels are lower in diabetics than in normoglycemics (p = 0.001).	The cytokine IL-10 turned out to be a highly rewired with a 400-fold increase in connections in normoglycemics and a 20-fold increase in hyperglycemia.
11	Belkina et al, 2020^Citation44	USA	To measure immune cell frequencies, surface phenotypes, and ex vivo effector function in the gingival tissue immune compartment of patients with PD or T2D-potentiated PD.	40 patients consist of 5 healthy patients, 26 periodontitis patients, and 9 periodontitis patients with T2D.	T2D	Periodontal disease	Gingival tissue	ELISpot (MAIPN4550; Sigma Millipore)	Myeloid cells (CD11b+) from PD/T2D samples produced higher amounts of IL-10 compared to PD samples.	IL-10 trended higher in T2D with periodontitis than in periodontitis samples.

Abbreviations: DM, diabetes mellitus; GCF, gingival crevicular fluid; PD, periodontal disease; T2D, type 2 diabetes; ELISA, enzyme-linked immunosorbent assay; IL-10, interleukin-10; sICAM-1, intercellular adhesion molecule-1; IL-1β, interleukin-1 beta; PPD, probing pocket depth; CP/CPD, chronic periodontitis; IFN-γ, interferon-gamma; TNF-α, tumor necrosis factor-alfa; IL-6, interleukin-6; LPS, lipopolysaccharide; LTA, lipoteichoic acid; MMPs; matrix metalloproteinases; HbA1c, glycated hemoglobin; ITIID, inadequately controlled type II diabetes; GP, generalized periodontitis; GP, generalized periodontitis; NG, normoglycemic; ELISPOT, enzyme-linked immunosorbent spot.

Table 2 Risk of Bias Assessment (RoB)

No	Researcher	Risk of Bias Domain						Total Point	Assessment of RoB	Conclusion
		1	2	3	4	5	6
1	Andriankaja et al, 2023^Citation34	1	1	1	0	0	1	4	Low risk of bias	High quality
2	Ikbal et al, 2023^Citation35	1	1	1	0	0	1	4	Low risk of bias	High quality
3	Halimi et al, 2022^Citation36	1	1	1	0	0	1	4	Low risk of bias	High quality
4	Liu et al, 2022^Citation37	1	1	1	0	0	1	4	Low risk of bias	High quality
5	Zhang H. et al, 2021^Citation38	1	1	1	0	0	1	4	Low risk of bias	High quality
6	Elazazy et al, 2021^Citation39	1	1	1	0	0	1	4	Low risk of bias	High quality
7	Rangel et al, 2021^Citation40	1	1	1	1	0	1	5	Low risk of bias	High quality
8	Kassab et al, 2021^Citation41	1	1	1	0	0	1	4	Low risk of bias	High quality
9	Rabelo et al, 2021^Citation42	1	1	1	0	0	0	3	Low risk of bias	High quality
10	Kumar et al, 2020^Citation43	1	1	1	0	0	1	4	Low risk of bias	High quality
11	Belkina et al, 2020^Citation44	1	1	1	0	0	1	4	Low risk of bias	High quality
Domain Assessment (%)		100	100	100	9.1	0	90.9	–	–	–

Notes: Item 1 = Selection of participants; Item 2 = Confounding variables; Item 3 = Intervention (exposure) measurement; Item 4 = Blinding of outcome assessment; Item 5 = Incomplete outcome data; Item 6 = Selective outcome reporting; 1 = Yes/available; 0 = No/not available; Total point 0–2 = High risk of bias; Total point 3–6 = Low risk of bias.

Figure 2 Author assessment of each RoBANS domain for the included articles. Green denotes a low risk of bias, yellow denotes an unclear risk, and red denotes a high risk. The six domains are “participant selection, confounding variables, measurement of exposure, blinding of the outcome, incomplete outcome data, and selective outcome reporting”.

Andriankaja OM, Adatorwovor R, Kantarci A, Hasturk H, Shaddox L, Levine MA. Periodontal disease, local and systemic inflammation in Puerto Ricans with type 2 diabetes mellitus. Biomedicines. 2023;11(10):1–15. doi:10.3390/biomedicines11102770

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Ikbal SKA, Gupta S, Tiwari V, Dhinsa G, Verma N. Association of serum interleukin-10 level with glycemic status to predict glycemic alteration with periodontitis: a cross-sectional, observational study. Contemp Clin Dent. 2023;8:11–19. doi:10.4103/ccd.ccd

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Halimi A, Mortazavi N, Memarian A, Zahedi M, Niknejad F, Sohrabi A. The relation between serum levels of interleukin 10 and interferon ‑ gamma with oral candidiasis in type 2 diabetes mellitus patients. BMC Endocr Disord. 2022;22(1):1–6. doi:10.1186/s12902-022-01217-x

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Liu L, Xiao Z, Ding W, et al. Relationship between microRNA expression and inflammatory factors in patients with both type 2 diabetes mellitus and periodontal disease. Am J Transl Res. 2022;14(9):6627–6637.

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Zhang H, Zhang Y, Chen X, Li J, Zhang Z, Yu H. Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus. PLoS One. 2021;16:1–18. doi:10.1371/journal.pone.0244806

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Elazazy O, Amr K, Abd El Fattah A, Abouzaid M. Evaluation of serum and gingival crevicular fluid microRNA-223, microRNA-203 and microRNA-200b expression in chronic periodontitis patients with and without diabetes type 2. Arch Oral Biol. 2021;121:104949. doi:10.1016/j.archoralbio.2020.104949

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Rangel TP, Reis AA, Caponi L, et al. Subgingival endotoxin and lipoteichoic acid modulate cytokine production in diabetic subjects: a Case–control Study. Oral Dis. 2021;27(5):1325–1333. doi:10.1111/odi.13661

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Kassab A, Ayed Y, Elsayed SA, et al. Glycated hemoglobin influence on periodontal status, pathogens and salivary interleukins in type II diabetic Tunisian subjects with chronic periodontitis. J Dent Sci. 2021;16(2):614–620. doi:10.1016/j.jds.2020.09.018

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de Sousa Rabelo M, Gomes GH, Foz AM, et al. Short-term effect of non-surgical periodontal treatment on local and systemic cytokine levels: role of hyperglycemia. Cytokine. 2021;138:155360. doi:10.1016/j.cyto.2020.155360

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Kumar PS, Monteiro MF, Dabdoub SM, et al. Subgingival host-microbial interactions in hyperglycemic individuals. J Dent Res. 2020;99(6):650–657. doi:10.1177/0022034520906842

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Belkina AC, Azer M, Lee JJ, et al. Single-cell analysis of the periodontal immune niche in type 2 diabetes. J Dent Res. 2020;99(7):855–862. doi:10.1177/0022034520912188

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