ONLINE ONLY ARTICLES - ORIGINAL ARTICLE
|Year : 2022 | Volume
| Issue : 3 | Page : 421
Comparative evaluation of serum high-density lipoprotein and low-density lipoprotein levels and glycated hemoglobin levels and periodontal status in type 2 diabetic patients: A pilot project
Shreya Shetty1, Bebika Devi Thoudam2, Natasha Thokchom3, Sophia Khumukcham2, Akshata Sajjan4, Soumya Ponnan1
1 Associate Professor, Dentistry Program, IBN Sina National College of Medical Sciences, Jeddah, KSA
2 Department of Periodontology, Dental College, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India
3 Department of Oral Pathology and Microbiology, Dental College, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India
4 Periodontist, Chiniwalar's Dental Care, Gangavathi, Karnataka, India
|Date of Submission||27-Nov-2021|
|Date of Decision||02-Jan-2022|
|Date of Acceptance||24-Jan-2022|
|Date of Web Publication||17-Oct-2022|
IBN Sina National College of Medical Sciences, Jeddah
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: High levels of cholesterol in the body can be alarming and point toward a possible cardiac or diabetic problem. Current evidence reveals that the harmful low-density lipoproteins (LDL) cholesterol tend to increase in poorly controlled diabetes, whereas the useful high-density lipoprotein (HDL) cholesterol, known for its protective anti-inflammatory and antioxidant activities, is decreased. With a positive evidence of periodontal disease being implicated in diabetes, it was decided to investigate whether there was any association between serum HDL, LDL, glycated hemoglobin (HbA1c) and periodontal status with Type II diabetes mellitus patients.
Materials and Methods: A total of 500 nonsmoking patients (males and females) aged between 35 and 55 years with Type 2 diabetes mellitus and no other systemic disease were selected from the diabetic center, Diacon hospital, Bengaluru, Karnataka, India. Periodontal examination consisted of the clinical parameters, namely, attachment loss, gingival index (GI) and plaque index based on which the patients were divided into periodontally healthy and diseased groups. Blood samples were collected from each patient to evaluate the serum levels of HDL, LDL and HbA1c.
Results: No significant differences were observed between the HDL, LDL and HbA1c levels in both the periodontal groups (P > 0.05). Linear regression analysis showed significant positive correlations of clinical attachment level with LDL and negative correlation with HbA1c, whereas GI has a positive correlation with LDL and negatively with HDL and Hba1c levels (P < 0.05).
Conclusion: Varied associations were found between dyslipidemia, glycemic control and periodontal inflammation. Further longitudinal as well as interventional studies may be beneficial to ascertain the causal relationship between cholesterol levels, periodontal status and diabetes mellitus.
Keywords: Glycated hemoglobin, lipid profile, periodontitis, type 2 diabetes
|How to cite this article:|
Shetty S, Thoudam BD, Thokchom N, Khumukcham S, Sajjan A, Ponnan S. Comparative evaluation of serum high-density lipoprotein and low-density lipoprotein levels and glycated hemoglobin levels and periodontal status in type 2 diabetic patients: A pilot project. J Oral Maxillofac Pathol 2022;26:421
|How to cite this URL:|
Shetty S, Thoudam BD, Thokchom N, Khumukcham S, Sajjan A, Ponnan S. Comparative evaluation of serum high-density lipoprotein and low-density lipoprotein levels and glycated hemoglobin levels and periodontal status in type 2 diabetic patients: A pilot project. J Oral Maxillofac Pathol [serial online] 2022 [cited 2022 Nov 30];26:421. Available from: https://www.jomfp.in/text.asp?2022/26/3/421/358745
| Introduction|| |
There is sufficient evidence available today to suggest that Type II diabetes mellitus (T2DM) is associated with an increased prevalence, extent and severity of periodontal disease. These two diseases have the capacity to induce an inflammatory response, leading to the production of various mediators of inflammation. Glycated hemoglobin/glycosylated hemoglobin (hemoglobin A1C, HbA1c) is formed in a nonenzymatic glycation pathway on exposure of hemoglobin to plasma glucose and serves as a marker for diabetic control. The HbA1c test provides an estimate of glycemic control over a period of approximately 2–3 months before the test, and the normal value is <6%. Evidence has linked the risk of developing periodontal disease to the levels of HbA1c, and the risk of elevations of HbA1c was associated with developing periodontal pockets of ≥4 mm.
On the other hand, Type I diabetes mellitus (T1DM) is known to alter lipid metabolism, and depending on the level of metabolic control of the disease, both quantitative and qualitative abnormalities in the lipid profile have been observed. Alternately, lower levels of serum high-density lipoprotein (HDL) have been observed in subjects with chronic periodontitis than in periodontally healthy subjects,,,, and higher low-density lipoprotein (LDL) and triglyceride levels were reported in subjects with chronic periodontitis.,,, An evident association between serum lipid profile and periodontal infection was further supported by longitudinal studies in which significantly decreased levels of serum LDL and total cholesterol were found after intensive periodontal treatment in severely affected periodontitis patients., Furthermore, a statistically significant increase in the level of HDL along with successful periodontal intervention has also been reported.,,
In spite of there being abundant literature on the associations between T1DM, lipid profiles and periodontal disease, till date, there is limited evidence on the associations between the serum lipid profile and periodontal inflammation in Type 2 diabetic patients. One of the early studies by Cutler et al. observed that gingival inflammation tended to increase with an increasing level of serum triglycerides in Type 2 diabetic patients. Lim et al. reported that poor control of diabetes mellitus is associated with periodontal inflammation and LDL and total cholesterol, whereas no significant association was found between serum lipid profile (LDL, triglycerides and total cholesterol) and periodontal inflammation. Nassar et al. concluded that periodontal therapy led to improved lipid profiles in Type 2 diabetic patients, whereas Kalsi et al. concluded that in addition to effects on diabetes, periodontitis may contribute to elevated serum lipid levels and therefore potentially to systemic disease arising from chronic hyperlipidemia.
The present study was therefore carried out to investigate an association, if any, between HDL, LDL, glycated hemoglobin and periodontal status in patients with T2DM.
| Materials and Methods|| |
Following the approval from the institutional ethical committee (IEC NO-VEF/23052011), a total of 505 patients from Diacon hospital, Bengaluru, aged between 35 and 55 years with T2DM noninsulin-dependent diabetes mellitus were included after obtaining consent to participate in the study. Patients on insulin therapy, any other systemic disease or condition and smokers were excluded. Patient records from the hospital were used to retrieve data regarding the diabetic state and general health status of the subjects with details of blood investigations evaluating HDL, LDL and HbA1C recorded separately. Glycated hemoglobin (HbA1c) was analyzed using high performance liquid chromatographic technique. HDL and LDL were separated using ultracentrifugation method.
In addition, the clinical parameters, i.e., gingival index (GI), plaque index (PI), probing pocket depth (PPD) and clinical attachment level (CAL), were measured using UNC-15 periodontal probe. Based on the clinical periodontal parameters, the study population was divided into 2 groups based on the findings obtained on the periodontal parameters. Patients with GI and plaque scores under 1 with no probing depths and CAL were grouped under periodontally healthy, whereas those with GI and PI over 1 with evidence of probing depth and CAL were grouped under periodontal disease.
- Periodontally healthy: No gingival or periodontal disease
- Periodontitis: With periodontal disease.
Statistical analyses were performed using statistical software IBM SPSS Statistical Package for the Social Sciences, version 22 (IBM, Chiacago, Illinois, USA) for Windows. Unpaired t-tests were used to compare the HDL, LDL and HbA1C values between the two groups. Linear regression analysis was carried out to establish any association between the parameters, and the level of statistical significance was set at <5% (P < 0.05). All analyses were based on subject level data.
| Results|| |
The subject characteristics were presented as mean values (± standard deviation) per subject or frequency [Table 1]. Although the mean HDL and LDL values were higher in the periodontally healthy group compared to the diseased group, the differences were not statistically significant (P > 0.05) [Table 2] and [Table 3]. Similarly, there were no significant differences in the glycated hemoglobin levels in both the groups (P > 0.05), although the mean values in the periodontitis group were higher than the periodontally healthy group [Table 4].
|Table 2: Comparison of healthy and periodontitis groups with respect to high-density lipoprotein scores by unpaired t-test|
Click here to view
|Table 3: Comparison of healthy and periodontitis groups with respect to low-density lipoproteins scores by unpaired t-test|
Click here to view
|Table 4: Comparison of healthy and periodontitis groups with respect to glycated hemoglobin percentage scores by unpaired t-test|
Click here to view
Linear regression analysis showed a significant positive association between CAL and PPD (r2 = 0.483) and CAL and LDL levels (r2 = 0.134) and a significant negative association between CAL and glycated hemoglobin (HbA1C) levels (r2 = −0.133) (P < 0.05) [Table 5].
|Table 5: Association between clinical attachment level value and associated explanatory variables using linear regression analysis|
Click here to view
A significant negative association was found between GI scores and HDL levels (r2 = −0.233) and GI scores and glycated hemoglobin (HbA1C) levels (r2 = −0.119) (P < 0.05) and a significant positive correlation was found between GI scores and LDL levels (r2 = 0.132) (P < 0.05) [Table 6]. Similarly, a significant positive correlation was observed between PI scores and HDL levels (r2 = 0.127) (P < 0.05) [Table 7].
|Table 6: Association between gingival index and associated explanatory variables using linear regression analysis|
Click here to view
|Table 7: Association between plaque index and associated explanatory variables using linear regression analysis|
Click here to view
| Discussion|| |
The association between dyslipidemia, characterized by a reduction in serum HDL level, and periodontal inflammation has been suggested in a number of earlier studies,,,, HDL is said to have a protective association with periodontal inflammation by regulating the inflammatory processes via several key mechanisms. HDL has also been found to be effective in binding and neutralizing lipopolysaccharide of Gram-negative bacteria, thereby limiting the expression of cytokines and lipid peroxidation., Except for the qualitative abnormalities of lipoproteins in T1DM, serum triglycerides and LDL tend to increase in poorly controlled diabetes, whereas the level of HDL tends to decrease., In addition, the level of glycemic control is associated with periodontal inflammation.,
As a combined occurrence, researchers have also suggested that the decreased diabetic control in Type 2 diabetes may influence the increased serum triglycerides and periodontal health.,,,, Al-otaibi et al. have suggested that dyslipidemia may be a possible link between periodontal disease and diabetes mellitus.
With such diverse and complex associative evidence between the three chronic conditions, namely, dyslipidemia, diabetes and periodontal disease, the present study was attempted to investigate a possible association present between serum HDL, LDL, glycated hemoglobin and periodontal status in Type II diabetes mellitus patients.
The study population comprising 505 patients had an average age of 46.65 ± 6.83 with nearly equal number of males and females. The severity of periodontitis (periodontitis group) was high with CAL values over 5 mm. The mean HDL and LDL levels of the study group were reported as 44.45 ± 10.74 and 96.41 ± 32.13, respectively. Ying Ouyang et al. reported that HDL levels <40 mg/dl (corresponding to levels <1.04 mmol/l) have been considered an independent risk factor for coronary heart disease, whereas at levels ≥60 mg/dl (corresponding to levels ≥1.55 mmol/l), there may be a reduced risk. The mean glycated hemoglobin level was 8.70 ± 2.19, which was definitely high, reflecting on the poor glycemic control of the patients.
The HDL and LDL values were comparatively higher in the periodontally healthy group compared to the diseased group, although the results were not statistically significant, which were in accordance with Gita et al. who found that there was no association among periodontal disease and the levels of total cholesterol, LDL, HDL and triglycerides. However, a significant positive correlation was observed between periodontal attachment loss and gingival inflammation with LDL levels, thereby indicating that there may be a possible association between periodontal disease and dyslipidemia. Sharma et al. showed that high serum LDL cholesterol may be associated with periodontitis in healthy people. However, it is unclear whether periodontitis causes an increase in the levels of serum LDL or an increased LDL is a risk factor for both periodontitis and cardiovascular disease. Katz et al. found that the presence of periodontal pockets as measured by community periodontal index for treatment needs (CPITN) was positively associated with total cholesterol and LDL cholesterol and the findings of the study support the reports linking increased prevalence of cardiovascular mortality among patients with periodontal disease.
Our study also found a significant negative correlation between gingival inflammation and HDL and a significant positive correlation of PI with HDL. These findings are complex to substantiate, as a study by Passoja et al. also found a negative association between serum HDL and periodontal inflammation, whereas Heinrichs and Desvarioux found a positive one; however, several others found no significant association between HDL levels and periodontal disease., However, Passoja et al. controlled the most important confounding factors and concluded that serum HDL level may be regarded as a marker of susceptibility to periodontal inflammation and suggested that the anti-inflammatory and anti-infective functions of HDL cholesterol must be considered to verify a possible causal relationship between serum HDL and periodontal inflammation in a longitudinal study.
There were no significant differences between the healthy and periodontitis group with regard to glycated hemoglobin, although the mean HbA1C levels were higher in the periodontitis group. However, a significant negative correlation was found between HbA1c levels and CAL as well between HbA1c levels and gingival inflammation. Nevertheless, these findings are statistical outcomes and may or may not align with evidence which concluded that patients having poor glycemic control had more severe periodontitis as compared to patients having a fair one and also that the level of glycemic control as measured by HbA1c is the most consistent risk factor associated with the extent and severity of periodontal disease.
The focus of our study was on the combined association of HDL, LDL, HbA1c levels and the periodontal status and linear regression analysis showed that the severity of periodontal disease (CAL) was positively correlated with LDL while showing a negative one with HbA1c and none with HDL, whereas the parameters of periodontal inflammation (GI and PI) were negatively correlated with HDL and HbA1c while being positively correlated with LDL levels (GI) with only PI being positively correlated with HDL levels. These correlations although diverse from other evidence, suggest varied associations between lipid levels, glycemic control and periodontal disease in T2DM. Passoja et al. found a negative association between periodontal inflammation and serum HDL level in subjects with T1DM and also that an association between periodontal inflammation and serum HDL level was evident and even stronger after considering the potential confounding effect of the IL-6 _174 genotype (GG vs. GC/CC) of the subjects. However, analogous to cardiovascular diseases, in which the antioxidant and anti-inflammatory activities of HDL are associated with protection against inflammation, high HDL levels were associated with fewer inflamed periodontal sites in our study. Nepomuceno et al. observed that dyslipidemia patients also affected by poorly controlled diabetes presented increased severity of periodontitis, collectively negatively affecting health and quality of life. They further concluded that dyslipidemia appears to be the primary disease that is associated with gene expression of immune-related genes, while parameters of T2DM and periodontal disease were correlated with the expression of these important immune genes. Hyperlipidemia may persist even in subjects with good glycemic control and elevations in serum lipids may be more important, and much more destructive than the glycemic state.,,
Although we excluded an important risk factor such as smoking, our study could establish a noteworthy association between periodontal inflammation, disease severity and lipoproteins (positive with LDL and negative with HDL), and in addition, a negative one with HbA1c. Nevertheless, the exact nature of this connection is still elusive and it may not be possible to draw concrete conclusions.
| Conclusion|| |
Within the limitations of the study, the mean HDL, LDL and HbA1c levels were higher in the periodontally diseased group. However, the precise nature of the association is inconclusive. Perhaps, longitudinal studies verifying the cause-and-effect relationship between these parameters may aid in providing a definite inference. Additionally, including a nondiabetic control group with periodontal disease would have allowed us to have a better understanding on the influence of diabetes mellitus on the association between serum lipid levels and the extent of periodontal inflammation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Molina C, Ojeda L, Jiménez M, Portillo C, Olmedo I, Hernández T, et al
. Diabetes and periodontal diseases: An established two-way relationship. J Diabetes Mellitus 2016;6:209-29.
Sandini MT, Paulo JD, Conto MF, José DG, Oliveira SD, Hugo L. Prevalence and severity of periodontal disease in type 2 diabetes mellitus patients: A cross-sectional study. Biosci J 2018;34:1114-23.
Morita I, Inagaki K, Nakamura F, Noguchi T, Matsubara T, Yoshii S, et al.
Relationship between periodontal status and levels of glycated hemoglobin. J Dent Res 2012;91:161-6.
Vergès B. Lipid disorders in type 1 diabetes. Diabetes Metab 2009;35:353-60.
Adil Ahmed MA, Judyangel D, Rajathi R, Rafiya S, Kumari P, Pragadeeswari D. Serum lipid levels in periodontitis patients: A case-control study. Int J Pharm Pharm Sci 2017;10:171-3.
Chandrasekhar H, Savitha G, Santosh Kumar MP. Evaluation of association between periodontitis and hyperlipidemia. J Pharm Sci Res 2017;9:2429-30.
Nibali L, D'Aiuto F, Griffiths G, Patel K, Suvan J, Tonetti MS. Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: A case-control study. J Clin Periodontol 2007;34:931-7.
Monteiro AM, Jardini MA, Alves S, Giampaoli V, Aubin EC, Figueiredo Neto AM, et al.
Cardiovascular disease parameters in periodontitis. J Periodontol 2009;80:378-88.
Katz J, Flugelman MY, Goldberg A, Heft M. Association between periodontal pockets and elevated cholesterol and low density lipoprotein cholesterol levels. J Periodontol 2002;73:494-500.
D'Aiuto F, Nibali L, Parkar M, Suvan J, Tonetti MS. Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res 2005;84:269-73.
D'Aiuto F, Parkar M, Nibali L, Suvan J, Lessem J, Tonetti MS. Periodontal infections cause changes in traditional and novel cardiovascular risk factors: Results from a randomized controlled clinical trial. Am Heart J 2006;151:977-84.
Pussinen PJ, Jauhiainen M, Vilkuna-Rautiainen T, Sundvall J, Vesanen M, Mattila K, et al.
Periodontitis decreases the antiatherogenic potency of high density lipoprotein. J Lipid Res 2004;45:139-47.
Lal V, Lohra P, Rath S, Dubey D. Effect of chronic periodontal infection on systemic lipid profile: A clinical and biochemical study. J Int Clin Dent Res Organ 2015;7:106. [Full text]
Buhlin K, Hultin M, Norderyd O, Persson L, Pockley AG, Pussinen PJ, et al.
Periodontal treatment influences risk markers for atherosclerosis in patients with severe periodontitis. Atherosclerosis 2009;206:518-22.
Cutler CW, Shinedling EA, Nunn M, Jotwani R, Kim BO, Nares S, et al.
Association between periodontitis and hyperlipidemia: Cause or effect? J Periodontol 1999;70:1429-34.
Lim LP, Tay FB, Sum CF, Thai AC. Relationship between markers of metabolic control and inflammation on severity of periodontal disease in patients with diabetes mellitus. J Clin Periodontol 2007;34:118-23.
Nassar PO, Walker CS, Salvador CS, Felipetti FA, Orrico SR, Nassar CA. Lipid profile of people with diabetes mellitus type 2 and periodontal disease. Diabetes Res Clin Pract 2012;96:35-9.
Kalsi DS, Chopra J, Sood A. Association of lipid profile test values, type-2 diabetes mellitus, and periodontitis. Indian J Dent 2015;6:81-4.
] [Full text]
Nofer JR, Kehrel B, Fobker M, Levkau B, Assmann G, von Eckardstein A. HDL and arteriosclerosis: Beyond reverse cholesterol transport. Atherosclerosis 2002;161:1-16.
Levine DM, Parker TS, Donnelly TM, Walsh A, Rubin AL. In vivo
protection against endotoxin by plasma high density lipoprotein. Proc Natl Acad Sci U S A 1993;90:12040-4.
Casanova L, Hughes FJ, Preshaw PM. Diabetes and periodontal disease: A two-way relationship. Br Dent J 2014;217:433-7.
Lösche W, Karapetow F, Pohl A, Pohl C, Kocher T. Plasma lipid and blood glucose levels in patients with destructive periodontal disease. J Clin Periodontol 2000;27:537-41.
Al-Otaibi DH, Babay NA, Habib SS, Almas K. Assessment of lipid profile in Saudi type 2 diabetic and non-diabetic periodontal patients. Saudi Med J 2008;29:723-7.
Ying Ouyang X, Mei Xiao W, Chu Y, Ying Zhou S. Influence of periodontal intervention therapy on risk of cardiovascular disease. Periodontol 2000 2011;56:227-57.
Gita B, Sajja C, Padmanabhan P. Are lipid profiles true surrogate biomarkers of coronary heart disease in periodontitis patients?: A case-control study in a south Indian population. J Indian Soc Periodontol 2012;16:32-6.
] [Full text]
Sharma S, Lamsal M, Sharma SK, Niraula SR, Koirala B. Association of serum LDL cholesterol level with periodontitis among patients visiting a tertiary-care hospital. JNMA J Nepal Med Assoc 2011;51:104-8.
Passoja A, Knuuttila M, Hiltunen L, Karttunen R, Niemelä O, Raunio T, et al.
Serum high-density lipoprotein cholesterol level associated with the extent of periodontal inflammation in type 1 diabetic subjects. J Clin Periodontol 2011;38:1071-7.
Gomes-Filho IS, Santos PN, Cruz SS, Figueiredo AC, Trindade SC, Ladeia AM, et al.
Periodontitis and its higher levels of severity are associated with the triglyceride/high density lipoprotein cholesterol ratio. J Periodontol 2021;92:1509-21.
Machado AN, Quirino MR, Nas Cimento LF. Relation between chronic periodontal disease and plasmatic levels of triglyc-erides, total cholesterol. Clin Infect Dis 2005;38:88-92.
Taleghani F, Shamaei M, Shamaei M. Association between chronic periodontitis and serum lipid levels. Acta Med Iran 2010;48:47-50.
Tandon V, Tangade P, Lingesha RT, Tirth A, Pal SK, Yadav V. Glycemic control and periodontal disease in type 2 diabetes mellitus patients: A cross-sectional study. J Indian Assoc Public Health Dent [Serial online] 2015;13:297-301.
McGrowder D, Riley C, Morrison EY, Gordon L. The role of high-density lipoproteins in reducing the risk of vascular diseases, neurogenerative disorders, and cancer. Cholesterol 2011;2011:496925.
Nepomuceno R, Villela BS, Corbi SC, Bastos AS, Dos Santos RA, Takahashi CS, et al.
Dyslipidemia rather than type 2 diabetes mellitus or chronic periodontitis affects the systemic expression of pro- and anti-inflammatory genes. Mediators Inflamm 2017;2017:1491405.
Yadav N, Singh S, Gupta S, Mishra S, Singh K. Correlation between glycemic control and dyslipidemia in type 2 diabetes mellitus patient. Int J Basic Clin Pharmacol 2019;8:1387.
Ozder A. Lipid profile abnormalities seen in T2DM patients in primary healthcare in Turkey: A cross-sectional study. Lipids Health Dis 2014;13:183.
Sadeghi E, Hosseini SM, Vossoughi M, Aminorroaya A, Amini M. Association of lipid profile with type 2 diabetes in first-degree relatives: A 14-year follow-up study in Iran. Diabetes Metab Syndr Obes 2020;13:2743-50.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]