Periodontal conditions and treatment outcomes for subjects with diabetes mellitus : special emphasis on HbA1c levels and T-cells

A two way relationship between periodontal disease (PD) and diabetes mellitus has previously been reported. This thesis was aimed to further analyze the influence of PD on blood glucose levels of subjects with type 2 diabetes mellitus (T2D) and vice versa. Periodontal conditions (bleeding on probing [BOP], plaque index [PI], periodontal pocket depth [PPD] [4mm < 6mm and ≥ 6mm]) and marginal bone levels) were investigated in subjects with pre-diabetes as well as those with or without diabetes mellitus. HbA1c levels in individuals with periodontal disease and diabetes mellitus were analyzed after non-surgical and surgical treatments. This thesis also assessed the influence of diabetes on infiltration of inflammatory cells, T lymphocytes and B lymphocytes in gingiva and the effect of glucose control on T-cell motility.

AIMS: Study I aimed to evaluate the difference in periodontal conditions between subjects with prediabetes, well or poorly controlled diabetes mellitus and non-diabetes. Hemoglobin A1c levels, BMI and WC were also measured. Study II aimed to study the effect of periodontal treatment (non-surgical and surgical) on HbA1c levels in subjects with or without PD and with or without diabetes mellitus. HbA1c, BOP, PI and PPD 4mm <6mm; ≥6mm were recorded. Study III aimed to investigate the infiltration of T and B lymphocytes in gingival biopsies of diabetic and non-diabetic subjects with or without periodontal disease. Study IVexamined the influence of D-glucose on T cell motility.

RESULTS: In study I, thirty-seven percent of all individuals who reported to be non-diabetics were prediabetics. An increase in the number of PPD ≥ 6mm was seen in subjects with poorly controlled diabetes as compared to pre-diabetics and non-diabetics (P<0.05). In study II, periodontal inflammatory conditions in all groups improved with non-surgical and surgical treatment. Subjects with diabetes mellitus showed decreased levels in HbA1c over a period of 3 and 6 months. No changes were detected in PPD 4mm <6mm in diabetics after treatment. Subjects with diabetes require periodontal treatment for at least 6 months to reduce blood sugar levels. In study III, the number of gingival CD4 and CD19 positive cells was reduced in diabetic individuals suggesting that diabetes inhibits lymphocyte entry into gingival tissues. In study IV, it was demonstrated that D-glucose, at a high concentration, intially stimulated Tcell motility while subsequently causing inhibition. These effects were associated with increased cell surface expression of TSP-1 and LRP-1.

In conclusion: This thesis shows that diabetes mellitus influences the periodontal conditions and treatment of periodontal disease has an influence on blood sugar status. Furthermore, diabetes mellitus influences the immunological status where high blood glucose sugar levels influence T cells. Overall, this thesis strenghtens the bidirectional relationship between PD and diabetes mellitus from both a pre-clinical and a clinical aspect.

List of scientific papers

I. Altamash M, Arledal S, Klinge B, Engström P.E. Pre-diabetes and diabetes: Medical risk factors and periodontal conditions. Acta Odontologica Scandinavica. 2013; 71:1625-31.
https://doi.org/10.3109/00016357.2013.788207

II. Altamash M, Klinge B, Engström P.E. Periodontal treatment and HbA1c levels in subjects with diabetes mellitus. Journal of Oral Rehabilitation. 2016; 43:31-8.
https://doi.org/10.1111/joor.12339

III. Altamash M, Hasan SM, Engström P.E, Sundqvist K. Type 2 diabetes mellitus reduces the number of gingival T and B cells in patients with periodontitis. [Manuscript]

IV. Altamash M, Engström P.E, Sundqvist K. Glucose control of T cell motility through endogenous thrombospondin-1 and its receptor low density lipoprotein receptor-related protein-1. [Manuscript]