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1 Supplementary Online Content Engebretson SP, Hyman LG, Michalowicz BS, et al. The effect of nonsurgical periodontal therapy on hemoglobin A1c levels among persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial. JAMA. doi: /jama etable 1. 6-month Change in HbA 1c by Levels of Response to Periodontal Therapy in the Treatment Group and the Control Group (Per Protocol) etable 2. 3-month and 6-month Change in Clinical Measurements of Periodontitis by Treatment Group (Per Protocol) etable 3. 3-month and 6-month Change in Weight, Blood Pressures, Fasting Glucose, Fasting Insulin, HOMA2 Insulin Sensitivity (%S), and HOMA2 β-cell function (%β) by Treatment Group (Per Protocol) This supplementary material has been provided by the authors to give readers additional information about their work.

2 etable 1. 6-month Change in HbA 1c by Levels of Response to Periodontal Therapy in the Treatment Group and the Control Group (Per Protocol a ) Baseline HbA 1c c 6-month change in HbA 1c (Δ=Follow up- Baseline) Treatment Control Treatment Control Level of Periodontal Response mean (SD) mean (SD) Mean d Mean d to Treatment (Tertiles b ) (95% C.I.) (95% C.I.) P value d Probing Depth (mm, mean sites/person e ) Most (n=80) 7.79 (0.65) (Reduction > 0.64 mm) (-0.07, 0.47) Moderate (n=80) 7.83 (0.63) 7.77 (0.60) (Reduction 0.24 to 0.64 mm) (-0.04, 0.46) (-0.08, 0.26) Least (n=80) 7.89 (0.68) (Reduction < 0.24 mm) (-0.20, 0.31) Clinical Attachment Loss (mm, mean sites/person e ) Most (n=80) 7.79 (0.65) (Reduction > 0.58 mm) (-0.07, 0.45) Moderate (n=78) 7.88 (0.69) 7.77 (0.60) (Reduction 0.15 to 0.58 mm) (-0.02, 0.50) (-0.08, 0.26) Least (n=82) 7.84 (0.62) (Reduction < 0.15 mm) (-0.21, 0.30) Bleeding on Probing (% sites/person e ) Most (n=79) 7.82 (0.65) (Reduction > 28% sites) (-0.06, 0.47) Moderate (n=79) 7.95 (0.72) 7.77 (0.60) (Reduction 11% to 28% sites) (-0.08, 0.44) (-0.08, 0.26) Least (n=82) 7.76 (0.59) (Reduction < 11% sites) (-0.17, 0.34) a Per protocol: Analyses were based on all participants with HbA 1c data at the 6-month visit (n=240 in the Treatment group, n=235 in the Control Group). b Based on the distributions of changes in periodontal measurements (Reduction= 6-month minus Baseline) in the Treatment Group. c A positive change in HbA 1 c indicates worsening over time.

3 d e Mean changes and 95% CI s were determined from linear regression models with 6 month change in HbA 1 c included as dependent variables, treatment group as an independent factor and the Clinical Site as a covariate; p values were based on t tests comparing mean changes between the two groups. Each periodontal measurement was evaluated on 6 sites of each tooth. A participant-based summary measurement was determined by first calculating an average of the six sites per tooth and then calculating an average for all teeth measured for that participant.

4 etable 2. 3-month and 6-month Change in Clinical Measurements of Periodontitis by Treatment Group (Per Protocol a ) Baseline 3-month Change (Δ=3-month- Baseline) 6-month Change (Δ=6-month- Baseline) Treatment Control Treatment Control Treatment Control Study Outcome mean (SD) mean (SD) mean b mean b p value b mean b mean b p value b (95% C.I.) (95% C.I.) (95% C.I.) (95% C.I.) Periodontal N=240 N=235 N=233 N=227 N=240 N=233 Measurements c Probing Depth (mm) 3.3 (0.6) 3.3 (0.7) < <.0001 (mean sites/person) (-0.5, -0.3) (-0.2, -0.1) (-0.5, -0.4) (-0.2, -0.1) # sites /Person % sites /person >4mm 50.9 (26.5) 49.5 (27.6) < <.0001 (-21.7, -15.9) (-8.0, -1.8) (-23.2, -17.4) (-10.1, -3.7) >5mm 28.8 (21.3) 28.3 (22.3) < <.0001 (-14.2, -10.1) (-6.6, -2.3) (-15.3, -11.0) (-7.6, -2.9) >7mm 3.4 (6.2) 3.6 (8.4) d d (-2.5, -1.2) (-1.1, 0.3) (-2.5, -1.0) (-1.3, 0.3) >4mm 33.7 (17.3) 33.9 (18.9) < <.0001 (-14.5, -10.6) (-5.5, -1.3) (-15.6, -11.6) (-6.8, -2.4) >5mm 19.0 (14.1) 19.5 (15.8) < <.0001 (-9.6, -6.8) (-4.6, -1.7) (-10.2, -7.3) (-5.2, -2.0) >7mm 2.2 (4.1) 2.6 (6.3) d d (-1.6, -0.8) (-0.7, 0.2) (-1.7, -0.6) (-1.0, 0.3) Clinical Attachment Loss 3.5 (0.8) 3.5 (0.9) < <.0001 (mm) (mean sites/person) (-0.4, -0.3) (-0.1, 0.0) (-0.4, -0.3) (-0.2, 0.0) # sites /person >4mm 59.7 (29.3) 57.6 (30.6) < <.0001 (-17.2, -11.0) (-6.1, 0.4) (-18.8, -12.6) (-8.5, -1.7)

5 % sites /person >5mm 35.7 (25.3) 33.8 (25.9) < <.0001 (-13.6, -9.4) (-5.5, -1.0) (-14.4, -9.8) (-6.5, -1.4) >7mm 24.2 (17.9) 23.6 (18.7) < <.0001 (-9.0, -6.2 (-3.7, -0.8) (-9.6, -6.5) (-4.3, -0.9) >4mm 40.1 (20.5) 39.7 (21.5) < <.0001 (-11.1, -7.0) (-4.1, 0.2) (-12.3, -8.2) (-5.5, -1.0) >5mm 6.6 (9.7) 7.1 (12.2) d d (-3.0, -1.2) (-1.4, 0.5) (-3.3, -1.4) (-1.3, 0.8) >7mm 4.7 (7.2) 5.2 (9.5) d d (-2.0, -0.7) (-1.0, 0.4) (-2.3, -0.9) (-0.9, 0.6) Bleeding on Probing e (% 60.6 (24.0) 59.3 (25.9) < <.0001 sites/person) (-22.9, -16.2) (-7.3, -0.2) (-22.4, -15.7) (-9.6, -2.3) Gingival Index (mean sites 1.4 (0.4) 1.4 (0.4) < <.0001 /person) (-0.5, -0.3) (-0.2, -0.0) (-0.4, -0.3) (-0.2, -0.0) Plaque score (% sites 86.7 (17.9) 84.5 (20.8) < <.0001 /person) (-29.4, -20.6) (-11.6, -2.5) (-18.4, -10.8) (-7.5, 0.8) a Per protocol: Analyses were based on all participants with HbA 1c data at the 6-month visit (n=240 in the Treatment group, n=235 in the Control Group). Periodontal data were missing for 2 Control participants at the 6 month visit. 6 participants in the Treatment Group and 7 in the Control Group missed their 3 month visit. In addition, periodontal data were missing for 1 Treatment Group participant and 1 Control. b Mean changes and 95% CI s were determined from linear regression models with 3-month and 6 month change in periodontal outcomes included as dependent variables, treatment group as an independent factor and the Clinical Site as a covariate; p values were based on t tests comparing mean changes between the two groups. c Each periodontal measurement was evaluated on 6 sites of each tooth. A participant-based summary measurement was determined by first calculating an average of the six sites per tooth and then calculating an average for all teeth measured for that participant. d P values were > 0.05 after adjustment for multiple comparisons using Bonferroni s correction. e Bleeding on Probing data not obtained (n=1 at the 3-month visit in the Treatment Group; n=1 at the 6-month visit in the Control Group).

6 etable 3. 3-month and 6-month Change in Weight, Blood Pressures, Fasting Glucose, Fasting Insulin, HOMA2 Insulin Sensitivity (%S), and HOMA2 β-cell function (%β) by Treatment Group (Per Protocol a ) Baseline 3-month Change (Δ=3-month- Baseline) 6-month Change (Δ=6-month- Baseline) Treatment Control Treatment Control Treatment Control mean mean mean b mean b mean b mean b Study Outcome (SD) (SD) (95% C.I.) (95% C.I.) p value b (95% C.I.) (95% C.I.) p value b N=240 N=235 N=231 N=226 N=238 N=232 Weight (kg) (23.8) (21.1) (-0.5, 0.3) (-0.4, 0.3) (-1.0, 0.1) (-1.1, -0.0) Blood Pressure N=240 N=235 N=233 N=228 N=240 N=234 Systolic (mm Hg) (21.1) (20.4) (-4.2, 0.9) (-4.6, 0.6) (-5.4, 0.0) (-7.7, -2.2) Diastolic (mm Hg) (12.5) (10.9) (-2.4, 0.8) (-2.1, 1.0) (-3.0, 0.25) (-4.7, -1.3) N=240 N=235 N=232 N=228 N=240 N=235 Fasting Glucose (mg/dl) (41.6) (42.9) (-4.1, 12.2) (-5.9, 10.6) (5.6, 23.3) (4.8, 22.8) N=123 N=128 N=114 N=120 N=109 N=122 Fasting Insulin e (pmol/l) (60.4) (82.8) (-12.1, 24.8) (3.9, 40.9) (-8.9, 25.6) (-4.5, 29.4) HOMA2 Insulin Sensitivity (%S) c,d HOMA2 β-cell Function (%β) c,d (47.7) (59.7) (-2.4, 15.3) (-3.9, 14.1) (-12.7, 7.4) (-12.5, 8.1) (177.1) (121.5) (-19.9, 17.3) (-23.4, 14.6) (-44.2, 0.79) (-38.1, 8.1) a Per protocol: Analyses were based on all participants with HbA 1c data at the 6-month visit (n=240 in the Treatment group, n=235 in the Control Group). Differences in sample sizes reflect missing data due to missed visits or inability to collect or processs data at the 3 or 6 month visit.

7 b Mean changes and 95% CI s were determined from linear regression models with 3-month and 6 month change in outcome included as dependent variables, treatment group as an independent factor and the Clinical Site as a covariate; p values were based on t tests comparing mean changes between the two groups. c Excluded participants reporting insulin use. d HOMA2 was calculated using the HOMA2 calculator version 2.2 (

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