Clinical Case Report of Long-term Follow-up in

Type-2 Diabetes Patient with Severe Chronic

Title
Periodontitis and Nifedipine-induced Gingival
Overgrowth.

Author(s) Shibukawa, Y; Fujinami, K; Yamashita, S

Journal Bulletin of Tokyo Dental College, 53(2): 91-99

URL http://hdl.handle.net/10130/2831

Right

Posted at the Institutional Resources for Unique Collection and Academic Archives at Tokyo Dental College,
Available from http://ir.tdc.ac.jp/
Bull Tokyo Dent Coll (2012) 53(2): 91–99

Case Report

Clinical Case Report of Long-term Follow-up in Type-2

Diabetes Patient with Severe Chronic Periodontitis and
Nifedipine-induced Gingival Overgrowth

Yoshihiro Shibukawa, Koushu Fujinami and Shuichiro Yamashita*

Division of Conservative Dentistry, Department of Clinical Oral Health Science,
Tokyo Dental College,
2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
* Division of Prosthodontics, Department of Clinical Oral Health Science,
Tokyo Dental College,
2-9-18 Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan

Received 10 January, 2012/Accepted for publication 20 February, 2012

Abstract
In this case report, we describe the clinical course over a 14-year follow-up in a
47-year-old diabetes patient with severe chronic periodontitis and nifedipine-induced
gingival overgrowth. The patient had a history of hypertension for over 5 years and
uncontrolled type 2 diabetes. Overgrown gingiva was observed in most of the teeth
and was marked in the upper and lower anterior teeth. A probing pocket depth of
≥4 mm and bleeding on probing (BOP) were observed in 94 and 90% of sites examined,
respectively. At baseline, his hemoglobin A1c (HbA1c) was 8.5%. The patient received
periodontal and diabetic treatment simultaneously. Medication was changed from nife-
dipine chloride to an angiotensin-converting enzyme inhibitor. After initial therapy
and subsequent periodontal surgery, gingival overgrowth disappeared and probing
depth and BOP showed a significant improvement. No recurrence was observed during
supportive periodontal therapy (SPT). The HbA1c level improved from 8.5 to 6.3% after
periodontal treatment, subsequently remaining at a good level during SPT over 10 years.
This study demonstrated that periodontal treatment, withdrawal of medication and
control of diabetes can result in remarkable improvements in type 2 diabetes patients
with chronic periodontitis and nifedipine-induced gingival overgrowth. These results
suggest that comprehensive periodontal treatment in combination with treatment for
diabetes mellitus can exert a positive influence on blood glucose levels and periodontal
condition in diabetic patients.
Key words: Chronic periodontitis­ — Nifedipine — Gingival overgrowth — 
Type 2 diabetes — Case report

Introduction (DM) has often been associated with severe

periodontal disease18,21). Diabetes mellitus is
Poor metabolic control of diabetes mellitus a complex disease with both metabolic and

91
92 Shibukawa Y et al.
vascular components, and is characterized
by hyperglycemia due to defects in insulin
secretion or action or both. It is a systemic
disease of the innate immune system14), and
patients with DM are prone to severe peri­
odontitis11), which is considered its sixth
complication8). No significant differences
were observed in the subgingival biofilm
between periodontitis patients with or with-
out DM24). Therefore, it was hypothesized that
DM-induced exaggeration of host immune
responses played a crucial role in periodontal
pathogenesis12), as glucose-mediated advanced
glycation end products can increase the pro-
duction of proinflammatory cytokines and
mediators, which could contribute to peri-
odontal destruction22).
Periodontal disease may also affect blood
glucose levels in diabetic patients through
insulin resistance5). There has been a recent
focus on understanding the negative influ-
ences of oral chronic inflammation on sys-
temic health10,12).
Nifedipine, a dihydropyridine, is a calcium
channel blocker that has been widely pre-
scribed for various cardiovascular diseases,
particularly hypertension3). The most promi-
nent side effect of nifedipine therapy in
oral tissue is gingival overgrowth9), which is
characterized by an accumulation of extracel-
lular matrix in the gingival connective tissue
and epithelial hyperplasia with elongated,
branched rete pegs penetrating deep into
the connective tissue, with various degrees
of chronic inflammatory infiltration1).
In this case report, we describe the clinical
course over a 14-year follow-up in a 47-year-
old type 2 diabetes patient with severe chronic
periodontitis and nifedipine-associated gingi-
val overgrowth. His diabetes and periodontal
condition were evaluated longitudinally over
14 years.
Case
In September 1993, a 47-year-old man was
referred to the Clinic of Conservative Den-
tistry at the Chiba Hospital of Tokyo Dental
College with the chief complaint of gingival
swelling around the upper and lower anterior
teeth. The patient provided informed consent
before entry into this study.
1. Clinical Oral Examination
Overgrown gingiva was observed at all
the intradental gingival papillae in most of
the teeth and was marked in the upper and
lower anterior teeth. The consistency was
generally fibrotic, with an erythematic appear-
ance (Fig. 1). The patient stated that he first
noticed the gingival enlargement approxi-
mately 6 months prior to the initial visit
and reported rapid growth during this period
of time. The maxillary and mandibular ante-
rior teeth were flared out, and the patient had
lost several teeth and had no prosthodontic
treatment. The plaque control record (PCR)
(O’Leary et al.13)) score was 85%. A probing
pocket depth of ≥4 mm and bleeding on
probing (BOP) were observed in 94 and 90%
of sites examined, respectively (Table 1).
Teeth with severe bone loss showed mobility
ranging from 2 to 3 (Lindhe and Nyman7)).
Radiographic examination revealed moder-
ate horizontal alveolar bone loss, calculus,
and localized severe vertical alveolar bone loss
(#16, 17, 31, 37, 41, 42, 44, 45, 46) (Fig. 2).
2. Systemic condition
The patient’s weight was 80.2 kg and height
173.6 cm. Hypertension had been diagnosed
5 years prior to the patient’s initial visit
and medication (calcium antagonist; nife-
dipine 40 mg/day) had been prescribed and
taken for 18 months. Blood pressure was
135/85 mmHg. Two years prior to visiting
our hospital, type 2 diabetes had also been
diagnosed in this patient, who had been
taking an oral antidiabetic agent (metformin,
500 mg/day) for 18 months. Further medical
examination revealed uncontrolled type 2
diabetes. The hemoglobin A1c (HbA1c) value
was 8.5%. No diabetic complications or his-
tory of smoking were found.
3. Diagnosis
Based on the clinical findings, a diagnosis
 Periodontitis with Gingival Overgrowth and DM 93

Fig.  1  Oral photographs at baseline

Moderate gingival inflammation and overgrowth were observed. Hard and fibrotic swelling was noted in
upper and lower anterior gingiva, which may be attributable to effect of calcium antagonist (nifedipine).

Table  1  Clinical findings at baseline, after initial therapy and SPT

Re-evaluation
Baseline SPT (0 y) SPT (11y)
(After initial therapy)
No. of teeth 27 27 20 20
Mean probing depth (%)*
  <4 mm 6 34 98 100
  ≥4 mm, <6 mm 18 27 2 0
  ≥6 mm 76 39 0 0
Bleeding on probing (%) 90 23 3 2
HbAlc (%) 8.5 6.5 6.3 6.3
*Percent of sites with indicated probing depth
Baseline, first visit (September 1993)
Re-evaluation (after initial therapy) (September 1994)
SPT (0 y); start of supportive periodontal therapy phase ( January 1996)
SPT (11 y); ( January 2007)

of severe generalized chronic periodontitis 4. Treatment

with gingival overgrowth associated with nife-
dipine was made. It was also considered
possible that high blood glucose levels result-
ing from uncontrolled type 2 diabetes may
have exacerbated periodontal inflammation.
A collaborative dental-medical treatment
plan was devised for diabetes-associated severe
chronic periodontitis and nifedipine-induced
gingival overgrowth.
First of all, a physician was consulted regard-
94
Fig.  2  Dental radiographs at baseline
Generalized horizontal alveolar bone loss was observed. Advanced bone loss was observed at lower incisor,
molar and upper right molar.
ing the patient’s uncontrolled type 2 diabetes
and changes in dietary habits combined
with an oral antidiabetic agent (metformin,
750 mg/day) were prescribed. The goal of
dental treatment was to reduce periodontal
infection and bacteremia, which may have
affected the diabetic condition and gingi-
val overgrowth, and to restore masticatory
function, which may have affected dietary
care for diabetes. Moreover, a physician was
consulted regarding gingival overgrowth,
which was a side effect of nifedipine, and
whether it was possible change the medi­
cation. The patient had been taking nife-
dipine for 18 months, but now the medication
was changed to an angiotensin-converting
enzyme inhibitor (enalapril maleate, 10 mg/
day). Thus, treatment was restricted to
periodontal therapy that mainly focused
on plaque control until improvement of
glycemic control. Treatment consisted of
meticulous oral hygiene instruction and
supragingival scaling. Pocket irrigation with
0.2% ethacridine lactate (acrinol®) was per-
formed following the above procedures.
During the first 2 months on the new
medication, gingival overgrowth gradually
subsided. Tooth-brushing instruction resulted
in an improvement in oral hygiene (PCR
19%). In March 1994, subgingival scaling and
Shibukawa Y et al.
root planing were performed using Gracey
curettes and an ultrasonic scaler as the base-
line HbA1c (8.5%) had decreased to 6.9%.
Although prognosis for teeth #16, 17, 27,
37, 44, 45, and 46 was judged to be hopeless,
they were retained during initial therapy until
HbA1c dropped to 6.5% or less16).
In June 1994, the HbA1c decreased to 6.5%
and these teeth were extracted with premedi-
cation using cephem antibiotics. A temporary
prosthesis was applied.
In September 1994, re-evaluation was per-
formed. The initial therapy resulted in an
improvement in clinical parameters. Gingival
inflammation, in particular, showed a sig-
nificant reduction (BOP, 23%, Fig. 3A, 3B,
Table 1). Periodontal surgery (flap opera-
tion) was carried out between October 1994
and March 1995 in areas (teeth #11–15,
21–26, 31–-34, 38, 41–43, 48) where probing
depth was ≥5 mm and osseous defects were
present. The flap operation was performed
with premedication using cephem antibiotics.
To prevent postoperative infection, cephem
antibiotics (3 days) were prescribed and
irrigation with 0.2% ethacridine lactate
(acrinol®) performed frequently at the wound
surface. Postoperative healing was unevent-
ful. Re-evaluation after 3 months healing
showed a marked improvement in clinical
 Periodontitis with Gingival Overgrowth and DM 95

Fig.  3 Oral photographs at baseline (A), re-evaluation at after initial therapy (B), re-evaluation
at after periodontal surgery (C) and SPT (D)
Gingival inflammation and swelling were significantly reduced after initial therapy and subsequent
periodontal surgery.

parameters (Fig. 3C). A reduction in prob-
ing depth was obtained at all the surgically
treated sites. A removable partial denture was
applied to the right-side maxillary posterior
area (#16, 17) and bilateral mandibular
posterior area (#35–37, 44–47, Fig. 3D). The
upper and lower anterior teeth were fixed
and restored by using a hard resin facing
crown (#11, 12, 21, and 22, and #31, 32, 33,
41, 42 and 43, Fig. 3D).
5. Supportive periodontal therapy
After surgery and prosthodontic treatment,
the patient was placed on a supportive peri-
odontal therapy (SPT) program, consisting
mainly of oral hygiene instruction and profes-
sional plaque control once a month. Changes
in periodontal condition and HbA1c are
shown in Figs. 4, 5, 6. Assessment was per-
formed based on the method of Shimoe
et al.17). Gingival inflammation was resolved
(Fig. 4), and all sites had probing pocket
depths ≤3 mm (Table 1). Radiographic
examination clearly revealed lamina dura in
the alveolar bone (Fig. 5). The patient was
motivated to maintain daily plaque control
(average PCR, 19%), and his systemic and
oral condition remained good for 11 years
following commencement of SPT (Fig. 6).
The baseline HbA1c value (8.5%) decreased
to 6.3% after periodontal surgery. The HbA1c
value ranged from 6.3 to 6.5% during SPT
(Fig. 6). The patient remained on the same
medication for his systemic condition for 14
years from baseline. Blood pressure remained
within the normal range during the observa-
tion period.
Discussion
This case report demonstrated the success-
ful recovery and maintenance of healthy
periodontal conditions over a 14-year period
96 Shibukawa Y et al.

Fig.  4  Oral photographs during supportive periodontal therapy

Gingival redness and swelling had disappeared. A prosthetic denture was applied
to replace upper and lower teeth.

Fig.  5  Dental radiographs during supportive periodontal therapy

Crestal lamina dura was clearly visible at interproximal sites in the alveolar bone.

following a diagnosis of nifedipine-induced
gingival overgrowth in a patient with diabetes
and advanced chronic periodontitis. More-
over, the patient’s HbA1c level improved from
8.5 to 6.3% after periodontal treatment, sub-
sequently remaining at a good level during
SPT over a 10-year period. The present find-
ings agree with data previously reported in
treatment and maintenance studies of short
duration20). Controlled studies have shown
that the response of diabetics to non-surgical
and surgical periodontal therapy is similar
 Periodontitis with Gingival Overgrowth and DM 97

Fig.  6  Improvement in clinical data during periodontal treatment

Horizontal axis represents time course from baseline and vertical axis represents clinical data.
Circles: percent sites with deep periodontal pockets (≥4 mm), squares: BOP rate, triangles: HbA1c level.
A: At baseline (BL) in September 1993. B: Re-evaluation (after initial therapy) in September 1994. C: Re-evaluation
(after periodontal surgery) in June 1995. D: Start of supportive periodontal therapy phase ( January 1996). E: 11
years from start of SPT ( January 2007).

to that of non-diabetics23). On the other hand, odontal therapy.

it was reported that poorly controlled dia-
betics respond less successfully to periodon-
tal therapy relative to well-controlled and
non-diabetics19). Tervonen and Karjalainen19)
reported that although poorly controlled
diabetics responded to nonsurgical therapy
similarly to controls in the short term (4
weeks), in the absence of maintenance ther-
apy, more rapid recurrence of periodontal
pockets and subgingival calculus was found.
The data from the present study, however,
seem to indicate that careful control of dis-
ease in patients with diabetes will result in a
similar low frequency of recurrent periodon-
titis to that seen in non-diabetic patients if
they receive treatment for periodontal disease
and follow a careful plaque control program.
These findings suggest that information on
the level of glycemic control in diabetics
is useful in determining periodontal progno-
sis and the need for periodontal therapy on
an individual basis. Therefore, assessment of
metabolic status is important in determining
the prognosis and recall interval for peri-
In the present case, the patient’s HbA1c
level showed a marked improvement from
8.5 to 6.3% after periodontal treatment. Much
evidence indicates a bidirectional relationship
between diabetes and periodontal disease10,12).
It is possible that periodontitis plays some
role in the development of insulin resistance2).
Iwamoto et al.5) reported that antimicrobial
periodontal therapy was effective in improv-
ing metabolic control in diabetics, possibly
through reduced serum TNF-α and improved
insulin resistance. The authors also suggested
that increased TNF-α caused by chronic inflam-
mation may have an additive effect on insulin
resistance in type 2 diabetes patients. This
indicates that controlling periodontal infec-
tion would play an important role in the
overall management of this disease. However,
to date, relatively few intervention studies
have examined the effect of periodontal
therapy on the metabolic status of diabetes.
Therefore, there is no consistent agreement
as to the beneficial effects of periodontal
treatment on the metabolic control of patients
98 Shibukawa Y et al.
with diabetes. In the present case, too, it
is unclear as to the precise reason for the
observed improvement in the patient’s dia-
betes, as periodontal and diabetic treatment
were performed simultaneously. The improve-
ment in HbA1c level may have been due to
the improvement in insulin resistance follow-
ing reduction of circulating levels of several
proinflammatory cytokines, which is probably
associated with the effect of periodontal treat-
ment10,12). Moreover, periodontal treatment
including restoration of masticatory function
appears to affect dietary care for diabetes.
In this case, the withdrawal of medication
and removal of plaque provided relative reso-
lution of gingival tissues. Earlier reports on
treatment for nifedipine-induced gingival
overgrowth involved reduction or elimina-
tion of the drug or surgical excision9,15). It was
been reported that the presence of dental
plaque and inflammation might be a signifi-
cant risk factor for gingival overgrowth4). We
emphasized plaque control as the first step in
our treatment program and during SPT. A
recent study on patients with type 2 diabetes
showed that nifedipine intake was associ-
ated with a significantly deeper probing depth
and greater extent of sites with increased
probing depth6). It remains unknown as to
whether hyperglycemic status and its effects
on gingival tissue play a synergistic role in
drug-influenced gingival enlargement. This
study demonstrated that withdrawal of medi-
cation and control of diabetes resulted in
remarkable improvements. Further controlled
investigations should be carried out to further
clarify this possible complex interaction.
In summary, this study demonstrated that
periodontal treatment, withdrawal of medi­
cation and control of diabetes can result in
remarkable improvements in type 2 diabetes
patients with chronic periodontitis and nife-
dipine-induced gingival overgrowth. These
results suggest that comprehensive periodon-
tal treatment in combination with treatment
for diabetes mellitus can exert a positive influ-
ence on blood glucose levels and periodontal
condition in diabetic patients.
Acknowledgements
We would like to thank Associate Professor
Jeremy Williams, Tokyo Dental College, for
his assistance with the preparation of this
manuscript.
References
1) Barak S, Engelberg IS, Hiss J (1987) Gingival
hyperplasia caused by nifedipine. Histopatho-
logic findings. J Periodontol 58:639–642.
2) Benguigui C, Bongard V, Ruidavets JB,
Chamontin B, Sixou M, Ferriéres J, Amar J
(2010) Metabolic syndrome, insulin resis-
tance, and periodontitis: a cross-sectional
study in a middle-aged French population.
J Clin Periodontol 37:601–608.
3) Ferlinz J (1986) Nifedipine in myocardial
ischemia, systemic hypertension, and other
cardiovascular disorders. Ann Intern Med
105:714–729.
4) Hancock RH, Swan RH (1992) Nifedipine-
induced gingival overgrowth. Report of a case
treated by controlling plaque. J Clin Periodon-
tol 19:12–14.
5) Iwamoto Y, Nishimura F, Nakagawa M, Sugi­
moto H, Shikata K, Makino H, Fukuda T, Tsuji
T, Iwamoto M, Murayama Y (2001) The effect
of antimicrobial periodontal treatment on
circulating tumor necrosis factor-alpha and
glycated hemoglobin level in patients with
type 2 diabetes. J Periodontol 72:774–778.
6) Li X, Luan Q, Wang X, Sha Y, He L, Cao C,
Jin L (2008) Nifedipine intake increases the
risk for periodontal destruction in subjects
with type 2 diabetes mellitus. J Periodontol
79:2054–2059.
7) Lindhe J, Nyman S (1987) Clinical trials in
periodontal therapy. J Periodontal Res 22:
217–221.
8) Löe H (1993) Periodontal disease. The sixth
complication of diabetes mellitus. Diabetes
Care 16:329–334.
9) Lucas RM, Howell LP, Wall BA (1985)
Nifedipine-induced gingival hyperplasia. A
histochemical and ultrastructural study. J
Periodontol 56:211–215.
10) Mealey BL, Oates TW (2006) Diabetes melli-
tus and periodontal diseases. J Periodontol
77:1289–1303.
11) Nelson RG, Shlossman M, Budding LM,
Pettitt DJ, Saad MF, Genco RJ, Knowler WC
(1990) Periodontal disease and NIDDM in
Pima Indians. Diabetes Care 13:836–840.
 Periodontitis with Gingival Overgrowth and DM
12) Nishimura F, Iwamoto Y, Soga Y (2007) The
periodontal host response with diabetes.
Periodontol 2000 43:245–253.
13) O’Leary TJ, Drake RB, Naylor JE (1972) The
plaque control record. J Periodontol 43:38.
14) Pickup JC (2004) Inflammation and activated
innate immunity in the pathogenesis of type
2 diabetes. Diabetes Care 27:813–823.
15) Pilloni A, Camargo PM, Carere M, Carranza
FA Jr (1998) Surgical treatment of cyclo-
sporine A- and nifedipine-induced gingival
enlargement: gingivectomy versus periodontal
flap. J Periodontol 69:791–797.
16) Shichiri M, Kishikawa H, Ohkubo Y, Wake N
(2000) Long-term results of the Kumamoto
Study on optimal diabetes control in type 2
diabetic patients. Diabetes Care 23:21–29.
17) Shimoe M, Yamamoto T, Iwamoto Y, Shiomi
N, Maeda H, Nishimura F, Takashiba S (2011)
Chronic periodontitis with multiple risk factor
syndrome: a case report. J Int Acad Peri­
odontol 13:40–47.
18) Taylor GW, Burt BA, Becker MP, Genco RJ,
Shlossman M (1998) Glycemic control and
alveolar bone loss progression in type 2 dia­
betes. Ann Periodontol 3:30–39.
19) Tervonen T, Karjalainen K (1997) Periodontal
disease related to diabetic status. A pilot study
of the response to periodontal therapy in type
1 diabetes. J Clin Periodontol 24:505–510.
20) Tervonen T, Knuuttila M, Pohjamo L, Nurk-
kala H (1991) Immediate response to non­
surgical periodontal treatment in subjects
99
with diabetes mellitus. J Clin Periodontol 18:
65–68.
21) Tsai C, Hayes C, Taylor GW (2002) Glycemic
control of type 2 diabetes and severe peri-
odontal disease in the US adult population.
Community Dent Oral Epidemiol 30:182–
192.
22) Vlassara H, Brownlee M, Manogue KR,
Dinarello CA, Pasagian A (1988) Cachectin/
TNF and IL-1 induced by glucose-modified
proteins: role in normal tissue remodeling.
Science 240:1546–1548.
23) Westfelt E, Rylander H, Blohmé G, Jonasson
P, Lindhe J (1996) The effect of periodontal
therapy in diabetics. Results after 5 years.
J Clin Periodontol 23:92–100.
24) Zambon JJ, Reynolds H, Fisher JG, Shlossman
M, Dunford R, Genco RJ (1988) Microbiologi-
cal and immunological studies of adult perio-
dontitis in patients with noninsulin-dependent
diabetes mellitus. J Periodontol 59:23–31.
Reprint requests to:
Dr. Yoshihiro Shibukawa
Division of Conservative Dentistry,
Department of Clinical Oral
Health Science,
Tokyo Dental College,
2-9-18 Misaki-cho, Chiyoda-ku,
Tokyo 101-0061, Japan
E-mail: sibukawa@tdc.ac.jp