CE Sponsored by Colgate in
Partnership with the American
Academy of Periodontology
Diabetes and Periodontal Diseases
ZLIKOVEC/ISTOCK/GETTY IMAGES PLUS
Inflammation is the link that binds these two common
By Marcelo Freire, DDS, PhD, DMSc
After reading this course, the participant should be able to:
1. Discuss the diabetes epidemic.
2. Identify the bidirectional link between diabetes and periodontal diseases.
3. Explain the role that inflammation plays in diabetes and periodontal diseases.
In April 2013,
evidence-based information and recommendations for day-to-day patient
management were disseminated in a joint publication of the American Academy of
Periodontology (AAP) and the European Federation of Periodontology. The
Colgate-Palmolive Company is committed to ensuring that practicing dental
professionals have access to the latest educational resources. Hence, we are
delighted to have provided an unrestricted educational grant to support the
article "Diabetes and Periodontal Diseases"—the first in a series created in
collaboration with the AAP. This article provides a useful review of the
literature, highlighting the mechanisms behind the bidirectional relationships
between diabetes mellitus and periodontal diseases. Dental professionals have a
unique opportunity to improve patient outcomes with periodontal disease
management and patient education. I hope you find this article to be a valuable
resource to help manage the patients with diabetes in your practice.
—Matilde Hernandez,DDS, MS, MBA
Scientific Affairs Manager Professional Oral Care
Colgate Oral Pharmaceuticals
From the American Academy of Periodontology
The link between
diabetes and periodontal diseases has been the subject of study for many years,
prompting the dental and medical communities to work together in the care of
both inflammatory conditions. In 2012, the American Academy of Periodontology
(AAP)―in collaboration with
the European Federation of Periodontology—released a consensus report on
periodontitis and systemic diseases, finding that periodontal health can impact
diabetes management and vice versa. The relationship between oral health and
overall health grants dental professionals (particularly dental hygienists who
perform preventive and nonsurgical care) a responsibility to educate all
patients about the bidirectional relationship of diabetes and periodontal
diseases and what it means for their risk and treatment. In this article,
educator and AAP periodontist Marcelo Freire, DDS, PhD, DMSc, sheds light on
the sweeping worldwide incidence of diabetes and its connection to periodontal
disease, which affects one of every two United States adults older than 30.
The AAP is proud to
work with Dimensions of Dental Hygiene and Colgate-Palmolive to bring
you insights that will support your patients' oral and overall health.
—Terrence J. Griffin, DMD
President, American Academy of
inflammatory diseases, such as diabetes mellitus and periodontal diseases,
significantly impact public health. Both conditions influence quality of life,
lifespan, and health care costs across the
globe. The prevalence of type 2 diabetes and periodontal diseases has increased
worldwide.1 According to the International Diabetes Federation,
about 415 million adults have diabetes.2 Unfortunately, the current
incidence is estimated to increase to 640 million by 2040.2 The
prevalence of periodontal diseases is also high, with nearly half of all
Americans exhibiting periodontitis.3
In order to
adequately treat diabetes and periodontal diseases, clinicians must remain up
to date on advancements in basic biology and translational science that guide
patient management. Chronic inflammation is the known mechanism that links
periodontal diseases and diabetes. The long-term consequences of these
associated pathologies include tissue damage, increased disease severity, and
extensive treatment. The biological mechanisms behind disease initiation, establishment,
and progression are regulated by immune and metabolic interactions.
Understanding these complex molecular communications is important for the
multidisciplinary team in order to provide optimal treatment options.
DIABETES—A GLOBAL EPIDEMIC
Diabetes is a chronic metabolic condition
characterized by hyperglycemia, with defective production of insulin or
defective insulin actions. As an essential hormone produced in the pancreas,
insulin is required to conduct major biological functions including glucose
transport and energy. There are three main types of diabetes: type 1, type 2,
and gestational diabetes. Less common types of diabetes are monogenic diabetes,
which arises from gene mutations, such as neonatal diabetes mellitus, and
secondary diabetes, which is a comorbidity of other diseases, such as Cushing
disease.4 Changes in diet and lifestyle and population growth have
likely influenced the increase in the prevalence of diabetes worldwide.5
first time in history, it is estimated that more than half a million children
age 14 and younger are living with type 1 diabetes.6 Today, 415
million adults age 20 to 79 worldwide have diabetes, including 193 million
individuals who remain undiagnosed.1 A further 318 million adults
are estimated to have prediabetes, which puts them at high risk of developing
diabetes is caused by an autoimmune reaction, in which the body's defense
system attacks the insulin-producing beta cells in the pancreas. People
diagnosed with type 1 diabetes require daily insulin. Type 2 diabetes is the
most common form of diabetes. While the pancreas is able to produce insulin,
the body is not able to process it (insulin resistance). Table 1 highlights key
comparisons for type 1 and type 2 diabetes.
patients diagnosed with type 2 diabetes do not require daily insulin treatment
to survive. The cornerstone of type 2 diabetes treatment is the adoption of a
healthy diet, increased physical activity, and maintenance of a normal body
weight. Patients with both types of diabetes need to work closely with their
health care team to receive diabetes education, regular checkups, and ongoing
support to manage their health.7 Poorly managed diabetes leads to
serious complications and early death.
consequences of high blood sugar levels (hyperglycemia) are immediate and can
be lethal. Frequent urination, excessive thirst, weight loss, and blurred
vision are common symptoms of both types of diabetes. In type 1, the onset of
clinical manifestations is more sudden, while individuals with type 2 may
remain in a prediabetic state for years. Many people with type 2 diabetes
remain unaware of their condition because the symptoms are usually less
noticeable than in type 1 diabetes.8 During this time, however, the
body is being damaged by excess blood glucose. As a result, many people already
have evidence of complications when they are diagnosed with type 2 diabetes.
diagnosis is mostly based on glucose and insulin levels. The glycated
hemoglobin test (HbA1c) measures the blood glucose for 2 months to 3 months,
whereas the fasting plasma glucose (FPG) requires 8 hours of fasting. The oral
glucose tolerance test checks glucose before and 2 hours after ingestion of a
glucose-enriched drink. Table 2 compares the diagnoses threshold for normal,
prediabetes, and diabetes.9 Because many individuals stay in a
prediabetes state for years before diagnosis, the interdisciplinary
team—including oral health professionals—is charged with monitoring glucose
values over the long term.
with diabetes are at increased risk for a number of disabling and
life-threatening health problems. Consistently high blood glucose levels can
lead to serious diseases affecting the heart and blood vessels, eyes,
periodontal tissues, kidneys, and nerves. People with uncontrolled diabetes are
also at increased risk of infection in general. In almost all high-income
countries, diabetes is a leading cause of cardiovascular diseases, blindness,
kidney failure, periodontal diseases, and lower-limb amputations.10
The growth in the prevalence of type 2 diabetes in low- and middle- income
countries means that without effective strategies to better manage diabetes, it
is likely that the rates of these complications will significantly increase.
rates for heart attack were 1.8 times higher among adults with diabetes than
among adults without diabetes.11 Hyperglycemic crisis was the cause
of 175,000 emergency department visits for people of all ages in 2011.12 Diabetes
is the leading cause of retinopathy and kidney failure, in addition to
increasing the chance of stroke by 1.5 times.13 Individuals with
diabetes are more likely to experience nerve damage and poor circulation to the
feet due to damaged blood vessels. These problems increase the risk of
ulceration, infection, and amputation. People with diabetes face a risk of
amputation that may be more than 25 times greater than in those without
diabetes.14 In fact, cardiovascular diseases are the most common
cause of death and disability among people with diabetes.15
The inflammation triggered by diabetes
directly impacts periodontal tissues and other organs. The increase of systemic
inflammation leads to insulin resistance and reduced pancreatic B-cell function
and apoptosis (programmed cell death).16 Periodontitis also
contributes to systemic inflammation, and its severity and prognosis is
influenced by diabetes-originated inflammation. A potential relationship
between inflammatory pathways and metabolic diseases—such as type 2 diabetes
and periodontal diseases—remains under scientific investigation.17,18
evidence shows that 47% of adults older than 30 were found to have
periodontitis.3 The prevalence of periodontitis was higher in men,
Mexican-Americans, and individuals of low socioeconomic status.3 In
a more detailed analysis of National Health and Nutrition Examination Survey
(NHANES) data, 60% of those with diabetes were found to have moderate to severe
periodontitis.19 A World Health Organization survey showed a
positive association between periodontal diseases and diabetes, depending on
the socioeconomic status of the country.20 It is now clear that the
majority of patients with type 2 diabetes present with some form of periodontal
diseases.21,22 Increased probing depths and attachment loss were
observed in individuals with type 2 diabetes.23 The prevalence of
periodontitis is also increased in patients with prediabetes.19
diseases, including gingivitis and periodontitis, are inflammatory diseases initiated
by microbial biofilms. The etiology of periodontitis is multifactorial, and a
number of behavioral, environmental, microbial, systemic, and genetic risk
factors influence the host-susceptibility and disease progression. The local
acute periodontal inflammatory response is initiated by the challenge posed by
microbial biofilm. The dysbiosis (microbial imbalance) of immunome and
microbiome is characterized by increased inflammation and elevated expression
of pathologic genes/microorganisms, which lead to chronic innate immune
response, followed by an acquired immune response that results in tissue
destruction or periodontitis.24
with diabetes are at two times to three times greater risk for developing
chronic periodontitis than those without diabetes.25 Those with
chronically elevated HbA1c have a significantly higher prevalence of
periodontitis and more tooth loss than those without elevated HbA1c levels.19
While high glucose levels affect periodontal status, acute and chronic
infections can also influence glycemic control. Effective treatment of
periodontitis can modify glycemic control, as suggested by recent evidence.22,
26–28 As such, nonsurgical periodontal therapy, including scaling and
root planing, is important to the diabetes-periodontal disease treatment plan.
Maintaining an effective self-care program, including twice-daily brushing with
an antimicrobial toothpaste and rinsing with an antimicrobial mouthrinse, is
key to controlling the pathogenic bacterial load common among patients with
diabetes and periodontal diseases.29,30
additional studies are published, the impact of periodontal therapy on diabetic
control becomes more clear. Recent meta-analyses included studies with at least
3 months of follow-up after periodontal therapy measuring type 2 diabetes
outcomes.31 Nine studies found a significant decrease of HbA1c (−0.36%
HbA1c; 95% CI −0.66, −0.19) when periodontal maintenance is effective.
Reductions of HbA1c have been the standard treatment outcome for diabetes and
the development of new treatment modalities, because reducing HbA1c has been
shown to delay the onset of diabetic complications. However, there is currently
no evidence of a "threshold" for the benefit of reducing HbA1c. To reduce HbA1c
levels, metformin is the preferred oral medication in the treatment of patients
with type 2 diabetes.32
50% of all patients with type 2 diabetes are treated with one or more drugs to
achieve metabolic control.33 When considering the effects of
periodontal actions on glycemic controls, the treatment or first drug of choice
must be considered an additive. Thus the individualized actions of one
treatment can be studied in combination with the other. In order, to weigh the
clinical relevance of any HbA1c reduction due to periodontal treatment, its
impact must be compared with a second drug for example, in addition to
metformin. Several drugs have been used as add-on treatments to metformin. The
additional reduction of HbA1c over metformin alone was 0.85%, 0.61%, and 0.42%
for sulphonylureas, α-glucosidase inhibitors, and
thiazolidinediones, respectively.34,35 Thus, if periodontal therapy
can improve HbA1c levels by 0.4% to 0.5%, then its effect may be comparable to
additional pharmacotherapies and it may find a place in the management
protocols for patients with diabetes.
randomized clinical trials should include patients who are using different
diabetic treatment approaches to determine whether periodontal treatment works
equally well in all patients with diabetes, irrespective of drugs used.
FIGURE 1. Chronic inflammation is the common link between a variety of diseases.
YURI_ARCURS/ISTOCK/GETTY IMAGES PLUS
Inflammation is a protective biological
response against disease (Figure 1). Patients with diabetes need to understand
that part of their treatment goal is to resolve inflammation. Historically,
tissue response to injury and infection was first recorded by the ancient
Egyptian and Greek cultures. Cornelius Celsus' studies documented inflammation signs
in humans. Four cardinal signs of inflammation were identified: "rubor et tumor
cum calore et dolore" (redness and swelling with heat and pain). Loss of tissue
function (function laesa) was added as the fifth sign by Rudolph Virchow, a
19th century German pathologist. More recently, advanced cellular and molecular
mechanisms governing the fate of inflammation (resolution vs chronicity) have
is an active biological response that aims to maintain health and tissue integrity.
It turns on when the host tissue is challenged by pathogens, foreign bodies, or
injury. The initial process is characterized by vascular dilation, enhanced
permeability of capillaries, and increased blood flow in addition to leukocyte
recruitment.36 Polymorphonuclear neutrophils (PMN) are the first
cells to accumulate in the inflamed gingival tissue. These cells serve as the
first line of defense of the innate immune system due to their phagocytosis and
microbicidal functions. Next, mononuclear cells, monocytes, and macrophages
enter the inflammatory site and clear cellular debris and apoptotic PMN by
phagocytosis (consumption of bacteria by phagocytes and amoeboid protozoans).
inflammation is protective, chronic activation is detrimental to tissue
function. Failure to remove noxious materials via phagocytosis and lymphatic
drainage characterizes the initiation of pathological lesion and disease
establishment. The incomplete elimination of leukocytes from a lesion is
observed in susceptible individuals, such as those with periodontal abscesses
and uncontrolled diabetes. A new class of resolution lipid mediators can
activate endogenous cells to return to homeostasis (resolvins, lipoxins,
protectins, and maresins).18 Accordingly, loss of resolution and
failure to return tissue to homeostasis results in neutrophil-mediated
destruction and chronic inflammation, which is a major cause of human
In summary, unresolved inflammation is a
hallmark of various human diseases, including diabetes and periodontitis.
Diabetes directly affects periodontal health and disease. Continuous release of
cell/bacterial debris and toxins results in local tissue damage, prolonged
inflammatory response, and loss of resolution results in the chronic lesion.
Emerging evidence suggests oral infections, especially periodontal diseases,
are risk factors for initiation and progression of diabetes. There is evidence
that periodontal treatment can reduce glycated hemoglobin when periodontal
disease is present. A multidisciplinary health care team—including oral health
professionals—can effectively address the biological mechanisms behind disease
initiation and progression.
The author is supported by National
Institute of Dental and Craniofacial Research grant K99/R00DE 0235804. The
author would like to thank Thomas E. Van Dyke, DDS, PhD; Corneliu Sima, DMD,
DSc, MSc; Erin Breen, DDS; Alaa Ahmed, DMD; and Ana Metzger, MD, PhD.
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From Dimensions of Dental Hygiene. February 2017;15(2):37-42.