ples were drawn from the patient to assess glucose and CRP with regard to risk for CVD was described in depth HbA1c levels as well as systemic levels of pro-inflamma- in a previous issue of Grand Rounds in Oral-Systemic tory cytokines. The baseline and post therapy ( 4 months) Medicine. ⁴⁶ High sensitivity C-reactive protein (hsCRP) blood chemistry test results are listed in Table 1. is one of the best indicators of risk for CVD, and along with cholesterol levels, provides the most accurate risk

Clearly, with serum glucose levels at 288 mg/dL and assessmentforfuturecardiovascularevents.⁴⁷Itisimpor-

HbA1c at 9.1% at baseline, the patient mistakenly believed tant to keep levels of hsCRP low in diabetics and patients that his diabetes was well controlled. When contacted, the with metabolic syndrome since these are patient popu-patient’s physician reported the patient did not visit the lations known to be at greater risk for death from CVD. physician’s office regularly for medical checkups and al- The Minnesota Heart Survey has monitored the trends in though he was referred back to his physician for medical coronary heart disease morbidity since 1970.⁴⁸ The odds evaluation the patient did not comply with the referral. El- ratio for in-hospital death after a myocardial infarction evated serum levels (TNF-α and IL- 6) are associated with (MI) for individuals with diabetes was 1. 5 (p<.01) times insulin resistance. ²⁸ To that end, it is reasonable to surmise that of persons without diabetes, after controlling for age, that the elevated levels of cytokines at baseline (Table 1) sex, and year of MI occurrence. ⁴⁸ Among the MI survi-contributed to this patient’s lack of metabolic control. vors from this study, the risk of death after 6 years of follow-up was 40% (p<.01) higher in patients with diabetes

This patient became an extremely compliant dental pa- compared to those without diabetes and was more pro-
tient, never missing an appointment with relatively good nounced in women than men. In a cross-sectional study⁴⁹
oral hygiene. Treatment consisted of extraction of hope- of 3,873 subjects from the National Health and Nutrition
less teeth, full mouth scaling and root planing and host Examination Survey (NHANES) the reported odds ratio
modulatory therapy with sub-antimicrobial doxycycline for CVD was 1.99 (95% CI, 1. 10-3.59) in subjects with
hyclate (Periostat). This treatment protocol resulted in neither metabolic syndrome nor diabetes with high CRP
a decline in the systemic levels of the pro-inflammatory levels. For those subjects with metabolic syndrome and
mediators (IL-1β, IL- 6 and TNF-α) without a concurrent intermediate CRP levels, the odds ratio jumped to 2.67
drop in the blood glucose or HbA1c levels after 4 months ( 1. 30-5. 48). Subjects with metabolic syndrome and high
of initial periodontal therapy (Table 1). Significant clinical CRP had a similar odds ratio for CVD of 3. 33 ( 1.80-6.16)
improvements in probing depths encouraged us to move compared to those with diabetes and a low CRP level at
to the next stage of therapy to further reduce probing 3. 21 ( 1. 27-8.09). Finally, the data demonstrate that the
depths which was achieved with the use of locally applied likelihood of CVD was highest in those with diabetes and
antimicrobials at localized sites, surgical intervention and either intermediate or high CRP levels with reported odds
adjunctive use of Periostat. When there was evidence of ratios for CVD of 6.01 ( 2.54-14.20) and 7.73 ( 3.99-14.95),
improved glycemic control, regenerative surgical proce- respectively.
dures were performed at certain sites. One year later the
periodontal therapy was successfully completed and an The Insulin Resistance Atherosclerosis Study (IRAS) pro-
HbA1c level of 7.5% was achieved. vided evidence demonstrating that
Both the physician and the patient inflammation is associated with insu-
were impressed by the final clinical lin sensitivity even in patients without
and systemic outcome of this case. diabetes. ⁵⁰ The study found a strong
independent association between the
levels of CRP and insulin sensitivity.
Higher levels of CRP are associated
with a greater degree of insulin re-
sistance. Serum concentrations of
CRP and other markers of inflam-
mation were significantly related to
the development of type 2 diabetes in
1,047 non-diabetic subjects followed
for 5 years in the IRAS. ⁵¹ The IRAS
investigators concluded that chronic

Periodontitis, C-reactive Protein,
and Diabetes
The persistent chronic inflammation
associated with untreated periodon-
titis ultimately results in elevations
of the systemic inflammatory mark-
er C-reactive protein (CRP). CRP is
produced by the liver in response
to bacterial challenge and chronic
inflammation. ^41-45 The relevance of

Figure 5

Case 4. Clinical presentation of severe periodontal disease of a 34-year-old, type 1 diabetic female.