Diabetes Care 1 Anna Norhammar,1,2 Barbro Kjellstrom,¨ 1 Undetected Dysglycemia an Natalie Habib,1 Anders Gustafsson,3 Bjorn¨ Klinge,3,4 Ake˚ Nygren,5 Per Nasman,¨ 6 Important Risk Factor for Two Elisabet Svenungsson,1 and Lars Ryden´ 1 Common Diseases Myocardial Infarction and Periodontitis: A Report From the PAROKRANK Study https://doi.org/10.2337/dc19-0018 OBJECTIVE Information on the relationship among dysglycemia (prediabetes or diabetes), myocardial infarction (MI), and periodontitis (PD) is limited. This study tests the hypothesis that undetected dysglycemia is associated with both conditions. RESEARCH DESIGN AND METHODS The PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study included 805 patients with a first MI and 805 matched control subjects. All participants without diabetes (91%) were examined with an oral glucose tolerance CARDIOVASCULAR AND METABOLIC RISK test. Abnormal glucose tolerance ([AGT] = impaired glucose tolerance or diabetes) was categorized according to the World Health Organization). Periodontal status 1Department of Medicine K2, Karolinska Institu- was categorized from dental X-rays as healthy (‡80% remaining alveolar bone tet, Stockholm, Sweden height), moderate (79–66%), or severe (<66%) PD. Odds ratios (ORs) and 95% CIs 2Capio St. Gorans¨ hospital, Stockholm, Sweden 3 were calculated by logistic regression, and were adjusted for age, sex, smoking, Department of Dental Medicine, Karolinska In- stitutet, Stockholm, Sweden education, marital status, and explored associated risks of dysglycemia to PD and 4Faculty of Odontology, Department of Periodon- MI, respectively. tology, Malmo¨ University, Malmo,¨ Sweden 5Department of Clinical Sciences Danderyds Hos- RESULTS pital, Karolinska Institutet, Stockholm, Sweden 6 AGT was more common in patients than in control subjects (32% vs. 19%; P < 0.001) Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden and was associated with MI (OR 2.03; 95% CI 1.58–2.60). Undetected diabetes was – Corresponding author: Anna Norhammar, anna. associated with severe PD (2.50; 1.36 4.63) and more strongly in patients (2.35; [email protected] – – 1.15 4.80) than in control subjects (1.80; 0.48 6.78), but not when categorized as Received 3 January 2019 and accepted 25 April AGT (total cohort: 1.07; 0.67–1.72). Severe PD was most frequent in subjects 2019 with undetected diabetes, and reversely undetected diabetes most frequent in This article contains Supplementary Data online patients with severe PD. at http://care.diabetesjournals.org/lookup/suppl/ doi:10.2337/dc19-0018/-/DC1. CONCLUSIONS © 2019 by the American Diabetes Association. In this large case-control study previously undetected dysglycemia was indepen- Readers may use this article as long as the work dently associated to both MI and severe PD. In principal, it doubled the risk of a first is properly cited, the use is educational and not for profit, and the work is not altered. More infor- MI and of severe PD. This supports the hypothesis that dysglycemia drives two mation is available at http://www.diabetesjournals common diseases, MI and PD. .org/content/license. Diabetes Care Publish Ahead of Print, published online June 10, 2019 2 Undetected Dysglycemia in Two Common Diseases Diabetes Care The global prevalence of dysglycemia (di- used. A detailed description of the study (Redhot Diagnostics, Sodert¨ alje,¨ Swe- abetes or prediabetes) is rapidly increasing procedures and selection of control sub- den) by an ELISA method (MP Biomed- (1). Diabetes is an important risk factor for jects has been published previously (6), icals). myocardial infarction (MI) and periodonti- whereas information of particular impor- The national quality registry SWEDE- tis (PD), both of which are significant public tance for this report is described below. HEART (The Swedish Web-system for health problems. The progress of athero- Participants with established diabetes Enhancement and Development of sclerosisispromotedbychronicinflam- (patients 10%; control subjects 8%) Evidence-based care in Heart disease matory conditions, and active systemic were excluded from the present report. Evaluated According to Recommended inflammation increases the risk for ath- An oral glucose tolerance test (OGTT) was Therapies; www.swedeheart.se), modi- erosclerotic plaque rupture leading to performed at all study sites since the fied to comply with the study needs, was unstable angina or MI (2,3). Counteracting study protocol contained the prespeci- used to collect medical information from inflammation reduces cardiovascular (CV) fied objective to analyze PD severity in the patients at the time of their initial events in patients with established CV relation to glycemic state. hospitalization and at the follow-up 6– disease as recently shown by The Patients (n = 805) were ,75 years of 10 weeks after the MI. Equivalent in- Canakinumab Antiinflammatory Throm- age and had received a diagnosis of a first formation was collected for the control bosis Outcome Study (CANTOS) trial, which MI according to international guidelines population with data entered into a sep- established a causal relationship between (13,14). Exclusion criteria were previous arate database. inflammation and atherosclerosis (4). PD is heart valve replacement, any conditions a chronic inflammatory condition, predom- limiting the ability to participate in the OGTT and Definitions of Glucose inantly induced by Gram-negative bacteria study or unwillingness to participate. Tolerance States colonizing the gingival crevice succes- Recruitment occurred from May 2010 Participants without previously known sively degrading the tissues attaching to February 2014 at 17 Swedish coro- diabetes underwent a standardized OGTT the teeth to the alveolar bone (5). The nary care units. OGTTs and dental exami- consisting of 75 g glucose diluted in Swedish case-control study PAROKRANK nations were performed at the local 200 mL of water (15). Venous plasma (Periodontitis and Its Relation to Coronary cardiology outpatient clinic and the glucose was measured before ingestion Artery Disease) recently revealed that the hospital dental care unit within 6–10 of the glucose solution and 120 min after risk for MI among those with PD was weeks after hospital discharge. After using a bedside point-of-care system increased even after adjustment for rele- the exclusion of patients with already (HemoCue 201 System; HemoCue AB, vant confounders, thereby strengthening established diabetes, 719 patients re- Angelholm,¨ Sweden). Glucose levels ob- the possibility of an independent relation- mained. tained during the OGTT were used to ship between PD and MI (6). Control subjects (n = 805) were per- classify study participants according to A two-way relationship between di- sons matched for age, sex, and geogra- the World Health Organization definition abetes and PD has been proposed and phy (by postal code) who had been (15) as normal glucose tolerance (NGT), was recently reviewed (i.e., that hyper- selected from the national population impaired glucose tolerance (IGT), or di- glycemia increases the risk for the de- registry. To be considered, control sub- abetes (Supplementary Table 1). Abnor- velopment of PD and that the presence of jects should be free from prior MI or heart mal glucose tolerance (AGT) was defined PD increases the risk for diabetes) (7). valve replacement and be willing to as the presence of either IGT or diabetes Whether this association also extends participate in the study investigations. detected by the OGTT performed accord- to persons with previously undetected Study visits at the Departments of Car- ing to the study protocol. dysglycemia has, however, not been diology and Dental Care were scheduled extensively elucidated, especially not in in close proximity to the matched pa- Dental Examination populations including subjects both with tient’s study visit. After the exclusion of A dental examination, following a stan- and without prevalent CV disease (8–10). control subjects with already established dardized protocol, was completed, and a Since both established diabetes and un- diabetes, 739 control subjects remained. panoramic dental X-ray was performed detected dysglycemia are associated with (6). The X-rays were analyzed according MI (11,12) and since PD seems to be Study Protocol to standardized protocol centrally at the related to MI (6), it can be hypothesized The matched control subjects were se- Department of Dental Medicine, Karo- that PD should be more common among lected and investigated soon after the linska Institute Huddinge by dentists patients with previously undetected dys- outpatient visit of their corresponding blinded to whether the study partici- glycemia who have experienced an MI patients. Prior to the visit at the cardi- pants were patients or control subjects. than in healthy control subjects. ology outpatient clinic, study participants Each tooth was measured. Measure- The objective with this report was to fasted for 12 h, including abstaining from ments were made from the marginal test the hypothesis that undetected dys- smoking. Blood samples were collected bone crest to the tooth apex (total glycemia is associated with both MI and during the study visit 6–10 weeks after bone height) and from the cemento- PD. the MI in patients and at baseline in enamel junction to the tooth apex control subjects. Blood samples were (total root length) mesially and distally RESEARCH DESIGN AND METHODS analyzed at the local hospital laboratory (for further