That periodontitis and diabetes mellitus are related is known for more than 100 years. While Beck et al. (2019), in their contribution to the JDR Centennial Series on 100 Years of Progress in Periodontal Medicine, start out with a paper by Williams and Mahan (1960), which is mentioned as the first landmark paper (allegedly the first study showing that periodontal therapy reduces insulin requirement; but this study had only shown that removing all teeth with advanced decay improved glycemic control), the latter authors quote a booklet by Otto Georg Grunert of 1899 a patient guidebook for diabetics: Ueber Krankheitserscheinungen in der Mundhöhle beim Diabetes: Therapeutische Winke für Diabetiker. In particular the medical profession had known about the link of diabetes mellitus and oral disease for long.
Further landmark, or “milestone”, papers in Beck et al.’s list on the diabetes-periodontitis relationship appeared around 1996, when late Professor Robert J. Genco, for the first time, had used a slide with the message, Floss or Die! on the occasion of the annual meeting of the American Academy of Periodontology in New Orleans. Some of these studies indeed sparked the idea that it would be possible to reduce HbA1c, the marker of diabetic control, by proper periodontal treatment of diabetic patients.
Earlier this year, delegates of the European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) had met in Madrid for a joint workshop on an update of the Perio-Diabetes link. I had reported on the event and some key findings, quickly posted on the EFP web page, here.
Already on and after 24 August 2017, a Consensus Report by the two organizations was prematurely published, and quickly (temporarily) withdrawn, in the EFP’s Journal of Clinical Periodontology and the IDF’s Diabetes Research and Clinical Practice. I had managed to get a print-out of the not-yet edited (and later withdrawn) draft version published on the JCP Accepted Articles page and had noticed that most of the evidence presented was derived of yet-to-be published review articles based on the workshop proceedings.
The final version of the Consensus Report (Sanz et al. 2017, Early View Articles), including guidelines for patients and health professionals dealing with patients suffering from diabetes and periodontal disease, went online this week, but still references to review papers presented on the occasion of the workshop have a 2017 assignment and are not paginated which may make it more difficult for scientists and clinicians outside periodontology or dentistry to locate the final papers.
To be clear, when it comes to keeping our medical collegues, and in particular diabetologists, interested in the very long-known link between periodontitis and metabolic diseases, proving beneficial effects of periodontal treatment on diabetic control is crucial. All was fine as long as numerous published, small-scale, mostly single-center, and often poorly executed, trials apparently showed that thorough subgingival scaling in patients with both periodontitis and diabetes led to an about 0.4% reduction of glycated hemoglobin (HbA1c), at least after three or four months. As that would in effect spare an additional antidiabetic drug, diabetologists stayed interested. Although results in a few trials indicated that the effect was not long-lasting, i.e., no longer discernable after, say, six months.
After rather devastating negative conclusions made in a systematic review (SR) of the literature regarding the long claimed, possibly causal, relationship between periodontitis and atherosclerotic vascular disease by Lockhart et al. (2012), a highly alerted group of members of our specialty organizations, the Amercian Academy of Periodontology and the European Federation of Periodontology, had hastily organized a joint workshop, in the end of 2012, to fix unwelcome results of a number of large intervention studies by creating new systematic reviews on the Perio-Systemic link. The clear aim was to cement, once and forever, the claim of the number one clinical problem: periodontal disease and general health are closely related.
While the proceedings had been published, open access, in special issues of our main professional journals, the Journal of Clinical Periodontology and the Journal of Periodontology, workshop participants of the EFP presumptuously condensed the 209 pages of the 16, mostly valuable, papers in a nutshell, strangely called Manifesto.
Currently, teachers experience a general problem, a surge of published systematic reviews where slightly modified search criteria have led to slightly different bunch of papers with slightly different results of meta-analyses. Systematic reviews have once been welcomed as valuable tool to either end a story once and forever (if evidence for or against a certain treatment or association was overwhelming), or call for more conclusive randomized controlled trials (RCT) after still open questions had been identified. If, after any new RCT, editors of our professional journals would accept considering a new systematic review for publication, which basically ruminates already published RCT summaries but adds just another study without changing main conclusions, it will in fact become difficult to keep pace with what some call “emerging evidence”.
One main reason why evidence based medicine has to be taught to undergraduate students is to provide future health care workers with proper tools and train specific skills to conduct brief systematic reviews of identified randomized controlled trials themselves. Here on this blog, I had posted a couple of quick examples, see here, here and here.
In particular the latter of the above examples has dealt with the question whether the large multi-center trial by Engebretson et al. (2013), which had reported no effects of periodontal therapy on HbA1c levels in diabetics, would nullify the conclusion (that nonsurgical periodontal treatment may reduce HbA1c levels by about 0.4%) of previous meta-analyses of smaller and mainly single-center RCTs with similar settings.
Engebretson et al. (2013) had listed possible shortcomings of their study. However, that oral hygiene of study participants had not improved was considered by most of our professional leaders scandalous. Further issues for unprecedented criticism included “nearly normal” HbA1c levels at the outset and extreme obesity of participants. Engebretson’s unwelcome results had been reviled by an armada of 21 editors of our key journals, presidents of our main scientific societies, and further periodontal experts. Criticism had culminated in a very strange recommendation.
“Given the inconlusive nature of these data, we recommend that the existing body of evidence in which meta-analyses consistently conclude that successful periodontal therapy appears to improve glycemic control, should instruct us until results from future studies are reported. We urge all interested parties to refrain from using these study results as a basis for future scientific texts, new research projects, guidelines, policies, and advice regarding the incorporation of necessary periodontal treatment in diabetes management.” (My emphasis.)
In other words, forget about Engebretson et al. and continue quoting more favorable results from existing meta-analyses of RCTs on the effect of periodontal therapy on diabetes control. A quick analysis revealed that it won’t nullify a mean HbA1c reduction in diabetics by nonsurgical periodontal therapy, but that considerable heterogeneity was introduced by including Engebretson’s study which may in fact lower the grade of evidence. I had entered meta-data of Engebretson and Kocher 2013 in an amazing tool for meta-analysis and had added findings by Engebretson et al. (2013). That might have been premature, see below.
In an announcement for his talk about periodontal treatment effects on type 2 diabetes at Europerio 8 in London later this year, exasperated Professor Thomas Kocher of Greifswald University in Germany promises to “dissect” the large multicenter trial by Engebretson et al. (2013) who could not find an effect on glycated hemoglobin in type 2 diabtes mellitus. The study had been published in late 2013 in JAMA, not in New England (Journal of Medicine). The large multicenter trial had long been attacked for not yielding the desired results (“a publication which we were really waiting for”).
Kocher was asked to talk in London about “why all the other small studies showed an effect” and he wants to find out “the issues why we [?] couldn’t see anything in the Engebretson study”. Well, it was actually Wenche Borgnakke who had got 20 other “reviewers” aboard who had already dissected the study by Engebretson et al. and has called for censorship.
As noted by Engebretson and Kocher 2013 in one of the numerous previous systematic reviews of RCTs on the effect of nonsurgical periodontal therapy and reported in Table 1 of their article, problems with the design of these small-scale, mainly single-center studies, which included some trials with adjunctive antibiotics, were plentiful. Problems with low and high baseline HbA1c levels and with questionable periodontal outcomes had been reported as well. Engebretson and Kocher (2013) report possible publication bias which means nothing else that studies without an effect on HbA1c might have gone unpublished. Based on this particular and numerous other systematic reviews, the evidence that nonsurgical periodontal therapy in fact has a relevant beneficial effect on HbA1c levels in type 2 diabetics may actually be regarded moderate. The study by Engebretson et al. adds heterogeneity to any meta-analysis which may downgrade this evidence to low. That is what our thought leaders alerts. That’s why censorship.