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after 24 August 2017, a Consensus Report by the two organizations was prematurely published, and quickly (temporarily) withdrawn, in the EFP’s Journal of Clinical Periodontology and the IDF’s Diabetes Research and Clinical Practice. I had managed to get a print-out of the not-yet edited (and later withdrawn) draft version published on the JCP Accepted Articles page and had noticed that most of the evidence presented was derived of yet-to-be published review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.
In a recent commentary in the Journal of Periodontology, Merchant and Josey (2016) had suggested directed acyclic graphs to better comprehend the partly conflicting results from randomized controlled trials (RCT) on diabetic control after periodontal treatment in diabetic patients. In particular the influence of obesity caught their attention.
As a matter of fact, a remarkable number of systematic reviews (whose varying quality have recently been reviewed in at least two further SRs of SRs) have shown that numerous small-scale, single-center, often poorly designed RCTs had shown that the marker for diabetic control, HbA1c, might be reduced by, say 0.4% 3 months after in essence non-surgical periodontal therapy. The only large-scale, multi-center trial (DPTT) by Engebretson et al. (2013) couldn’t confirm that, though, which sparked harsh criticism of a large number of our thought leaders. A professor in the Department of Epidemiology and Biostatistics at the University of South Carolina, Columbia, Dr. Anwar Merchant himself had written a letter to the editors of JAMA pointing first to the fact that most participants in the paper by Engebretson et al. were utterly obese. He had further noticed that, “[i]n RCTs conducted among mostly nonobese individuals, periodontal treatment has been shown to reduce systemic inflammation2,4 and improve glycemic control among those with type 2 diabetes.2 However, periodontal treatment has not been shown to affect glycemic control in RCTs conducted among predominantly obese individuals with type 2 diabetes.1,3”
Obesity is positively correlated with inflammatory markers in the blood and strongly related to insulin resistance and metabolic dysregulation mediated by chronic systemic inflammation.5 These findings, taken together with results from RCTs evaluating the effects of periodontal treatment, suggest that the lack of effect of periodontal treatment on glycemic control observed in the study by Engebretson et al may be attributed to the high level of obesity in the study population. Therefore, the findings may be generalizable only to predominantly obese populations with type 2 diabetes.
Claims and denials of clinically relevant effects of, in particular, non-surgical periodontal treatment on markers of diabetic control have not only led to a surge of new randomized clinical trials and systematic reviews thereof. If anybody had hope that the current frenzy has found a happy end with the updated and very comprehensive Cochrane review by Simpson et al. (2015) (s)he has been mistaken. In the June issue of the Australian Dental Journal, Botero et al. (2016) report on an umbrella review in which they systematically reviewed all systematic reviews on the subject, be it with or without meta-analysis, published between 1995 and 2015. The paper has been accepted for publication on January 20, 2016. It has to be emphasized that using the term “umbrella review” is somewhat misleading. In a strict sense, an umbrella review assembles together several systematic reviews on the same condition in the presence of many treatments or many important outcomes.
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.
After my recent comment on the concerted action of 19 eminent and self-proclaimed eminent periodontal scientists spearheaded by Drs. Borgnakke and Chapple (2014) aiming at smashing findings of a large multicenter randomized controlled trial by Engebretson et al. 2013 on HbA1c levels in type 2 diabetics with moderate or severe periodontitis, I had honestly decided not to report any more on the issue unless an updated systematic review by the Cochrane Collaboration was published. A reader of my blog had contacted CC’s Dr. Terry Simpson who promised that, due to “logistical problem[s] including difficulties with authors not supplying vital information [sic!],” they would likely be able to publish it around the turn of the year.
Now, the final paper was published yesterday in the Journal of Evidence-Based Dental Practice with a few editorial amendments. Borgnakke’s, well, rant is remarkable since it assembles (as reviewers who are also listed as authors) in essence all editors and many members of the editorial boards of our core journals in periodontology and implant dentistry as well as the editor of Journal of Dental Research. I had reported on the history of the paper here and had noted that, after a first version had been withdrawn by the authors earlier this year, Panos N. Papapanou was no longer listed as reviewer in the version which went online on 13 August 2014. Instead, Fusanori Nishimora (an editorial board member of Journal of Periodontal Research who is involved in the so-called Hiroshima Study, see below) had joined the group. While the online early version of Borgnakke’s paper had got the title “The randomized controlled trial (RCT) published by the Journal of the American Medical Association (JAMA) on the impact of periodontal therapy on glycated hemoglobin (HbA1c) has fundamental flaws,” a slightly moderated version is now provided: “The Multi-Center Randomized Controlled Trial (RCT) Published by the Journal of the American Medical Association (JAMA) on the Effect (sic!) of Periodontal Therapy on Glycated Hemoglobin (HbA1c) Has Fundamental Problems (sic!).”