DIABETOLOGIA

New research from Wuhan, China shows that, in patients with COVID-19 but without a previous diagnosis of diabetes, abnormally high blood sugar is associated with more than double the risk of death and also an increased risk of severe complications. The study is by Dr Yang Jin, Union Hospital and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, and colleagues. The study is published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]).

Previous studies have established that hyperglycemia (abnormally high blood sugar) is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, heart attacks, trauma and surgery, among other conditions. A number of studies have also shown links between diabetes and poor outcomes in COVID-19 patients. However, direct correlation between fasting blood glucose (FBG) level at admission to hospital and clinical outcomes of COVID-19 patients without diagnosed diabetes has not been well established. In this new study the authors examined the association between FBG on admission and the 28-day mortality of COVID-19 patients without previously diagnosed diabetes in two hospitals.

The retrospective study assessed all consecutive COVID-19 patients with a known outcome at 28-days and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. The CRB-65 score is an effective measure for assessing the severity of pneumonia and is based on four indicators: level of confusion, respiratory rate (over 30 breaths per min), systolic blood pressure (90 mmHg or less) or diastolic blood pressure (60 mmHg or less), and age (65 years or over).

A total of 605 COVID-19 patients were enrolled, including 114 who died in hospital. The median age of participants was 59 years and 322 (53.2%) were men. A total of 208 (34%) had one or more underlying conditions (but not diagnosed diabetes), of which high blood pressure was the most common. Almost one third (29%) of patients fell into the highest category of FBG on admission (7.0 mmol/L) which if found consistently would result in a diagnosis of type 2 diabetes. A further 17% were in the range that would be considered pre-diabetic (6.1-6.9 mmol/L), while more than half (54%) were in the ‘normal’ FBG range of 6.0 mmol/L or below.

The results showed that patients in the highest FBG group were 2.3 times more likely to die than those in the lowest, a statistically significant result. Those in the middle (pre-diabetic) FBG group were 71% more likely to die than those in the lowest group, although this result only had borderline statistical significance. The data also showed that men were 75% more likely to die than women; and that patients with higher CRB65 scores (and thus worse pneumonia) were also at higher risk of death: those with a score of 3-4 were more than 5 times more likely to die than those with a score of 0, while for those with a score of 1-2 there was a 2.7 times increased risk.

When looking at FBG and CRB65 scores together, the patients in the highest FBG group had an increased risk of death compared to the lowest, regardless of whether or not the CRB65 score was zero or higher, further underlining that FBG independently increases the risk of death in COVID-19 patients. However, the increased risk of death for the highest FBG group was lower in patients with CRB65 scores of above zero compared with those with a CRB65 score of zero. The risk of complications was also found to be 4 times higher in the highest FBG group compared to the lowest, and 2.6 times higher in the middle (pre-diabetic) group compared to the lowest.

The authors say: “This study shows, for the first time, that elevated FBG (?7.0 mmol/l) at admission is independently associated with increased 28-day mortality and percentages of in-hospital complications in COVID-19 patients without previous diagnosis of diabetes… we have also shown that FBG of 7.0 mmol/l or higher is associated with increased mortality, regardless of whether the patient has pneumonia that is more or less severe.”

They add: “These results indicate that our study included both undiagnosed diabetic patients and non-diabetic patients with hyperglycaemia caused by an acute blood-glucose disorder, since the 29% found in the highest FBG group is much higher than the estimated prevalence of diabetes in the Chinese population at 12%. Similarly to what was found in a previous study, COVID-19 patients might suffer from high blood sugar brought about by other conditions, and critically ill patients may develop acute insulin resistance, manifested by high levels of blood sugar and insulin levels. Patients with conditions not related to diabetes, such as severe sepsis, systemic inflammatory response syndrome (SIRS) and traumatic brain injury tend to have abnormally high blood sugar.”

The authors note several limitations with their study. First, this was a retrospective study. Second, they did not analyse glycated haemoglobin (HbA1c), a long-term blood sugar control indicator that helps distinguish patients with poor long-term blood sugar control from those with stress hyperglycaemia. Also, they did not have sufficient data to study the effect of glucose-lowering treatment (e.g. insulin, metformin) on the outcome of the patients in their study. However, they believe that acute hyperglycaemia is more important than long-term glycaemic control in predicting the prognosis of hospitalised COVID-19 patients.

The authors suggest that possible mechanisms for this increased mortality include hyperglycaemia-induced changes in coagulation (clotting), worsening of endothelial function (the function of the walls of blood vessels), and overproduction of inflammatory cytokines produced by the immune system (the so-called cytokine storm).

The authors conclude: “In conclusion, a fasting blood glucose level of 7.0 mmol/l or higher at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Blood sugar testing and control should be recommended to all COVID-19 patients even if they do not have pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. During a pandemic of COVID-19, measuring fasting blood glucose can facilitate the assessment of prognosis and early intervention of hyperglycaemia to help improve the overall outcomes in treatment of COVID-19.”

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From EurekAlert!

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From Retraction Watch

A Stanford professor who sued a critic and a scientific journal for $10 million — then dropped the suit — has been ordered to pay the defendants’ legal fees based on a statute “designed to provide for early dismissal of meritless lawsuits filed against people for the exercise of First Amendment rights.”

Mark Jacobson, who studies renewable energy at Stanford, sued in September 2017 in the Superior Court of the District of Columbia for defamation over a 2017 paper in the Proceedings of the National Academy of Sciences (PNAS) that critiqued a 2015 article he had written in the same journal. He sued PNAS and the first author of the paper, Christopher Clack, an executive at a firm that analyzes renewable energy.

At the time, Kenneth White, a lawyer at Southern California firm Brown White & Osborn who frequently blogs at Popehat about legal issues related to free speech, said of the suit:

It’s not incompetently drafted, but it’s clearly vexatious and intended to silence dissent about an alleged scientist’s peer-reviewed article.

In February 2018, following a hearing at which PNAS argued for the case to be dismissed, Jacobson dropped the suit, telling us that he “was expecting them to settle.” The defendants then filed, based on the anti-SLAPP — for “Strategic Lawsuit Against Public Participation” — statute in Washington, DC, for Jacobson to pay their legal fees.

In April of this year, as noted then by Forbes, District of Columbia Superior Court Judge Elizabeth Carroll Wingo, who has been presiding over the case, ruled that Jacobson would have to pay those fees. In that ruling, Wingo wrote that the Court 

finds that the three asserted “egregious errors” are statements reflecting scientific disagreements, which were appropriately explored and challenged in scientific publications; they simply do not attack Dr. Jacobson’s honesty or accuse him of misconduct.

Jacobson appealed that decision, but Wingo upheld it in a June 25 order.

Jacobson could be on the hook for more than $600,000, the total of what the plaintiffs have told the court were their legal costs — $535,900 for PNAS, and $75,000 for Clack.

Paul Thaler of Cohen Seglias, which has been representing Jacobson, noted in comments to Retraction Watch that the judge had not yet ruled on how much Jacobson should pay:

The Court must now determine the level of attorneys’ fees to charge, which ranges from $0 to the amounts requested by the Clack and NAS attorneys (see legal fee requests and replies for arguments in both directions). Once that is done, Prof. Jacobson will decide whether to appeal the questions of whether the publication of false facts with provable “yes/no” answers (such as the false claim that a table has maximum values when it factually has average values) are indeed questions of fact or of scientific disagreement and whether legal fees are allowed in a case of a voluntary dismissal without prejudice.

Despite dropping the suit, and the judge’s ruling, Jacobson continues to insist in comments to Retraction Watch that there were false claims in the Clack et al paper:

This case has always been about three false factual claims, including two of modeling “errors” or “bugs,” claimed by Dr. Clack and published by NAS that damaged the reputations of myself and my coauthors. What has come out is that the Clack attorney has now admitted in a Court document that Dr. Clack now makes no claim of a “bug in the source code” of our model, despite Dr. Clack’s rampant claim throughout his paper that we made “modeling errors.” Dr. Clack has also admitted in writing that our paper includes Canadian hydropower, yet neither he nor NAS has corrected this admitted error in the Clack Paper. Third, all evidence points to the fact that Table 1 of our paper contains average, not maximum values, indicating that Dr. Clack’s claim regarding modeling error on this issues is factually wrong as well. Thus, it is more clear than ever that the three false facts published by the Clack Authors were indeed false facts and not questions of scientific disagreement. I regret that it was impossible to have these errors corrected upon our first request rather than having to go through this drawn-out process to restore the reputations of myself and my coauthors.

Clack told Retraction Watch that Jacobson’s comments were not an accurate reflection of the paper he and his colleagues published. (For Clack’s responses to each of Jacobson’s claims, see this PDF; for our attempts to fact-check Jacobson’s claims by asking for evidence, see this PDF.) Clark said:

We have had to repeatedly defend against this individual who is unhappy that his responses to critique were not well received and many scientists and the public did not consider his responses adequate to explain the errors and implausible assumptions in his original PNAS paper.

Clack also said:

Jacobson sued myself and PNAS for publishing a critique of his work that he didn’t like. He chose not to sue the entire author team, but rather only myself. To get published in PNAS, we had passed peer reviewed, and editorial reviews; one reason it took so long to publish. There was a lot of information in our paper and there were many, many problems (a lot were contained in the [supplemental information]). We had 21 authors who all worked on the paper, checked the working and agreed on its content and conclusions. Jacobson had an opportunity to respond concurrently with the release of our paper. We just noted the content of his (and coauthors’) PNAS paper and showed that there were assumption issues, errors, mistakes and wrong conclusions drawn from them.

Full Story Here.

HT/RayG

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