Does COVID-19 vaccination affect rheumatic and musculoskeletal disease flares?

Does COVID-19 vaccination affect rheumatic and musculoskeletal disease flares?
Does COVID-19 vaccination affect rheumatic and musculoskeletal disease flares?


In a study of 1,377 patients with rheumatic and musculoskeletal diseases—such as inflammatory arthritis and lupus—flares of their conditions were uncommon following two-dose COVID-19 mRNA vaccination. In a study of 1,377 patients with rheumatic and musculoskeletal diseases—such as inflammatory arthritis and lupus—flares of their conditions were uncommon following two-dose COVID-19 mRNA vaccination.

In the Arthritis & Rheumatology study, 11% of patients reported flares after vaccination that required treatment, and there were no reports of severe flares. Flares were associated with prior SARS-CoV-2 infection, flares in the six months preceding vaccination, and use of combination immunomodulatory therapy.

“’Our findings demonstrate that the vaccines are safe and should alleviate the safety concerns of any hesitant patients,” said first author Caoilfhionn Connolly, MD, MSc, of Johns Hopkins University School of Medicine. “This study highlights that most of our rheumatic patients tolerated the vaccine well with mostly having local reactions such as injection site pain, which was quite reassuring, but most importantly, we did not observe any severe flares of their underlying autoimmune disease,” added co–senior author Julie J. Paik, MD, MHS, also of Johns Hopkins University School of Medicine.

Artificial pancreas trialed for outpatients with type 2 diabetes for first time

Artificial pancreas trialled for outpatients with type 2 diabetes for first time
Artificial pancreas trialled for outpatients with type 2 diabetes for first time

An artificial pancreas could soon help people living with type 2 diabetes and who also require kidney dialysis. Tests led by the University of Cambridge and Inselspital, University Hospital of Bern, Switzerland, show that the device can help patients safely and effectively manage their blood sugar levels and reduce the risk of low blood sugar levels.

Diabetes is the most common cause of kidney failure, accounting for just under a third (30%) of cases. As the number of people living with type 2 diabetes increases, so too does the number of people requiring dialysis or a kidney transplant. Kidney failure increases the risk of hypoglycaemia and hyperglycaemia – abnormally low or high levels of blood sugar respectively – which in turn can cause complications from dizziness to falls and even to coma.

Managing diabetes in patients with kidney failure is challenging for both patients and healthcare professionals. Many aspects of their care are poorly understood, including targets for blood sugar levels and treatments. Most oral diabetes medications are not recommended for these patients, so insulin injections are the most commonly used diabetes therapy – though optimal insulin dosing regimens are difficult to establish.

A team at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust has previously developed an artificial pancreas with the aim of replacing insulin injections for patients living with type 1 diabetes. In research published today in Nature Medicine, the team – working with researchers at Bern University Hospital and University of Bern, Switzerland – has shown that the device can be used to support patients living with both type 2 diabetes and kidney failure.

The artificial pancreas is powered by software in the user’s smartphone that sends a signal to an insulin pump to adjust the level of insulin the patient receives. A glucose monitor measures the patient’s blood sugar levels and sends these back to the smartphone to enable it to make further adjustments.

Unlike the artificial pancreas being used for type 1 diabetes, this version is a fully closed loop system – whereas patients with type 1 diabetes need to tell their artificial pancreas that they are about to eat to allow adjustment of insulin, for example, with this new version they can leave the device to function entirely automatically.

Dr Charlotte Boughton from the Wellcome Trust-MRC Institute of Metabolic Science at the University of Cambridge, who led the study, said: “Patients living with type 2 diabetes and kidney failure are a particularly vulnerable group and managing their condition – trying to prevent potentially dangerous highs or lows of blood sugar levels – can be a challenge. There’s a real unmet need for new approaches to help them manage their condition safely and effectively.”

The artificial pancreas is a small, portable medical device designed to carry out the function of a healthy pancreas in controlling blood glucose levels, using digital technology to automate insulin delivery. The system is worn externally on the body, and is made up of three functional components: a glucose sensor, a computer algorithm to calculate the insulin dose, and an insulin pump.

The team recruited 26 patients requiring dialysis between October 2019 and November 2020. Thirteen participants were randomised to receive the artificial pancreas first and 13 to receive standard insulin therapy first. The researchers compared how long patients spent in the target blood sugar range (5.6 to 10.0mmol/L) over a 20 day period as outpatients.

Patients using the artificial pancreas spent on average 53% of their time in the target range, compared to 38% when they used the control treatment. This equated to around 3.5 additional hours every day spent in the target range compared with the control therapy.

Mean blood sugar levels were lower with the artificial pancreas (10.1 vs. 11.6 mmol/L). The artificial pancreas reduced the amount of time patients spent with potentially dangerously low blood sugar levels, or ‘hypos’.

The efficacy of the artificial pancreas improved considerably over the study period as the algorithm adapted, and the time spent in the target blood sugar range increased from 36% on day one to over 60% by the twentieth day. This finding highlights the importance of using an adaptive algorithm, which can adjust in response to an individual’s changing insulin requirements over time.

When asked about their experiences of using the artificial pancreas, everyone who responded said they would recommend it to others. Nine out of ten (92%) reported that they spent less time managing their diabetes with the artificial pancreas than during the control period, and similar numbers (87%) were less worried about their blood sugar levels when using it.

Other benefits of the artificial pancreas reported by study participants included less need for finger-prick blood sugar checks, less time required to manage their diabetes resulting in more personal time and freedom, and improved peace of mind and reassurance. Downsides included discomfort wearing the insulin pump and carrying the smartphone.

Senior author Professor Roman Hovorka, also from the Wellcome Trust-MRC Institute of Metabolic Science, said: “Not only did the artificial pancreas increase the amount of time patients spent within the target range for the blood sugar levels, but it also gave the users peace of mind. They were able to spend less time having to focus on managing their condition and worrying about the blood sugar levels, and more time getting on with their lives.”

Dr Boughton added: “Now that we’ve shown the artificial pancreas works in one of the more difficult-to-treat groups of patients, we believe it could prove useful in the wider population of people living with type 2 diabetes.”

The team is currently trialling the artificial pancreas for outpatient use in people living with type 2 diabetes who do not need dialysis and exploring the system in complex medical situations such as perioperative care.

Dr Lia Bally, who co-led the study in Bern, said: “The artificial pancreas has the potential to become a key feature of integrated personalised care for people with complex medical needs.”

The research was supported by the NIHR Cambridge Biomedical Research Centre, The Novo Nordisk UK Research Foundation, Swiss Society for Endocrinology and Diabetes, and Swiss Diabetes Foundation and Swiss Kidney Foundation.

Low glycaemic diet shows meaningful improvements for people with diabetes

Low glycaemic diet shows meaningful improvements for people with diabetes
Low glycaemic diet shows meaningful improvements for people with diabetes


For people with diabetes, sticking to a low glycaemic diet results in small but important improvements in blood sugar levels, cholesterol, weight and other risk factors, finds a study published by The BMJ today.

These improvements were seen over and above existing drug or insulin therapy, suggesting that a low glycaemic diet might be especially helpful as add-on treatment to help those with diabetes better achieve their targets, say the researchers.

The glycaemic index (GI) rates how quickly different foods affect blood sugar levels and research has shown that low-GI foods, such as vegetables, most fruits, pulses and wholegrains, can help keep blood sugar levels steady and reduce the risk of heart disease in people with diabetes.

A low GI or GL (glycaemic load) diet is therefore recommended for people with diabetes by clinical guidelines across the world. However, the last European Association for the Study of Diabetes (EASD) guidelines were published over 15 years ago and several trials have been published since then.

So researchers set out to summarise the effect of low GI/GL dietary patterns on blood sugar control and other known risk factors in diabetes to help inform the update of the EASD guidelines for nutrition treatment.

Their results are based on 27 randomised controlled trials published up to May 2021 investigating the effect of diets with low GI/GL in diabetes for three or more weeks.

The trials involved a total of 1,617 participants with type 1 or 2 diabetes, who were predominantly middle aged, overweight or obese with moderately controlled type 2 diabetes treated with drugs or insulin. 

The trials were of varying quality, but the researchers were able to assess the certainty of evidence using the recognised GRADE system.

The results show that low-GI/GL dietary patterns were associated with small but clinically meaningful reductions in blood sugar levels (HbA1c) compared with higher-GI/GL control diets.

Reductions also occurred in other risk factors including fasting glucose (blood sugar levels after a period of fasting), LDL cholesterol, body weight, and C-reactive protein (a chemical associated with inflammation), but not blood insulin levels, HDL cholesterol, waist circumference, or blood pressure. 

The certainty of evidence was high for reduction in blood sugar levels and moderate for most other outcomes, suggesting the available evidence provides a good indication of the likely benefit in this population.

The researchers point to some limitations that may have affected their results, such as imprecision in the evidence for the effect of low GI/GL dietary patterns on LDL cholesterol and waist circumference, and the small number of available trial comparisons for blood pressure and inflammatory markers.

However, they say their findings show that low GI/GL dietary patterns “are considered an acceptable and safe dietary strategy that can produce small meaningful reductions in the primary target for glycaemic control in diabetes, HbA1c, fasting glucose, and other established cardiometabolic risk factors.”

“Our synthesis supports existing recommendations for the use of low GI/GL dietary patterns in the management of diabetes,” they conclude. 

“Where does it hurt?” predicts chronic pain outcomes, study shows

'Where does it hurt?' predicts chronic pain outcomes, study shows

Heatmap with body map region on horizontal axis and each row on the vertical axis representing an individual patient out of the entire cohort (N = 21,658 unique patients) organized by cluster membership. CREDIT Alter et al, 2021, PLOS ONE (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)

Pain distribution as reported on a body map, on its own, can be used to assign patients to distinct subgroups that are associated with differences in pain intensity, pain quality, pain impact and clinically-relevant three-month outcomes, according to a new study published this week in the open-access journal PLOS ONE by Benedict Alter of University of Pittsburgh, US, and colleagues.

In clinical practice, the bodily distribution of chronic pain is often used in conjunction with other signs and symptoms to diagnose and treat patients. Recent work on fibromyalgia has revealed that clinical pain syndromes thought to be distinct entities may share clinically-relevant features, especially regarding the impact of pain distribution on outcomes. However patterns of pain distribution have not been previously examined in a systematic way as predictors of pain characteristics or outcomes.

In the new study, researchers analyzed data on 21,658 patients seen at the seven pain management clinics of the University of Pittsburgh between 2016 and 2019. All patients completed a pain body map, in which areas of pain are selected on two side-by-side drawings of the front and back of the body, with 74 possible regions of pain. Other information on patients’ pain, health, and outcomes was available in the electronic medical record. Patients were 83% white, 60% female, 22% insured by Medicaid and 10% had at least one comorbidity.

Data from all patients revealed 9 distinct groupings of pain distribution. Demographic and medical characteristics, pain intensity, pain impact, and neuropathic pain quality all varied significantly across cluster subgroups. For instance, the pain intensity of the “Neck and Shoulder” group was less than that of “Lower Back Pain below knee” and “Neck, Shoulder and Lower Back Pain,” while the group with the highest pain intensity consisted of patients with widespread heavy pain, also associated with low physical function, high anxiety and depression and high sleep disturbance. In a subset of 7,138 patients who completed 3-month follow-up questionnaires, subgroups predicted the likelihood of improvement in pain and physical function; those in the “Abdominal Pain” group were the most improved, with 49% self-reporting clinically significant


improvements, while those in the “Neck, Shoulder and Lower Back Pain” group were the least improved, with only 37% reporting improvements. The authors conclude that algorithmic clustering by pain distribution may, in the future, be an important facet of the personalization of pain management. 

The authors add: “Using an algorithmic approach, we found that how a patient reports the bodily distribution of their chronic pain affects nearly all aspects of the pain experience, including what happens three months later. This emphasizes that chronic pain is a disease process and suggests that this facet of the chronic pain phenotype will be important for future developments in diagnosis and personalized pain management.” 

Synthetic hinge could hold key to revolutionary ‘smart’ insulin therapy

Insulin can be stored out of refrigeration in hot settings


For people with diabetes who are insulin dependent, glycemic control is a full-time job. But what if their medication could do the work for them—an insulin whose activity in the bloodstream responds to the blood glucose levels and adjusts accordingly? An invention from Indiana University School of Medicine Distinguished Professor Michael A. Weiss, MD, PhD, could lead to just that.

In a breakthrough study published in the peer-reviewed journal PNAS, Weiss and his team describe the use of a synthetic “switch” that can be opened or closed using a simple sugar sensor. The study was in part collaborative with Thermalin, Inc., a small biotech company that Weiss began in 2008.

Their concept exploits a natural mechanism, designated the “protective hinge,” that is built into vertebrate insulins. The protective hinge is a natural structural feature that evolved more than half a billion years ago to keep the hormone stable in its closed state but foldable and functional in its open state.

“The reason a glucose-responsive insulin is important is that the biggest barrier to the effective use of insulin, especially in Type 1 diabetes, is the fear of the consequences of blood sugar going too low,” said Weiss, who is also the Chair of the Department of Biochemistry and Molecular Biology.

Immediate consequences of severely low blood sugar (hypoglycemia) can include delirium, convulsions or loss of consciousness, and repeated episodes of severe hypoglycemia can cause cognitive decline. On the other hand, chronic high blood sugar (hyperglycemia) can lead to blindness, stroke or amputation. Staying in the desired blood glucose range is a delicate balance that insulin-dependent diabetics face every day.

But Weiss said that he envisions a future when people do not have to choose to risk their long-term health to protect themselves from the immediate dangers of severe hypoglycemia.

“The promise of this kind of ‘smart’ insulin is that it would transform diabetes care, so people wouldn’t have to worry anymore,” said Weiss. “With our invention, we envision that when the blood sugar goes low, the hinge would close. But there will be much work to do to translate our proof of principle to an FDA-approved product.”

In the 100 years since the discovery of insulin, its use as a treatment for diabetes has gone through many significant changes. C. Ronald Kahn, MD, chief academic officer at the Joslin Diabetes Center at Harvard Medical School, said that glucose-responsive insulin could be the next.

“In the recent study from the Weiss laboratory appearing in PNAS, we see an example of the next exciting phase of insulin development, namely development of an insulin analogue which through chemical modification can sense the level of sugar present in the blood,” said Kahn.  “While the current analogue has been designed to sense fructose, it seems likely that this same approach can be used to develop analogues to sense glucose.  Whether these can be sensitive enough to be modulated by changes within the physiological range remains to be determined, but if so, this would be an important new tool in the management of diabetes.”

Other types of glucose-responsive insulins are being developed elsewhere. What makes Weiss’ invention unique is its simplicity. The synthetic hinge exploits naturally occurring processes and introduces fewer external or artificial elements compared to other approaches.

While their study uses fructose as model (representative of a monosaccharide like glucose), it proves that Weiss’ synthetic hinge concept works. His team is already working on glucose-responsive insulin candidates that open and close at the desired high and low glucose thresholds, which are respectively 70 to 180 milligrams per deciliter. By replacing the fructose sensor with glucose sensors, a revolutionary insulin therapy may be closer than we think.

The above referenced study is titled “Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone–receptor activation.” Contributing authors include Yen-Shan Chen, PhD, Yanwu Yang, PhD, Balamurugan Dhayalan, PhD, Mark A. Jarosinski, PhD, and Deepak Chatterjee, PhD, from Indiana University; Nelson B. Phillips, PhD, from Case Western Reserve University; Yule Liu, PhD, Laurie Broadwater, PhD, Thomas Hattier, PhD, and M. Dodson Michael, PhD, from Thermalin, Inc; and Michael C. Lawrence from the University of Melbourne.

This work is supported in part by grants from the JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, and the National Institutes of Health (R01 DK040949 and R01 DK127761).