Jared Kaltwasser

A new report suggests that COVID-19 may lead to severe craniofacial pain in a subset of patients with diabetes.

The paper comes from a team of investigators from Egypt, the Czech Republic, and Italy. They report that, between April and August 2020, 21 patients of the 5,730 

 who sought outpatient care at their clinics sought specialist care for pain in their facial regions.

Most of the 21 consecutive patients were in relatively good health prior to their infections and 76% had their diabetes under control. The mean hemoglobin A1c (HbA1c) level of the group was 6.7. The patients had an average age of 51.71 years, were mostly male (66.67%), and had a mean body mass index of 21.76. 

Six of the patients had no systemic comorbidities, but 3 had cardiac conditions, 4 had renal impairment, and 8 had asthma. The patients were taking a variety of antidiabetic drugs, including thiazolidinediones, sodium-glucose cotransporter 2 inhibitors, metformin, and insulin.

The patients’ reported COVID-19 cases were not severe. Most (18 patients) had mild cases and the remaining patients (3) had moderate cases. Only 3 patients had a fever, and it was considered mild in all cases. Four patients had a dry cough, and 2 patients had a sore throat. Two patients reported myalgia.

COVID-19 symptoms were generally unremarkable

, one key feature of their clinical representation was unique: they reported severe pain in the masseter (12 patients) and temporalis (4 patients) regions, or in both regions (5 patients). For 10 patients, the pain was bilateral. For the remaining 11 patients, it was focused on one side or the other. 

When asked to rank the pain from 0 (no pain) to 10 (pain as bad as you can imagine), the patients chose an average severity of 7.4. For most patients (85.7%), the pain was made worse when they touched the affected region, and when they chewed (52.4%).

When asked what provided relief, more than half of the patients (62%) said hot fomentation helped. Paracetamol gave relief to 24% of patients, and ibuprofen and diclofenac potassium aided 5% each.

Corresponding author Abanoub Riad, DDS, of Masaryk University, in the Czech Republic, and colleagues, wrote that many potential explanations for the craniofacial distress experienced by these patients could be excluded.

For instance, diabetic neuropathies were unlikely to be the cause since those are mainly caused by long-standing hyperglycemia, and these 21 patients had their blood glucose levels under control. Another possible cause could be paid due to increases in psycho-emotional stress associated with the pandemic, which could increase bruxism and temporomandibular disorders. However, none of the patients in the series had a history of bruxism or orofacial pain.

That left Riad and colleagues to conclude that the coronavirus infection must play a key role in the pain. They pointed to a number of potential factors at play.

“In addition to the well-known pathophysiologic mechanisms by which the diabetic patients are imposed to a greater risk of viral infections such as impaired neutrophil chemotaxis and phagocytosis; the increased expression of angiotensin-converting enzyme 2 in pancreatic islets and the persistent hyperglycemia in [severe acute respiratory syndrome] patients indicated transient damage to beta cells,” Riad and colleagues wrote.

They also noted that viral infections can amplify the cytokine response in adipose tissues, which could lead to craniofacial inflammation.

“Given that our cases’ median age was 49 years old, the relationship between diabetes and pain in the orofacial muscles can be related to glutamate’s role whose neurotoxicity is mediated by the NMDA receptors found on neuronal tissues and peripheral non-nueruonal tissues and cells as β-cells,” they said.

The authors concluded that their cases are the first reported evidence suggesting a link between COVID-19 and pain in the craniofacial tissues. They said the link warrants further investigation.

Craniofacial pain in COVID‐19 patients with diabetes mellitus: Clinical and laboratory description of 21 cases

Articles

The authors of a research letter say a small minority of patients with diabetes have facial pain that cannot otherwise be easily explained.

Report: Subset of Patients with Diabetes and COVID-19 Experience Craniofacial Pain

Collaboration among healthcare providers in the primary care setting leads to markedly better patient outcomes in patients with 

, according to a new systematic review and meta-analysis.

The study focused on the concept of interprofessional collaborative practice (ICP), which the World Health Organization defines as when “multiple health workers from different professional backgrounds 

 with patients, families, carers, and communities to deliver the highest quality of care.”

Corresponding author Jeannie K. Lee, PharmD, of the University of Arizona College of Pharmacy, and colleagues, noted that while ICP aligns philosophically with many of the goals of the modern healthcare system, there remains little thorough evidence to show its effect, if any, on patient outcomes.

In an effort to change that, Lee and colleagues searched a number of databases for studies published between 2013 and 2018 that evaluated ICP in a primary care setting and which involved adults with 

 and assessed HbA1c and systolic and diastolic blood pressure. In the study, ICP was defined as using 3 or more healthcare professionals, including physicians, nurses, dieticians, pharmacists, and other providers.

Out of more than 6,000 articles identified through the searches, the team screened 3,543 studies and identified 50 articles that met their criteria for systematic review. Of those, 39 were included in the meta-analysis; the remaining 11 did not have adequate data. Fifteen of the 39 studies in the meta-analysis were randomized controlled trials (RCTs).

The team used standardized mean difference (SMD) as its metric to determine the impact of ICP. In the case of HbA1c, the investigators found suitable data in 34 studies encompassing 12,599 people. They found collaborative practices in the primary care setting had a positive effect on HbA1c in all settings, but the effect was most pronounced in patients with the highest HBA1c at baseline.

The SMDs in patients with baseline HbA1c of less than 8 had an SMD of -0.13 in ICP settings; those with HbA1c between 8 and 9 had an SMD of -0.24; those with HbA1c of 9 or higher had an SMD of -0.60 in the studies.

Meanwhile, systolic (SBP) and diastolic (DBP) blood pressure had SMDs of -0.31 (based on 25 studies) and -0.28 (based on 24 studies), respectively, in an ICP setting. The observed blood pressure effects were not linked with baseline levels.

Lee and colleagues said they believe their study offers the most comprehensive and up-to-date picture of the impact of ICP in these patients. One strength of their study, they said, was that they included both RCTs and real-world studies.

“Conducted in controlled environments involving specified patient populations and using precise interventions, RCTs have a superior study design with a lower risk of bias,” the investigators said. “Yet, the findings from RCTs may lack real-life scenarios and patient behaviors in response to clinical interventions that more closely reflect everyday experience.”

The authors said the data make a strong case that ICP helps improve patient outcomes in diabetes and hypertension. However, they also said there is a practical reason practices should consider using ICP. They said global increases in chronic diseases like diabetes and the growing elderly population could overwhelm primary care physicians, particularly in areas with limited healthcare resources.

“ICP appears to be a plausible option for areas with limited access to care and in patients with poorer diabetes control,” Lee and colleagues wrote. “Using our findings, primary care practices may wish to consider providing ICP involving at least 3 professions to improve diabetes and hypertension outcomes.”

Assessment of Interprofessional Collaborative Practices and Outcomes in Adults With Diabetes and Hypertension in Primary Care

Study finds team collaboration could also help primary care practices deal with an expected boom in the number of elderly people with chronic conditions.

Collaborative Primary Care Improves Outcomes in Diabetes, Hypertension

Women with diabetes are at a higher risk of a number of 

 if they become pregnant, including preterm birth, low or high birth weights, stillbirth, and congenital anomalies. 

Existing evidence has shown that lifestyle interventions can help reduce complications and improve outcomes in patients with diabetes, but whether the complications associated with pregnancy can be reversed is less well-understood. The problem is particularly troublesome in terms of 

, which is a growing problem in many parts of the world.

Helen R. Murphy, MD, of the University of East Anglia, and colleagues, recently completed a 

 of more than 15,000 pregnancies in the United Kingdom, Wales, and the Isle of Man that were completed between 2014 - 2018 and included in the UK’s National Pregnancy in Diabetes database. 

 asked Murphy to discuss what her findings and what they say about the benefits of intervention.

 Diabetes in pregnancy has been studied before, but your study is notable for its size and scope. Half of the pregnancies were in women with type 1 diabetes (T1D) and half were in women with type 2 diabetes. What are the implications of having such a large study population?

Yes, this is by far the largest contemporary study in diabetes pregnancy. Historically there have been some studies of 5,000 pregnancies in women with type 1 diabetes but usually over more than a 15-year time period (eg Sweden 1991-2003), so by the time they’re published these are already outdated. Our data are contemporary and very relevant to current clinical practice. In particular, no previous study has included large numbers of women with type 2 diabetes, which is a growing concern in women of reproductive years, especially those from disadvantaged or Black and minority ethnic groups.

Your study identified maternal glycemia and body mass index (BMI) as key modifiable risk factors in pregnant women with diabetes. How should physicians advise women with diabetes who plan to become pregnant?

There was an important impact of maternal pre-pregnancy BMI on glucose levels during pregnancy, so I think encouraging women to optimize their dietary intake and enter pregnancy with as near as possible to a healthy weight before pregnancy is a really important component of planning for pregnancy both in T1 and in T2D.

Should the emphasis be on making interventions prior to pregnancy, or can meaningful changes also be made during pregnancy?

During pregnancy, efforts can be made to limit excessive gestational weight gain, but it’s too late to ‘undo’ the effects of overweight/obese BMI at pregnancy entry.

Was there any particular finding that surprised you?

 I was surprised about the impact of maternal weight in T1D. We already knew that maternal glycemia was important, but I wasn’t aware that early pregnancy BMI had such a strong impact on maternal glucose levels during pregnancy and thus also on pregnancy outcomes.

In T2D, I expected maternal obesity to have an impact, but was surprised at the impact of maternal glucose – which was far stronger than expected.

What are the key takeaways for clinicians?

The good news is that maternal glucose is relatively easily modifiable in T2D pregnancy, so the take-home messages for me were to focus a bit more on maternal weight before pregnancy in T1D and on maternal glucose levels during pregnancy in T2D pregnancy.

The other key message is that changes are needed across all clinics in order to intensify glycemic management. In T1D that means the introduction of [continuous glucose management] for all pregnant women in all maternity clinics, and for T2D we have to get serious about pre-pregnancy diabetes prevention and weight management programs.

Helen R. Murphy, MD, explains that physicians who take a proactive approach to diabetes management in women planning to become pregnant can make meaningful reductions in risk.

Q&A: How Can Clinicians Reduce Risk in Pregnant Women with Diabetes?

Intensive lifestyle intervention (ILI) programs can lead to long-term benefits in estimated glomerular filtration rate (eGFR), cholesterol, and serum creatinine even if patients are unable to maintain their weight loss, according to new research.

However, the study also showed that patients who regained the weight lost during the program saw rapid deterioration in hemoglobin A1c and serum triglycerides, but not systolic blood pressure (SBP).

Obesity is a major contributing factor to rising rates of 

, and patients who develop diabetes and are obese are at a higher risk of complications such as kidney disease. As such, these patients are often recommended for weight-loss programs or, in some cases, 

Investigators from the Joslin Diabetes Center at Harvard Medical School wanted to find out what would happen to real-world patients who took a 12-week ILI program called Why WAIT? (Weight Achievement and Intensive Treatment) and then were tracked for 5 years. Specifically, the investigators wanted to know how the program would affect long-term weight loss and renal function in patients with diabetes.

To find out, they recruited 104 patients with diabetes, 86.6% of whom had type 2 diabetes; the remainder had type 1 diabetes. The patients had an average age of 53.8 years and had a median duration of diabetes of 10.7 years. After 1 year, patients were stratified into 2 groups: those who had maintained at least 7% weight loss (Group A; 49.1%) and those who had not (Group B; 50.9%).

At baseline, the 2 groups had similar scores in terms of serum creatinine, eGFR, blood urea nitrogen (BUN), and albumin/creatinine ratio, or cardiovascular risk factors. The only area where a significant difference existed at baseline was triglyceride levels, which was significantly lower in Group B than Group A (117.9 mg/dL vs. 149.3 mg/dL, 

The patients in both groups lost an average of 8.8 kg at 1 year, and after 5 years, the average weight loss was 6.2 kg. The 5-year weight-loss broke down to an average of 8.3 kg in group A and 4.2 kg in group B.

Both groups saw improvements in SBP, but only group B’s improvement reached statistical significance (from 128.6 mmHg to 121.4 mmHg, 

< .05). Both groups saw decreases in serum creatinine (group A: from 0.92 mg/dL to 0.85 mg/dL, 

< .01; group B: from 0.92 mg/dL to 0.84 mg/dL, 

< .01). eGFR also increased in both groups (group A from 86.0 mL/min/1.73 m2 to 97.7 mL/min/1.73 m2, 

< .001; group B from 84.3 mL/min/1.73 m2 to 97.2 mL/min/1.73 m2; 

< .01). No changes were noted in albumin/creatinine ratio.

On the other hand, A1c decreased by 0.3% in group A (

< .001) but increased by 0.9% in group B (

Corresponding author Osama Hamdy, MD, PhD, and colleagues said there are several possible reasons that renal function appeared to improve in these patients regardless of blood pressure or glycemic control improvement, such as a reduction in chronic inflammatory processes related to obesity and diabetes, or perhaps specific features of the Why WAIT program, a diet that includes low glycemic index carbohydrates, higher monounsaturated fat and fibers, and less sodium. However, the investigators said the current study was not designed to compare the Why WAIT program to other programs, and thus its particular benefits would need to be studied in a subsequent trial.

The authors noted some limitations, such as the lack of a control group and the fact that the study was conducted at a single tertiary care center. Still, the authors said the study gives an important window into the 

, showing that some of its renal function benefits are durable for 5 years.

“This improvement is seen with weight change over time and is not related to weight maintenance or weight regain after the intensive weight loss period,” they concluded. "This improvement is also independent of the change in systolic blood pressure and glycemic control.”

The Effect of Intensive Lifestyle Intervention on Renal Function in Patients with Diabetes and Obesity in Real-World Practice: A 5-Years Longitudinal Study

In the five-year post-program assessment, those who regained their lost weight still saw improvements in liver function.