Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative, 2025, Soff+

SNT Gatchaman

SNT Gatchaman

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Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative N3C
Samuel Soff, Yun Jae Yoo, Carolyn Bramante, Jane E B Reusch, Jared Davis Huling, Margaret A Hall, Daniel Brannock, Til Sturmer, Zachary Butzin-Dozier, Rachel Wong, Richard Moffitt, The N3C Consortium

INTRODUCTION
Elevated glycosylated hemoglobin (HbA1c) in individuals with type 2 diabetes is associated with increased risk of hospitalization and death after acute COVID-19, however the effect of HbA1c on Long COVID is unclear.

OBJECTIVE
Evaluate the association of glycemic control with the development of Long COVID in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS
We conducted a retrospective cohort study using electronic health record data from the National COVID Cohort Collaborative. Our cohort included individuals with T2D from eight sites with longitudinal natural language processing (NLP) data. The primary outcome was death or new-onset recurrent Long COVID symptoms within 30–180 days after COVID-19. Symptoms were identified as keywords from clinical notes using NLP in respiratory, brain fog, fatigue, loss of smell/taste, cough, cardiovascular and musculoskeletal symptom categories. Logistic regression was used to evaluate the risk of Long COVID by HbA1c range, adjusting for demographics, body mass index, comorbidities, and diabetes medication. A COVID-negative group was used as a control.

RESULTS
Among 7430 COVID-positive patients, 1491 (20.1%) developed symptomatic Long COVID, and 380 (5.1%) died. The primary outcome of death or Long COVID was increased in patients with HbA1c 8% to <10% (OR 1.20, 95% CI 1.02 to 1.41) and ≥10% (OR 1.40, 95% CI 1.14 to 1.72) compared with those with HbA1c 6.5% to <8%. This association was not seen in the COVID-negative group. Higher HbA1c levels were associated with increased risk of Long COVID symptoms, especially respiratory and brain fog. There was no association between HbA1c levels and risk of death within 30–180 days following COVID-19. NLP identified more patients with Long COVID symptoms compared with diagnosis codes.

CONCLUSION
Poor glycemic control (HbA1c≥8%) in people with T2D was associated with higher risk of Long COVID symptoms 30–180 days following COVID-19. Notably, this risk increased as HbA1c levels rose. However, this association was not observed in patients with T2D without a history of COVID-19. An NLP-based definition of Long COVID identified more patients than diagnosis codes and should be considered in future studies.

Link | PDF (BMJ Open Diabetes Research & Care) [Open Access]
 
It is interesting that Beentjes pulled out insulin resistance as going with ME/CFS.

Maybe poor glycemic control is an aggravating factor if there is ME/CFS or LC present. I doubt that it is involved in the mechanism of the illness directly but things may turn out in an unexpected way.
 
Interestingly, we found that metformin, SGLT-2 inhibitors and GLP-1 agonists were associated with a lower risk of Long COVID and death in the 6 months following COVID infection, which has also been seen in other studies. Metformin has been shown to decrease the risk of Long COVID, with hypothesized mechanisms of action including reduction in oxidative stress and inflammation, and prevention of senescent phenotype induction by SARS-CoV-2. The role of other hypoglycemic agents in mitigating Long COVID is under investigation. Insulin use was associated with an increased risk of Long COVID or death, and may be a marker for more severe or longer duration of diabetes and hyperglycemia, a trend noted in previous studies as well.
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Surprisingly, in COVID-negative patients, higher BMIs were associated with a reduced risk of Long COVID-like symptoms or death following a negative COVID test. This trend was not observed in the COVID-positive cohort. One possible explanation for this paradoxical finding may be that higher BMI individuals may be more likely to be on GLP-1 or SGLT-2 medications which reduce symptoms and death. The ‘obesity paradox’ has been noted in several studies, which found patients with elevated BMI have lower all-cause and cardiovascular mortality compared with patients of normal weight.
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All of these findings lately are making me think about the fact that I have had 'blood sugar crashes' since my late teens, the time when I developed several other issues that seem to have been almost a pre-ME or very mild-ME state. In these episodes I would get very woozy and dizzy and disorientated and feel quite unwell. It usually would resolve shortly after eating something but not always. When I got ME at 26 they got worse and progressively became even worse as I sank down through moderate into severe. Now they often occur in my worst crashes and can be totally unrelated to whether or not I've eaten recently. I have been tested for diabetes quite a few times in my life because of these episodes.

My partner also has ME and also gets very light headed from blood sugar type episodes.

I'm not sure how typical this is.
 
I’ve never measured blood sugar — but my POTS and some ME flares really feel similarly to how people describe low blood sugar episodes.

[My caregivers make me try random diets and I’ve been off sugar for a while so that may contribute — but I’m too energyless to fight it and I don’t have the capacity to feed myself so I kind of just go along with their diets]
 
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