Correlation of Glycemic Control and Rates of Infection 

Study finds that each 1% elevation in HbA1c increased risk for cellulitis in diabetes patients. 

It is well established that people with diabetes are predisposed to common infections, such as cellulitis and pneumonia, yet the relationship between the level of glycemic control and the rate of infection is undetermined. The latest diabetes medications allow targeting a lower HbA1c level with a reduced risk of hypoglycemia compared to insulin therapy. Infections such as pneumonia and cellulitis have a more significant bearing in individuals with diabetes. Poor glycemic control has been correlated with poor outcomes, such as microvascular complications.  

Still, the relationship between glycemic control and the risk of infection is uncertain. There have been numerous analyses with inconsistent results. A population-based case-control study showed that poor long-term glycemic control amplified the risk of hospitalization with pneumonia for patients with diabetes compared with patients without a diagnosis of diabetes. This research aimed to investigate the relationship between glycemic regulation and the occurrence of an infection in patients with type 2 diabetes. 

This prospective cohort study assessed the association between glycemic control in patients with diabetes and the incidence of various infections using the Meuhedet HMO database. The Meuhedet database uses a diabetes register to identify all patients with diabetes. The infections chosen for analysis were cellulitis, cholecystitis, diverticulitis, upper respiratory tract infection (URTI), UTI, influenza, sinusitis, herpes zoster, and pneumonia. The period of research was from October 2014 until September 2017. Glycemic control was assessed using the HbA1c test. After the first HbA1c test during the study period, a search was then performed for an infection diagnosis 60 days after the test. This research design allowed an excellent estimate of the glycemic control of a patient at the time of the infection 

4,806 patients had at least one infection over 60 days after the first HbA1c examination. There were 3,161 cases of URTI, 1,004 cases of UTI, 441 cases of pneumonia, and 407 cases of cellulitis among those infections. For all subsequent infections, the mean HbA1c test result was 7.2 percent, the mean HbA1c test results were 7.6 percent and 7.2 percent, respectively, with subsequent cellulitis and pneumonia infections; the mean HbA1c test results were slightly lower at 7.2 percent and 7.1 percent for patients diagnosed with URTI and UTI. 

This study found that an HbA1c greater than 7.5% was associated with a 1.4-fold increased risk of cellulitis. There was a 1.12- fold increased risk of cellulitis for every 1% elevation in HbA1c. There was a tendency for higher HbA1c levels and higher occurrence of pneumonia. The study did not find a positive association between poor glycemic control and the incidence of UTI. For patients with UTI, HbA1c was slightly lower, but no association was found in multivariate analysis. Researchers found an association between URTI and HbA1c, 7.5%. This may be because patients who frequently visit their physician tend to have better medication adherence and glycemic control. Patients who visit less often may simply self-medicate for URTI. A limitation of this study is that it used a real-world database that relies on many different physicians’ clinical diagnoses. As an observational study, it did not allow adjustment for unknown confounders.  

This research adds to existing evidence indicating that cellulitis is correlated with poor glycemic control and is the first to quantify the additional risk as a glycemic control variable evaluated as a continuous variable. These findings have clinical effects that are probable. Cellulitis was a common infection in the cohort study, with 72.6 cases per 1,000 patient-years. Therefore, a 1.4-fold increase is clinically significant. Future studies should explore the potential effectiveness of treating chronic cellulitis with stronger glycemic regulation if additional drugs are not contraindicated. 

Practice Pearls: 

• An HbA1c greater than 7.5% was associated with an increased risk of cellulitis and pneumonia.  
• Future research should examine the possible efficacy of treating chronic cellulitis with tighter glycemic control if there are no contraindications to additional medications. 
•  A lower HbA1c level may reduce the risk of cellulitis and pneumonia. 

Zacay, Galia, et al. “Glycemic Control and Risk of Cellulitis.” Diabetes Care, American Diabetes Association, February 1, 2021  

Stratton, I M et al. “Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.” BMJ (Clinical research ed.) vol. 321,7258 (2000):  

Shalonda Kimble, PharmD Candidate, South College School of Pharmacy 

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