Risk of Sepsis and Death Among Patients with Type 2 Diabetes


Editor: David L. Joffe, BSPharm, CDE, FACA

Study found sepsis was independently associated with a fourfold increased risk of death in patients with type 2 diabetes. 

The increased mortality rate among patients diagnosed with type 2 diabetes has been associated with sepsis due to its involvement with the impaired defense system of the host patient. There has been a growing body of research about the regulation of sugar in the body and its significance in developing sepsis and the consequential deaths among type 2 diabetes patients. One such study was conducted in Sweden to investigate the relationship between sepsis and HbA1c, and the cause of death among patients who have type two diabetes. Approximately 11 million sepsis deaths and 48.9 million cases were recorded globally in 2017 alone. This accounted for a whopping 19.7 % of global deaths recorded in the same year. Diabetes is a risk factor for sepsis because of its associability with the impaired defense system of the host patient. 

This study involved 502,871 participants with type 2 diabetes that were obtained from the Swedish National Diabetes Register. The study’s main objective was to investigate the nature of the relationship between sepsis and HbA1c among patients diagnosed with type 2 diabetes, and to explore the relationship between mortality rate and sepsis among such patients. An observational and prospective study was conducted on adults more than 18 years of age with type 2 diabetes from the Swedish national register between 1 Jan. 2005 and 31 Dec. 2005. Additional information about the medical history and conditions of the study population was obtained from the inpatient register, Register for Longitudinal Integration Database for Health Insurance and Labor Market Studies, the cause of death register, and the prescribed drug register. R version 4.0.4 was used in data analysis. Percentages were used to represent categorical data, while median and interquartile ranges were used to represent and summarize continuous data. Cox regression analysis method was used to assess the period from diagnosis of type 2 diabetes to development of sepsis using Adjusted and Unadjusted for age and sex. 

The following cofounders were also included in the statistical test: country of origin, age, blood pressure, socioeconomic factors, diabetes treatment, smoking, body mass index, and sex. A likelihood test was used in testing for potential non-linearity among the data. Researchers, conducted two sensitivity analyses, excluding immunosuppressed patients because of their high propensity to infections. Patients receiving treatments with immunosuppressant medicines were also excluded from the study. Finally, an association between the mortality rate of type 2 diabetes patients and HbA1c was analyzed using the Cox regression technique before and at the end of the adjustment. The tests were two-tailed with a significance level of 0.05. The outcome of this study was measured from the period the patients were diagnosed with type 2 diabetes to the first episode of sepsis during the study period. The patient was considered positive with sepsis when the ICD-10 sepsis codes A41.9, R65.1, and R57.2 were recorded during death or inpatient registers. The result indicated that out of the total participants that participated in the study, 14,534 participants developed sepsis during the study period. The tables provided in the study summarize the baseline characteristics of sepsis patients. Sepsis follow-up median in years was 6.0 (3.6-8.3) in the sepsis group and 5.8 in the no sepsis group. A comparison of HbA1c of 48–52 mmol/mol (6.5–6.9%) and fully adjusted multivariable cox analysis yielded a sepsis ratio of .15 (95% CI 1.07–1.24)  “for HbA1c <43 mmol/mol (6.1%), 1.00 (0.93–1.07) for HbA1c 43–47 mmol/mol (6.1–6.5%), 0.93 (0.87–0.99) for HbA1c 53–62 mmol/mol (7.0–7.8%), 1.05 (0.97–1.13) for HbA1c 63–72 mmol/mol (7.9–8.7%), 1.14 (1.04–1.25) for HbA1c 73–82 mmol/mol (8.8–9.7%), and 1.52 (1.37–1.68) for HbA1c >82 mmol/mol (9.7%).” On adjusted analyses, it was found there was a strong U-shaped relationship between HbA1c and sepsis; the lowest risk was observed at 53 mmol/mol (7.0%). Furthermore, it was observed that sepsis was independently associated with a fourfold increased risk of death among individuals with type 2 diabetes. HbA1c was not associated with mortality among individuals who developed sepsis. 

Findings from this research indicate that the likelihood of patients with a high level of unregulated HbA1c to develop sepsis is high, a factor that increases the mortality rate of individuals with type 2 diabetes. The implication of these results on public health is significant because of its descriptive relationship between the adjustable and variable factor (HbA1c) and sepsis. The implication of these results to maintain the (HbA1c) level at 53 mmol/mol to prevent microvascular complications is also applicable to individuals with type 2 diabetes. Future research in factors that might affect the concentration of HbA1c is needed for understanding the relationship between the high level of HbA1c and the risk of development of sepsis. 

Practice Pearls:

  • Patients with an unregulated level of HbA1c have a high risk of developing sepsis, which increases the mortality rate of type 2 diabetes patients. 
  • Sepsis was responsible for a fourfold increase in the level of death risk among type 2 diabetes patients. 
  • Sepsis accounts for approximately 19.7% of all global deaths. 

 

Balintescu A, Lind M, Franko MA, et al. Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes. Diabetes Care. 2022;45(1):127-133. doi:10.2337/dc21-1050 

 

Njideka Aginam, PharmD Candidate, South College School of Pharmacy 

 

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