Impact of diabetes and poor glycaemic control on risk of bacteraemia with haemolytic streptococci groups A, B, and G

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Summary

Background

Diabetes has been associated with bacteraemia due to haemolytic streptococci but epidemiological evidence is limited.

Methods

We conducted a 15-year population-based case-control study of all adults with first-time bacteraemia with groups A, B, and G haemolytic streptococci and matched population controls. The study setting was Northern Denmark between 1992 and 2006. We computed odds ratios (ORs) for streptococcal bacteraemia according to diabetes and glycaemic control, using regression analysis for confounder adjustment.

Results

We identified 397 adult patients with bacteraemia due to haemolytic streptococci (median age 67 years, 51% women), of which 63 (17%) had diabetes. Persons with diabetes had a 2.1-fold increased risk of streptococcal bacteraemia compared with population controls (adjusted odds ratio (OR) 2.1; 95% confidence interval (CI), 1.5–2.9). For persons with type 1 diabetes, the adjusted OR was 14.8 (2.4–91.2). Longer diabetes duration and poor glycaemic control conferred higher risk estimates: adjusted OR 1.5 (0.8–3.0) for HbA1c level <7%, and OR 3.6 (1.6–8.1) for HbA1c level ≥9%. The association between diabetes and HS bacteraemia was independent of the underlying foci of infection and was strongest for group B streptococcal bacteraemia (OR 3.5; 1.8–7.0) and for group G streptococcal bacteraemia (OR 2.6; 1.6–4.4). There was no clear increase in risk for group A streptococcal bacteraemia (OR 1.2; 0.7–2.2).

Conclusions

Diabetes is a strong risk factor for group B and group G, but not group A, haemolytic streptococcal bacteraemia. The risk increase is particularly high for type 1 diabetes, long diabetes duration, and poor long-term glycaemic control.

Introduction

Haemolytic streptococci (HS) are an increasingly common cause of severe bacteraemia and sepsis worldwide.1, 2 A recent population-based surveillance study from the US showed that the incidence of adult invasive group B streptococcal (GBS) infection has more than doubled between 1990 and 2007 to 7.3 cases per 100,000 persons in 2007, and now approaches the incidence of invasive pneumococcal infections in elderly people.3 Similarly, there have been reports of global increases in invasive group A streptococcal (GAS) infections with average annual incidences of 2.8 cases per 100,000 in eight European countries in 2003–2004,4 and between 3.5 and 4.8 cases per 100,000 in the US 1995–19995 and in Canada 1999–2004.2, 6 Group G streptococci (GGS) are also increasingly recognized as causing invasive infections, with annual incidences of 1.8 per 100,000 in Canada 1999–20042 and 2.2 per 100,000 in Denmark in 2002.1

The increasing prevalence of adults with chronic medical conditions remains the most plausible explanation for the increasing incidence of adult invasive HS disease. In particular, several studies have indicated a strikingly high prevalence of diabetes among patients with invasive HS disease.7 For GBS invasive disease, many case series from both North America, Asia and Europe have reported diabetes prevalences of approximately 30%.8, 9, 10, 11, 12, 13, 14, 15 Among patients with severe GAS infections, 8% (with a wide range of 0%–22%) had diabetes in a recent 2-year prospective surveillance study in 11 European countries.4 In Denmark in 1999–2002, Ekelund et al. found comparable prevalences of diabetes in patients with invasive infection due to GAS (11%), GBS (14%) and GGS (16%).1 However, most available studies have been hampered by absence of proper control groups and lack of confounder control. Only two case-control studies of HS invasive disease have reported on the role of diabetes among a variety of risk factors. In Factor et al.’s GAS case-control study including 139 patients with invasive GAS disease in the US and Canada16 the relative risk associated with diabetes was 2.1 among persons 18–44 years old (crude odds ratio (OR), 2.1; 95% confidence interval (CI), 0.6–7.1) (adjusted OR not reported). Among persons 45+ years old the crude OR was 2.3 (95% CI, 1.2–4.5) and the adjusted OR 2.3 (95% CI, 1.1–4.8). In Jackson et al.’s GBS case-control study of 219 nonpregnant adult GBS cases the adjusted OR for diabetes was 3.0 (95% CI, 1.9–4.7).17

Diabetic persons may have increased susceptibility to HS bacteraemia for several reasons, including hyperglycaemia and related effects on phagocytic function and cell-mediated immunity, and coexisting morbidities and diabetic complications such as foot and leg ulcers.7 The impact of poor glycaemic control on the risk of HS bacteraemia in diabetic persons has to our knowledge never been examined. Given the rising incidence of HS bacteraemia and the rapidly increasing prevalence of diabetes worldwide,18 it is important to quantify the risk of HS bacteraemia associated with diabetes and poor glycaemic control. Using population-based databases that included all bacteraemia episodes, we examined diabetes as a risk factor for HS bacteraemia in North Denmark over a 15-year period.

Section snippets

Setting

We conducted this population-based case-control study in the Danish former county of North Jutland, now a part of the North Denmark Region, with a mixed rural and urban population of approximately 500,000 people. The Danish National Health service provides tax-supported health care for all residents, including free access to primary care and hospitals, and reimbursement of a portion of the cost of most prescription drugs.19 The civil registration number, a unique personal identifier assigned to

Descriptive data

The study involved 397 adult patients with HS bacteraemia (median age 67 years, 51% women). Thirty eight percent of the patients had GAS bacteraemia, 22% had GBS bacteraemia, and 32% had GGS bacteraemia, with a skin or soft tissue focus of infection as the overall most prevalent source (Table 1).

Characteristics of HS bacteraemia cases and controls are shown in Table 2. Compared with population controls, bacteraemia patients were much more likely to have a history of hospital-diagnosed

Discussion

Our population-based study provides strong evidence of a substantially increased risk for GBS and GGS bacteraemia among diabetic individuals, independent of the underlying focus of infection. In contrast, diabetes did not materially increase the risk for GAS bacteraemia in our study. The excess risk for HS bacteraemia is most pronounced for persons with longer diabetes duration and poor glycaemic control, and is particularly high for type 1 diabetes.

Our confounder-adjusted results for GBS

Conclusion

In conclusion, this study provides evidence that diabetes is a strong risk factor for HS bacteraemia group B and G episodes, but not for group A episodes. The risk of HS bacteraemia increases with diabetes duration and is associated with poor long-term glycaemic control. Among young and middle-aged adults, more than 10% of HS bacteraemia episodes may be caused by diabetes. Since there is increasing evidence that diabetes may also be associated with worse outcome of severe infections due to

Conflicts of interest

All authors do not have a commercial or other association that pose a conflict of interest.

Acknowledgements

The Department of Clinical Epidemiology is a member of the Danish Center for Strategic Research in Type 2 Diabetes (Danish Research Council, grant no. 09-075724 and 10-079102). Sia Kjeldsen has received a 3-month scholarship from Aarhus University Hospital, Aalborg.

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