New research suggested that weight-loss interventions could potentially reduce the risk of severe infections in individuals with diabetes. The study, presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting, provided evidence indicating a causal relationship between higher body mass index and severe infections.

Rhian Hopkins and Ethan de Villiers, from the University of Exeter Medical School, conducted the study using data from the UK Biobank, which contained medical and genetic information on approximately 500,000 UK residents. They employed Mendelian randomization, a genetic epidemiology technique that used genetic variants as instrumental variables to infer causality between an exposure (in this case, body mass index [BMI] and glycemic control) and an outcome (severe infections). This method helped overcome limitations of traditional observational studies by reducing confounding and reverse causation. By using genetic variants associated with BMI and glycemic control, the researchers could estimate the causal effect of these factors on infection risk.

The researchers analyzed information on 486,924 participants, categorizing them into three groups: those hospitalized for bacterial infections (n=64,005), those hospitalized for viral infections (n=14,562), and an infection-free control group (n=408,357).

Key Findings

• BMI and infection risk: a 5-point increase in BMI (for instance, an increase from 30 kg/m² to 35 kg/m²) was associated with a 30% higher likelihood of hospitalization for bacterial infections. Similarly, a 5-point BMI increase correlated with a 32% higher risk of severe viral infections.
• Glycemic control and infection risk: each 10 mmol/mol increase in HbA1c was linked to a 32% higher risk of bacterial infection hospitalization and a 29% higher likelihood of severe viral infections.
• Causal relationships: Mendelian randomization analysis suggested that higher BMI was a causal factor for severe bacterial and viral infections. However, mild hyperglycemia did not appear to have a causal relationship with severe infections.

While the study did not specifically focus on individuals with diabetes, the findings were potentially relevant to this population due to their increased vulnerability to infections. Ms. Hopkins noted, "Up to one in three hospitalizations in people with diabetes are for infections, and people with diabetes are twice as likely to be hospitalized with infections than the general population. They are also at high risk of [hospital] readmission."

In a follow-up interview, Louise Vennells, Head of External Communication at the Faculty of Health and Life Sciences, University of Exeter, emphasized the importance of these findings for clinical practice. "Our study strongly suggests that we need an emphasis on weight management as part of infection prevention, given the causal role we have found," Vennells stated. "Our results indicate that we can reduce infection risk by helping people lose weight."

Vennells highlighted the potential of recent medical advancements in this area: "In the last few years, we have seen a whole new range of weight loss treatments become available which could support weight loss in people who are overweight and most vulnerable to infection." She added that weight loss strategies should be tailored to each individual, noting the increasing availability of medications that help with both diabetes control and weight loss.

The research suggested that weight-loss interventions could be a potential strategy to reduce the risk of severe infections in high-risk individuals, including those with diabetes. Clinicians could consider discussing weight-loss options with patients who have a high BMI and are at risk of severe infections or hospital readmission due to infections.

Regarding specific subgroups that might benefit most from these interventions, Vennells commented, "We should consider targeting weight loss interventions to people who are overweight with diabetes who have the highest infection risk. This particularly includes people who have been admitted to hospital with severe infections in the past, who we know are at very high risk of readmission with another infection."

While the study did not establish a causal relationship between mild hyperglycemia and severe infections, Vennells noted that more research is needed in this area. "We still need to learn more about the impact of moderate and severe hyperglycaemia on infection risk, but this is challenging using genetic methods," she explained. "We don't yet know if moderate or severe hyperglycaemia cause infection, but the observational data does suggest that it is likely."

Vennells emphasized that glycemic control remains crucial: "It remains important that we focus on controlling blood sugar levels because we know this prevents other diabetes complications."

"While this message may be particularly relevant to people with diabetes, it applies more widely, too," Ms. Hopkins added.

The authors declared no conflict of interest. This study was presented at EASD 2024; the findings are considered preliminary until published in a peer-reviewed journal.