Being Underweight May Increase All-Cause Mortality Risk in T1D

Among patients with type 1 diabetes (T1D), those who are underweight are at a significantly higher risk of all-cause mortality compared with those considered “normal” weight, according to new research published in the Journal of Obesity & Metabolic Syndrome.

In this study, weight class was determined by body mass index (BMI), as determined by the World Health Organization:

• underweight, BMI <18.5 kg/m2
• normal weight, BMI between 18.5 to <25 kg/m2
• overweight, BMI, 25 to <30 kg/m2
• obese, BMI ≥30 kg/m2

The authors used the Newcastle-Ottawa Scale to assess risk of bias, and pooled hazard ratios (HRs) for all-cause mortality for each weight class were calculated in reference to the normal weight group.

Large-scale prospective studies on the topic and among the general population have found J- or U-shaped relationships, suggesting increased mortality risks in individuals who are either underweight or obese. However, several other meta-analyses have demonstrated a protective effect of being overweight or mildly obese, referred to as the “obesity paradox.”

Further, the review authors said there has not been a systematic review done before on the relationship between BMI and mortality risk among patients with T1D, noting that inadequate evidence can lead to uncertainty and inconsistency in weight management among those with T1D.

“Prior reports on BMI and mortality among patients with T1DM are limited, and many of the existing studies omitted the assumption of non-linear association, drawing a hasty conclusion of a non-significant or inverse relationship,” they said.

The current systematic literature review included 3 prospective studies involving 23,407 adults. T1D duration ranged from 19 to 24 years and the mean or median follow-up duration varied among the studies, ranging from 8.5 years to 18.2 years.

The studies included the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) by Conway et al, the Vestberg et al study based on Swedish National Diabetes Registry (NDR) data, and the Dahlström et al study based on the Finnish Diabetic Nephropathy (FinnDiane) study data.

In the EDC study, normal weight was associated with the lowest mortality risk, while obesity was associated with the highest. However, in the other 2 studies, being overweight was linked to the lowest risk, and being underweight was linked to the highest risk.

The pooled analysis demonstrated that having underweight BMI increased the risk of all-cause mortality by 3.4 times compared with normal BMI (95% CI, 1.67-6.85).

“One possible explanation for the higher mortality from underweight in patients with diabetes is a hyperglycemia-induced exacerbation of protein catabolism and oxidative muscle damage, leading to restricted mobility and frailty,” the authors said. “It is also possible that other comorbidities in underweight individuals with diabetes may be linked to increased mortality, such as malignancy, gastrointestinal motility disorders, infection, stroke, dementia, or periodontal disease.”

While not statistically significant, the overweight and obese weight groups showed a tendency toward lower (HR, 0.90; 95% CI, 0.66-1.22) and higher (HR, 1.36; 95% CI, 0.86-2.15) mortality risks, respectively, compared with the normal weight group. The authors noted this likely due to the heterogeneity of results across the 3 studies.

Originally, there was a fourth study included in the review, but it was excluded due to a lack of baseline data for patients with T1D and the fact it was considerably heterogeneous compared with the other 3 studies. However, the study demonstrated similar results, showing a 2.83 times greater mortality risk in the underweight group compared with the normal weight group.

Limitations of this review include the significant level of heterogeneity among the included studies, the inability of BMI to differentiate between body fat and muscle mass, the lack of data to assess the effect of weight change over time, and the inability to evaluate outcomes beyond all-cause mortality like cardiovascular diseases.

“Despite these limitations, our report is the first systematic review of the relationship between BMI and mortality in patients with T1DM,” the authors said. “The limitations of this study stem primarily from the small number of available longitudinal studies on T1DM, which supports the need for more research in this area.”

Reference

Jung HN, Kim S, Jung CH, Cho YK. Association between body mass index and mortality in type 1 diabetes mellitus: a systematic review and meta-analysis. J Obes Metab Syndr. Published online June 7, 2023. doi:10.7570/jomes22061