Is Diabetes a Risk Factor for a Severe Clinical Presentation of Dengue? - Review and Meta-analysis

Background: The mean age of acute dengue has undergone a shift towards older ages. This fact points towards the relevance of assessing the influence of age-related comorbidities, such as diabetes, on the clinical presentation of dengue episodes. Identification of factors associated with a severe presentation is of high relevance, because timely treatment is the most important intervention to avert complications and death. This review summarizes and evaluates the published evidence on the association between diabetes and the risk of a severe clinical presentation of dengue. Methodology/Findings: A systematic literature review was conducted using the MEDLINE database to access any relevant association between dengue and diabetes. Five case-control studies (4 hospital-based, 1 population-based) compared the prevalence of diabetes (self-reported or abstracted from medical records) of persons with dengue (acute or past; controls) and patients with severe clinical manifestations. All except one study were conducted before 2009 and all studies collected information towards WHO 1997 classification system. The reported odds ratios were formally summarized by random-effects meta-analyses. A diagnosis of diabetes was associated with an increased risk for a severe clinical presentation of dengue (OR 1.75; 95% CI: 1.08–2.84, p = 0.022). Conclusions/Significance: Large prospective studies that systematically and objectively obtain relevant signs and symptoms of dengue fever episodes as well as of hyperglycemia in the past, and at the time of dengue diagnosis, are needed to properly address the effect of diabetes on the clinical presentation of an acute dengue fever episode. The currently available epidemiological evidence is very limited and only suggestive. The increasing global prevalence of both dengue and diabetes justifies further studies. At this point, confirmation of dengue infection as early as possible in diabetes patients with fever if living in dengue endemic regions seems justified. The presence of this co-morbidity may warrant closer observation for glycemic control and adapted fluid management to diminish the risk for a severe clinical presentation of dengue. Author Summary: Both dengue and diabetes have reached epidemic dimensions and pose a joint threat to a large proportion of populations in low- and middle-income countries. Dengue is no longer a disease primarily affecting children. Therefore the influence of non-communicable diseases such as diabetes, which are increasingly prevalent in adults, on the clinical presentation of a dengue episode becomes a public health priority. We conducted a systematic literature review to assess the available evidence on the effect of diabetes mellitus (DM) on the clinical presentation of dengue. The meta-analysis of published evidence combined with supporting biological evidence point to an increased risk for potentially life threatening symptoms of dengue among patients with diabetes. The current evidence is limited by statistical power and other study limitations and does not allow conclusions about a causal effect of diabetes. Yet, based on the currently available evidence, diabetes patients with fever and living in a dengue endemic region should seek confirmation of dengue infection as early as possible. Diabetes should be considered in the triage of patients for close observation and early intervention, which are challenges, particularly during dengue outbreaks. Timeliness of intervention is the most important factor averting serious complications and death in patients with acute dengue.