Journal reference: Danquah I, Bedu-Addo G, Mockenhaupt F. Type 2 diabetes mellitus and increased risk for malaria infection. Emerg Inf Dis 2010; 16 (1): 1601-1604 ^[1]

Link: http://dx.doi.org/10.3201/eid1610.100399

Published: October 2010

Evidence cookie says...

There may be an association between type 2 diabetes and malaria infection.  The evidence is low in quality and unreliable. Nevertheless, this finding reinforces current travel advice for travellers to malaria endemic regions (mosquito avoidance, protective clothing, chemoprophylaxis).

Article details:

Study design:

Study aim:

Study aim was not clearly stated, however implied it attempted to define “risk factors” for type 2 diabetes and hypertension.

Study conclusion:

This study provides evidence for increased risk for P. falciparum infection in patients with type 2 diabetes mellitus.

Critical appraisal:

Methodology:

Participants: who was studied?

• Total 1466 participants
• Patients with type 2 diabetes (n-495) and hypertension (n- 451) between August 2007- June 2008 in a teaching hospital in Ghana.
• Control group consisted of recruited community members, patient relatives or friends (n= 222); outpatient department patients (n= 150) and staff members (n= 148)

Outcomes: what was measured?

• History of fever or recent infection
• Microscopic blood film examination
• PCR for malarial parasites was performed
• secondary objectives: clinical and biochemical parameters

• participants were assessed with medical history, social history, physical examination, blood and urinary analysis.
• blood was tested for fasting plasma glucose, haemoglobin, malarial parasites
• statistics: comparisons between groups done using Mann-Whitney U, Chi squared and Fisher exact tests → odds ratios and confidence intervals were determined
• multivariate analysis was performed for glucose concentrations

Are the trial results valid?

Internal validity: Wikipedia

Was the defined representative sample of patients assembled at a common point in the course of their disease?

Unclear.

• the definitions used to define diabetes included being medicated with oral hypoglycaemics
• there was no indication of compliance with oral medications, stage of disease or length of diagnosis of diabetes

Were they representative?

• the population appears to be representative of the population in Ghana, but is not representative of the Australian community which is culturally heterogeneous, and with different prevalence of both diabetes and malaria

Were the groups similar at the start of the trial?

No.

• participants with type 2 diabetes were significantly more likely to have been:
  • older (54.7 vs 47.1 years)
  • illiterate (45.8 vs 26.1%)
  • having no formal education (35.7 vs 16.5%)
  • living in crowded conditions (26.7 vs 15.3%)
  • unemployed (36.9 vs 17.5%)

Was patient follow up sufficiently long and complete?

Unclear.

• there was no information provided about the follow up or subsequent treatment outcomes for those with malaria and diabetes
• this study does not shed light on whether the apparent association with asymptomatic carriage of malarial parasites is clinically significant and led/leads to malaria

If subgroups with different prognoses are identified, did adjustment for important prognostic factors take place?

Yes.

• subgroup analysis included a multivariate model examining incremental increases in blood glucose concentration versus risk of malaria
• it concluded that each mmol/L increase in blood glucose resulted in a 5% increased risk for P. falciparum infection, with a significant threshold reached at 8.6mmol/L

What were the results?

Outcome

• overall 0.9% of participants had malaria parasites seend on microscopy where as 14.1% were positive by PCR analysis
• statistically significant adjusted odds ratio (OR) was calculated between Type 2 diabetes group versus control group:
  • OR = 1.68, 95% CI 1.06-2.65

Will the results help me care for my patient?

External validity: Wikipedia

Are the participants different to my patient?

• homogeneous population in Ghana does not have broader applicability to Australian population (e.g., genetic factors may play a role in susceptibility to malaria; G6PD deficiency)
• this study was done in a country where malaria is endemic, in a population with constant exposure presumably some degree of baseline immunity
  • this may account for why those “infected” with malarial parasites were asymptomatic and afebrile
  • this may not be the case in the Australian population travelling to a malaria endemic country

Will this evidence make a clinically important impact on my conclusions about what to offer to tell my patients?

• this study describes an interesting observation: that people with Type 2 diabetes have an increased risk of malaria
• this may be of interest to diabetic travellers to a malaria endemic region, and reinforces the need for mosquito avoidance, mosquito repellent, protective clothing, and malaria prophylaxis

Study weaknesses (summary)

• screening in asymptomatic population may not reflect clinically significant infection
• there was a very low rate of positive malaria microscopiy of 0.9% overall, reflecting the low pre test probability in an asymptomatic population
• use of PCR to diagnose malaria is not the recommended diagnostic test, and may be overly sensitive in detection of malarial parasites.
• PCR may detect non viable malarial parasites, and may not reflect active disease
• there were substantial differences between the cases and their controls

Study strengths (summary)

• recruitment of cases and controls and the numbers achieved in the study considering the setting

Biases and conflicts of interests

• the study was supported by a grant from HemoCue, a manufacturer of diagnostic point of care devices

Clinical relevance to primary health care

This association between type 2 diabetes and Plasmodium falciparum infection in this study is interesting but hardly definitive.  The group with type 2 diabetes were substantially different to the control group without diabetes and many of these demographic factors are conceivably risk factors for malaria (older and greater socioeconomic disadvantage).  Causative conclusions cannot be made.

Nevertheless, the finding is of relevance to diabetic travellers to a malaria endemic region.  It reinforces current travel advice for mosquito avoidance, protective clothing and chemoprophylaxis.

References

1. Danquah I, Bedu-Addo G, Mockenhaupt F. Type 2 diabetes mellitus and increased risk for malaria infection. Emerg Inf Dis 2010; 16 (1): 1601-1604

Editor: Michael Tam