Sub-Saharan Africa (SSA) accounts for 80% of the global HIV burden and 60% of new HIV infections [
The majority of studies on dysglycemia in PLHIV come from high-income country settings (HIC), and as a result, the extent to which identified risk factors associated with dysglycemia burden, morbidity, and mortality can be extrapolated to SSA populations is unclear. PLHIV in SSA have several characteristics that may lead to differences in dysglycemia risk compared to PLHIV in HIC. These include (i) higher levels of inflammation biomarkers such as high sensitivity C-reactive protein (hsCRP) and fibrinogen in HIV-negative SSA populations compared to HIC populations potentially reflecting a higher background inflammatory state [
HIV and dysglycemia are independent risk factors for cardiovascular disease (CVD) and CVD events, such as stroke and myocardial infarction, chronic kidney disease (CKD), neurocognitive decline, and other comorbidities [
We searched PUBMED using the keywords “diabetes,” “insulin resistance,” “glucose intolerance,” “dysglycemia,” “sub-Saharan Africa,” “HIV,” “prevalence,” “pathophysiology,” “risk factors,” “mortality,” “morbidity,” and their related terms. Studies were considered for inclusion if they were original research articles and described any of the following: the prevalence, risk factors, pathophysiology, or clinical outcomes of dysglycemia (CVD-related morbidity and mortality, and microvascular or macrovascular complications) in PLHIV in SSA. Additionally, we screened the reference lists of retrieved articles for other sources. Articles published through August 2017 were considered, with no restriction on the start date. We excluded conference abstracts, narrative or systematic reviews, and articles not in English. Results were summarized descriptively in narrative and tabular form. No additional statistical methods were deployed as we did not pool data.
Prevalence data came from 15 studies across 8 countries (Figure
Prevalence of diabetes mellitus (DM) and prediabetes (pre-DM) in HIV-infected patients.
Summary of studies on prevalence and risk factors of diabetes mellitus and prediabetes among PLHIV.
Author(s) and country (reference number) | Study design and population | Dysglycemia definition | Prevalence | Identified independent risk factors |
Comments |
---|---|---|---|---|---|
Noumegni et al., Cameroon [ |
Cross-sectional: 452 adults age 30–74 years of whom 400 were on ART | DM: FPG ≥7.0 mmol/l on two separate occasions at least 48 hours apart or self-report of taking antidiabetic medicine | DM: 2.0% | BMI ≥ 30 kg/m2 associated with insulin resistance: OR 2.28 | Patients on ART had significantly higher BMI, waist circumference, waist-hip ratio, obesity, and abdominal obesity compared to those not on ART |
Chimbetete et al., Zimbabwe [ |
Retrospective: 4110 PLHIV aged ≥ 16 years starting ART | DM: at baseline, an RBS > 11.0 mmol/l in the presence of DM symptoms or FPG > 7.0 mmol/l or known diagnosis of DM prior to ART initiation | DM: 0.77% | Male gender: aHR 2.31 |
While this was an incidence study of 4110 PLHIV starting ART, 42 of the 5467 PLHIV in the initial cohort were excluded due to prevalent DM defined as a known diagnosis of DM or DM diagnosed at the baseline visit |
Magodoro et al., Zimbabwe [ |
Retrospective: 1033 PLHIV aged ≥ 18 years on ART | Known diagnosis of DM as per patient records | DM: 2.1% | Associations with dysglycemia not reported | Median duration on ART was 5.3 years |
Levitt et al., South Africa [ |
Cross-sectional: PLHIV aged ≥ 18 years in three groups: 393 ART-naive PLHIV, 439 PLHIV on 1st line ART, and 108 PLHIV on 2nd line ART | DM: FPG ≥ 7.0 mmol/l or 2 hr glucose ≥ 11.1 mmol/l |
DM: |
Age (years): 35–44 (OR 1.82), 45–54 (3.27), and 55–64 (OR 4.75) |
1st line ART regimens comprised dual NRTI plus one NNRTI while 2nd line ART regimens comprised dual NRTI plus a boosted PI |
Isa et al., Nigeria [ |
Retrospective: 2632 ART-naive PLHIV aged ≥ 18 years | DM: RBS ≥ 11.1 mmol/l or FPG ≥ 7.0 mmol/l or self-reported use of antidiabetic drugs | DM: 2.3% | Age > 40 years associated with prevalent dysglycemia: aOR 3.5 |
At one year follow-up after initiating ART, an additional 5.3% of the cohort developed diabetes driving up prevalence to 7.6% |
Mohammed et al., Ethiopia [ |
Cross-sectional: 393 PLHIV aged ≥ 21 years of whom 285 were on ART and 109 were ART-naive | DM: FPG ≥ 7.0 mmol/l |
DM: 6.4% |
Age ≥ 40 years: aOR 4.8 |
Lack of OGTT may have underestimated the prevalence of DM and pre-DM |
Maganga et al., Tanzania [ |
Cross-sectional: Adults aged > 18 years in three groups: 150 PLHIV on ART for ≥2 years, 151 recently diagnosed ART-naive PLHIV, and 153 HIV-negative | DM: FPG ≥ 7.0 mmol/l or 2 hr glucose ≥ 11.1 mmol/l |
DM: |
ART use ≥ 2 years: aOR 5.72 associated with prevalent dysglycemia | HIV-negative participants were not aged- or sex-matched |
Oni et al., South Africa [ |
Retrospective: electronic prescription refill records for 32,474 receiving ≥ 1 prescription for HIV, TB, DM, or/and HTN medications | DM: prescription refill for either metformin, glibenclamide, or insulin | DM: 17% | Associations with dysglycemia not reported | Case ascertainment was not possible as details on how DM diagnosis had been made was not available |
Kagaruki et al., Tanzania [ |
Cross-sectional: 671 PLHIV aged ≥ 18 years of whom 354 were on ART and 317 were ART-naive | DM: FPG ≥ 6.1 mmol/l or prior known diagnosis | DM: |
Associations with dysglycemia not reported | Overall cases of DM were too low to assess between-group difference or associated risk factor relationships |
Ngatchou et al., Cameroon [ |
Cross-sectional: 108 ART-naive PLHIV and 96 HIV-negative aged-matched controls | IFG: FPG ≥ 5.6–6.9 mmol/lDM: FPG > 6.9 mmol/l | DM: |
Associations with dysglycemia not reported | Dysglycemia prevalence may have been underestimated due to lack of OGTT and exclusion of patients with known, or on treatment for, DM, hypertension or dyslipidemia, cigarette smokers or alcohol users, and patients with a first-degree familial history of DM |
Negin et al., South Africa [ |
Survey: 194 PLHIV and 2864 HIV (−) adults aged ≥ 18 years | Self- report of known DM | DM: |
Associations with dysglycemia not reported | Case ascertainment was not possible as DM diagnosis based on self-report |
Dave et al., South Africa [ |
Cross-sectional: 443 PLHIV on ART for ≥6 months and 406 ART-naive PLHIV | DM: FPG ≥ 7.0 mmol/L or 2 hr glucose ≥ 11.0 mmol/l |
DM: |
Male gender: OR 1.96 |
Dysglycemia prevalence difference was not statistically significant between on ART and ART-naive group and may be underestimated by the exclusion of known history of DM or IGT |
Anastos et al., Rwanda [ |
Cross-sectional: women aged ≥ 25 years divided into two groups: 606 ART-naive PLHIV and 218 HIV-negative | DM: FPG > 6.9 mmol/l or self-reported history of DM | DM: |
Associations with dysglycemia not reported | This analysis was based on the Rwanda Women’s Inter-association Study and Assessment and inclusion was based on the availability of fasting lipoprotein levels and not glucose levels |
Manuthu et al., Kenya [ |
Cross-sectional: 134 PLHIV on ART for ≥4 weeks and 161 ART-naive PLHIV | DM: FPG ≥ 7.0 mmol/l or 2 hr glucose ≥ 11.0 mmol/l |
DM: 1.5% |
No significant associations with dysglycemia reported | Excluded patients with known DM status thus may underestimate prevalence |
Mutimura et al., Rwanda [ |
Cross-sectional: 150 PLHIV on ART for ≥6 months and 50 HIV (−) controls | Dysglycemia: IFG > 5.6 mmol/l | PLHIV: |
Associations with dysglycemia not reported | Distinction was not made between DM and prediabetes |
ADA: American Diabetes Association; aHR: adjusted hazard ratio; aOR: adjusted odds ratio; ART: antiretroviral therapy; FPG: fasting blood glucose; HIV: human immunodeficiency virus; HTN: hypertension; IGT: impaired glucose tolerance; LDL: low-density lipoprotein; LDS: lipodystrophy; NNRTI: nonnucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; OGTT: oral glucose tolerance test; OR: odds ratio; PI: protease inhibitor; PLHIV: people living with HIV; PY: person-years; DM: diabetes mellitus; TB: tuberculosis.
Ngatchou et al. reported the highest DM (26%) and pre-DM (47%) prevalence in a cohort of 108 ART-naive PLHIV in Cameroon that was predominantly (74%) female, had a mean age of 39 years, and had a mean BMI of 25.1 kg/m2 [
Four studies compared dysglycemia (DM and pre-DM) prevalence between PLHIV on ART versus ART-naive and reported differing results [
Five studies compared the prevalence of dysglycemia between PLHIV and HIV-negative controls [
Commonly identified risk factors for dysglycemia in our reviewed studies included older age in six studies [
Obesity prevalence is rising in the general population and among PLHIV in SSA [
The handful of studies of IFG and DM risk factors among PLHIV in SSA highlights potential pathophysiologic features which may contribute to the development of glucose intolerance in the absence of more widely recognized risk factors, such as obesity or advanced age. Circulating inflammatory cytokine levels are elevated in many PLHIV on ART in SSA, due in part to impaired mucosal defenses, chronic gastrointestinal enteropathy, and opportunistic infections, which may have a role in the development of dysglycemia [
A study from Ethiopia found elevated low-density lipoprotein (LDL) was independently associated with the development of DM in predominantly non-overweight/obese PLHIV [
While most patients gain weight after starting ART, particularly those with a lower pretreatment BMI [
In a recent, large longitudinal study in Zambia and Tanzania of PLHIV who started ART at a low BMI, the risk of developing IFG or DM after treatment initiation was paradoxically
Summary of factors associated with prevalent or incident diabetes in studies of PLHIV from sub-Saharan Africa.
Data on morbidity and mortality attributable to cardiovascular, microvascular, and macrovascular complications associated with comorbid dysglycemia in SSA PLHIV are scarce. In a study in Malawi of 281 patients with DM, 14% of whom were PLHIV, vision-threatening diabetic retinopathy was not associated with HIV status [
While our review noted numerous gaps in the literature on dysglycemia in SSA PLHIV, we chose to highlight three specific areas that may form research priorities for future investigations. These are (i) the establishment of longitudinal PLHIV cohorts to improve our understanding of the causative associations between various risk factors and dysglycemia incidence, (ii) research into the interruption of progression from pre-DM to DM in SSA PLHIV, and (iii) studies on the clinical outcomes associated with comorbid HIV/DM.
While current studies show overlap between various risk factors that are associated with dysglycemia in SSA PLHIV, such associations remain correlative due to the use of cross-sectional and retrospective study designs in most analyses. An enhanced understanding of the causative risk factors may inform strategies to prevent dysglycemia in PLHIV. There is therefore a need for more longitudinal studies evaluating dysglycemia in SSA PLHIV cohorts. These may take the form of prospective observational studies that begin with a normoglycemic PLHIV cohort and follows them for a long period of time as has been done in some HIC settings [
The range of pre-DM prevalence (19% to 47%) was consistently high across our reviewed studies, representing an opportune area for research into interruption of disease progression in this cohort. Studies from the general population in HIC indicate that rates of pre-DM progression to overt DM may be decreased by 58% through the use of pharmacological interventions and lifestyle modification [
There is a paucity of data on clinical outcomes among SSA PLHIV with DM, particularly with respect to CVD mortality and morbidity, and microvascular/macrovascular complications of DM and/or HIV. DM and HIV are both CVD risk factors, portending an elevated risk in patients with comorbid HIV/DM. Furthermore, studies suggest that control of DM, and other NCD comorbidities such as dyslipidemia and hypertension, is poorer compared to HIV-negative individuals [
The prevalence of DM and pre-DM among PLHIV in SSA ranges from 1% to 26% and 19%–47%, respectively, reflecting an overall high burden of dysglycemia. However, variations in the study population assessed and diagnostic criteria limit firm conclusions. Older age, male gender, and an elevated BMI in the overweight/obese range are commonly associated risk factors for dysglycemia in SSA PLHIV. The interplay between HIV disease, ART, inflammation, and traditional risk factors in the pathophysiology of dysglycemia in SSA PLHIV is yet to be fully understood. There is a need for long-term longitudinal studies to elucidate the role of various risk factors in incident dysglycemia, future research in evaluating interventions to disrupt the progression of pre-DM to overt DM, and clinical outcome studies in comorbid DM/HIV patients in SSA.
There are no conflicts of interests or any funding sources to declare.