Ayesha A. Motala

Diabetes in sub-Saharan Africa

In Sub-Saharan Africa, prevalence and burden of type 2 diabetes are rising quickly. Rapid uncontrolled urbanisation and major changes in lifestyle could be driving this epidemic. The increase presents a substantial public health and socioeconomic burden in the face of scarce resources. Some types of diabetes arise at younger ages in African than in European populations. Ketosis-prone atypical diabetes is mostly recorded in people of African origin, but its epidemiology is not understood fully because data for pathogenesis and subtypes of diabetes in sub-Saharan African communities are scarce. The rate of undiagnosed diabetes is high in most countries of sub-Saharan Africa, and individuals who are unaware they have the disorder are at very high risk of chronic complications. Therefore, the rate of diabetes-related morbidity and mortality in this region could grow substantially. A multisectoral approach to diabetes control and care is vital for expansion of socioculturally appropriate diabetes programmes in sub-Saharan African countries.

The African Genome Variation Project shapes medical genetics in Africa

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Global estimates of undiagnosed diabetes in adults

AIMS The prevalence of diabetes is rapidly increasing worldwide. Type 2 diabetes may remain undetected for many years, leading to severe complications and healthcare costs. This paper provides estimates of the prevalence of undiagnosed diabetes mellitus (UDM), using available data from high quality representative population-based sources. METHODS Data sources reporting both diagnosed and previously undiagnosed diabetes were identified and selected according to previously described IDF methodology for diabetes in adults (aged 20-79). Countries were divided into 15 data regions based on their geographic IDF Region and World Bank income classification. The median UDM proportion was calculated from selected data sources for each of data region. The number of UDM cases in 2013 was calculated from country, age and sex-specific estimates of known diabetes cases and data region-specific UDM proportion. RESULTS Of 744 reviewed data sources, 88 sources representing 74 countries had sufficient information and were selected for generation of estimates of UDM. Globally, 45.8%, or 174.8 million of all diabetes cases in adults are estimated to be undiagnosed, ranging from 24.1% to 75.1% across data regions. An estimated 83.8% of all cases of UDM are in low- and middle-income countries. At a country level, Pacific Island nations have the highest prevalence of UDM. CONCLUSIONS There is a high proportion of UDM globally, and especially in developing countries. Further high-quality studies of UDM are needed to strengthen future estimates.

The Prevalence of Metabolic Syndrome and Determination of the Optimal Waist Circumference Cutoff Points in a Rural South African Community

OBJECTIVE To determine the prevalence of metabolic syndrome and to define optimal ethnic-specific waist-circumference cutoff points in a rural South African black community. RESEARCH DESIGN AND METHODS This was a cross-sectional survey conducted by random-cluster sampling of adults aged >15 years. Participants had demographic, anthropometric, and biochemical measurements taken, including a 75-g oral glucose tolerance test. Metabolic syndrome was defined using the 2009 Joint Interim Statement (JIS) definition. RESULTS Of 947 subjects (758 women) studied, the age-adjusted prevalence of metabolic syndrome was 22.1%, with a higher prevalence in women (25.0%) than in men (10.5%). Peak prevalence was in the oldest age-group (≥65 years) in women (44.2%) and in the 45- to 54-year age-group in men (25.0%). The optimal waist circumference cutoff point to predict the presence of at least two other components of the metabolic syndrome was 86 cm for men and 92 cm for women. The crude prevalence of metabolic syndrome was higher with the JIS definition (26.5%) than with the International Diabetes Federation (IDF) (23.3%) or the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (ATPIII) (18.5%) criteria; there was very good agreement with the IDF definition (κ = 0.90 [95% CI 0.87–0.94]) and good concordance with ATPIII criteria (0.77 [0.72–0.82]). CONCLUSIONS There is a high prevalence of metabolic syndrome, especially in women, suggesting that this community, unlike other rural communities in Africa, already has entered the epidemic of metabolic syndrome. Waist circumference cutoff points differ from those currently recommended for Africans.

Diabetes and Other Disorders of Glycemia in a Rural South African Community: Prevalence and associated risk factors

OBJECTIVE—The purpose of this study was to determine the prevalence of diabetes, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG), and associated risk factors in a rural South African black community. RESEARCH DESIGN AND METHODS—This was a cross-sectional survey conducted by random cluster sampling of adults aged >15 years. Participants had a 75-g oral glucose tolerance test using the 1998 World Health Organization criteria for disorders of glycemia. RESULTS—Of 1,300 subjects selected, 1,025 subjects (815 women) participated (response rate 78.9%). The overall age-adjusted prevalence of diabetes was 3.9%, IGT 4.8%, and IFG 1.5%. The prevalence was similar in men and women for diabetes (men 3.5%; women 3.9%) and IGT (men 4.6%; women 4.7%) but higher in men for IFG (men 4.0%; women 0.8%). The prevalence of diabetes and IGT increased with age both in men and women, with peak prevalence in the 55- to 64-year age-group for diabetes and in the ≥65-year age-group for IGT. Of the cases of diabetes, 84.8% were discovered during the survey. In multivariate analysis, the significant independent risk factors associated with diabetes included family history (odds ratio 3.5), alcohol ingestion (2.8), waist circumference (1.1), systolic blood pressure (1.0), serum triglycerides (2.3), and total cholesterol (1.8); hip circumference was protective (0.9). CONCLUSIONS—There is a moderate prevalence of diabetes and a high prevalence of total disorders of glycemia, which suggests that this community, unlike other rural communities in Africa, is well into an epidemic of glucose intolerance. There is a low proportion of known diabetes and a significant association with potentially modifiable risk factors.

Epidemiology of Type 1 and Type 2 Diabetes in Africa

Until recently, there was a paucity of data on the epidemiology of diabetes mellitus in Africa. Over the past decade, information on the prevalence of type 2 diabetes has increased, albeit still limited, but there is still a lack of adequate data on type 1 diabetes in sub-Saharan Africa (SSA). For type 2 diabetes, although the prevalence is low in some rural populations, moderate and even high rates have been reported from other countries. In low diabetes prevalence populations, the moderate to high rates of impaired glucose tolerance is a possible indicator of the early stage of a diabetes epidemic. Diabetes prevalence is higher in urban, migrant and African-origin populations living abroad. There is evidence for a significant association with preventable and modifiable risk factors viz. adiposity, known diabetes, physical activity; but a dearth of data on the impact of dietary and genetic factors. For type 1 diabetes, the limited available data suggest that in SSA the frequency is low and that age of onset occurs later than in the western world. There is evidence for the role of genetic and immunological factors in its pathogenesis. The impact of HIV/AIDS on projected estimates for diabetes prevalence in Africa needs to be established.

Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis

Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, −0.59; 95% CI, −0.86 to −0.31), BMI (SMD, −0.32; 95% CI, −0.45 to −0.18), SBP (SMD, −0.40; 95% CI, −0.55 to −0.25) and DBP (SMD, −0.34; 95% CI, −0.51 to −0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, −0.34; 95% CI, −0.62 to −0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

South African Indians Show a High Prevalence of NIDDM and Bimodality in Plasma Glucose Distribution Patterns

OBJECTIVE To determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT) and to test for bimodality in the plasma glucose distribution in South African Indians. RESEARCH DESIGN AND METHODS Subjects were selected by systematic cluster sampling in various areas of Durban. They underwent a modified glucose tolerance test whereby fasting and 2-h postglucose (75 g) plasma glucose levels were measured. The program MIX was used to test for bimodality in the plasma glucose distribution. RESULTS We tested 2,479 subjects (1,441 women and 1,038 men). Based on the revised World Health Organization criteria, the crude prevalence of diabetes mellitus was 9.8%, and the crude prevalence of IGT was 5.8%; the age- and sex-adjusted prevalence was 13.0 and 6.9%, respectively. IGT was significantly more common in men (7.6%) than in women (4.4%). Obesity was a feature of both diabetes mellitus and IGT, particularly in women. Both fasting and 2-h plasma glucose values did not conform to a single normal distribution pattern in any age-group, whereas unequivocal evidence of bimodality was seen in the 55- to 74-year age-group of both sexes for fasting and 2-h glucose and also in the 2-h levels of men in the 25- to 34-year age-group. CONCLUSIONS This study has highlighted a high prevalence of non-insulindependent diabetes mellitus in South African Indians and bimodality in the plasma glucose distribution.

Diabetes trends in Africa.

Diabetes is an important cause of morbidity and mortality in Africa. Although a dramatic increase in disease burden is projected, it remains to be seen what effect the ongoing devastation of HIV disease will have on the epidemiology of such chronic diseases as diabetes. Recent data on type 2 diabetes prevalence indicate low rates in some rural populations, moderate rates similar to those in developed areas in some countries, and alarmingly high rates in others. The frequent observation of moderate to high prevalence of impaired glucose tolerance, particularly in populations with a low prevalence of diabetes, may indicate the early stage of a diabetes epidemic. Risk factors include urbanization, age, and family history of disease, as well as such modifiable risk factors as adiposity and physical inactivity. For type 1 diabetes, limited data indicate that the prevalence is low in sub‐Saharan Africa and that onset occurs later in life there than in other parts of the world. Mortality associated with diabetes is unacceptably high and is disproportionately due to preventable acute metabolic and infective causes. With long duration of disease, there is a high frequency of hypertension and microvascular complications. The apparent low frequency of chronic macrovascular complications needs fuller documentation – as does the apparent high frequency of hypertension even in the non‐diabetic population. Efforts to prevent this disease and its complications in Africa are impeded by inadequate health care infrastructure, inadequate supply of medications, absence of educational programs, and lack of available health care facilities and providers. Copyright

Diabetes in the Africa region: An update

The Africa Region (AFR), where diabetes was once rare, has witnessed a surge in the condition. Estimates for type 1 diabetes suggest that about 39,000 people suffer from the disease in 2013 with 6.4 new cases occurring per year per 100,000 people in children <14 years old. Type 2 diabetes prevalence among 20-79-year-olds is 4.9% with the majority of people with diabetes <60 years old; the highest proportion (43.2%) is in those aged 40-59 years. Figures are projected to increase with the numbers rising from 19.8 million in 2013 to 41.5 million in 2035, representing a 110% absolute increase. There is an apparent increase in diabetes prevalence with economic development in AFR with rates of 4.4% in low-income, 5.0% in lower-middle income and 7.0% in upper-middle income countries. In addition to development and increases in life-expectancy, the likely progression of people at high risk for the development of type 2 diabetes will drive the expected rise of the disease. This includes those with impaired glucose tolerance, the prevalence of which is 7.3% among 20-79-year-olds in 2013. Mortality attributable to diabetes in 2013 in AFR is expected to be over half a million with three-quarter of these deaths occurring in those <60 years old. The prevalence of undiagnosed diabetes remains unacceptably high at 50.7% and is much higher in low income (75.1%) compared to lower- and upper-middle income AFR countries (46.0%). This highlights the inadequate response of local health systems which need to provide accessible, affordable and optimal care for diabetes.