Clinical and biological characteristics of diabetic patients under age 40 in Cameroon: Relation to autoantibody status and comparison with Belgian patients☆
Introduction
Over the next 20 years, Africa is the continent facing the highest increase in diabetes prevalence with an expected rise from the current 14.7 million to 28 million [1]. Apart from classical type 1 and type 2 diabetes, ketosis-prone atypical diabetes, malnutrition-related diabetes and tropical diabetes have also been described in sub-Saharan Africa (SSA) [2]. These variant disease phenotypes are characterized by mixed features of both type 1 and type 2 diabetes, thus complicating disease classification on clinical grounds [3]. This challenge may lead to the irrational use of insulin therapy in economically disadvantaged SSA [4], and to inadequate disease management with the risk of a future upsurge of diabetes complications. In addition to the increasing burden of diabetes [1], [5], the need for the implementation of additional measures for disease classification has never been more relevant.
Autoantibodies against incompletely identified islet cell cytoplasmic antigens or against molecularly defined antigens such as insulin, glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and zinc transporter 8 (ZnT8A) constitute the hallmark of immune-mediated type 1 diabetes in Caucasians. They have been instrumental in discriminating between type 1 and type 2 diabetes, especially in early adulthood [6], [7], [8]. About 90% of clinically classified type 1 diabetes patients in Caucasian populations are positive for at least one of these autoantibodies at disease onset [9], [10]. In sub-Saharan Africa, the impact of the immune markers in disease classification is still uncertain. Two published studies found no association of islet cell cytoplasmic autoantibodies with the disease pattern in SSA [11], [12]. Meanwhile, other reports involving molecular Abs have proposed a significant role of these immune markers for disease classification in Africa [13]. To date, no study from SSA has investigated the role of the recently identified ZnT8A. Comparison of study results from SSA is difficult due to the differences in the inclusion criteria of study participants, or the diagnostic methods used for antibody determinations. Moreover, most of the study populations in SSA are handicapped by their low numbers, while including subjects who have longstanding diabetes [14], or are older than the pediatric population in most Caucasian studies. The present study was undertaken to investigate the occurrence of GADA, IA-2A and ZnT8A in newly diagnosed diabetes patients under age 40 from Cameroon, in relation to clinical disease phenotype and other biological markers of immune-mediated type 1 diabetes (C-peptide, HLA-DQ, ketonuria) in order to assess their potential contribution to disease classification and choice of treatment. The data obtained were compared with those of a Belgian cohort using the same methodologies for subject recruitment and immune, genetic and hormonal markers.
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Research participants
Between August 2007 and August 2011, 308 patients aged 0–39 years were consecutively recruited in the framework of the “Cameroon Diabetes Epidemiology and Registry (CAMDER)”. This Vlaamse Interuniversitaire Raad (VLIR)-sponsored project is a collaboration between the Faculty of Medicine and Biomedical Sciences of the University of Yaoundé 1 in Cameroon, and the Diabetes Research Center of the Brussels Free University in Belgium. Patients were recruited from the National Obesity Centre and the
Characteristics of Cameroonian patients according to age
Of the 302 Cameroonian patients, only 27 (9%) were aged 0–14 years and 275 (91%) were aged 15–39 years (Table 1). There were 167 (55%) male and 135 (45%) female patients with a male/female ratio of 1.2. Of all patients, 115 (38%) were clinically classified as type 1 and 108 (36%) as type 2, while 79 (26%) were unclassifiable. Patients under age 15 were all on insulin therapy and had a significantly lower BMI (p < 0.001) than the older patients (Table 1). Although glycaemia tended to be slightly
Discussion
A major finding in our study was the low prevalence of children with diabetes (9%) and of Ab+ type 1 diabetes (29%) in Cameroon. This low prevalence in patients aged under 40 years at diagnosis is in sharp contrast with the much higher values (>80%) for Belgian patients in the same age group [23]. Moreover, Cameroonian patients presented Ab positivity at lower titers than Belgian patients. Another striking observation was that ZnT8A could not differentiate Cameroonian diabetes patients from
Conflict of interest
None reported.
Acknowledgements
The study was performed under the framework of the CAMDER project (ZEIN2007PR343) sponsored by the Vlaamse Interuniversitaire Raad (VLIR). The Belgian Diabetes Registry (BDR) supplied recruitment materials for sample procurement, and supervised the analysis of all samples. The Vrije Universiteit Brussel (VUB) sponsored PhD students who participated in this research.
The present work was supported by grants from the Juvenile Diabetes Research Foundation (JDRF Center Grant 4-2005-1327), the
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A preliminary report of this study has been presented by the first author at the African Diabetes Congress in Arusha, Tanzania, held from 25th to 28th July 2012 (Abstract booklet, p. 56, #46).
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On behalf of the Belgian Diabetes Registry (the complete list of members can be found in the Supplementary data) and the Cameroon Diabetes Epidemiology and Registry Project (names of collaborators are listed in the Acknowledgment section).