Clinical and biological characteristics of diabetic patients under age 40 in Cameroon: Relation to autoantibody status and comparison with Belgian patients

Abstract

Aims

We investigated the prevalence of diabetes autoantibodies (Abs) in Cameroonian patients and controls, assessed their contribution in disease classification and compared results with data from Belgium.

Methods

Abs against GAD (GADA), IA-2 (IA-2A) and zinc transporter 8 (ZnT8A) were assessed in 302 recently diagnosed Cameroonian patients with diabetes and 184 control subjects without diabetes aged below 40 years.

Results

Only 27 (9%) Cameroonian patients were younger than 15 years. Overall, 29% of patients presented at least one diabetes-associated antibody vs 9% in healthy controls (24% vs 7% for GADA (p < 0.001), 10% vs 3% for IA-2A (p < 0.006), 4% vs 2% for ZnT8A). Ab⁺ patients had lower C-peptide levels (p < 0.001), were more often insulin-treated (p < 0.002) and were as frequently diagnosed with type 1 diabetes as Ab⁻ patients. Only 43% of Ab⁺ patients aged 15–39 years were clinically classified as having type 1 diabetes in Cameroon vs 96% in Belgium (p < 0.001). Not one Ab⁺ Cameroonian patient carried HLA-DQ2/DQ8 genotype vs 23% of Belgian Ab⁺ patients (p < 0.001). Younger age at diagnosis and antibody positivity were independent predictors of insulin therapy. Ab⁺ Cameroonian patients were older (p < 0.001), had higher BMI (p < 0.001) and lower Ab titers than Belgian Ab⁺ patients. In ketonuric patients, prevalence of autoantibodies was similar as in non-ketonuric patients.

Conclusions

In Cameroonian patients with diabetes aged under 40 years, antibody-positivity is not clearly related to disease phenotype, but may help predict the need for insulin treatment.

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.