Complete HLA genotyping of type 1 diabetes patients and controls from Mali reveals both expected and novel disease associations.

HLA genotyping was performed on 99 type 1 diabetes (T1D) patients and 200 controls from Mali. Next-generation sequencing of the classical HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci revealed strong T1D association for all loci except HLA-C and -DPA1. Class II association is stronger than class I association, with most observed associations predisposing or protective as expected based on previous studies. For example, HLA-DRB1*03:01, HLA-DRB1*09:01, and HLA-DRB1*04:05 predispose for T1D, whereas HLA-DRB1*15:03 is protective. HLA-DPB1*04:02 (OR = 12.73, p = 2.92 × 10-05 ) and HLA-B*27:05 (OR = 21.36, p = 3.72 × 10-05 ) appear highly predisposing, although previous studies involving multiple populations have reported HLA-DPB1*04:02 as T1D-protective and HLA-B*27:05 as neutral. This result may reflect the linkage disequilibrium between alleles on the extended HLA-A*24:02~HLA-B*27:05~HLA-C*02:02~HLA-DRB1*04:05~HLA-DRB4*01:03~HLA-DQB1*02:02~HLA-DQA1*02:01~HLA-DPB1*04:02~HLA-DPA1*01:03 haplotype in this population rather than an effect of either allele itself. Individual amino acid (AA) analyses are consistent with most T1D association attributable to HLA class II rather than class I in this data set. AA-level analyses reveal previously undescribed differences of the HLA-C locus from the HLA-A and HLA-B loci, with more polymorphic positions, spanning a larger portion of the gene. This may reflect additional mechanisms for HLA-C to influence T1D risk, for example, through expression differences or through its role as the dominant ligand for killer cell immunoglobulin-like receptors (KIR). Comparison of these data to those from larger studies and on other populations may facilitate T1D prediction and help elucidate elusive mechanisms of how HLA contributes to T1D risk and autoimmunity.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Mali.

OBJECTIVE: Limited information is available regarding youth-onset diabetes in Mali. We investigated demographic, clinical, biochemical, and genetic features in new diabetes cases in children and adolescents. RESEARCH DESIGN AND METHODS: The study was conducted at Hôpital du Mali in Bamako. A total of 132 recently-diagnosed cases <21 years were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase-65 (GAD-65) and islet antigen-2 (IA2) autoantibodies) were assessed. DNA was genotyped for HLA-DRB1 using high-resolution genotyping technology. RESULTS: A total of 130 cases were clinically diagnosed as type 1 diabetes (T1D), one with type 2 diabetes (T2D), and one with secondary diabetes. A total of 66 (50.8%) T1D cases were males and 64 (49.2%) females, with a mean age at diagnosis of 13.8 ± 4.4 years (range 0.8-20.7 years) peak onset of 15 years. 58 (44.6%) presented in diabetic ketoacidosis; with 28 (21.5%) IA2 positive, 76 (58.5%) GAD-65 positive, and 15 (11.5%) positive for both autoantibodies. HLA was also genotyped in 195 controls without diabetes. HLA-DRB1 genotyping of controls and 98 T1D cases revealed that DRB1*03:01, DRB1*04:05, and DRB1*09:01 alleles were predisposing for T1D (odds ratios [ORs]: 2.82, 14.76, and 3.48, p-values: 9.68E-5, 2.26E-10, and 8.36E-4, respectively), while DRB1*15:03 was protective (OR = 0.27; p-value = 1.73E-3). No significant differences were observed between T1D cases with and without GAD-65 and IA2 autoantibodies. Interestingly, mean C-peptide was 3.6 ± 2.7 ng/ml (1.2 ± 0.9 nmol/L) in T1D cases at diagnosis. CONCLUSIONS: C-peptide values were higher than expected in those diagnosed as T1D and autoantibody rates lower than in European populations. It is quite possible that some cases have an atypical form of T1D, ketosis-prone T2D, or youth-onset T2D. This study will help guide assessment and individual management of Malian diabetes cases, potentially enabling healthier outcomes.

Rapid increases in observed incidence and prevalence of Type 1 diabetes in children and youth in Mali, 2007-2016.

AIMS: Determine incidence, prevalence and mortality of Type 1 diabetes (T1D) in children and youth <25 years (y) in Mali during the first 10 years of the Santé Diabète/Life for a Child program. METHODS: Data were collected from the prospective program register. Diagnosis of T1D was clinical, based on presentation, clinical features, immediate requirement for insulin, and no suggestion of other diabetes types. RESULTS: Total of 460 cases were diagnosed with T1D <25 years in 2007-2016. Male-to-female ratio was 1.04:1. Peak age at onset was 15-16 years (range 1.1-24 years). T1D incidence <25 years per 100,000 population/year increased from 0.12 in 2007 to 0.74 in 2016 (an 18% annualized increase, p < 0.001). Incidence peaked at 0.80 in 2014, the year after an education campaign was conducted. Incidence <15 years rose from 0.12 to 0.35 per 100,000/year in 2007 and 2016, respectively, (14% annualized increase, p < 0.001). There was a steep, consistent increase in prevalence (per 100,000) from 0.43 in 2007 to 2.90 in 2016 (p < 0.001). Prevalence <15 years was 0.34/100,000 in 2007 and 1.02/100,000 by 2016 (p < 0.001). Overall crude mortality rate was 30.0/1000 patient years, equating to a standardized mortality rate of 9.0, with vital status known for 99.8% of cases. CONCLUSION: Known incidence and prevalence of diabetes in Mali increased rapidly from 2007 to 2016, contemporaneous with the introduction and development of the Santé Diabète/Life for a Child program. Improved diagnosis and care resulting in lower mortality are likely contributors. True incidence may still be underestimated, with some cases still dying undiagnosed and full study ascertainment being uncertain.

Apport de l'éducation thérapeutique sur le niveau psychologique des malades diabétiques au service de médecine de l'hopital du Mali 2018

Objectif: la prise en charge des malades atteints de diabète se fait en mettant l'accent prioritairement sur la composante « biologique » par rapport aux autres déterminants de la santé à savoir l'aspect psychosocial. Ce travail avait pour objectif d'étudier l'apport de l'éducation thérapeutique sur le niveau psychologique des patients. Méthode : une étude transversale, réalisée dans le service de médecine de l'Hôpital du Mali durant le premier semestre 2018 et qui a concernée tous les 115 malades hospitalisés pendant cette période. Résultats: parmi ces malades, 52,20% avaient plus de 50 ans, avec 52,2 % de sexe féminin contre 47,8% pour le sexe masculin. La dépression a été constatée chez 64,31% des patients, les patients qui n'ont jamais reçu d'Education Thérapeutique constituaient 67,83%, la corrélation était significative entre le niveau psychologique du patient et sa participation à une éducation thérapeutique avec un coefficient de corrélation r= 0,518 et un niveau p<0,001. Conclusion: éduquer un patient permet de l'aider à supporter sa maladie et à bien la gérer. Cependant, cette éducation est complexe parce qu'il s'agit d'une véritable formation devant aboutir à un transfert de compétences du soignant vers le soigné