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1.
Diabetologia ; 63(10): 2158-2168, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32705316

RESUMO

AIMS/HYPOTHESIS: We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations. METHODS: A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (n = 236, ≤35 years) and control participants (n = 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and HLA-DRB1 alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants. RESULTS: Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16-25 and 26-35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes. HLA-DRB1*03:01 (p = 0.0014) and HLA-DRB1*04 (p = 0.0001) were positively associated with this form of diabetes, while HLA-DRB1*15 was protective (p < 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (p = 1.60 × 10-7). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans. CONCLUSIONS/INTERPRETATION: The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.


Assuntos
Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Transportador 8 de Zinco/imunologia , Adolescente , Adulto , Idade de Início , População Negra/genética , Peptídeo C/sangue , Criança , Diabetes Mellitus Tipo 1/genética , Etiópia , Feminino , Estudo de Associação Genômica Ampla , Cadeias HLA-DRB1/genética , Humanos , Masculino , Análise de Componente Principal , Adulto Jovem
2.
Glob Pediatr Health ; 8: 2333794X21990344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614845

RESUMO

Background. Administration of antenatal corticosteroids to pregnant mothers is one of the most effective interventions to decrease preterm neonatal mortality. In this study we assessed antenatal steroid utilization by the mother and its effect on preterm babies. Method. Two years prospective, multicenter, observational study was conducted in selected hospitals of Ethiopia. Significance of the study outcomes was tested by chi-square and binary logistic regression. Result. Out of 4919 participants, 1575 preterm babies whose gestational ages were below 35 weeks were included in the study. Use of antenatal dexamethasone was 37.5% among study participants. The risk of early onset neonatal sepsis 235 (40.4%) was higher in preterm babies whose mother took antenatal dexamethasone (P-value .002) than those who did not. Conclusion. Antenatal dexamethasone use in our study was comparable with other low and middle-income countries. Risk of early onset neonatal sepsis was higher among infants whose mother took antenatal dexamethasone.

3.
Glob Pediatr Health ; 7: 2333794X20957655, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974416

RESUMO

Background. Globally, prematurity is the leading cause of neonatal mortality, and hypothermia is one of its contributing factors. The goal of this study was to determine the association between hypothermia and mortality. Methods. A prospective, multi-center, descriptive clinical study was conducted in 5 hospitals in Ethiopia. Axillary temperatures were taken at the time of admission to the newborn intensive care units (NICU) and followed during the NICU stay. Results. A total of 3852 premature neonates (<37 weeks) were admitted to the NICUs from July 2016 to May 2018. Of these infants, 1109 (28.8%) died and 2991 (79.6%) had hypothermia. Hypothermia was associated with perinatal asphyxia (89.5%), RDS (86.2%), and resuscitation at birth (82.7%). Admission temperatures in preterm newborns were inversely associated with mortality and morbidity. Conclusion. Hypothermia at admission is associated with neonatal mortality in premature neonates in Ethiopia. RDS and perinatal asphyxia were the main factors associated with hypothermia. The very high prevalence and association with mortality warrants quality improvement interventions.

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