ABSTRACT
Diabetes is on the increase worldwide and presents higher threat to global tuberculosis (TB) control than earlier understood to an extent of destroying the achievements of numerous decades. This trend being as a result of increased consumption of unbalanced diets and inactivity, resulting in metabolic disorder and increase in fasting blood sugar. In recent time tripling of TB in Type -2- diabetes Mellitus (T2DM) patients has been observed. Tuberculosis is the leading cause of death among people living with human immuno deficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). Multidrug-resistant-TB (MDR-TB) is associated with high mortality among these individuals. There are several reports on the association between TB and diabetes mellitus (DM); HIV and DM, but there is need for more research on the association between the three diseases HIV/TB/T2DM. Genes of Human Leukocyte Antigen (HLA) system have been implicated in the susceptibility of several diseases including T2DM. This study aimed to determine the role of HLA Class I A allele in occurrence of T2DM among HIV patients with TB co-infection in Lagos, Nigeria. Questionnaire study and Laboratory investigations were carried out for the patients and controls namely: HIV, Pulmonary TB and MDR- TB, T2DM, CD4 and CD8 counts, plasma concentrations of tumor necrotic factor alpha (TNF-α) and interleukins (IL-): IL-6, IL-10, IL17, Low-density lipoprotein (LDL-c), High density lipoprotein (HDL-c) and Total cholesterol (TC). Body mass index (BMI) was measured, HIV viral load assay was carried out for HIV positive patients. Buffy coat DNA were obtained from the participants, 53 buffy coat DNA samples were amplified and sequenced using 4th generation whole genome sequencer: Oxford Nanopore Technologies’ (ONT) single-molecule sequencing technology. Results showed that a total of 1000 individuals completed the questionnaire but 899 of them were recruited for various laboratory tests and 288(32.0 %) of the participants were people living with HIV and AIDS. Most of them 187(64.9%) were females with the mean age of 42.48 years ± 10.58. HIV/T2DM comorbidity was found among 8.3 %, 11.8 % were HIV/TB coinfected and HIV/TB/T2DM multi-morbidity prevalence was 10/288(3.5%) in the study population but was 10/44(22.7%) among HIV/TB co-infected cohort. MDR-TB was detected in 2.3 % of HIV/ TB co-infected patients. Prevalence of undiagnosed T2DM among 327 apparently healthy participants was 5.2%. HIV/TB/T2DM patients had mean age of 43.7±15.7 years, BMI mean value of 27.6 ± 7.1 kg/m2 and CD8 was 238.3 ± 170.6 cells/mg/dl. Their geometric mean for CD4 was 174.5 range 10-1529cells/ µl and viral load 541.0 range 20 - 1229915.0 copies/ml, TC mean value was 74.8 ± 96.1 mg/dl, cytokines: TNF- α was 19.7 ± 1.5 pg/ml, interleukins (IL-): IL-6 and IL-10 were 17.5 ± 3.5 pg/ml and 72.7 ± 95.6 pg/ml respectively. Twenty-one HLA A genes were documented out of the 53 amplicon samples. Haplotype network with mutation in hatches and haplotype network with mutation in numbers were obtained. HLA A*26:01:01:03N, A*29:01:01:02N and A*03: 01 new made patients susceptible to T2DM but A*03:01:01:02N, A* 68:01:02: 01, A*30:28 and A* 02:05:01 offered protection to the control groups.
