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

Fawwad, Asher; Govender, Denira; Ahmedani, Mohammad Yakoob; Basit, Abdul; Lane, Julie A.; Mack, Steven J.; Atkinson, Mark A.; Wasserfall, Clive; Noble, Janelle A.

doi:10.1016/j.diabres.2019.01.023

Cited by 15 publications

(22 citation statements)

References 47 publications

(49 reference statements)

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“…For example, HLA-DRB1*03 and HLA-DRB1*04, both previously associated with LADA [ 28 ], also confer an increased risk for ulcerative colitis (OR = 3.6) and Crohn’s disease (OR = 3.9), respectively [ 29 ]. HLA-DRB1*03:01 was associated with the development of type 1 diabetes of the youth in a Pakistani population [ 30 ] and is also associated with increased susceptibility to systemic lupus erythematosus with the production of anti-Ro and anti-La antibodies [ 31 ]. Some of these alleles have been described in patients with ICI-induced IDDM in other studies [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus

Muniz

Araújo

Savage

et al. 2021

Cancers

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Immune checkpoint inhibitor (ICI)-induced insulin-dependent diabetes mellitus (IDDM) is a rare but potentially fatal immune-related adverse event (irAE). In this multicentre retrospective cohort study, we describe the characteristics of ICI-induced IDDM in patients treated across five Canadian cancer centres, as well as their tumor response rates and survival. In 34 patients identified, 25 (74%) were male and 19 (56%) had melanoma. All patients received anti-programed death 1 (anti-PD1) or anti-programmed death ligand-1 (anti-PD-L1)-based therapy. From ICI initiation, median time to onset of IDDM was 2.4 months (95% CI 1.1–3.6). Patients treated with anti-PD1/PD-L1 in combination with an anti-cytotoxic T lymphocyte antigen 4 antibody developed IDDM earlier compared with patients on monotherapy (1.4 vs. 3.9 months, p = 0.05). Diabetic ketoacidosis occurred in 21 (62%) patients. Amongst 30 patients evaluable for response, 10 (33%) had a complete response and another 10 (33%) had a partial response. Median overall survival was not reached (95% CI NE; median follow-up 31.7 months). All patients remained insulin-dependent at the end of follow-up. We observed that ICI-induced IDDM is an irreversible irAE and may be associated with a high response rate and prolonged survival.

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Section: Discussionmentioning

confidence: 99%

CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus

Muniz

Araújo

Savage

et al. 2021

Cancers

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“…This was highlighted by the association of DRB1*03:01:01∼DQB1*02:01 and DRB1*04:01:01∼DQB1*03:02 haplotypes with increased susceptibility to T1D among Bahraini Arabs ( Al-Jenaidi et al, 2005 ). As the frequencies of HLA alleles, haplotypes, and genotypes show considerable population and ethnic differences, population studies confirmed that the relationship of HLA with T1D also varies according to the geographical location and ethnic background ( Al-Jenaidi et al, 2005 ; Ahmadov et al, 2018 ; Fawwad et al, 2019 ; Zabeen et al, 2019 ). Compared to numerous studies performed on European populations, limited numbers of studies have been conducted on populations in the Middle East-North Africa (MENA) region ( Al-Jenaidi et al, 2005 ; Noble et al, 2013 ).…”

Section: Introductionmentioning

confidence: 92%

HLA-DRB1 and –DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations

et al. 2022

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Background: HLA class II (DR and DQ) alleles and antigens have historically shown strong genetic predisposition to type 1 diabetes (T1D). This study evaluated the association of DRB1 and DQB1 alleles, genotypes, and haplotypes with T1D in United Arab Emirates.Materials and Methods: Study subjects comprised 149 patients with T1D, and 147 normoglycemic control subjects. Cases and controls were Emiratis and were HLA-DRB1 and -DQB1 genotyped using sequence-based typing. Statistical analysis was performed using Bridging Immunogenomic Data-Analysis Workflow Gaps R package.Results: In total, 15 DRB1 and 9 DQB1 alleles were identified in the study subjects, of which the association of DRB1*03:01, DRB1*04:02, DRB1*11:01, DRB1*16:02, and DQB1*02:01, DQB1*03:02, DQB1*03:01, and DQB1*06:01 with altered risk of T1D persisted after correcting for multiple comparisons. Two-locus haplotype analysis identified DRB1*03:01∼DQB1*02:01 [0.44 vs. 0.18, OR (95% CI) = 3.44 (2.33–5.1), Pc = 3.48 × 10−10]; DRB1*04:02∼DQB1*03:02 [0.077 vs. 0.014, OR = 6.06 (2.03–24.37), Pc = 2.3 × 10−3] and DRB1*04:05∼DQB1*03:02 [0.060 vs. 0.010, OR = 6.24 (1.79–33.34), Pc = 0.011] as positively associated, and DRB1*16:02∼DQB1*05:02 [0.024 vs. 0.075, OR = 0.3 (0.11–0.74), Pc = 0.041] as negatively associated with T1D, after applying Bonferroni correction. Furthermore, the highest T1D risk was observed for DR3/DR4 [0.104 vs. 0.006, OR = 25.03 (8.23–97.2), Pc = 2.6 × 10−10], followed by DR3/DR3 [0.094 vs. 0.010, OR = 8.72 (3.17–25.32), Pc = 3.18 × 10−8] diplotypes.Conclusion: While DRB1 and DQB1 alleles and haplotypes associated with T1D in Emiratis showed similarities to Caucasian and non-Caucasian populations, several alleles and haplotypes associated with T1D in European, African, and Asian populations, were not observed. This underscores the contribution of ethnic diversity and possible diverse associations between DRB1 and DQB1 and T1D across different populations.

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“…The duration of study was between December 30, 2013 to December 23, 2015, and was an additional investigation from the main study "Epidemiology of youth-onset T1DM in Pakistan: clinical features, biochemistry and HLA-DRB1". 11 Ethical approval was obtained from the Institutional Review Board (IRB) of BIDE with Ref no: BIDE/IRB/Prof.Yakoob/03/27/13/119. Written informed consent was obtained for subjects >18 years prior to enrolment in the study, and for subjects <18 years, their parents/guardians gave written informed consent.…”

Section: This Prospective Study Was Conducted At Baqaimentioning

confidence: 99%

Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan

et al. 2020

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Objective: To determine the relationship of C-peptide levels with duration of type 1 diabetes mellitus. Methods: This prospective study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University (BMU), Karachi-Pakistan from December 2013 to December 2015. A total of 184 subjects were recruited during the study period, 100 in Group-A and 84 in Group-B. Subjects clinically diagnosed with type 1 diabetes Mellitus (T1DM) were categorized into two groups based on duration of diabetes: Group-A (with ≤1-year duration of diabetes) and Group-B (with >1-year duration of diabetes). Ninety-nine of the 100 enrolled subjects in Group-A were diagnosed as having T1DM, with one subject who presented at 11.9 years of age and diagnosed with T2DM excluded from this study. Blood samples were drawn for biochemical parameters. Data for baseline characteristics and clinical parameters (HbA1c and C-peptide) were obtained from hospital management system of BIDE. Results: Fifty-seven (57.6%) subjects in Group-A, and 39 (46.4%) in Group-B were males. Mean±SD duration of diabetes (years) was 0.64±0.6 (range 0-1) in Group-A, and 7.65±5.5 (range 1-23) in Group-B. Family history of T1DM and T2DM was 1(1%) and 27(27.3%) in Group-A, and 8(9.52%) and 21(25%) in Group-B, respectively. Twenty-one (21.2%) subjects presented in diabetic ketoacidosis (DKA) in Group-A and 18(21.4%), in Group-B. Mean±SD for HbA1c was non-significantly higher in Group-A 11.12±2.31 compared to Group-B 10.42±1.45. Mean±SD for C-peptide was 1.91±1.53 ng/mL (0.60±0.481 nmol/L) in Group-A, and 1.82±1.01 (0.57±0.32 nmol/L) in Group-B (p=0.984). Conclusion: The study found that subjects with longer duration of T1DM had non-significantly decreased C-peptide levels compared to a group in which C-peptide was measured at or soon after diagnosis. Furthermore, C-peptide levels in many subjects with longer duration were higher than expected in classic T1DM. doi: https://doi.org/10.12669/pjms.36.4.1531 How to cite this:Fawwad A, Waris N, Askari S, Ogle G, Ahmedani MY, Basit A. Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan. Pak J Med Sci. 2020;36(4):---------. doi: https://doi.org/10.12669/pjms.36.4.1531 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

Cited by 15 publications

References 47 publications

CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus

CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus

HLA-DRB1 and –DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations

Relationship of C-peptide levels to duration of Type 1 diabetes – A study from Sindh, Pakistan

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