The association of Human Leukocyte Antigens Complex with Type 1 Diabetes in Omanis

Background: Identifying the human leukocyte antigens (HLA) high risk alleles, genotypes and haplotypes in different populations is beneficial for understanding their roles in type 1 diabetes (T1D) pathogenesis and intervention practices. Objective: The aim of this study was to identify T1D associated HLA gene alleles in the Omani population. Methods: Our case-control study included 73 diabetic seropositive children (mean age 9.08±3.27 years) and 110 healthy controls. HLA–A, -B, -C, -DRB1, and -DQB1 genes were genotyped using sequence specific primer polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, while one class I (B*51) and three class II (DQB1*05, DQB1*06, and DRB1*16) alleles were associated with T1D protection. HLA- DRB1*03 and DQB1*02 alleles showed the strongest risk association among all alleles. Six DRB1 residues (E9, S11, S13, Y30, V70 and K71) were significantly associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and DQB1*02/*03 were significantly associated with T1D susceptibility (P=4.29E-07, OR=63.2 and P=0.02, OR=3.6, respectively). Furthermore, we detected a significant combined action of DRB1*03-DQB1*02 haplotype in T1D risk (P=1.76E-05, OR=15), and DRB1*16-DQB1*05 haplotype in protection (P=3.12E-2, OR=0.48). Conclusion: Known HLA class II gene alleles are associated with T1D in Omani children. Keywords: Type 1 diabetes; human leukocytes antigens; zygosity; alleles; residues; haplotypes, case-control study; Oma

Switching to Multiple Daily Insulin Injections in Children and Adolescents with Type 1 Diabetes: Revisiting Benefits from Oman

Objectives: Optimal glycemic control is an important goal in the management of type 1 diabetes mellitus (T1DM). Although the use of multiple daily injections (MDI) is a common regimen worldwide, its use is not yet universal in many countries. Our aim was to evaluate the effects of switching from a twice daily (BID) to a MDI insulin regimen in children and adolescents with T1DM in order to revisit its benefits in the Omani population. Methods: We conducted a retrospective cohort study of children and adolescents with T1DM at Sultan Qaboos University Hospital, Muscat, Oman, between January 2007 and June 2013. Patients using the BID regimen for more than six months who were then switched to MDI were included in the analysis. We compared glycated hemoglobin levels (HbA1c) before and after the regimen change. Results: Fifty-three children were eligible for the study. Ten patients were excluded for various reasons. The remaining 43 patients were 58% male and 42% female, with a mean age of 9.4±3.7 years. There was significant decrease in the overall mean HbA1c level from baseline (10.0) compared to three months after switching to MDI (9.5); p=0.023. Nevertheless, the improvement was not significant in the subsequent follow-up visits at six and nine months. The reduction in HbA1c values was observed mainly in children five to 11 years. Conclusions: Switching from a BID to MDI insulin regimen has favorable effects on the overall control of T1DM in children and adolescents, as assessed by HbA1c levels. In addition, this regimen has been proved to be safe and well tolerated by patients

Demographic and Clinical Characteristics of Type 1 Diabetes Mellitus in Omani Children - Single Center Experience

Objectives: To describe the demographic characteristics and clinical presentation of Omani children with type 1 diabetes mellitus at Sultan Qaboos University Hospital, Muscat, Oman. Methods: A retrospective analysis of all children with type 1 diabetes mellitus attending the Pediatric Endocrine Unit at Sultan Qaboos University Hospital, Oman from June 2006 to May 2013. Results: One hundred and forty-four patients were included in the study. The mean±SD of age at diagnosis was 6.7 ± 3.7 years. The median duration of symptoms was 10 days (IQR; 5-14). The most commonly reported presenting symptoms were polyuria (94%), polydipsia (82%), and weight loss (59%). Diabetic ketoacidosis at initial presentation was diagnosed in 31% of the patients. Different insulin regimens were prescribed: multiple daily injections in 109 (76%) patients, twice daily insulin regimen in 23 (16%) patients, and insulin pump therapy in 12 (8%) patients. Family history of type 1 diabetes mellitus was present in 31 (22%) patients. There were no significant differences in presenting complaints (polyuria, p=0.182; polydipsia, p=0.848), duration of symptoms (p=0.331), reported weight loss (p=0.753), or diabetic ketoacidosis at presentation (p=0.608) between patients with and without family history of type 1 diabetes mellitus. Conclusion: Polyuria, polydipsia and weight loss are the most common presenting symptoms. Family history of type 1 diabetes mellitus is highly prevalent among the studied patients. Diabetic ketoacidosis was found to be less common in Oman compared to other diabetes centers in the Middle East

The Pattern of Sensitisation to Inhalant Allergens in Omani Patients with Asthma, Allergic Rhinitis and Rhinoconjunctivitis

Objective: Identification of relevant allergens that are prevalent in each environment which may have diagnostic and therapeutic implications in allergic diseases. This study aimed to identify the pattern of sensitisation to inhalant allergens in Omani patients with asthma, allergic rhinitis and rhinoconjunctivitis. Methods: The study was carried out during three consecutive years (2004-2006) at the allergy skin test laboratory of Sultan Qaboos University Hospital, Oman. Records of patients who had undergone an allergy skin prick test with a referring diagnosis of asthma, allergic rhinitis or rhinoconjunctivitis were reviewed. Two panels were used during the 3 years period. The frequencies of positive skin tests were analysed. Results: 689 patients were tested, 384 for the first panel and 305 for the second panel. In the first panel, the commonest positive allergens were: house dust mites (37.8%), hay dust (35.4%), feathers (33.3%), sheep wool (26.6%), mixed threshing dust (25.8%), cat fur (24.2%), cockroach (22.7%), straw dust (22.7%), horse hair (17.4%), maize (16.1%), grasses (11.5%), cotton flock (10.7%), trees (10.4%), cow hair (7.8%), Alternaria alternata (3.6%), Aspergillus Niger (3.4%), and Aspergillus fumigatus (1.3%). In the second panel, the commonest positive allergens were also house dust mites: Dermatophagoides pteronyssinus (50.8%), Dermatophagoides farinae (47.9%); Mesquite (Prosopis glandulosa) (35.7%), Russian thistle (Salsola kali) (34.4%), cockroach (32.1%), Bermuda grass (Cynodon dactylon) (19.7%), grass mix-five standard (18.0%), wheat cultivate (14.1%), cats (13.8%), Penicillium notatum (4.3%), Alternaria tenius (3.9%), Aspergillus Niger (3.3%), feather mix (3.0%), dog (2.6%), horse hair and dander (2.6%), and Aspergillus fumigatus (1.6%). Conclusion: The pattern of sensitisation to environmental allergens in Oman seems to be similar to other reports from the Arabian Peninsula. Methods to identify and characterise environment specific allergens like a pollen survey may help in the management of patients with allergic asthma, allergic rhinitis and rhinoconjunctivitis

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346–3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias