Materials and Methods: All the variants' information was retrieved from the Ensembl genome database, and then different variation prediction analyses were performed. UTRScan was used to predict UTR variants while MaxEntScan was used to predict splice site variants. Meta-analysis by PredictSNP2 was used to predict sSNPs. Parallel prediction analyses by five different software packages including SIFT, PolyPhen-2, Mutation Assessor, I-Mutant2.0 and SNPs&GO were used to predict the effects of nsSNPs. The level of evolutionary conservation of deleterious nsSNPs was further analyzed using ConSurf server. Mutant protein structures of deleterious nsSNPs were modelled and refined using SPARKS-X and ModRefiner for structural comparison.

Results: A total of 56 deleterious variants were identified in this study, including 12 UTR variants, 18 splice site variants, eight sSNPs and 18 nsSNPs. Among these 56 deleterious variants, seven variants were also identified in the Alzheimer's Disease Sequencing Project (ADSP), Alzheimer's Disease Neuroimaging Initiative (ADNI) and Mount Sinai Brain Bank (MSBB) studies.

Methods: The UKPDS-Outcome Model version 2.0 (UKPDS-OM2) was used to evaluate the cost and consequence of diabetes-related complication. The effectiveness of the insulin was derived from the literature review, and the patients' epidemiology characteristics were retrieved from the Malaysian Diabetes Registry. A discount rate of 3% was applied to both costs and health effects. Another simple mathematical model was used to compare the benefit of reducing the hypoglycemia events between LAIA and NPH insulin. The outputs of the models were combined to obtain the final result. One-way sensitivity analyses were performed to assess the uncertainties.

Results: The net cost difference (without accounting for hypoglycemia) was RM4868 for insulin Glargine and RM6026 for insulin Detemir. The saving from preventing severe hypoglycemia was RM4377 for insulin Glargine and RM12,753 for insulin Detemir. The total additional QALY gained from insulin Glargine was 0.1317 and from insulin Detemir was 0.8376. The sensitivity analysis shows the discount rate, and drug acquisition cost may affect the incremental cost-effectiveness ratio (ICER) value.

OBJECTIVE: Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

METHODS: We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015. Two reviewers performed data extraction and assessed the quality of the data using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines.

RESULTS: Seven of the included studies assessed short-acting insulin analogues, 12 assessed biphasic insulin analogues, 30 assessed long-acting insulin analogues and one assessed a combination of short- and long-acting insulin analogues. Only 17 studies involved patients with T1DM, all were modelling studies and 12 were conducted in Canada. The incremental cost-effectiveness ratios (ICERs) for short-acting insulin analogues ranged from dominant to $US435,913 per quality-adjusted life-year (QALY) gained, the ICERs for biphasic insulin analogues ranged from dominant to $US57,636 per QALY gained and the ICERs for long-acting insulin analogues ranged from dominant to $US599,863 per QALY gained. A total of 15 studies met all the CHEERS guidelines reporting quality criteria. Only 26 % of the studies assessed heterogeneity in their analyses.