The impact of phenotype, ethnicity and genotype on progression of Type 2 diabetes mellitus

Aim: To conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression. Methods: We conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined. Results: Our search yielded 2785 articles; based on title, abstract and full-text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: 'Initiation of insulin', 'Initiation of oral antidiabetic drug', 'treatment intensification', 'antidiabetic therapy failure', 'glycaemic deterioration', 'decline in beta-cell function' and 'change in insulin dose'. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi-ethnic studies. Conclusion: We have identified the major determinants of diabetes progression-younger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large-scale studies of diabetes progression in different ethnic groups.