Systematic Review of Monogenic Diabetes Prognostics

Background- Individuals with monogenic diabetes are at risk for diabetes-related complications; however, overall prognosis and whether prognosis is similar to other diabetes forms is poorly understood. Aim: To assess diabetes-related microvascular and macrovascular complications in the common forms of monogenic diabetes. Methods: Systematic review with data sources from Pubmed, Medline and Embase was performed to assess diabetes-related complications in KCNJ11-neonatal diabetes, ABBC8-neontal diabetes, HNF1A-diabetes, HNF4- diabetes and GCK-related hyperglycemia. Results: Data was extracted from 67 studies. Most studies had moderate to high risk of bias. In neonatal diabetes, 16 of 20 studies reported at least one microvascular complication, with complications occurring as early as the second decade of life. Macrovascular complications were reported in only 1 individual who was 40 years old at the time of study. Diabetes complications were frequent in HNF1A-diabetes and HNF4A-diabetes, but did show a temporal trend of improved prognosis (e.g., 47% versus 13.6% retinopathy) and better prognosis compared to type 1 diabetes. Death due to cardiovascular disease was higher in HNF1A-diabetes compared to unaffected relatives (66% versus 43%). GCK-related hyperglycemia showed overall low rates of complications. Conclusion: While KCNJ11-neonatal diabetes, ABBC8-neontal diabetes, HNF1A-diabetes and HNF4- diabetes are clearly at risk for diabetes-related complications, microvascular complications were infrequently reported before the third decade of life. GCK-related hyperglycemia showed a low prevalence of complications with rates not significantly different from control groups except for mild retinopathy. Future prospective studies to determine age at onset of complications and the impact of precision therapy are warranted to best guide surveillance practices for each subtype.