IMPE2023 Poster Presentations Diabetes and Insulin (16 abstracts)
1Division of Endocrinology, Metabolism and Diabetes, Shiga Medical Center for Children, Moriyama, Japan. 2Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan. 3Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan
Objectives: KCNK16 gene encodes the two-pore-domain K+ channel, TALK-1, which is expressed on both the β-cell plasma membrane and the ER membrane. The KCNK16-containing locus is strongly associated with type 2 diabetes mellitus in multiple genome-wide association studies in the general population. Its mutation inducing a gain of function in TALK-1 has been recently reported to cause MODY. No case of KCNK16-MODY has been reported to date besides the family members of the first reported patient. Therefore, details regarding KCNK16-MODY are still unclear.
Methods: We report a Japanese family with KCNK16-MODY.
Results: The proband was an 11-year-old non-obese Japanese girl who was referred for hyperglycemia. Her HbA1c and glycemic albumin were 6.4% and 17.1%, respectively. Her plasma glucose levels after fasting and 2 hours after 75 g glucose of oral glucose tolerance test were 125 mg/dL and 342 mg/dL, respectively. HOMA-βof 18.6% and insulinogenic index of 0.083 indicated impaired insulin secretion, and HOMA-R of 0.98 indicated scarce insulin resistance. Initially, she was observed without medication. However, her HbA1c increased. Therefore, she was started on metformin at the age of 12, basal insulin injections one year later, and intensive insulin therapy four months later. Her total daily insulin dose was approximately 22 units at the age of 16, and she maintained HbA1c of 6.8% – 7.1% without any diabetes-related complications and with detectable insulin secretion. Additionally, her nonobese mother had diabetes and had begun insulin injections at the age of 10. Currently, her mother’s total daily insulin dose was approximately 32 units, and she maintained HbA1c of 5.8% – 6.1% without any diabetes-related complications and with scarce but detectable insulin secretion even more than 30 years after the onset. Both daughter and mother were initially diagnosed with T1bDM because autoimmune antibodies were not detectable. They were however suspected to have MODY because of the detectable insulin secretion in the mother. Sanger sequencing was negative for mutations in GCK, HNF1A, HNF1B, and HNF4A, but a nonsynonymous coding mutation in KCNK16 (c.341T>C, p.Leu114Pro) was identified with whole exome sequencing.
Conclusions: This KCNK16 mutation is the same as that reported previously in 2021. TALK-1 is reported to be unresponsive to sulfonylureas. Therefore, we decided to continue their insulin therapies. Diabetes-related complications have not been reported in KCNK16-MODY patients to date in the literature and in our cases. However, careful follow-up is required because of the scarcity of information.