Non-insulin-dependent diabetes mellitus due to a variant in MAPK8IP1: a case report

Mario Angulo-Mosquera; Marisol Aguirre; Harry Pachajoa; Rodrigo Lemus; Liliana Mejia-Zapata; Isabella Larrañaga

Introduction: non-insulin-dependent diabetes mellitus (type II) is an increasing problem in childhood. With the advancement of genetic testing and genome-wide association studies, mutations in genes causing loss or dysfunction of the pancreatic cell have been associated with type II diabetes. A heterozygous mutation of the MAPK8IP1 (Mitogen-activated protein kinase 8 interacting protein 1) gene is associated with a rare form of diabetes with few cases reported.

Objective: to increase awareness of type II diabetes due to a variant in the MAPK8IP1 gene.

Case: 14-year-old boy with insulin resistance developed type II diabetes due to a missense heterozygous variant in MAPK8IP1: (NM_005456.3): c.1895G>A (P.Gly632Glu), maternally inherited and responded to the administration of glucagon-like peptide 1(GLP-1) receptor agonist.

Table 1. Laboratories and anthropometric measurements, 2019-2022
Measurements	Dates
	Apr-19	Jul-19	Oct-19	May-20	Jun-20	Jul-20	Oct-20	May-21	Jan-22
Fasting glucose (mg/dl)	98	74	88	87	83	75	85	90.8	81.8
Oral glucose tolerance test (mg/dl)	122	152	124	104	228	80	119	101	104.7
Fasting insulin (uUl/ml)	91	41.8	28.8	43.3	18.9	43.5	25.7	22.1	20
Insulin levels 2 hours after glucose load (uUl/ml)	501	697	255	132	412	295	222	200	90
HbA1c test (%)			5.5		5.2	5.3	4.9	4.9	5.2
ALT (U/L)		40
AST (U/L)		21
HOMA	150.9	261.5	78.1	33.8	231.9	58.2	65.2	44.4	18
Weight kg		48.6	52.2	55.2		54.2	57.0	56.8	58.1
Height cm		156.5	159.5	164		164.4	165.0	168	169
BMI (kg/m2) (Percentile, p%)		19.7; p75	20.5; p80	20.5; p76		20.1; p71	20.9; p61	20.1;p52	20.1;p50
Medications	Metformin 500 mg BID	Metformin 850 mg TID	Metformin 850 mg TID	Metformin 850 mg tid	Metformin changed for Liraglutide 1.8 mg per day	Liraglutide 1.8 mg per day	Liraglutide 1.8 mg per day	Liraglutide 1.8 mg per day	Liraglutide 1.8 mg per day

Discussion: MAPK8IP1 encodes IB1, a regulator of the pancreatic beta-cell function, that is a DNA binding transactivator of the glucose transporter GLUT2, and a homologous of JIP (regulator of the c-Jun amino-terminal kinase), which plays an important role in cellular apoptosis and increased inflammatory response that causes type II diabetes. Administration of glucagon-like peptide 1 (GLP-1) receptor agonist improved glucose levels due to the positive effect on the pathogenic mechanisms.

Conclusion: Upon an uncommon presentation of type II diabetes, a molecular genetic test should be performed allowing early assessment and management of this condition.

ESPE Abstracts

P1-45