Diabetic Ketoacidosis with Encephalopathy in Patient with Longstanding History of Poorly Controlled Neonatal Diabetes Due to KCNJ11 Mutation and Long-Term Use of SGLT2 Inhibitor

Thursday, May 12, 2022

4:35 PM – 4:50 PM

Location: Station 3, Sapphire West Foyer

Submitter(s)

IA
Israa Ali, MBChB
Fellow
UTMB
league city, Texas, United States

Primary Author(s)

IA
Israa Ali, MBChB
Fellow
UTMB
league city, Texas, United States

Co-Author(s)

WP
Wentong Pan

Introduction : •Maturity-onset diabetes of the young (MODY) is an unusual form of diabetes with specific features that distinguish it from type 1 and type 2 diabetes.

•There are 14 known subtypes of MODY, and mutations in three genes (HNF1A, HNF4A, GCK) account for about 95% of all MODY cases

Case Description : •30-year-old Caucasian/White male who was diagnosed with diabetes at age 2 months old treated as type 1 DM with insulin

•Patient was treated as T1DM with insulin MDI that was switched to insulin pump at age 9 years old.

Age	Medications	HgA1C
2 M-13 YO	Insulin	8%-9%
17 years old	Insulin pump	>14%
18 YO Genetic testing confirmed confirming monogenic neonatal DM MODY 13	On glyburide titrated dose	7.9%
19-20 YO	Januvia, metformin and exenatide were added stepwise.	7.6%
21 YO	Insulin was added	9.2%
23 YO	Canagliflozin and glyburide dose was titrated up	9%
28 YO	Has an episode of Acute pancreatitis with DKA	A1C up to 11.4%
28 YO- 30 YO	While on insulin and Glipizide	A1C down to 6.9% to 7.4%

•At age 17 years old he had diabetic genetic testing done that was positive for KCNJ11 R201C confirming monogenic neonatal DM MODY 13

• Patient has long history of noncompliance with medications especially his glyburide which played also a big role in his poorly controlled diabetes in addition to poor compliance with low carbohydrate diet

• At age 28 years old he developed DKA and acute pancreatitis and was admitted to the hospital, that was attributed to SGLT2 with hypertriglyceridemia.

Discussion :

Patient has many contributing factors to his poorly controlled diabetes and needed to be in insulin including:
Long history of noncompliance with diet and medications
The fact that older age with diagnosis contribute to more chances of pancreatic damage
Long Hx of uncontrolled diabetes leads to direct damage to pancreatic cell by 5% yearly
Hypertriglyceridemia with acute pancreatitis and DKA

MODY 13/KNCNJ11 mutation causes permeant neonatal diabetes through pancreatic ATP- sensitive potassium channel activation

90% of patients successfully transferred from insulin to oral sulfonylurea with an excellent initial glycemic control, however whether this control is maintained in the long term is unclear

High dose sulfonylurea facilitates the response to alternative pathway stimuli and increases insulin secretion in KCNJ11 permanent neonatal diabetes

Although in KCNJ11 permanent neonatal diabetes there is fixed β-cell defect that does not change over time but the Prescence of other factors that lead to pancreatic damage over the years like noncompliance, pancreatitis, hypertriglyceridemia, older age at diagnosis that contribute to the need to be on insulin mainly around puberty as it is associated with increased insulin resistant