PMID- 36988218
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231105
IS  - 2052-0573 (Print)
IS  - 2052-0573 (Electronic)
IS  - 2052-0573 (Linking)
VI  - 2023
IP  - 1
DP  - 2023 Mar 29
TI  - First report of type 2 diabetes mellitus in an adult with 
      3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency.
LID - 22-0413 [pii]
LID - 10.1530/EDM-22-0413 [doi]
AB  - SUMMARY: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency is an 
      inborn error of metabolism resulting in a lack of ketogenesis and leucine 
      catabolism. Hallmarks of decompensation include hypoglycemia without ketosis (or 
      hypoketosis), metabolic acidosis, and hyperammonemia. Management includes 
      avoiding fasting and restricting dietary protein and fat. Conversely, type 2 
      diabetes mellitus (T2DM) requires carbohydrate restriction and/or 
      anti-hyperglycemic agents; thus, managing these co-existing disorders is 
      challenging. A 36-year-old male with HMG-CoA lyase deficiency and T2DM 
      (Hemoglobin A1c (HbA1c): 7.9%) presented with confusion and shock. Blood work 
      revealed metabolic acidosis, hyperammonemia, hyperglycemia, and hypoketosis. The 
      patient was diagnosed with hyperosmolar non-ketotic hyperglycemia and 
      hyperammonemia secondary to HMG-CoA lyase metabolic decompensation requiring 
      intensive care unit admission. Hyperammonemia management was challenging because 
      alternative calories with i.v. dextrose (due to hyperglycemia) and i.v. lipids 
      (due to HMG-CoA lyase deficiency) could not be provided as usual. The patient was 
      started on hemodialysis and i.v. insulin with marked improvement. Once 
      stabilized, metformin and insulin were initiated. T2DM impaired cellular glucose 
      uptake and produced a state similar to hypoglycemia, despite the patient being 
      profoundly hyperglycemic, which led to metabolic decompensation of HMG-CoA lyase 
      deficiency. Managing T2DM and HMG-CoA lyase deficiency warrants special 
      considerations due to the potential for metabolic decompensation with both 
      hyperglycemia and hypoglycemia. LEARNING POINTS: In a patient with 
      3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) lyase deficiency and type 2 
      diabetes mellitus (T2DM), management principles include avoiding hypoglycemia to 
      prevent metabolic decompensation, providing insulin for proper glucose 
      utilization, and moderation of carbohydrate intake to prevent consequences of 
      chronic hyperglycemia. The development of insulin resistance in the form of T2DM 
      in HMG-CoA lyase deficiency likely triggered a state similar to hypoglycemia, 
      leading to cellular energy deficiency and subsequently metabolic decompensation. 
      It is important to avoid hypoglycemia in patients with HMG-CoA lyase deficiency 
      and T2DM, as the risk of metabolic decompensation is increased due to the lack of 
      ketogenesis in HMG-CoA lyase deficiency. Selection of antidiabetic agents in this 
      patient population requires careful consideration, and agents that have a higher 
      risk of hypoglycemia should be avoided.
FAU - Lai, Valerie
AU  - Lai V
AUID- ORCID: 0000-0003-0187-8168
AD  - Department of Medicine, University of Alberta, Edmonton, AB, Canada.
FAU - Shahidi, Mariam
AU  - Shahidi M
AD  - Department of Medicine, University of Alberta, Edmonton, AB, Canada.
AD  - Division of Endocrinology and Metabolism, University of Alberta, Edmonton, AB, 
      Canada.
FAU - Chan, Alicia
AU  - Chan A
AD  - Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
FAU - Jain-Ghai, Shailly
AU  - Jain-Ghai S
AD  - Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
LA  - eng
PT  - Journal Article
DEP - 20230329
PL  - England
TA  - Endocrinol Diabetes Metab Case Rep
JT  - Endocrinology, diabetes & metabolism case reports
JID - 101618943
PMC - PMC10083644
COIS- There are no conflicts of interests to disclose that could be perceived as 
      prejudicing the impartiality of the research reported.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:01
PMCR- 2023/03/29
CRDT- 2023/03/29 08:23
PHST- 2022/12/19 00:00 [received]
PHST- 2023/02/13 00:00 [accepted]
PHST- 2023/03/30 06:01 [medline]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/29 08:23 [entrez]
PHST- 2023/03/29 00:00 [pmc-release]
AID - 22-0413 [pii]
AID - EDM220413 [pii]
AID - 10.1530/EDM-22-0413 [doi]
PST - epublish
SO  - Endocrinol Diabetes Metab Case Rep. 2023 Mar 29;2023(1):22-0413. doi: 
      10.1530/EDM-22-0413.