Abstract
Background: Type 1 diabetes mellitus is reportedly characterized by deficiencies of plasma total and free carnitine. Several inherited defects in fatty acid oxidation are associated with carnitine deficiency and with recurrent hypoglycemia. Hypoglycemia continues to be the major limiting factor in the management of type 1 diabetes. Herein, we sought to identify a subset of patients with abnormalities in carnitine profiles. Associations between carnitine abnormalities and glycemic control were also sought. Methods: We performed a single center, prospective, observational study including 153 type 1 diabetic participants and 21 healthy control participants. We measured total, free, and acylcarnitine levels by high performance liquid chromatography-mass spectrometry. Glucose measurements were downloaded from patients’ meters. Results: In contrast to previous reports, no differences were found in free or total acylcarnitine levels between diabetic and control participants. Diabetic participants displayed high levels of C8 and C10 compared to controls. They also displayed biochemical evidence for reduced carnitine palmitoyl transferase 1 (CPT-1) enzymatic activity (as measured by free carnitine/C16 + C18) compared to controls. Patients with the lowest CPT-1 activity displayed a reduction in hemoglobin A 1c levels compared to the remaining population, but no unusual rates of hypoglycemia. We identified two patients who were heterozygous carriers of medium chain acyl-Co A dehydrogenase deficiency. These patients also displayed no detectable increased rates of hypoglycemia. Conclusions: We conclude that deficiencies in free and total carnitine are not as common as previously reported in pediatric patients with type 1 diabetes. Patients with Type 1 diabetes display elevated medium chain acylcarnitines and biochemical evidence for a relative reduction in CPT-1 activity compared to the control population. We did not identify a subset of patients exhibiting both carnitine abnormalities and unusual rates of hypoglycemia.
Highlights
Type 1 diabetes mellitus is reportedly characterized by deficiencies of plasma total and free carnitine
One study documented decreased free carnitine and increased acylcarnitine levels in children with type 1 diabetes in ketoacidosis, which normalized with insulin treatment and reversal of ketoacidosis [1]
Diabetic subjects displayed differences in several individual acylcarnitine values compared to healthy controls (Table 1)
Summary
Type 1 diabetes mellitus is reportedly characterized by deficiencies of plasma total and free carnitine. Several inherited defects in fatty acid oxidation are associated with carnitine deficiency and with recurrent hypoglycemia. One study documented decreased free carnitine and increased acylcarnitine levels in children with type 1 diabetes in ketoacidosis, which normalized with insulin treatment and reversal of ketoacidosis [1]. Eleven disorders of fatty acid metabolism have been described, almost all of which are associated with abnormal carnitine or acylcarnitine levels and recurrent hypoglycemia [3]. The most common of these fatty acid oxidation disorders, medium chain acyl-CoA dehydrogenase deficiency (MCADD), classically presents as severe hypoglycemia during a prolonged fast or during acute illness. Patients with this disorder can remain completely asymptomatic for years [4]
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