Diminished arginine bioavailability during hyperglycaemia distinguishes individuals with A−β+ ketosis-prone diabetes from those with type 2 diabetes: implications for the pathogenesis of ketoacidosis in A−β+ ketosis-prone diabetes
Main finding · Arginine bioavailability decline, euglycaemic to hyperglycaemic (Protocol 1)Result — go to the resultGreater decline of arginine bioavailability 42.5%Authors' conclusion
Arginine potentiates insulin secretion during sustained hyperglycaemia, hence its diminished bioavailability in individuals with KPD could contribute to the development of ketoacidosis during a hyperglycaemic crisis. Individuals with KPD retain responsiveness to exogenous arginine during hyperglycaemia and normalise endogenous arginine availability with citrulline supplementation
Study context
- Population
- Individuals with A−β+ ketosis-prone diabetes (KPD), T2D and non-diabetic controls; Protocol 2: adults with KPD diagnosed after unprovoked diabetic ketoacidosis (DKA), lacking islet autoantibodies, substantial beta cell functional reserve, HbA1c <58.5 mmol/mol [7.5%] on metformin aloneProtocol 2: 10 KPD
- Comparison
- KPD vs T2D vs non-diabetic controls (Protocol 1); citrulline vs alanine (placebo) supplementation in KPD (Protocol 2)
- Outcome
- Arginine flux (Protocol 2)
Methodological detailsstable isotope tracer infusions, euglycaemic and hyperglycaemic conditions, Protocol 2: blinded, randomised crossover trial, single clinical research centre
- Stable isotope tracer infusions
- Euglycaemic and hyperglycaemic conditions
- Protocol 2: blinded, randomised crossover trial
- Single clinical research centre
Main finding
As reported in the abstract
Greater decline of arginine bioavailability
42.5%
P = 0.035
- Protocol 2: citrulline but not alanine increased arginine flux in KPD (effect size)
- 0.746 (95% CI 0.258, 0.931)
Further findings
Arginine de novo synthesis, hydrolysis, nitric oxide (NO) synthesis, ornithine flux (Protocol 1)
- KPD and T2D did not differ
Insulin response after hyperglycaemia (Protocol 1)
- Both diabetes groups had blunted insulin response to glucose bolus; KPD showed increased insulin response to arginine
Arginine synthesis and NO synthesis (Protocol 2)
- Increased with citrulline but not alanine in KPD
Safety
Adverse effects (Protocol 2)
- Citrulline supplementation without adverse effects
Original publication
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