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Diabetes Publish Ahead of Print published online ahead of print April 4, 2008
DOI: 10.2337/db08-0276
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Original Research

EFFECT OF ORAL AMINO ACID ON COUNTERREGULATORY RESPONSES AND COGNITIVE FUNCTION DURING INSULIN-INDUCED HYPOGLYCEMIA IN NON-DIABETIC AND TYPE 1 DIABETIC PEOPLE

Paolo Rossetti, MD, Francesca Porcellati, MD, PhD, Natalia Busciantella Ricci, MD, Paola Candeloro, PhD, Patrizia Cioli, RD, K. Sreekumaran Nair, MD, Fausto Santeusanio, MD, Geremia B. Bolli, MD, and Carmine G. Fanelli, MD, PhD

Department of Internal Medicine, University of Perugia, Perugia, Italy

Objective: Amino acids (AA) stimulate glucagon responses to hypoglycaemia, and may be utilized by the brain. Aim of study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of AA mixture.

Research Design and Methods: 10 nondiabetic and 10 diabetic type 1 subjects were studied on three different occasions during intravenous insulin (2 mU/kg/min) + variable glucose for 160 minutes. In two studies, clamped hypoglycemia (plasma glucose 47 mg/dl for 40 min) was induced and either oral placebo (P) or AA mixture (42g) was given at +30 min. In the third study AA were given, but euglycemia was maintained.

Results: Plasma glucose and insulin were no different in the hypoglycemia studies both with P and AA (p>0.2). After AA, plasma AA concentration increased to levels observed after mixed meal (2.4±0.13 vs P study 1.7±0.1 mmol/l, p=0.02). During clamped euglycemia, AA resulted in transient increase in glucagon concentrations, which returned to basal by the end of study. During clamped hypoglycemia, glucagon response was sustained and increased more in AA studies vs P in nondiabetics and diabetics (p<0.05), but other counterregulatory hormones and total symptom score were not different. Beta-OH-butyrate was less suppressed after AA (200±15 vs 93±9 µmol/L, p=0.01). Among the cognitive tests administered, the following indicated less deterioration after AA than P: Trail-making B, PASAT (2 sec), Digit span forward, Stroop colored words and verbal memory tests (nondiabetics), and Trail-Making B, Digit span backwards and Stroop color tests (diabetics).

Conclusions: Oral amino acids improve cognitive function in response to hypoglycemia, and enhance the response of glucagon in nondiabetic and in diabetic subjects.

Correspondence: gbolli{at}unipg.it

Key Words: Type 1 Diabetes • hypoglycemia • glucagon secretion • amino acid • cognitive function


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