Effect of Oral Amino Acids on Counterregulatory Responses and Cognitive Function During Insulin-Induced Hypoglycemia in Nondiabetic and Type 1 Diabetic People

Abstract

OBJECTIVE-Amino acids stimulate glucagon responses to hypoglycemia and may be utilized by the brain. The aim of this study was to assess the responses to hypoglycemia in nondiabetic and type 1 diabetic subjects after ingestion of an amino acid mixture.RESEARCH DESIGN AND METHODS-Ten nondiabetic and 10 diabetic type 1 subjects were studied on three different occasions during intravenous insulin (2 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) plus variable glucose for 160 min. In two studies, clamped hypoglycemia (47 mg/dl plasma glucose for 40 min) was induced and either oral placebo or an amino acid mixture (42 g) was given at 30 min. In the third study, amino acids were given, but euglycemia was maintained.RESULTS-Plasma glucose and insulin were no different in the hypoglycemia studies with both placebo and amino acids (P Ͼ 0.2). After the amino acid mixture, plasma amino acid concentrations increased to levels observed after a mixed meal (2.4 Ϯ 0.13 vs. placebo study 1.7 Ϯ 0.1 mmol/l, P ϭ 0.02). During clamped euglycemia, ingestion of amino acids resulted in transient increases in glucagon concentrations, which returned to basal by the end of the study. During clamped hypoglycemia, glucagon response was sustained and increased more in amino acid studies versus placebo in nondiabetic and diabetic subjects (P Ͻ 0.05), but other counter-regulatory hormones and total symptom score were not different. ␤-OH-butyrate was less suppressed after amino acids (200 Ϯ 15 vs. 93 Ϯ 9 mol/l, P ϭ 0.01). Among the cognitive tests administered, the following indicated less deterioration after amino acids than placebo: Trail-Making part B, PASAT (Paced Auditory Serial Addition Test) (2 s), digit span forward, Stroop colored words, and verbal memory tests for nondiabetic subjects; and Trail-Making part B, digit span backward, and Stroop color tests for diabetic subjects.CONCLUSIONS-Oral amino acids improve cognitive function in response to hypoglycemia and enhance the response of glucagon in nondiabetic and diabetic subjects.

Changes in plasma phenylalanine, isoleucine, leucine, and valine are associated with significant changes in intracranial pressure and jugular venous oxygen saturation in patients with severe traumatic brain injury

“…A detailed prospective study including larger patient number including multiparametric analysis is required to address the impact of enteral nutrition with its specific amino acid composition on brain metabolism and brain-specific parameters as e.g., ICP, SjvO 2 . While (Oertel et al (2009) were able to demonstrate significant positive influence of protein-rich diet in neurosurgical patients without, however, addressing the individual amino acids, Rossetti et al (2008) were able to show significant influence of increased plasma amino acids on cognitive functions without, however, defining the impact of BCAA.…”

Are bedtime nutritional strategies effective in preventing nocturnal hypoglycaemia in patients with type 1 diabetes?

“…Amino acids may be a substrate for gluconeogenesis and may increase glucagon response, which is impaired in patients with T1D during hypoglycaemia . In 15 adult patients under artificial conditions (plasma glucose was lowered to approximately 5.6 mmol/l at bedtime by intravenous insulin administration; then, a single dose of NPH insulin was injected), Saleh and Cryer compared four bedtime conditions in a randomized crossover trial : No treatment Standard snack: 240 ml milk and 1 slice of toast; approximately 31 g carbohydrate, approximately 11 g protein and approximately 6 g fat Alanine condition: 40 g given orally with 10 g of glucose Terbutaline condition: as an agonist of beta‐adrenergic receptors, terbutaline stimulates the action of epinephrine (not discussed in this review) …”

“…Amino acids may be a substrate for gluconeogenesis and may increase glucagon response, which is impaired in patients with T1D during hypoglycaemia [33][34][35]. In 15 adult patients under artificial conditions (plasma glucose was lowered to approximately 5.6 mmol/l at bedtime by intravenous insulin administration; then, a single dose of NPH insulin was injected), Saleh and Cryer compared four bedtime conditions in a randomized crossover trial [36]:…”

Acute Hypoglycemia Impairs Executive Cognitive Function in Adults With and Without Type 1 Diabetes

“…During hypoglycemia, alternative substrates may be used as energy sources, although in general, they ameliorate but do not reverse the effects of neuroglycopenia (33). Administration of some of these alternative fuels (e.g., amino acids, lactate) has been shown to reduce the decrement in cognitive performance observed during hypoglycemia (34,35). In these studies, insufficient information was given to determine whether there had been a significant improvement in the quality of the answers given.…”