Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes

Abstract

IntroductionHypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes.Research design and methodsTwenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.ResultsIn total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10−3) and isoleucine (p=2.2×10−3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days.ConclusionsIn individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations.Trial registration numberNCT01337362.

Metabolic effect of adrenaline infusion in people with type 1 diabetes and healthy individuals

“…However, the latter finding was most likely due to a diminished adrenaline response in the type 1 diabetes group. Several studies have shown increased lipolysis during adrenaline infusion [ 25 – 27 ], and a seemingly increased β-adrenergic response in adipose tissues during hypoglycaemia in type 1 diabetes [ 28 – 30 ]. Our findings support the latter result: because, during the last infusion (50 ng adrenaline kg −1 min −1 ), our participants showed adrenaline concentrations resembling levels induced by hypoglycaemia [ 24 , 27 , 29 , 31 ], our results reflect metabolic changes expected to occur during the hypoglycaemia experienced in daily life in individuals with type 1 diabetes.…”

Recovery Phase Nutrition and Insulin Strategies for a Collegiate Distance Runner with Type 1 Diabetes Mellitus: A Case Study

“…Though prevalence of postexercise hypoglycemia in T1DM is unclear [10], studies suggest that late and nocturnal hypoglycemia are common, especially among children and those performing exercise in the afternoon [11]. Despite the reality of post-exercise hypoglycemia and the potential for increased risk with antecedent hypoglycemic episodes diminishing counterregulatory responses [12], there is little published research indicating specific strategies for mitigating hypoglycemia during the exercise recovery phase, and a "trial and error" approach is generally recommended [4]. Research-based suggestions include reducing bolus insulin by 20-50% with the first meal post exercise, and a similar reduction of basal rate during the first 6-12 h post exercise [4,8,13].…”

“…Unfortunately, few extant strategies encompass exercise intensities and durations frequently encountered by CDRT1, necessitating a synthesis of strategies extrapolated from a combination of studies involving runners without diabetes and non-runners with diabetes. Although these acute strategies can be effective for preventing exercise-induced hypoglycemia [5,14], applying commonly used strategies to CDRT1 may lead to deteriorated glycemic control following exercise [15], potentially compromising recovery [16] and glycogen repletion [17], glycemic stability during subsequent training bouts [12], and body composition goals [18].…”