Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Crossover Study

Ranjan, Ajenthen; Schmidt, Signe; Damm‐Frydenberg, Camilla; Steineck, Isabelle Isa Kristin; Clausen, T.; Holst, Jens J.; Madsbad, Sten; Nørgaard, Kirsten

doi:10.2337/dc16-1472

Cited by 72 publications

(59 citation statements)

References 19 publications

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“…Further, at some point, the estimated optimum glucagon dose was, in our opinion, too high (>500 μg) as treatment option for mild hypoglycaemia, especially due to the increased risk of side effects. In a previous study, a single bolus of 500 μg glucagon tended to cause more nausea than 100 μg glucagon during mild hypoglycaemia . In the present study, we found that 500 μg glucagon was needed if serum insulin was 2.5 times baseline insulin levels, IOB was 2 U, or IOB was 6% of TDD.…”

Section: Discussionsupporting

confidence: 48%

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Ranjan

Wendt

Schmidt

et al. 2017

Basic Clin Pharma Tox

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Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin-dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose-insulin-glucagon model was used to describe seven virtual patients with insulin pump-treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba-insulin), insulin on board (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre-defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin levels, regardless of how insulin was estimated. A 125-μg glucagon dose was needed to optimally treat mild hypoglycaemia when insulin levels were equal to baseline levels. In contrast, glucagon doses >500 μg were needed when se/ba-insulin >2.5, IOB >2.0 U or IOB/TDD >6%. Although the proposed model-based glucagon regimen needs confirmation in clinical trials, this is the first attempt to develop an insulin-dependent glucagon dosing regimen for treatment of insulin-induced mild hypoglycaemia in patients with type 1 diabetes.

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Section: Discussionsupporting

confidence: 48%

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Ranjan

Wendt

Schmidt

et al. 2017

Basic Clin Pharma Tox

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“…For instance, we have previously showed that the effect of low-dose glucagon is attenuated when carbohydrate intake has been limited to 50 g per day for 1 week. 22 We speculate whether the main driver of the observed differences in glycaemic control between LCD and HCD is simply carbohydratecounting skills. The participants in our study were experienced users of advanced carbohydrate counting.…”

Section: Discussionmentioning

confidence: 90%

“…Finally, it is probable that there are other consequences of adhering to low carbohydrate diets than the ones investigated in the current study. For instance, we have previously showed that the effect of low‐dose glucagon is attenuated when carbohydrate intake has been limited to 50 g per day for 1 week …”

Section: Discussionmentioning

confidence: 99%

Low versus high carbohydrate diet in type 1 diabetes: A 12‐week randomized open‐label crossover study

Schmidt

Christensen

Serifovski

et al. 2019

Diabetes Obesity Metabolism

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Aims To compare the effects of a low carbohydrate diet (LCD < 100 g carbohydrate/d) and a high carbohydrate diet (HCD > 250 g carbohydrate/d) on glycaemic control and cardiovascular risk factors in adults with type 1 diabetes. Materials and methods In a randomized crossover study with two 12‐week intervention arms separated by a 12‐week washout, 14 participants using sensor‐augmented insulin pumps were included. Individual meal plans meeting the carbohydrate criteria were made for each study participant. Actual carbohydrate intake was entered into the insulin pumps throughout the study. Results Ten participants completed the study. Daily carbohydrate intake during the two intervention periods was (mean ± standard deviation) 98 ± 11 g and 246 ± 34 g, respectively. Time spent in the range 3.9‐10.0 mmol/L (primary outcome) did not differ between groups (LCD 68.6 ± 8.9% vs. HCD 65.3 ± 6.5%, P = 0.316). However, time spent <3.9 mmol/L was less (1.9 vs. 3.6%, P < 0.001) and glycaemic variability (assessed by coefficient of variation) was lower (32.7 vs. 37.5%, P = 0.013) during LCD. No events of severe hypoglycaemia were reported. Participants lost 2.0 ± 2.1 kg during LCD and gained 2.6 ± 1.8 kg during HCD (P = 0.001). No other cardiovascular risk factors, including fasting levels of lipids and inflammatory markers, were significantly affected. Conclusions Compared with an intake of 250 g of carbohydrate per day, restriction of carbohydrate intake to 100 g per day in adults with type 1 diabetes reduced time spent in hypoglycaemia, glycaemic variability and weight with no effect on cardiovascular risk factors.

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“…There is evidence from ketogenic diets that low‐carbohydrate diets can be nutritionally inadequate and result in growth failure . Restricted carbohydrate diets may increase the risk of hypoglycemia or potentially impair the effect of glucagon in hypoglycemia treatment …”

Section: Introductionmentioning

confidence: 99%

ISPAD Clinical Practice Consensus Guidelines 2018: Nutritional management in children and adolescents with diabetes

et al. 2018

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Low-Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Crossover Study

Abstract: The LCD reduces the treatment effect of glucagon on mild hypoglycemia. Carbohydrate intake should be considered when low-dose glucagon is used to correct hypoglycemia.

Cited by 72 publications

References 19 publications

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Low versus high carbohydrate diet in type 1 diabetes: A 12‐week randomized open‐label crossover study

ISPAD Clinical Practice Consensus Guidelines 2018: Nutritional management in children and adolescents with diabetes

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