Symptomatic and counterregulatory hormonal responses to acute hypoglycaemia induced by insulin aspart and soluble human insulin in Type 1 diabetes

Frier, Brian M.; Ewing, Fiona M.E; Lindholm, Anders; Hylleberg, Birgitte; Kanc, Karin

doi:10.1002/1520-7560(2000)9999:9999<::aid-dmrr120>3.0.co;2-1

Cited by 23 publications

(7 citation statements)

References 23 publications

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“…It is therefore unsurprising that when infused intravenously, both preparations elicited similar falls in serum potassium. Previous work has demonstrated comparable counter‐regulatory and symptomatic responses during hypoglycaemia [27] and we confirmed that rises in adrenaline (and glucagon) were no different during hypoglycaemia induced by either insulin.…”

Section: Discussionsupporting

confidence: 87%

Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization

Robinson

Harris

Ireland

et al. 2003

Brit J Clinical Pharma

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Aims Sudden death in young diabetic patients has been associated with nocturnal hypoglycaemia perhaps as a result of cardiac dysrhythmias following abnormal cardiac repolarization during hypoglycaemia. It was therefore important to compare the effect of soluble human insulin (HI) and a rapid-acting insulin analogue, insulin aspart (IAsp), on these aspects of cardiac function. Methods A total of 17 healthy males underwent identical hyperinsulinaemic hypoglycaemic clamps with blood glucose maintained at 5 m M for 30 min and reduced to 2.5 m M after an additional 30 min. Subjects received either HI or IAsp on two different occasions separated by 4-6 weeks. Regular measurements were made of two measures of cardiac repolarization, QT dispersion and QTc as well as of counter-regulatory hormones. Results The blood glucose lowering effect did not differ between IAsp and HI and the clearance rates were similar (HI mean ± SD 1.24 ± 0.12 l h -1 kg -1 , IAsp mean ± s.d. 1.22 ± 0.32 l h -1 kg -1 ). There were similar significant increases but no difference between treatments in QTc after hypoglycaemia induced by either IAsp or HI (480 ± 37 ms vs 480 ± 25 ms; NS). However, QT dispersion during hypoglycaemia was less pronounced with IAsp than with HI (92 ± 36 ms vs 107 ± 42 ms; P < 0.05). Plasma adrenaline increased significantly and similarly after both insulins (initial and final concentration, HI, 0.23 ± 0.01 to 4.87 ± 0.48 n M , P < 0.001, IAsp, 0.24 ± 0.01 to 4.99 ± 0.48 n M , P < 0.001). Serum potassium decreased significantly but by a similar amount between the groups (initial and final concentration, HI, 4.18 ± 0.3 to 4.2 ± 0.2 m M , P < 0.001, IAsp, 4.2 ± 0.3 to 4.2 ± 0.3 m M , P < 0.001). Conclusions Soluble human insulin and insulin aspart had similar effects upon hypoglycaemia-induced alterations in cardiac repolarization, presumably because the effects of both regular insulin and insulin aspart on the sympathoadrenal response and potassium concentration were the same.

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Section: Discussionsupporting

confidence: 87%

Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization

Robinson

Harris

Ireland

et al. 2003

Brit J Clinical Pharma

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“…Although experimental hypoglycaemic studies involving other basal insulins have generally used a model incorporating i.v. delivery [23–25], we considered s.c. administration more appropriate. This approach is more clinically relevant, particularly as the mode of protraction for both IDeg and IGlar is activated by s.c. administration.…”

Section: Discussionmentioning

confidence: 99%

Insulin degludec is not associated with a delayed or diminished response to hypoglycaemia compared with insulin glargine in type 1 diabetes: a double-blind randomised crossover study

et al. 2013

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Aims/hypothesisInsulin degludec (Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin; IDeg) is a new basal insulin with an ultra-long flat action profile. The acute physiological responses to hypoglycaemia with IDeg and insulin glargine (A21Gly,B31Arg,B32Arg human insulin; IGlar) were compared.MethodsTwenty-eight adult type 1 diabetic patients with normal hypoglycaemia awareness (age = 41 ± 12 years, HbA1c = 7.8 ± 0.6% [62.8 ± 7 mmol/mol]) were randomised to once-daily IDeg or IGlar for 5 days in a two-period crossover design. Participants and research staff were blinded to group assignment. Patients were assigned the lowest available randomisation number from a set of blinded randomisation codes provided by the trial sponsor. Hypoglycaemia was induced by administering three times the usual daily insulin dose at midnight on day 5. Plasma glucose (PG) was stabilised by glucose clamp (5.5 mmol/l) for 7–9 h post dosing. Next morning, PG was allowed to decrease stepwise from 5.5 to 3.5 mmol/l (maintained for 30 min) to 2.5 mmol/l (for 15 min). PG was then increased to 3.9 mmol/l (for 120 min), before being returned to baseline. Hypoglycaemic symptom score (HSS), hypoglycaemic awareness, cognitive function, counter-regulatory hormones and vital signs were assessed during each glucose plateau. The primary analysis was to compare IDeg vs IGlar with respect to HSS at nadir PG concentration (2.5 mmol/l).ResultsThe full analysis set for treatment comparisons comprised data from all 28 exposed patients. Rates of PG decline and PG at nadir were similar for IDeg and IGlar. No treatment differences in HSS (estimated difference: 0.17 [95% CI −1.71, 2.05]; p > 0.05), cognitive function or awareness were observed at any time. Growth hormone and cortisol responses during hypoglycaemia were greater with IDeg than IGlar (AUC treatment ratio [IDeg/IGlar]: 2.44 [1.30, 4.60], p < 0.01; and 1.23 [1.01, 1.50]; p < 0.05), and adrenaline (epinephrine) responses trended higher (1.40 [0.96, 2.04], p = 0.07). The rates of recovery from hypoglycaemia were similar.Conclusions/interpretationIDeg and IGlar elicit comparable symptomatic and cognitive responses to induced hypoglycaemia. IDeg may elicit a moderately greater endocrine response, but times to PG recovery were similar for the two insulins.Trial registrationClinicalTrials.gov NCT01002768.FundingNovo Nordisk.

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“…Therefore, after the introduction of the novel short‐ and long‐acting insulin analogues, their influence on hypoglycaemia awareness were studied. For aspart, lispro and glargine no differences in counter‐regulatory hormone and symptom response to hypoglycaemia compared to human [10–14] or porcine insulin [10] were described.…”

Section: Introductionmentioning

confidence: 99%

Insulin detemir causes increased symptom awareness during hypoglycaemia compared to human insulin

Tschritter

Schäfer

Klett

et al. 2009

Diabetes Obesity Metabolism

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Symptomatic and counterregulatory hormonal responses to acute hypoglycaemia induced by insulin aspart and soluble human insulin in Type 1 diabetes

Abstract: Insulin aspart and soluble human insulin elicit the same counterregulatory and symptomatic responses to acute hypoglycaemia in patients with Type 1 diabetes.

Cited by 23 publications

References 23 publications

Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization

Comparative effect of human soluble insulin and insulin aspart upon hypoglycaemia‐induced alterations in cardiac repolarization

Insulin degludec is not associated with a delayed or diminished response to hypoglycaemia compared with insulin glargine in type 1 diabetes: a double-blind randomised crossover study

Insulin detemir causes increased symptom awareness during hypoglycaemia compared to human insulin

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