Postprandial Glucose in Adolescents with Type 1 Diabetes Mellitus Treated with Ultra-Rapid Insulin Aspart

Study Objective: To assess the postprandial glucose (PPG) and glycemic control quality in adolescents with type 1 diabetes mellitus treated with ultra-rapid insulin aspart (URiAsp).

Study Design: prospective open-label controlled clinical study.

Materials and Methods. We examined 21 adolescents with DM1 aged 12 to 15 years old, with the mean age of 13.2 ± 1.2 years old, including 12 (57.1%) boys (mean age: 13.3 ± 2.1 years old) and 9 (42.9%) girls (mean age: 12.9 ± 2.1 years old). Duration of the disease was 4.1 ± 1.3 years (1–8 years). The children were treated with multiple daily injections of insulin; basal insulin was Glargine and Degludec; for bolus injections, Lispro or Aspart were used. Glucose flash monitoring was used. Glycemic control was assessed on the basis of Time In Range (TIR), Time Above Range (TAR), and Time Below Range (TBR). Preprandial glucose levels and glucose 30, 60 and 120 minutes after meal at school were measured. Patients were transferred to URiAsp in outpatient settings. 3 months after the change in the insulin therapy, TIR, TAR and TBR at school, and preprandial glucose levels and glucose 30, 60 and 120 minutes after meal at school were measured.

Study Results. Transition to URiAsp therapy allowed avoiding the need in a preprandial break before meal at school. Also, it resulted in significant improvement in glycemic control. Both total TIR (from 58.1 ± 12.4% to 66.3 ± 11.6%; p < 0.001) and TIR at school (from 52.3 ± 13.1% to 67.6 ± 10.3%; p < 0.001) rose, primarily due reduction in TAR – total TAR (from 32.5 ± 11.9% to 26.1 ± 10.4%; p < 0.001) and TAR at school (from 37.4 ± 12.3% to 24.2 ± 9.5%; p < 0.001). There were no statistically significant changes in TBR. Significant reduction in the rate of PPG increase (p < 0.001) and mean PPG in 30, 60 and 120 minutes after meals was noted.

Conclusion. URiAsp therapy in schoolchildren with DM1 ensures improved glycemic control due to reduced TAR without the risk of hypoglycaemia.

1. Funk S.D., Yurdagul A. Jr, Orr A.W. Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. Int. J. Vasc. Med. 2012; 2012: 569654. DOI: 10.1155/2012/569654

2. Akasaka T., Sueta D., Tabata N. et al. Effects of the mean amplitude of glycemic excursions and vascular endothelial dysfunction on cardiovascular events in nondiabetic patients with coronary artery disease. J. Am. Heart Assoc. 2017; 6(5): e004841. DOI: 10.1161/JAHA.116.004841

3. Diabetes Control and Complications Trial (DCCT): results of feasibility study. The DCCT Research Group. Diabetes Care. 1987; 10(1): 1–19. DOI: 10.2337/diacare.10.1.1

4. Diabetes Control Complications Trial Research Group; Nathan D.M., Genuth S. et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 1993; 329(14): 977–86. DOI: 10.1056/NEJM199309303291401

5. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352(9131): 837–53.

6. Diabetes Canada Clinical Practice Guidelines Expert Committee; Ali Imran S., Agarwal G. et al. Targets for glycemic control. Can. J. Diabetes. 2018; 42(suppl.1): S42–6. DOI: 10.1016/j.jcjd.2017.10.030

7. Coons M.J., Greiver M., Aliarzadeh B. et al. Is glycemia control in Canadians with diabetes individualized? A cross-sectional observational study. BMJ Open Diabetes Res. Care. 2017; 5(1): e000316. DOI: 10.1136/bmjdrc-2016-000316

8. Beck R.W., Bergenstal R.M., Cheng P. et al. The relationships between time in range, hyperglycemia metrics, and HbA1c. J. Diabetes Sci. Technol. 2019; 13(4): 614–26. DOI: 10.1177/1932296818822496

9. Ketema E.B., Kibret K.T. Correlation of fasting and postprandial plasma glucose with HbA1c in assessing glycemic control; systematic review and meta-analysis. Arch. Public Health. 2015; 73: 43. DOI: 10.1186/s13690-015-0088-6

10. Nicolucci A., Ceriello A., Di Bartolo P. et al. Rapid-acting insulin analogues versus regular human insulin: a meta-analysis of effects on glycemic control in patients with diabetes. Diabetes Ther. 2020; 11(3): 573–84. DOI: 10.1007/s13300-019-00732-w

11. Pettus J.H., Zhou F.L., Shepherd L. et al. Incidences of severe hypoglycemia and diabetic ketoacidosis and prevalence of microvascular complications stratified by age and glycemic control in U.S. adult patients with type 1 diabetes: a real-world study. Diabetes Care. 2019; 42(12): 2220–7. DOI: 10.2337/dc19-0830

12. Mohanty R.R., Das S. Inhaled insulin — current direction of insulin research. J. Clin. Diagn. Res. 2017; 11(4): OE01–02. DOI: 10.7860/JCDR/2017/23626.9732

13. Senior P., Hramiak I. Fast-acting insulin aspart and the need for new mealtime insulin analogues in adults with type 1 and type 2 diabetes: a Canadian perspective. Can. J. Diabetes. 2019; 43(7): 515–23. DOI: 10.1016/j.jcjd.2019.01.004

14. Basu A., Pieber T.R., Hansen A.K. et al. Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast-acting insulin aspart compared with insulin aspart. Diabetes Obes. Metab. 2018; 20(7): 1615–622. DOI: 10.1111/dom.13270

15. Fath M., Danne T., Biester T. et al. Faster-acting insulin aspart provides faster onset and greater early exposure vs insulin aspart in children and adolescents with type 1 diabetes mellitus. Pediatr. Diabetes. 2017; 18(8): 903–10. DOI: 10.1111/pedi.12506

16. Heise T., Stender-Petersen K., Hovelmann U. et al. Pharmacokinetic and pharmacodynamic properties of faster-acting insulin aspart versus insulin aspart across a clinically relevant dose range in subjects with type 1 diabetes mellitus. Clin. Pharmacokinet. 2017; 56(6): 649–60. DOI: 10.1007/s40262-016-0473-5

17. Slattery D., Amiel S.A., Choudhary P. Optimal prandial timing of bolus insulin in diabetes management: a review. Diabet. Med. 2018; 35(3): 306–16. DOI: 10.1111/dme.13525

18. Dimitriadis G.D., Maratou E., Kountouri A. et al. Regulation of postabsorptive and postprandial glucose metabolism by insulin-dependent and insulin-independent mechanisms: an integrative approach. Nutrients. 2021; 13(1): 159. DOI: 10.3390/nu13010159

19. Yamada M., Suzuki J., Nakaya T. et al. Comparative effects of insulin glulisine and lispro on postprandial plasma glucose and lipid profile in Japanese patients with type 2 diabetes mellitus. Diabetol. Int. 2020; 12(3): 330–5. DOI: 10.1007/s13340-020-00475-1

20. Teodoro J.S., Nunes S., Rolo A.P. et al. Therapeutic options targeting oxidative stress, mitochondrial dysfunction and inflammation to hinder the progression of vascular complications of diabetes. Front. Physiol. 2019; 9: 1857. DOI: 10.3389/fphys.2018.01857

21. Bergman M., Abdul-Ghani M., DeFronzo R.A. et al. Review of methods for detecting glycemic disorders. Diabetes Res. Clin. Pract. 2020; 165: 108233. DOI: 10.1016/j.diabres.2020.108233

22. Ma J., He H., Yang X. et al. A new approach for investigating the relative contribution of basal glucose and postprandial glucose to HbA1C. Nutr. Diabetes. 2021; 11(1): 14. DOI: 10.1038/s41387-021-00156-1

23. Logan A.D., Jones J., Kuritzky L. Structured blood glucose monitoring in primary care: a practical, evidence-based approach. Clin. Diabetes. 2020; 38(5): 421–8. DOI: 10.2337/cd20-0045

24. Peyser T.A., Balo A.K., Buckingham B.A. et al. Glycemic variability percentage: a novel method for assessing glycemic variability from continuous glucose monitor data. Diabetes Technol. Ther. 2018; 20(1): 6–16. DOI: 10.1089/dia.2017.0187

25. Adolfsson P., Hartvig N.V., Kaas A. et al. Increased time in range and fewer missed bolus injections after introduction of a smart connected insulin pen. Diabetes Technol. Ther. 2020; 22(10): 709–18. DOI: 10.1089/dia.2019.0411

26. Haahr H., Heise T. Fast-acting insulin aspart: a review of its pharmacokinetic and pharmacodynamic properties and the clinical consequences. Clin. Pharmacokinet. 2020; 59(2): 155–72. DOI: 10.1007/s40262-019-00834-5