Skip to main content

06-27-2018 | Hyperglycemia | Article

Contribution of BHG and PPHG to Overall Hyperglycemia in T2DM Patients Treated with LM25 and LM50: Post Hoc Analysis of a Randomized Crossover Trial

Journal: Diabetes Therapy

Authors: Wei Li, Fan Ping, Lingling Xu, Huabing Zhang, Yaxiu Dong, Hongmei Li, Qi Sun, Yuxiu Li

Publisher: Springer Healthcare




To investigate the relative contribution rates of basal hyperglycemia (BHG) and postprandial hyperglycemia (PPHG) to overall hyperglycemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin lispro mix 25 and 50 (LM25 and LM50) as evaluated by continuous glucose monitoring (CGM).


Eighty-one T2DM patients treated with premixed human insulin 70/30 (PHI70/30) were randomly divided into two groups and received a crossover protocol. In the first 16-week stage, one group received LM25 twice daily, the other group received LM50 twice daily. In the second 16-week stage, the two groups exchanged therapeutic regimen. Glycosylated hemoglobin (HbA1c) measurement and CGM were performed at enrollment and at the end of each treatment stage.


BHG’s contribution rate increased with increasing HbA1c (from 34.5% to 60.8%). PPHG’s contribution rates in the LM50 regimen were significantly lower than those in LM25 and PHI70/30 regimens at HbA1c levels < 7.5%. Compared with LM50, LM25 shows a significant difference in reducing HbA1c in the subgroup with baseline HbA1c ≥ 8.5% (ΔHbA1c LM25 vs. LM50 − 0.6 ± 0.1% vs. 0.3 ± 0.1%, p < 0.05).


For T2DM patients treated with premixed insulin analogues, postprandial hyperglycemia played a major role in the subgroup of patients with HbA1c < 8.5%, while fasting hyperglycemia became the major contributor to overall hyperglycemia in the subgroup of patients with HbA1c ≥ 8.5%.

Trial Registration

Chinese Clinical Trial Registry Identifier ChiCTR-TTRCC-12002516.


Lilly Suzhou Pharmaceutical Co., Ltd. (Shanghai Branch, China) and National Key Program of Clinical Science of China (WBYZ2011-873).
The Diabetes Control and Complications Trial Research Group. 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;329:977–86. CrossRef
Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002;287:2563–9. CrossRef
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, Lachin JM, White NH, et al. Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Diabetes. 2015;64:631–42. CrossRef
UK Prospective Diabetes Study (UKPDS) 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;352:837–53. CrossRef
Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89. CrossRefPubMed
Davis TM, Coleman RL, Holman RR. Ethnicity and long-term vascular outcomes in type 2 diabetes: a prospective observational study (UKPDS 83). Diabet Med. 2014;31:200–7. CrossRefPubMed
Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003;26:881–5. CrossRefPubMed
Peter R, Luzio SD, Dunseath G, et al. Relationship between HbA1c and indices of glucose tolerance derived from a standardized meal test in newly diagnosed treatment naive subjects with type 2 diabetes. Diabet Med. 2006;23:990–5. CrossRefPubMed
Monnier L, Colette C, Dunseath GJ, et al. The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes. Diabetes Care. 2007;30:263–9. CrossRefPubMed
Woerle HJ, Neumann C, Zschau S, et al. Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes Importance of postprandial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract. 2007;77:280–5. CrossRefPubMed
Peter R, Dunseath G, Luzio SD, et al. Relative and absolute contributions of postprandial and fasting plasma glucose to daytime hyperglycaemia and HbA(1c) in subjects with type 2 diabetes. Diabet Med. 2009;26:974–80. CrossRefPubMed
Kikuchi K, Nezu U, Shirakawa J, et al. Correlations of fasting and postprandial blood glucose increments to the overall diurnal hyperglycemic status in type 2 diabetic patients: variations with levels of HbA1c. Endocr J. 2010;57:259–66. CrossRefPubMed
Schernthaner G, Guerci B, Gallwitz B, et al. Impact of postprandial and fasting glucose concentrations on HbA1c in patients with type 2 diabetes. Diabetes Metab. 2010;36:389–94. CrossRefPubMed
Wang JS, Tu ST, Lee IT, et al. Contribution of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring. Diabetes Metab Res Rev. 2011;27:79–84. CrossRefPubMed
Monnier L, Colette C, Dejager S, et al. Residual dysglycemia when at target HbA(1c) of 7% (53 mmol/mol) in persons with type 2 diabetes. Diabetes Res Clin Pract. 2014;104:370–5. CrossRefPubMed
Riddle M, Umpierrez G, DiGenio A, et al. Contributions of basal and postprandial hyperglycemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes. Diabetes Care. 2011;34:2508–14. CrossRefPubMedPubMedCentral
Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26:3080–6. CrossRefPubMed
Janka HU, Plewe G, Riddle MC, et al. Comparison of basal insulin added to oral agents versus twice-daily premixed insulin as initial insulin therapy for type 2 diabetes. Diabetes Care. 2005;28:254–9. CrossRefPubMed
Gerstein HC, Yale JF, Harris SB, et al. A randomized trial of adding insulin glargine vs. avoidance of insulin in people with type 2 diabetes on either no oral glucose-lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment) Study. Diabet Med. 2006;23:736–42. CrossRefPubMed
Standl E, Maxeiner S, Raptis S. Once-daily insulin glargine administration in the morning compared to bedtime in combination with morning glimepiride in patients with type 2 diabetes: an assessment of treatment flexibility. Horm Metab Res. 2006;38:172–7. CrossRefPubMed
Yki-Jarvinen H, Kauppinen-Makelin R, Tiikkainen M, et al. Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Diabetologia. 2006;49:442–51. CrossRefPubMed
Bretzel RG, Nuber U, Landgraf W, et al. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008;371:1073–84. CrossRefPubMed
Shaefer C, Reid T, DiGenio A, et al. Patterns of postprandial hyperglycemia after basal insulin therapy: individual and regional differences. Diabetes Metab Res Rev. 2014. https://​doi.​org/​10.​1002/​dmrr.​2606. PubMedCrossRef
Li W, Ping F, Xu L, et al. Effects of insulin lispro mix 25 and insulin lispro mix 50 on postprandial glucose excursion in patients with type 2 diabetes: a prospective, open-label, randomized clinical trial. Diabetes Ther. 2018;9:699–711. CrossRefPubMedPubMedCentral
Chinese Diabetes Society, China Medicine Doctor Association Nutrition Doctor Specialized Committee. China medical nutrition therapy guideline for diabetes. Chin J Diabetes Mellitus. 2013;2015(7):73–88 (Chinese).
Chinese Diabetes Society. China guideline for type 2 diabetes mellitus (2013 Edition). Chin J Endocrinol Metab. 2014;30:893–942. https://​doi.​org/​10.​3760/​cma.​j.​issn.​1000-6699.​2014.​10.​020 (Chinese). CrossRef
Tanaka M, Ishii H. Pre-mixed rapid-acting insulin 50/50 analogue twice daily is useful not only for controlling post-prandial blood glucose, but also for stabilizing the diurnal variation of blood glucose levels: switching from pre-mixed insulin 70/30 or 75/25 to pre-mixed insulin 50/50. J Int Med Res. 2010;38:674–80. CrossRefPubMed
Nishimura R, Tsujino D, Taki K, et al. Continuous glucose monitoring with Humalog Mix 25 versus Humalog Mix 50, twice daily: a comparative pilot study -results from the Jikei-EValuation of insulin Lispro mixture on pharmacodynamics and glycemic VariancE (J-EVOLVE) study. Cardiovasc Diabetol. 2010;9:16. https://​doi.​org/​10.​1186/​1475-2840-9-16. CrossRefPubMedPubMedCentral
Watada H, Su Q, Li PF, Iwamoto N, Qian L, Yang WY. Comparison of insulin lispro mix 25 with insulin lispro mix 50 as an insulin starter in Asian patients with type 2 diabetes: a phase 4, open-label, randomized trial (CLASSIFY study). Diabetes Metab Res Rev. 2017;33:e2816. CrossRef
Su Q, Liu C, Zheng H, et al. Comparison of insulin lispro mix 25 with insulin lispro mix 50 as insulin starter in Chinese patients with type 2 diabetes mellitus (CLASSIFY study): subgroup analysis of a phase 4 open-label randomized trial. J Diabetes. 2017;9:575–85. CrossRefPubMed
Su Q, Liu J, Li P, Qian L, Yang W. Relative contribution of fasting and postprandial blood glucose in overall glycemic control: post hoc analysis of a phase IV randomized trial. Diabetes Ther. 2018. https://​doi.​org/​10.​1007/​s13300-018-0403-7. PubMedPubMedCentralCrossRef

New additions to the Adis Journal Club

A selection of topical peer-reviewed articles from the Adis journals, curated by the editors.

GLP-1 receptor agonists

Browse the latest news, clinical trial updates, and expert commentary.