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

Abstract

IntroductionTo 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).MethodsEighty-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.ResultsBHG’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).ConclusionsFor 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 RegistrationChinese Clinical Trial Registry Identifier ChiCTR-TTRCC-12002516.FundingLilly Suzhou Pharmaceutical Co., Ltd. (Shanghai Branch, China) and National Key Program of Clinical Science of China (WBYZ2011-873).

A new approach for investigating the relative contribution of basal glucose and postprandial glucose to HbA1C

“…These studies also revealed that BG plays a major role in the subgroup of patients with HbA1c levels > 8.5%, and the relative contribution of PPG decreased with increasing HbA1c (from 65.5% to 39.2%). The difference in the relative contribution of PPG between the studies performed by Li et al 20 and Riddle’s et al 7 may be that Riddle et al used 5.6 mmol/L as a baseline, whereas Li et al used 6.1 mmol/L as a baseline, leading to the overestimation of the relative contribution of PPG. The NGT curve considers physiological fluctuations in normal people after meals, and thus, can be used as a baseline to evaluate the relative contribution of PPG and BG to hyperglycaemia.…”

“…Recent studies of diabetes patients being administered insulin [20][21][22] and Glucagon like peptide-1 receptor agonists (GLP-1 RAs) 23 are a good complement to our research. These studies also revealed that BG plays a major role in the subgroup of patients with HbA1c levels > 8.5%, and the relative contribution of PPG decreased with increasing HbA1c (from 65.5% to 39.2%).…”

“…Bergenstal 28 stated that CGM has transformed glucose control and can be used to identify glucose excursions in patients with diabetes. The recent development of some new therapies specifically aimed at reducing BG or PPG has further increased the interest for studying the complex relationship between the contributions of BG and PPG, yet have yielded conflicting results 20 , 21 , 23 , 25 . Recently, the results of a randomised crossover trial conducted by CGMS pointed that the conflicting results may be related to differences in the study population, methodologies, etc 29 .…”

“…BG predominated when HbA1c was ≥9and ≥ 10% in oral antidiabetic drug- and insulin-treated patients. Li et al 20 , 22 (2018) 81 (a) T2DM treated with insulin (b) LM25 and LM50 (c)Chinese, China ≥6.1 (a) 4-point blood glucose profile at least one day (b) high-carbohydrate test meals on day 1 and high-fat test meals on day 2 and their habitual diets on day 3 7.8 ± 1.4 PPG played a major role of patients with HbA1c < 8.5%. PPG’s contribution rate decreased with increasing HbA1c (from 65.5% to 39.2%).…”

“…However, the A1 C -derived average glucose study 8 showed that BG was not a clear indicator of general glycaemia. Table 1 summarizes 17 relevant studies 6,7,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] published up to Jan 1, 2021. It shows the complex results on the relative contribution of PPG to HbA1c in diverse subjects, treatment regimens, and baseline criterias.…”