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Proposal 1668

Title of the Proposed Research

Quantitative Evaluation of Circadian Rhythm of Serum Glucose Level in Caucasian and Chinese Type 2 Diabetic Patients (Oct/2016)

Lead Researcher

Pei Hu

Affiliation

Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital

Funding Source

The study was supported by the “12th Five-year” National Key Technology R&D Program of China (Ministry of Science and Technology of the People's Republic of China; No. 2012ZX09303006-002) and the National Natural Science Foundation of China (No. 81403013).

Potential Conflicts of Interest

None

Data Sharing Agreement Date

31 January 2017

Lay Summary

Background:
Serum glucose level in diabetic patients fluctuates over a day, which was suggested to be caused by the changed rate of endogenous glucose production. The decrease of glucose after administration of anti-diabetic drugs contains effects from both of this auto-fluctuation and drug. Therefore, in order to evaluate drug effect accurately, we should deduct auto-fluctuation from overall glucose decrease, which need to understand the auto-fluctuation better. So far, key factor affecting magnitude of the fluctuation was neither found nor quantified in any studies. Recently, we found the extent of fluctuation differs significantly between males and females in Chinese diabetic patients using clinical trial data of a glucose kinase activator (GKA), HMS5552. Similar phenomenon was identified in Caucasian diabetic patients after we analyzed their mean data. However, the extent of the fluctuation was significantly different between two Caucasian and Chinese diabetic populations. The reason was unknown.

Significance:
The results of this present study could explain the difference of fluctuation extent between the two populations and quantitatively explore the source of these differences, which may improve the understanding of auto-fluctuation of serum glucose and further support new anti-diabetic drug development.

Aim:
The aim of my proposal is to develop a mathematical function including plasma drug concentration, serum glucose concentration, etc., for US2 (Piragliatin), another glucokinase activator, in US diabetic patients and to calculate the effects of key factors on the fluctuation extent in Caucasian diabetic patients. The results will be compared with our previous findings in Chinese diabetic patients.

Method:
By taking advantage of mathematical software and received dataset from Roche, we will develop a mathematical function to quantitatively analyze the effects of Piragliatin on glucose levels in Caucasian diabetic patients as well as to calculate the effect of the key factors on fluctuation of serum glucose levels in diabetic patients.

Interpretation:
These findings may improve the evaluation of drug efficacy in diabetic patients by separating natural fluctuation from drug effect.

Study Data Provided

ROCHE-NP17752: A multiple ascending dose study to investigate the pharmacokinetics, pharmacodynamics, safety and tolerability of RO4389620 in patients with type 2 diabetes mellitus
ROCHE-BM18249: A Randomized Double-blind Study to Determine the Effect of GK Activator (2) on Efficacy (HbA1c), Safety, Tolerability and Pharmacokinetics in Patients With Type 2 Diabetes Mellitus Treated With a Stable Dose of Metformin.

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.