J Korean Med Sci.  2016 Feb;31(2):231-239. 10.3346/jkms.2016.31.2.231.

In-Silico Trials for Glucose Control in Hospitalized Patients with Type 2 Diabetes

• Choi K
• Oh TJ
• Lee JC
• Kim M
• Kim HC
• Cho YM
• Kim S

• KMID: 2360047
• DOI: http://doi.org/10.3346/jkms.2016.31.2.231

Abstract

Although various basal-bolus insulin therapy (BBIT) protocols have been used in the clinical environment, safer and more effective BBIT protocols are required for glucose control in hospitalized patients with type 2 diabetes (T2D). Modeling approaches could provide an evaluation environment for developing the optimal BBIT protocol prior to clinical trials at low cost and without risk of danger. In this study, an in-silico model was proposed to evaluate subcutaneous BBIT protocols in hospitalized patients with T2D. The proposed model was validated by comparing the BBIT protocol and sliding-scale insulin therapy (SSIT) protocol. The model was utilized for in-silico trials to compare the protocols of adjusting basal-insulin dose (BBIT1) versus adjusting total-daily-insulin dose (BBIT2). The model was also used to evaluate two different initial total-daily-insulin doses for various levels of renal function. The BBIT outcomes were superior to those of SSIT, which is consistent with earlier studies. BBIT2 also outperformed BBIT1, producing a decreased daily mean glucose level and longer time-in-target-range. Moreover, with a standard dose, the overall daily mean glucose levels reached the target range faster than with a reduced-dose for all degrees of renal function. The in-silico studies demonstrated several significant findings, including that the adjustment of total-daily-insulin dose is more effective than changes to basal-insulin dose alone. This research represents a first step toward the eventual development of an advanced model for evaluating various BBIT protocols.

Keyword

Biomedical Engineering; Blood Glucose; Computer Simulation; Insulin; Models, Theoretical; Diabetes Mellitus, Type 2

MeSH Terms

Blood Glucose/analysis
Diabetes Mellitus, Type 2/*drug therapy
Hospitalization
Humans
Hypoglycemic Agents/*therapeutic use
Insulin/*therapeutic use
Models, Theoretical
Blood Glucose
Hypoglycemic Agents
Insulin

Figure

• 

  Fig. 1 Schematic of input-output relationships in the model depending on exogenous inputs. (A) Meal glucose absorption model, (B) subcutaneous insulin absorption model, and (C) insulin glucose dynamics model. Solid lines represent direct relationships, whereas dotted lines represent indirect relationships among the submodels. SC stands for subcutaneous.

• 

  Fig. 2 Changes in daily mean blood glucose level in virtual patients with normal renal function treated with BBIT1 (•), BBIT2 (○), and SSIT1 (▪). Data are presented as the mean + SD. *P < 0.001, ¶P < 0.01 vs. BBIT1; †P < 0.001 vs. BBIT2.

• 

  Fig. 3 Simulation results in standard- (0.5 unit/kg/day) and reduced-initial total daily insulin dose (iTDD) regimen (0.25 units/kg/day) in scenarios #1, 4, and 7. Changes in daily mean blood glucose level in (A) scenario #1, (B) scenario #4, and (C) scenario #7. Changes of TDD in (D) scenario #1, (E) scenario #4, and (F) scenario #7. Data are presented as the mean + SD. Values in parentheses represent the percentage of normal renal function. *P < 0.001; †P < 0.01; ‡P < 0.05.

• 

  Fig. 4 Three-day simulation demonstrating the effect of meal glucose input and BBIT2 on glucose control. From the second day to the last day, BBIT2 was applied to randomly selected patients with a body weight of 96.5 kg and an initial glucose concentration of 231 mg/dL. (A) Changes in glucose concentrations (black solid line): the gray solid line indicates the target range (100-140 mg/dL) and the gray dashed line indicates the hyperglycemia threshold (180 mg/dL of glucose); (B) meal time and amount of meal glucose; (C) injection time and amount of insulin; (D) rate of insulin appearance in blood (pM/kg/min) by endogenous secreted insulin and subcutaneously injected insulin; and (E) insulin concentration.

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