Hypoglycemia Impairs Quality of Blood Glucose Simulation in a Clinical Decision Support System

Abstract

Background:

Clinical decision support systems allow for decisions based on blood glucose simulations. The DiasNet simulation tool is based on accepted principles of physiology and simulates blood glucose concentrations accurately in type 1 diabetes mellitus (T1DM) patients during periods without hypoglycemia, but deviations appear after hypoglycemia, possibly because of the long-term glucose counter-regulation to hypoglycemia. The purpose of this study was to evaluate the impact of hypoglycemia on blood glucose simulations.

Method:

Continuous glucose monitoring (CGM) data and diary data (meals, insulin, self-monitored blood glucose) were collected for 2 to 5 days from 17 T1DM patients with poor glycemic control. Hypoglycemic episodes [CGM glucose <63 mg/dl (3.5 mmol/liter) for ≥20 min] were identified in valid (well-calibrated) CGM data. For 24 hours after each hypoglycemic episode, a simulated (DiasNet) glucose profile was compared to the CGM glucose.

Results:

A total of 52 episodes of hypoglycemia were identified in valid data. All subjects had at least one hypoglycemic episode. Ten episodes of hypoglycemia from nine subjects were eligible for analysis. The CGM glucose was significantly (p < .05) higher than simulated blood glucose for a period of 13 h, beginning 8 h after hypoglycemia onset.

Conclusions:

The present data show that hypoglycemia introduces substantial and systematic simulation errors for up to 24 h after hypoglycemia. This underlines the need for further evaluation of mechanisms behind this putative long-term glucose counter-regulation to hypoglycemia. When using blood glucose simulations in decision support systems, the results indicate that simulations for several hours following a hypoglycemic event may underestimate glucose levels by 100 mg/dl (5.6 mmol/liter) or more.

Keywords

clinical decision support systems continuous glucose sensors hypoglycemia physiopathology type 1 diabetes mellitus

References

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 (14): 977–86.

Cox

Irvine

Gonder-Frederick

Nowacek

Butterfield

. Fear of hypoglycemia: quantification, validation, and utilization. Diabetes Care. 1987; 10 (5): 617–21.

Richmond

. Effects of hypoglycaemia: patients' perceptions and experiences. Br J Nurs. 1996; 5 (17): 1054–9.

Anderson

. Patient empowerment and the traditional medical model. A case of irreconcilable differences?. Diabetes Care. 1995; 18 (3): 412–5.

Berger

Mühlhauser

. Implementation of intensified insulin therapy: a European perspective. Diabet Med. 1995; 12 (3): 201–8.

Assal

Jacquemet

Morel

. The added value of therapy in diabetes: the education of patients for self-management of their disease. Metabolism. 1997; 46 (12 Suppl 1): 61–4.

Corbett

. Patient knowledge and self-efficacy for diabetes management: impact of home care nurse interventions. In: Funk

Tornquist

Leeman

Miles

Harrell

, eds. Key aspects of preventing and managing chronic illness. New York: Springer; 2001, 261–74.

Cavan

. Giving power to the patients. Mod Diabetes Manag. 2001; 2 (4): 15–6.

Plougmann

Hejlesen

Cavan

. DiasNet—a diabetes advisory system for communication and education via the internet. Int J Med Inform. 2001; 64 (2–3): 319–30.

10.

Lehmann

. AIDA—a computer-based interactive educational diabetes simulator. Diabetes Educ. 1998; 24 (3): 341–6, 348.

11.

Franklin

Wilson

Butler

Greene

. A predictive tool for the self-management of diabetes (Librae): evaluation using a continuous glucose monitoring system. Diabet Med. 2006; 23 (1): 21–5.

12.

Hejlesen

Andreassen

Sando

. Optimization and evaluation of a probabilistic computer model of the glucose metabolism. Appl Med Inform. 1995; 1 (1): 11–24.

13.

Hejlesen

Andreassen

Frandsen

Sørensen

Sandø

Hovorka

Cavan

. Using a double blind controlled clinical trial to evaluate the function of a Diabetes Advisory System: a feasible approach? Comput Methods Programs Biomed. 1998; 56 (2): 165–73.

14.

Plougmann

Hejlesen

Turner

Kerr

Cavan

. Modelling the effect of alcohol in type 1 diabetes. Stud Health Technol Inform. 2002; 90: 66–71.

15.

Hejlesen

Andreassen

Cavan

Hovorka

. Analysing the hypoglycaemic counter-regulation: a clinically relevant phenomenon? Comput Methods Programs Biomed. 1996; 50 (3): 231–40.

16.

Hirsch

Smith

Havlin

Shah

Clutter

Cryer

. Failure of nocturnal hypoglycemia to cause daytime hyperglycemia in patients with IDDM. Diabetes Care. 1990; 13 (2): 133–42.

17.

Gale

Kurtz

Tattersall

. In search of the Somogyi effect. Lancet. 1980; 2 (8189): 279–82.

18.

Bolli

Gottesman

Campbell

Haymond

Cryer

Gerich

. Glucose counterregulation and waning of insulin in the Somogyi phenomenon (posthypoglycemic hyperglycemia). N Engl J Med. 1984; 311 (19): 1214–9.

19.

Tordjman

Havlin

Levandoski

White

Santiago

Cryer

. Failure of nocturnal hypoglycemia to cause fasting hyperglycemia in patients with insulin-dependent diabetes mellitus. N Engl J Med. 1987; 317 (25): 1552–9.

20.

Sachedina

Pickup

. Performance assessment of the Medtronic-MiniMed Continuous Glucose Monitoring System and its use for measurement of glycaemic control in type 1 diabetic subjects. Diabet Med. 2003; 20 (12): 1012–5.

21.

Caplin

O'Leary

Bulsara

Davis

Jones

. Subcutaneous glucose sensor values closely parallel blood glucose during insulin-induced hypoglycaemia. Diabet Med. 2003; 20 (3): 238–41.

22.

Pfützner

Forst

Butzer

Forst

Weber

Pfützner

. Performance of the continuous glucose monitoring system (CGMS) during development of ketosis in patients on insulin pump therapy. Diabet Med. 2006; 23 (10): 1124–9.

23.

Høi-Hansen

Pedersen-Bjergaard

Thorsteinsson

. Reproducibility and reliability of hypoglycaemic episodes recorded with Continuous Glucose Monitoring System (CGMS) in daily life. Diabet Med. 2005; 22 (7): 858–62.

24.

Stephenson

Schernthaner

. Dawn phenomenon and Somogyi effect in IDDM. Diabetes Care. 1989; 12 (4): 245–51.

25.

Havlin

Cryer

. Nocturnal hypoglycemia does not commonly result in major morning hyperglycemia in patients with diabetes mellitus. Diabetes Care. 1987; 10 (2): 141–7.