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Assessment of experts' approach to insulin therapy and development of a simulator for diabetes insulin adjustment.

OBJECTIVE: To develop a computer program (Macintosh) to predict changes in blood glucose after changes in insulin dose, timing, and regimen. RESEARCH DESIGN AND METHODS: We established program parameters (apparent insulin action profiles; different for insulin-dependent and non-insulin-dependent diabetes mellitus) to match predictions by five diabetes specialists at our hospital of blood glucose changes after insulin-dose adjustment in 22 hypothetical patient cases. We compared the action profiles, which represent the blood glucose changes predicted by the experts with glucose-clamp studies of insulin action. We tested the program's performance in 22 different hypothetical cases against the responses of 15 specialists from outside our hospital. RESULTS: The specialists, when predicting effects of insulin dose adjustment, integrate numerous processes (insulin action, diet, sequential blood glucose interactions). They could not specify algorithms for determining these individual factors, but they could easily predict the overall effect in the context of patient cases. The computer program's insulin-action profiles simulate this "composite" approach. The developed program incorporates multiple insulin regimens, which may be changed during the stimulation, and adjusts predicted responses according to the patient's estimated sensitivity to insulin. Its predicted change in 172 blood glucose levels (22 cases) correlated well with the corresponding means of the outside specialists (r = 0.83, P = 0.0001). Comparing this correlation with that of individual specialists ranked the program third. CONCLUSIONS: A computer program can simulate specialists' "composite" approach (not based purely on conscious application of physiological data) to insulin adjustment.

Blood Glucose↗

Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence is not a predictive factor for response to interferon-alpha therapy and development of hepatocellular carcinoma.

Genetic changes between codons 2209 and 2248 of NS5A of genotype 1b hepatitis C virus (HCV-1b) have been reported to be associated with the sensitivity to interferon-alpha (IFN-alpha). The present study was performed to analyze such relationship in Korean patients with chronic hepatitis C and HCV-1b (n=19), including 12 chronic hepatitis C patients treated with IFN-alpha, 3 chronic hepatitis C patients without treatment as controls, and 4 patients with hepatocellular carcinoma (HCC). Two serum samples, before and after the treatment, were analyzed for the mutations by reverse transcription-polymerase chain reaction, cloning and sequencing. The mutations were identified in 32% (6/19), including five intermediate type (1-3 mutations) and one mutant type (4 or more). In 12 patients treated with IFN-alpha, the number of amino acid substitutions in NS5A2209-2248 was not associated with outcome of the treatment. Two HCV isolates with NS5A2209-2248 mutations from HCC patients were intermediate type. These results do not support that the NS5A2209-2248 determines interferon sensitivity of HCV-1b and that the mutations is associated with development of HCC.

Adult↗