CGM-Based Prevention of Hypoglycemia Via Hypoglycemia Risk Assessment and Smooth Reduction of Insulin Delivery

• US 20140046159A1
• Filed: 08/30/2013
• Published: 02/13/2014
• Est. Priority Date: 02/25/2009
• Status: Active Grant

• Current Assignee: University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Kovatchev, Boris P., Breton, Marc D., Patek, Stephen D.
• Granted Patent: US 9,750,438 B2
• Time in Patent Office: Days
• US Class Current: 600/365
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/0004 characterised by the type of physiological signal transmitted
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61B 5/746 Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms alarms per se G08B
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 40/67 for remote operation
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders

Abstract

An aspect of an embodiment or partial embodiment of the present invention (or combinations of various embodiments in whole or in part of the present invention) comprises, but not limited thereto, a method and system (and related computer program product) for continually assessing the risk of hypoglycemia for a patient and then determining what action to take based on that risk assessment. A further embodiment results in two outputs: (1) an attenuation factor to be applied to the insulin rate command sent to the pump (either via conventional therapy or via open or closed loop control) and/or (2) a red/yellow/green light hypoglycemia alarm providing to the patient an indication of the risk of hypoglycemia. The two outputs of the CPHS can be used in combination or individually.

Claims

1. A method for preventing or mitigating hypoglycemia in a subject, comprising:

obtaining metabolic measurements associated with the subject;

continuously assessing a risk of hypoglycemia based on the metabolic measurements; and

evaluating the risk of hypoglycemia to determine one of the following outcomes;

no action is needed;

attenuation of insulin delivery is needed;

additional intervention is needed;

or

attenuation of insulin delivery and additional intervention are needed.

2. The method of claim 1, wherein said metabolic measurements is a direct measurement from the subject.

3. The method of claim 2, wherein said direct metabolic measurement comprises blood or interstitial glucose data.

4. The method of claim 1, wherein said metabolic measurement comprises blood or interstitial glucose data.

5. The method of claim 1, wherein said metabolic measurements is an indirect measurement from the subject.

6. The method of claim 5, wherein said indirect metabolic measurement comprises insulin data.

7. The method of claim 1, wherein said metabolic measurement comprises insulin data.

8. The method of claim 1, wherein said metabolic measurements is a direct measurement and an indirect measurement from the subject.

9. The method of claim 8, wherein said direct metabolic measurement comprises blood or interstitial glucose data.

10. The method of claim 8, wherein said indirect metabolic measurement comprises insulin data.

11. The method of claim 1, wherein said metabolic measurement comprises glucose data and insulin data.

12. The method of claim 1, wherein said continuous assessment occurs approximately once every second.

13. The method of claim 1, wherein said continuous assessment occurs approximately once every two seconds.

14. The method of claim 1, wherein said continuous assessment occurs approximately once every minute.

15. The method of claim 1, wherein said continuous assessment occurs approximately once every fifteen minutes.

16. The method of claim 1, wherein said continuous assessment occurs approximately once every thirty minutes.

17. The method of claim 1, wherein said continuous assessment occurs approximately once every sixty minutes.

18. The method of claim 1, wherein said continuous assessment occurs X times per second, where 1<

X<

1000.

19. The method of claim 1, wherein each outcome corresponds to a subject'"'"'s risk of hypoglycemia.

20. The method of claim 1, wherein the step of taking no action indicates a negligible risk of hypoglycemia.

21. The method of claim 1, wherein the step of attenuating insulin delivery indicates a low risk of hypoglycemia.

22. The method of claim 1, wherein the step of additional intervention indicates a high risk of hypoglycemia.

23. The method of claim 1, wherein the step of attenuating insulin delivery and additional intervention indicates a high risk of hypoglycemia.

24. The method of claim 1, further comprising communicating said determined outcome by presenting a signal.

25. The method of claim 24, wherein the signal is a visual signal.

26. The method of claim 25, wherein the visual signal is a light of predetermined color.

27. The method of claim 24, wherein the signal is an audio signal.

28. The method of claim 1, wherein additional intervention includes any one or combination of the following:

user intervention;

administering rescue carbohydrates;

ingesting glucose;

injecting glucose;

injecting glucagon;

or

injecting or ingesting any other hypoglycemia prevention substance.

29. The method of claim 1, further comprising disclosing said determined outcome to one or more individuals.

30. The method of claim 29, wherein the one or more individuals is the subject.

31. The method of claim 29, wherein the one or more individuals is the doctor.

32. The method of claim 29, wherein the one or more individuals is the subject and the doctor.

33. The method of claim 1, further comprising transmitting said determined outcome to an individual.

34. The method of claim 33, wherein the individual is remote from the evaluating device.

35. The method of claim 33, wherein the individual is local to the evaluating device.

36. The method of claim 33, wherein the transmission is performed via a wired connection.

37. The method of claim 33, wherein the transmission is performed via a wireless connection.

38. The method of claim 37, wherein the wireless connection is a phone network.

39. The method of claim 1, wherein the attenuation of insulin delivery is performed gradually.

40. The method of claim 39, wherein gradually is defined as reducing insulin delivery in stages.

41. The method of claim 40, wherein the reduction in insulin delivery may or may not lead to complete shutdown of insulin delivery.

42. The method of claim 1, wherein the risk assessment is defined as a brakes risk assessment, {tilde over (R)}(t), that is provided as a sample of raw risk values where:

43. The method of claim 42, wherein the threshold glucose concentration is the glucose concentration below which the risk function will be positive.

44. The method of claim 42, wherein the values for parameters α

(θ

), β

(θ

), and γ

(θ

) are as follows;

45. The method of claim 1, wherein the risk assessment is defined as a power brakes risk assessment, R_corrected(t), that is provided as a sample of raw risk values where:

46. The method of claim 45, wherein the threshold glucose concentration is the glucose concentration below which the risk function will be positive.

47. The method of claim 45, wherein the values for parameters α

(θ

), β

(θ

), and γ

(θ

) are as follows;

48. The method of claim 1, wherein the attenuation of insulin delivery is performed by using a brakes hypoglycemia attenuation factor.

49. The method of claim 48, wherein the brakes hypoglycemia attenuation factor is φ

_brakes(R(t)), where

φ

_brakes(R(t))=1/(1+k·

R(t)),

and wherein k is an aggressiveness factor.

50. The method of claim 49, wherein the aggressiveness factor corresponds to insulin sensitivity.

51. The method of claim 49, wherein the aggressiveness factor and threshold glucose concentration are generic to multiple subjects.

52. The method of claim 49, wherein the aggressiveness factor and threshold glucose concentration are adjusted to the specific subject.

53. The method of claim 49, wherein the aggressiveness factor and threshold glucose concentration are determined according to a subject'"'"'s physical characteristics.

54. The method of claim 53, wherein the subject'"'"'s physical characteristics include one or more of the following:

body weight;

age;

total daily insulin;

carbohydrate ratio; and

a correction factor.

55. The method of claim 53, wherein the aggressiveness factor and threshold glucose concentration are determined according to a regression formula involving the subject'"'"'s physical characteristics.

56. The method of claim 55, wherein the aggressiveness factor is k, where

k=exp(−

0.7672−

0.0091·

TDI+0.0449·

CF),

wherein TDI is total daily insulin and CF is a correction factor.

57. The method of claim 49, further comprising:

obtaining a programmed rate of insulin injection; and

multiplying the programmed rate of insulin injection by the brakes hypoglycemia attenuation factor to determine an attenuated insulin injection rate.

58. The method of claim 57, wherein the brakes hypoglycemia attenuation factor is used by an insulin delivery device to compute a reduced actual pump rate, J_actual(t).

59. The method of claim 58, wherein the reduced actual pump rate, J_actual(t) is determined as follows:

J_actual(t)=φ

_brakes(R(t))·

J_command(t),

wherein J_command(t) is the rate of insulin injection that the insulin delivery device is set to administer.

60. The method of claim 48, wherein the power brakes hypoglycemia attenuation factor is φ

_{power brakes}(R(t)), where

61. The method of claim 60, further comprising:

obtaining a programmed rate of insulin injection; and

multiplying the programmed rate of insulin injection by the power brakes hypoglycemia attenuation factor to determine an attenuated insulin injection rate.

62. The method of claim 61, wherein the power brakes hypoglycemia attenuation factor is used by an insulin delivery device to compute a reduced actual pump rate, J_actual(t).

63. The method of claim 62, wherein the reduced actual pump rate, J_actual(t) is determined as follows:

J<sub>actual(t)=φ

powerbrakes</sub>(R_corrected(t))·

J_command(t)

wherein J_command(t) is the rate of insulin injection that the insulin delivery device is set to administer.

64. The method of claim 1, wherein the attenuation of insulin delivery is performed by using a power brakes hypoglycemia attenuation factor.

65. The method of claim 1, wherein the assessment of a risk of hypoglycemia is determined solely from glucose information.

66. The method of claim 65, wherein the glucose information is a most recent glucose sample.

67. The method of claim 65, wherein the glucose information is an average of recent glucose samples.

68. The method of claim 1, wherein the assessment of a risk of hypoglycemia is performed by a processor.

69. The method of claim 1, wherein the evaluation of a risk of hypoglycemia is performed by a processor.

208. The method of claim 1, wherein said continuous assessment occurs X times per hour, where 1<

X<

1000.

209. The method of claim 1, wherein said continuous assessment occurs X times per day, where 1<

X<

1000.

70. A system for preventing or mitigating hypoglycemia in a subject, comprising:

an obtaining device for obtaining metabolic measurements associated with the subject;

an assessment device for continuously assessing a risk of hypoglycemia based on the metabolic measurements; and

an evaluation device for evaluating the risk of hypoglycemia to determine one of the following outcomes;

no action is needed;

attenuation of insulin delivery is needed;

additional intervention is needed;

or

attenuation of insulin delivery and additional intervention are needed.

71. The system of claim 70, wherein said metabolic measurements is a direct measurement from the subject.

72. The system of claim 71, wherein said direct metabolic measurement comprises blood or interstitial glucose data.

73. The system of claim 70, wherein said metabolic measurement comprises blood or interstitial glucose data.

74. The system of claim 70, wherein said metabolic measurements is an indirect measurement from the subject.

75. The system of claim 74, wherein said indirect metabolic measurement comprises insulin data.

76. The system of claim 70, wherein said metabolic measurement comprises insulin data.

77. The system of claim 70, wherein said metabolic measurements is a direct measurement and an indirect measurement from the subject.

78. The system of claim 77, wherein said direct metabolic measurement comprises blood or interstitial glucose data.

79. The system of claim 77, wherein said indirect metabolic measurement comprises insulin data.

80. The system of claim 70, wherein said metabolic measurement comprises glucose data and insulin data.

81. The system of claim 70, wherein said assessment device assesses a risk of hypoglycemia approximately once every second.

82. The system of claim 70, wherein said assessment device assesses a risk of hypoglycemia approximately once every two seconds.

83. The system of claim 70, wherein said assessment device assesses a risk of hypoglycemia approximately once every minute.

84. The system of claim 70, wherein said assessment device assesses a risk of hypoglycemia approximately once every fifteen minutes.

85. The system of claim 70, wherein said assessment device assesses a risk of hypoglycemia approximately once every thirty minutes.

86. The system of claim 70, wherein said assessment device assesses a risk of hypoglycemia approximately once every sixty minutes.

87. The system of claim 70, wherein said assessment device assesses a risk of hypoglycemia X times per second, where 1<

X<

1000.

88. The system of claim 70, wherein each outcome corresponds to a subject'"'"'s risk of hypoglycemia.

89. The system of claim 70, wherein the outcome of taking no action indicates a negligible risk of hypoglycemia.

90. The system of claim 70, wherein the outcome of attenuating insulin delivery indicates a low risk of hypoglycemia.

91. The system of claim 70, wherein the outcome of additional intervention indicates a high risk of hypoglycemia.

92. The system of claim 70, wherein the outcome of attenuating insulin delivery and additional intervention indicates a high risk of hypoglycemia.

93. The system of claim 70, further comprising a communication device for communicating said determined outcome by presenting a signal.

94. The system of claim 93, wherein the signal is a visual signal.

95. The system of claim 94, wherein the visual signal is a light of predetermined color.

96. The system of claim 93, wherein the signal is an audio signal.

97. The system of claim 70, wherein additional intervention includes any one or combination of the following:

user intervention;

administering rescue carbohydrates;

ingesting glucose;

injecting glucose;

injecting glucagon;

or

injecting or ingesting any other hypoglycemia prevention substance.

98. The system of claim 70, further comprising a disclosure device for disclosing said determined outcome to one or more individuals.

99. The system of claim 98, wherein the one or more individuals is the subject.

100. The system of claim 98, wherein the one or more individuals is the doctor.

101. The system of claim 98, wherein the one or more individuals is the subject and the doctor.

102. The system of claim 70, further comprising a transmission device for transmitting said determined outcome to an individual.

103. The system of claim 102, wherein the individual is remote from the evaluating device.

104. The system of claim 102, wherein the individual is local to the evaluating device.

105. The system of claim 102, wherein the transmission device is a wired transmission device.

106. The system of claim 102, wherein the transmission device is a wireless transmission device.

107. The system of claim 106, wherein the wireless transmission device transmits via a phone network.

108. The system of claim 70, wherein the attenuation of insulin delivery is performed gradually.

109. The system of claim 108, wherein gradually is defined as reducing insulin delivery in stages.

110. The system of claim 109, wherein the reduction in insulin delivery may or may not lead to complete shutdown of insulin delivery.

111. The system of claim 70, wherein the risk assessment is defined as a brakes risk assessment is {tilde over (R)}(t), that is provided as a sample of raw risk values where:

112. The system of claim 111, wherein the threshold glucose concentration is the glucose concentration below which the risk function will be positive.

113. The system of claim 111, wherein the values for parameters α

(θ

), β

(θ

), and γ

(θ

) are as follows;

114. The system of claim 70, wherein the risk assessment is defined as a power brakes risk assessment, R_corrected(t), that is provided as a sample of raw risk values where:

115. The system of claim 114, wherein the threshold glucose concentration is the glucose concentration below which the risk function will be positive.

116. The system of claim 114, wherein the values for parameters α

(θ

), β

(θ

), and γ

(θ

) are as follows;

117. The system of claim 70, wherein the attenuation of insulin delivery is performed by using a hypoglycemia attenuation factor.

118. The system of claim 117, wherein the hypoglycemia attenuation factor is φ

_brakes(R(θ

)), where

φ

_brakes(R(t))=1/(1+k·

R(t)),

and wherein k is an aggressiveness factor.

119. The system of claim 118, wherein the aggressiveness factor corresponds to insulin sensitivity.

120. The system of claim 118, wherein the aggressiveness factor and threshold glucose concentration are generic to multiple subjects.

121. The system of claim 118, wherein the aggressiveness factor and threshold glucose concentration are adjusted to the specific subject.

122. The system of claim 118, wherein the aggressiveness factor and threshold glucose concentration are determined according to a subject'"'"'s physical characteristics.

123. The system of claim 122, wherein the subject'"'"'s physical characteristics include one or more of the following:

body weight;

age;

total daily insulin;

carbohydrate ratio; and

a correction factor.

124. The system of claim 122, wherein the aggressiveness factor and threshold glucose concentration are determined according to a regression formula involving the subject'"'"'s physical characteristics.

125. The system of claim 124, wherein the aggressiveness factor is k, where

k=exp(−

0.7672−

0.0091·

TDI+0.0449·

CF),

wherein TDI is total daily insulin and CF is a correction factor.

126. The system of claim 118, further comprising:

a second obtaining device for obtaining a programmed rate of insulin injection; and

a multiplication device for multiplying the programmed rate of insulin injection by the hypoglycemia attenuation factor to determine an attenuated insulin injection rate.

127. The system of claim 126, wherein the hypoglycemia attenuation factor is used by an insulin delivery device to compute a reduced actual pump rate, J_actual(t).

128. The system of claim 127, wherein the reduced actual pump rate, J_actual(t) is determined as follows:

J_actual(t)=φ

_brakes(R(t))·

J_command(t),

wherein J_command(t) is the rate of insulin injection that the insulin delivery device is set to administer.

129. The system of claim 117, wherein the power brakes hypoglycemia attenuation factor is φ

_{power brakes}(R(t)), where

130. The system of claim 129, further comprising:

obtaining a programmed rate of insulin injection; and

multiplying the programmed rate of insulin injection by the power brakes hypoglycemia attenuation factor to determine an attenuated insulin injection rate.

131. The system of claim 130, wherein the power brakes hypoglycemia attenuation factor is used by an insulin delivery device to compute a reduced actual pump rate, J_actual(t).

132. The system of claim 131, wherein the reduced actual pump rate, J_actual(t) is determined as follows:

J_actual(t)=φ

_powerbrakes(R_corrected(t))·

J_command(t)

wherein J_command(t) is the rate of insulin injection that the insulin delivery device is set to administer.

133. The system of claim 70, wherein the attenuation of insulin delivery is performed by using a power brakes hypoglycemia attenuation factor.

134. The system of claim 70, wherein the assessment device assesses a risk of hypoglycemia solely from glucose information.

135. The system of claim 134, wherein the glucose information is a most recent glucose sample.

136. The system of claim 134, wherein the glucose information is an average of recent glucose samples.

137. The system of claim 70, wherein the assessment device contains a processor.

138. The system of claim 70, wherein the evaluation device contains a processor.

210. The system of claim 70, wherein said continuous assessment occurs X times per hour, where 1<

X<

1000.

211. The system of claim 70, wherein said continuous assessment occurs X times per day, where 1<

X<

1000.

139. A computer program product comprising a computer useable medium having a computer program logic for enabling at least one processor in a computer system to prevent or mitigate hypoglycemia in a subject, said computer logic comprising:

obtaining data of metabolic measurements associated with the subject;

continuously assessing a risk of hypoglycemia based on the metabolic measurements; and

evaluating the risk of hypoglycemia to determine one of the following outcomes;

no action is needed;

attenuation of insulin delivery is needed;

additional intervention is needed;

or

attenuation of insulin delivery and additional intervention are needed.

140. The computer program product of claim 139, wherein said metabolic measurements is a direct measurement from the subject.

141. The computer program product of claim 140, wherein said direct metabolic measurement comprises blood or interstitial glucose data.

142. The computer program product of claim 139, wherein said metabolic measurement comprises blood or interstitial glucose data.

143. The computer program product of claim 139, wherein said metabolic measurements is an indirect measurement from the subject.

144. The computer program product of claim 143, wherein said indirect metabolic measurement comprises insulin data.

145. The computer program product of claim 139, wherein said metabolic measurement comprises insulin data.

146. The computer program product of claim 139, wherein said metabolic measurements is a direct measurement and an indirect measurement from the subject.

147. The computer program product of claim 146, wherein said direct metabolic measurement comprises blood or interstitial glucose data.

148. The computer program product of claim 146, wherein said indirect metabolic measurement comprises insulin data.

149. The computer program product of claim 139, wherein said metabolic measurement comprises glucose data and insulin data.

150. The computer program product of claim 139, wherein said assessment device assesses a risk of hypoglycemia approximately once every second.

151. The computer program product of claim 139, wherein said assessment device assesses a risk of hypoglycemia approximately once every two seconds.

152. The computer program product of claim 139, wherein said assessment device assesses a risk of hypoglycemia approximately once every minute.

153. The computer program product of claim 139, wherein said assessment device assesses a risk of hypoglycemia approximately once every fifteen minutes.

154. The computer program product of claim 139, wherein said assessment device assesses a risk of hypoglycemia approximately once every thirty minutes.

155. The computer program product of claim 139, wherein said assessment device assesses a risk of hypoglycemia approximately once every sixty minutes.

156. The computer program product of claim 139, wherein said assessment device assesses a risk of hypoglycemia X times per second, where 1<

X<

1000.

157. The computer program product of claim 139, wherein each outcome corresponds to a subject'"'"'s risk of hypoglycemia.

158. The computer program product of claim 139, wherein the outcome of taking no action indicates a negligible risk of hypoglycemia.

159. The computer program product of claim 139, wherein the outcome of attenuating insulin delivery indicates a low risk of hypoglycemia.

160. The computer program product of claim 139, wherein the outcome of additional intervention indicates a high risk of hypoglycemia.

161. The computer program product of claim 139, wherein the outcome of attenuating insulin delivery and additional intervention indicates a high risk of hypoglycemia.

162. The computer program product of claim 139, further comprising a communication device for communicating said determined outcome by presenting a signal.

163. The computer program product of claim 162, wherein the signal is a visual signal.

164. The computer program product of claim 163, wherein the visual signal is a light of predetermined color.

165. The computer program product of claim 162, wherein the signal is an audio signal.

166. The computer program product of claim 139, wherein additional intervention includes any one or combination of the following:

user intervention;

administering rescue carbohydrates;

ingesting glucose;

injecting glucose;

injecting glucagon;

or

injecting or ingesting any other hypoglycemia prevention substance.

167. The computer program product of claim 139, further comprising a disclosure device for disclosing said determined outcome to one or more individuals.

168. The computer program product of claim 167, wherein the one or more individuals is the subject.

169. The computer program product of claim 167, wherein the one or more individuals is the doctor.

170. The computer program product of claim 167, wherein the one or more individuals is the subject and the doctor.

171. The computer program product of claim 139, further comprising a transmission device for transmitting said determined outcome to an individual.

172. The computer program product of claim 171, wherein the individual is remote from the evaluating device.

173. The computer program product of claim 171, wherein the individual is local to the evaluating device.

174. The computer program product of claim 171, wherein the transmission device is a wired transmission device.

175. The computer program product of claim 171, wherein the transmission device is a wireless transmission device.

176. The computer program product of claim 175, wherein the wireless transmission device transmits via a phone network.

177. The computer program product of claim 139, wherein the attenuation of insulin delivery is performed gradually.

178. The computer program product of claim 177, wherein gradually is defined as reducing insulin delivery in stages.

179. The computer program product of claim 178, wherein the reduction in insulin delivery may or may not lead to complete shutdown of insulin delivery.

180. The computer program product of claim 139, wherein the risk assessment is defined as a brakes risk assessment, {tilde over (R)}(t), that is provided as a sample of raw risk values where:

181. The computer program product of claim 180, wherein the threshold glucose concentration is the glucose concentration below which the risk function will be positive.

182. The computer program product of claim 180, wherein the values for parameters α

(θ

), β

(θ

), and γ

(θ

) are as follows;

183. The computer program product of claim 139, wherein the risk assessment is defined as a power brakes risk assessment, R_corrected(t), that is provided as a sample of raw risk values where:

184. The computer program product of claim 183, wherein the threshold glucose concentration is the glucose concentration below which the risk function will be positive.

185. The computer program product of claim 183, wherein the values for parameters α

(θ

), β

(θ

), and γ

(θ

) are as follows;

186. The computer program product of claim 139, wherein the attenuation of insulin delivery is performed by using a hypoglycemia attenuation factor.

187. The computer program product of claim 186, wherein the hypoglycemia attenuation factor is φ

_brakes(R(t)), where

φ

_brakes(R(t))=1/(1+k·

R(t)),

and wherein k is an aggressiveness factor.

188. The computer program product of claim 187, wherein the aggressiveness factor corresponds to insulin sensitivity.

189. The computer program product of claim 187, wherein the aggressiveness factor and threshold glucose concentration are generic to multiple subjects.

190. The computer program product of claim 187, wherein the aggressiveness factor and threshold glucose concentration are adjusted to the specific subject.

191. The computer program product of claim 187, wherein the aggressiveness factor and threshold glucose concentration are determined according to a subject'"'"'s physical characteristics.

192. The computer program product of claim 191, wherein the subject'"'"'s physical characteristics include one or more of the following:

body weight;

age;

total daily insulin;

carbohydrate ratio; and

a correction factor.

193. The computer program product of claim 191, wherein the aggressiveness factor and threshold glucose concentration are determined according to a regression formula involving the subject'"'"'s physical characteristics.

194. The computer program product of claim 193, wherein the aggressiveness factor is k, where

k=exp(−

0.7672−

0.0091·

TDI+0.0449·

CF),

wherein TDI is total daily insulin and CF is a correction factor.

195. The computer program product of claim 187, further comprising:

a second obtaining device for obtaining a programmed rate of insulin injection; and

a multiplication device for multiplying the programmed rate of insulin injection by the hypoglycemia attenuation factor to determine an attenuated insulin injection rate.

196. The computer program product of claim 195, wherein the hypoglycemia attenuation factor is used by an insulin delivery device to compute a reduced actual pump rate, J_actual(t).

197. The computer program product of claim 196, wherein the reduced actual pump rate, J_actual(t) is determined as follows:

J_actual(t)=φ

_brakes(R(t))·

J_command(t),

wherein J_command(t) is the rate of insulin injection that the insulin delivery device is set to administer.

198. The method of claim 186, wherein the power brakes hypoglycemia attenuation factor is φ

_{power brakes}(R(t)), where

199. The computer program product of claim 198, further comprising:

obtaining a programmed rate of insulin injection; and

multiplying the programmed rate of insulin injection by the power brakes hypoglycemia attenuation factor to determine an attenuated insulin injection rate.

200. The computer program product of claim 199, wherein the power brakes hypoglycemia attenuation factor is used by an insulin delivery device to compute a reduced actual pump rate, J_actual(t).

201. The computer program product of claim 200, wherein the reduced actual pump rate, J_actual(t) is determined as follows:

J_actual(t)=φ

_powerbrakes(R_corrected(t))·

J_command(t)

wherein J_command(t) is the rate of insulin injection that the insulin delivery device is set to administer.

202. The computer program product of claim 139, wherein the attenuation of insulin delivery is performed by using a power brakes hypoglycemia attenuation factor.

203. The computer program product of claim 139, wherein the assessment device assesses a risk of hypoglycemia solely from glucose information.

204. The computer program product of claim 203, wherein the glucose information is a most recent glucose sample.

205. The computer program product of claim 203, wherein the glucose information is an average of recent glucose samples.

206. The computer program product of claim 139, wherein the assessment device contains a processor.

207. The computer program product of claim 139, wherein the evaluation device contains a processor.

212. The computer program product of claim 139, wherein said continuous assessment occurs X times per hour, where 1<

X<

1000.

213. The computer program product of claim 139, wherein said continuous assessment occurs X times per day, where 1<

X<

1000.