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Hypoglycemia: from the laboratory to the clinic.

Amiel SA - Diabetes Care (2009)

View Article: PubMed Central - PubMed

ABSTRACT

Hypoglycemia remains a significant limitation to optimal treatment of diabetes with insulin and insulin secretagogues. Current research into the physiology of hypoglycemic counterregulation has helped us understand how to reduce risk of severe hypoglycemia, but much remains to be understood and exploited. In those with type 1 diabetes, risk for hypoglycemia is increased by the completeness of the insulin deficiency as well as the associated failure of glucagon responses to hypoglycemia and additional failure of other counterregulatory mechanisms created at least in part by repeated exposure to modest hypoglycemia itself. For those with long duration type 2 diabetes, hypoglycemia risk also increases with increasing insulin deficiency. Teaching patients to use insulin flexibly around changes in diet, exercise, alcohol ingestion, and other factors influencing insulin requirements and sensitivity can improve glycemic control while reducing hypoglycemia risk. Thereafter, increasing use of technology in both insulin delivery and, more recently, glucose sensing may be helpful. For the patient with truly intractable hypoglycemia, replacement of functional islet tissue by islet or organ transplantation is also a current therapeutic option. For the future, research into agents that may influence glucose sensing or cerebral and peripheral metabolism may offer new ways of enhancing defenses against hypoglycemia in the delivery of truly good glycemic control.

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Regions of enhanced 18-fluoro-deoxy-glucose uptake during hypoglycemia displayed on magnetic resonance imaging brain slices. A: Relatively greater 18-fluoro-deoxy-glucose uptake in amygdala, cerebellum, and brainstem in people with type 1 diabetes and hypoglycemia awareness than in people with type 1 diabetes and hypoglycemia unawareness, consistent with a greater anxiety and vigilance response in the former. B: Relatively reduced 18-fluoro-deoxy-glucose uptake in the right lateral orbitolfrontal cortex in people with good awareness of hypoglycemia compared with those who are unaware. The reduced activation of this brain region in those with awareness suggested by these data is compatible with the recognition of the unpleasantness or danger of the stimulus encouraging behavior to avoid hypoglycemia in future. This seems to be significantly less effective in those who are unaware. Reprinted with permission from Mason et al. (28).
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Figure 2: Regions of enhanced 18-fluoro-deoxy-glucose uptake during hypoglycemia displayed on magnetic resonance imaging brain slices. A: Relatively greater 18-fluoro-deoxy-glucose uptake in amygdala, cerebellum, and brainstem in people with type 1 diabetes and hypoglycemia awareness than in people with type 1 diabetes and hypoglycemia unawareness, consistent with a greater anxiety and vigilance response in the former. B: Relatively reduced 18-fluoro-deoxy-glucose uptake in the right lateral orbitolfrontal cortex in people with good awareness of hypoglycemia compared with those who are unaware. The reduced activation of this brain region in those with awareness suggested by these data is compatible with the recognition of the unpleasantness or danger of the stimulus encouraging behavior to avoid hypoglycemia in future. This seems to be significantly less effective in those who are unaware. Reprinted with permission from Mason et al. (28).

Mentions: A possible additional clinical significance of changes in the cortical response to acute hypoglycemia was illustrated in a recent analysis of 18-fluoro-deoxy-glucose uptake during hypoglycemia that differentiated between the aware and unaware (24). Engagement of appetite control and reward-seeking networks involved in food seeking was seen, but the responses of these networks were measurably reduced in hypoglycemia unawareness, with failure of amygdala and orbifrontal cortex responses in particular (Fig. 2). This suggests habituation of higher behavioral responses to hypoglycemia, akin to stress desensitization, being a basis for unawareness. If confirmed, this would argue that the hypoglycemia-unaware person is unaware both of the hypoglycemia itself but also of its dangers and unpleasantness. This may have important therapeutic implications.


Hypoglycemia: from the laboratory to the clinic.

Amiel SA - Diabetes Care (2009)

Regions of enhanced 18-fluoro-deoxy-glucose uptake during hypoglycemia displayed on magnetic resonance imaging brain slices. A: Relatively greater 18-fluoro-deoxy-glucose uptake in amygdala, cerebellum, and brainstem in people with type 1 diabetes and hypoglycemia awareness than in people with type 1 diabetes and hypoglycemia unawareness, consistent with a greater anxiety and vigilance response in the former. B: Relatively reduced 18-fluoro-deoxy-glucose uptake in the right lateral orbitolfrontal cortex in people with good awareness of hypoglycemia compared with those who are unaware. The reduced activation of this brain region in those with awareness suggested by these data is compatible with the recognition of the unpleasantness or danger of the stimulus encouraging behavior to avoid hypoglycemia in future. This seems to be significantly less effective in those who are unaware. Reprinted with permission from Mason et al. (28).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713613&req=5

Figure 2: Regions of enhanced 18-fluoro-deoxy-glucose uptake during hypoglycemia displayed on magnetic resonance imaging brain slices. A: Relatively greater 18-fluoro-deoxy-glucose uptake in amygdala, cerebellum, and brainstem in people with type 1 diabetes and hypoglycemia awareness than in people with type 1 diabetes and hypoglycemia unawareness, consistent with a greater anxiety and vigilance response in the former. B: Relatively reduced 18-fluoro-deoxy-glucose uptake in the right lateral orbitolfrontal cortex in people with good awareness of hypoglycemia compared with those who are unaware. The reduced activation of this brain region in those with awareness suggested by these data is compatible with the recognition of the unpleasantness or danger of the stimulus encouraging behavior to avoid hypoglycemia in future. This seems to be significantly less effective in those who are unaware. Reprinted with permission from Mason et al. (28).
Mentions: A possible additional clinical significance of changes in the cortical response to acute hypoglycemia was illustrated in a recent analysis of 18-fluoro-deoxy-glucose uptake during hypoglycemia that differentiated between the aware and unaware (24). Engagement of appetite control and reward-seeking networks involved in food seeking was seen, but the responses of these networks were measurably reduced in hypoglycemia unawareness, with failure of amygdala and orbifrontal cortex responses in particular (Fig. 2). This suggests habituation of higher behavioral responses to hypoglycemia, akin to stress desensitization, being a basis for unawareness. If confirmed, this would argue that the hypoglycemia-unaware person is unaware both of the hypoglycemia itself but also of its dangers and unpleasantness. This may have important therapeutic implications.

View Article: PubMed Central - PubMed

ABSTRACT

Hypoglycemia remains a significant limitation to optimal treatment of diabetes with insulin and insulin secretagogues. Current research into the physiology of hypoglycemic counterregulation has helped us understand how to reduce risk of severe hypoglycemia, but much remains to be understood and exploited. In those with type 1 diabetes, risk for hypoglycemia is increased by the completeness of the insulin deficiency as well as the associated failure of glucagon responses to hypoglycemia and additional failure of other counterregulatory mechanisms created at least in part by repeated exposure to modest hypoglycemia itself. For those with long duration type 2 diabetes, hypoglycemia risk also increases with increasing insulin deficiency. Teaching patients to use insulin flexibly around changes in diet, exercise, alcohol ingestion, and other factors influencing insulin requirements and sensitivity can improve glycemic control while reducing hypoglycemia risk. Thereafter, increasing use of technology in both insulin delivery and, more recently, glucose sensing may be helpful. For the patient with truly intractable hypoglycemia, replacement of functional islet tissue by islet or organ transplantation is also a current therapeutic option. For the future, research into agents that may influence glucose sensing or cerebral and peripheral metabolism may offer new ways of enhancing defenses against hypoglycemia in the delivery of truly good glycemic control.

Show MeSH
Related in: MedlinePlus