Evidence-Based Diabetes Management

The Persistent Complication of Hypoglycemia in Diabetics | Page 2

Published Online: May 22, 2014
Surabhi Dangi-Garimella, PhD
The second study demonstrated that peripheral glucosensory response from the PMV is essential for activation of a complete CRR during slow-onset hypoglycemia.5 The lead authors on the 2 papers, Casey Donovan, PhD, professor and section head, human and evolutionary biology, Department of Biological Sciences at the University of Southern California, and Alan Watts, DPhil, professor in the same department, said in an e-mail response, “While it’s been postulated that these various glucose-sensing loci constitute an extended neural network responsible for mediating the hypoglycemic CRR, there was not substantial evidence. These 2 papers now provide the first evidence demonstrating the existence of such a network. Specifically, we show that

PMV glucose sensing input is critical for the activation of hindbrain neurons during slow-onset hypoglycemia and the subsequent CRR.” They further pointed out that results from their neuronal

activation data suggest that distinct neural networks are in play during rapid- vs slow-onset hypoglycemia.

“The fact that hypoglycemia generally develops slowly in insulin-dependent diabetics points to the importance of fully understanding the functional organization of these glucose-engaged

neural networks,” say the authors. Philip E. Cryer, MD, Irene E. and Michael M. Karl Professor of Endocrinology and Metabolism in Medicine, Washington University School of Medicine,

and a past president of the American Diabetes Association, summarized the significance of these findings in an email: “The reports…provide evidence that signals from the periphery (eg,

from the PMV) travel through the brain stem to the hypothalamus to mediate the sympathoadrenal response to relatively slowly developing hypoglycemia in rats. “As developed in some detail,10 the mechanism of the attenuated sympathoadrenal response to hypoglycemia that follows recent antecedent hypoglycemia occurs during sleep or follows earlier exercise and characterizes

hypoglycemia-associated autonomic failure; however, its increased risk of iatrogenic hypoglycemia in diabetes is not known. It could directly involve the CNS (central nervous system) or the afferent or efferent components of the sympathoadrenal system.”

Cryer believes that understanding the physiology of this response could contribute to an improved understanding of the hypoglycemic episodes in diabetics. A better handle on the mechanism

of this avoidable phenomenon, via improved research efforts, is definitely the need of the day.


1. Hypoglycemia. The American Diabetes Association website. http://www.diabetes.org/living-with-diabetes/treatment-and-care/bloodglucose-control/hypoglycemia-low-blood.html. Accessed April 23, 2014.

2. Severe low blood sugar occurs often in patients with type 2 diabetes [press release]. Oakland, CA: Kaiser Permanente; July 30, 2013. http://share.kaiserpermanente.org/article/severe-low-blood-sugar-occurs-often-in-patientswith-type-2-diabetes/. Accessed April 23, 2014.

3. Lipska KJ, Warton M, Huang ES, et al. HbA1c and risk of severe hypoglycemia in type 2 diabetes: the diabetes and aging study. Diabetes Care. 2013;36(11):3535-3542.

4. Jokiaho AJ, Donovan CM, Watts AG. The rate of fall of blood glucose determines the necessity of forebrain-projecting catecholaminergic neurons for male rat sympathoadrenal responses
[published online April 16, 2014]. Diabetes. doi:10.2337/db13-1753.

5. Bohland M, Matveyenko AV, Saberi M, Khan AM, Watts AG, Donovan CM. Activation of hindbrain neurons is mediated by portal-mesenteric vein glucosensors during slow-onset hypoglycemia
[published online April 11, 2014]. Diabetes.doi:10.2337/db13-1600.

6. Pietri G, Kennedy K, Goldhammer M, Bouchard J. The cost of severe hypoglycemic events in diabetes: a retrospective claims database study. Poster presented at: ISPOR 17th Annual International Meeting; June 2012; Washington, DC. http://www.ispor.org/research_pdfs/40/pdffiles/PDB37.pdf. Accessed April 24, 2014.

7. Quilliam BJ, Simeone JC, Ozbay AB, Kogut SJ. http://www.ajmc.com/publications/issue/2011/2011-10-Vol17-n10/AJMC_11oct_Quilliam_673to680#sthash.A0WyNwqV.dpuf. Am J Manag Care. 2011;17(10):673-680.

8. Busko M. Insulin-related hypoglycemia: common, costly, preventable. Medscape. http://www.medscape.com/viewarticle/821764. Published March 11, 2014. Accessed April 24, 2014.

9. Seaquist ER, Anderson J, Childs B. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36(5):1384-1395.

10. Cryer PE. Mechanisms of hypoglycemiaassociated autonomic failure in diabetes. N Engl J Med. 2013;369:362-372.