What’s the connection between severe hypoglycemia and hypothermia?

The association of severe hypoglycemia and low body temperatures has been well documented at least since 1960s.  Hypothermia is thought to be caused by low blood glucose in the brain (neuroglucopenia) which may serve as a protective mechanism for decreasing energy demand during glucose deprivation.1-2

A 2012 retrospective study involving mostly patients with diabetes mellitus with severe hypoglycemia (majority with serum glucose 18-54 mg/dl) found that 23% of patients had hypothermia (defined as body temperature < 95◦F or 35◦C). The incidence of hypothermia was not affected by age, diabetes, season or time of day.  Two patients had extremely low temperatures (<90◦F).  There was an association between hypothermia and severity of hypoglycemia.1

An older experimental study (1974) involving 36 recumbent nude men in thermoneutral environment found that that insulin-induced hypoglycemia was associated with rectal temperatures below 96.2◦F (36◦C) in 33%.  Cooling was attributed to reduction in heat production and to secretion of sweat, peripheral vasodilatation and hyperventilation.2

But before you attribute hypothermia to hypoglycemia, make sure other causes of hypothermia such as sepsis, hypoadrenalism, hypothyroidism, alcohol and stroke are ruled out.3  

Bonus Pearl: Did you know that heat production is accomplished by shivering, which can increase the normal basal metabolic rate by 2-5 times as well as via non-shivering thermogenesis through increased levels of thyroxine and epinephrine?3

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References

  1. Tran C, Gariani K, Hermann FR, et al. Hypothermia is a frequent sign of severe hypoglycaemia in patients with diabetes. Diab Metab 2012;38:370-72. https://www.sciencedirect.com/science/article/abs/pii/S1262363612000535?via%3Dihub
  2. Strauch BS, Felig P, Baxter JD, et al. Hypothermia in hypoglycemia. JAMA 1969;210:345-46. https://jamanetwork.com/journals/jama/article-abstract/349081
  3. McCullough L, Arora S. Diagnosis and treatment of hypothermia. Am Fam Physician 2004;70:2325-2332. https://www.aafp.org/afp/2004/1215/p2325.html

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s the connection between severe hypoglycemia and hypothermia?

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?

You may have to!  That’s because patients with DM due to pancreatic disease (also known as “pancreatogenic [Type 3C] diabetes”) tend to have more labile blood glucoses with particular predisposition to severe hypoglycemic episodes due to the impairment of glucagon production by pancreatic alpha-cells. 1-3

This observation dates back to a 1977 study where a high rate of hypoglycemic episodes was found among 59 patients with chronic pancreatitis (most with insulin-dependent DM), including 3 deaths and 2 suffering from severe brain damage following hypoglycemic coma. Interestingly, low basal glucagon levels were found in the latter patients, supporting impairment in glucagon synthesis. Of note, while hypoglycemia is a serious problem in these patients, they are not spared from complications of chronic hyperglycemia, including retinopathy and kidney disease.2

As for the blood glucose management in type 3C DM, since the principle endocrine defect is insulin deficiency, insulin therapy is preferred for most patients, particularly those who are acutely ill or are hospitalized. For otherwise more stable patients with mild hyperglycemia, metformin is an ideal agent as it enhances hepatic insulin sensitivity without the risk of hypoglycemia. As a bonus, metformin may also decrease the risk of pancreatic cancer in chronic pancreatitis, based on observational studies. 4

Also, don’t forget that concurrent pancreatic exocrine insufficiency is common in patients with type 3C DM and requires oral pancreatic enzyme requirement with meals.

Fascinating Pearl: Did you know that in patients with type 3C DM, hyperglycemia is mediated not only by decreased production of insulin, but also by decreased synthesis of pancreatic polypeptide, a peptide that mediates hepatic insulin sensitivity and glucose production? 5

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References

  1. Linde, J, Nilsson LH, Barany FR. Diabetes and hypoglycemia in chronic pancreatitis. Scand J Gastroenterol. 2012;12, 369–373. https://www.ncbi.nlm.nih.gov/pubmed/867001
  2. Andersen D. The practical importance of recognizing pancreatogenic or type 3c diabetes. Diabetes Metab Res Rev. 2012;28:326-328. https://onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.2285
  3. Cui YF, Andersen DK. Pancreatogenic diabetes: Special considerations for management. Pancreatology. 2011;11(3):279-294. doi:10.1159/000329188. https://jhu.pure.elsevier.com/en/publications/pancreatogenic-diabetes-special-considerations-for-management-4
  4. Evans J, Donnelly L, Emsley-Smith A. Metformin and reduced risk of cancer in diabetic patients. Br Med J. 2005;330:1304-1305. https://www.researchgate.net/publication/7888859_Metformin_and_reduced_risk_of_cancer_in_diabetic_patients
  5. Rabiee A. Gafiatsatos P, Salas-Carnillo R. Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patents on insulin pump therapy. Diabetes Sci Technol 2011;5:1521-28.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262724/

Contributed by Hugo Torres, MD, MPH, Hospital Medicine Unit, Mass General Hospital, Boston, Massachusetts

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?