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eMedicine Specialties > Endocrinology > Diabetes Mellitus

Somogyi Phenomenon

Michael Cooperman, MD, Clinical Associate Professor of Endocrinology, Temple University; Chair, Department of Internal Medicine, Division of Endocrinology, Jeanes Hospital

Updated: Mar 30, 2009

Introduction

Background

In the 1930s, Somogyi speculated that hypoglycemia induced by insulin could cause a counterregulatory hormone response that produces hyperglycemia. (See image below and Image 1.) Unappreciated nocturnal hypoglycemia could lead to morning hyperglycemia; if the physician or patient increases the evening insulin, this could exacerbate the problem.1 This phenomenon is actually less common than morning hyperglycemia due to hypoinsulinemia resulting from the dawn phenomenon.2,3 Debate continues in the scientific community as to the actual presence of this reaction to hypoglycemia. Shanik et al, for example, suggested that the hyperglycemia attributed to Somogyi phenomenon actually is caused by an insulin-induced insulin resistance.4

Normal hypoglycemic counterregulation.

Normal hypoglycemic counterregulation.



Pathophysiology

The ability to suppress insulin release is an important physiologic response that people with insulin-requiring diabetes cannot carry out. (See image below and Image 2.) Defense against hypoglycemia involves counterregulatory hormones, which stimulate gluconeogenesis and glycogenolysis and counteract the anabolic effects of insulin.4 This mechanism is dependent on an intact glucose sensor system in the CNS, pancreas, and afferent nerves.5 Counterregulatory hormones include the following:

  • Glucagon - This hormone acts on the liver to stimulate glycogenolysis and gluconeogenesis and is probably the earliest and most important hormone in the Somogyi phenomenon.
  • Epinephrine - This hormone increases the delivery of substrates from the periphery, decreases insulin release, stimulates glucagon release, inhibits glucose utilization by several tissues, and stimulates a warning system with sweating, anxiety, and tachycardia.
  • Cortisol - This hormone may aid in prolonged and severe cases of Somogyi phenomenon by blocking glucose use and stimulating hepatic glucose output.
  • Growth hormone - The effects of growth hormone are similar to those of cortisol.


Mechanisms of insulin secretion.

Mechanisms of insulin secretion.



Studies have cast doubt on the importance of counterregulatory hormones in mediating glycemic rebound. Hypoinsulinemia (waning of the insulin dose), insulin resistance, and hypersensitivity to the effects of the counterhormones also may play a role.

Frequency

United States

Although no data on frequency are available, Somogyi phenomenon is probably rare. It occurs in diabetes mellitus type 1 and is less common in diabetes mellitus type 2.

Mortality/Morbidity

Unrecognized posthypoglycemic hyperglycemia can lead to declining metabolic control and hypoglycemic complications.

Sex

No sex predilection exists for Somogyi phenomenon.

Age

No age predilection exists for Somogyi phenomenon.

Clinical

History

  • Patients with Somogyi phenomenon present with morning hyperglycemia out of proportion to their usual glucose control. Nocturnal hypoglycemia is missed or asymptomatic, and posthypoglycemic hyperglycemia is not considered or confused with the dawn phenomenon.
  • The most common cause of morning hyperglycemia is hypoinsulinemia.
    • Patients have an increased need for insulin in the early morning primarily due to the release of growth hormone, which antagonizes insulin action.
    • Cortisol may play a supporting role.
    • Patients may experience falling insulin levels due to absorption or dose issues from the previous evening. This occurs as the insulin requirement is rising (dawn phenomenon) and results in a rapid rise of blood sugar at 4-8 AM.
  • This occurrence is common in people with either type 1 or type 2 diabetes.

Physical

The physical examination findings are unaffected in Somogyi phenomenon.

Causes

  • Excess or ill-timed insulin
  • Missed meals or snacks
  • Inadvertent insulin administration

Differential Diagnoses

Hypoglycemia

Other Problems to Be Considered

Dawn phenomenon
Uncontrolled diabetes

Workup

Laboratory Studies

  • Fasting blood sugar - The fasting blood sugar is expected to be inappropriately elevated due to hormonally induced rebound.
  • Nocturnal (3-4 AM) blood glucose - A glucose reading in the middle of the night will disclose hypoglycemia as a result of insulin therapy. This will establish the diagnosis.
  • Hemoglobin A1C (Hgb A1C) - Obtaining an Hgb A1C level may be helpful if it is within the reference range or low despite an elevated fasting glucose level. It supports the concept of a rebound fasting hyperglycemia in the face of normal glucose control. An elevated Hgb A1C does not rule out the phenomenon.
  • Frequent glucose sampling - Frequent glucose monitoring may be necessary to confirm the diagnosis and look for other periods of hypoglycemia that may lead to rebound hyperglycemia. Frequent hypoglycemia is responsible for hypoglycemic unawareness, through which the typical symptoms of hypoglycemia may be missed.

Treatment

Medical Care

  • Somogyi phenomenon should be suspected in patients presenting with atypical hyperglycemia in the early morning that resists treatment with increased insulin doses.
    • If nocturnal blood sugar is confirmatory or if suspicion is high, reduce evening or bedtime insulin.
    • Clinical signs, including weight gain, normal daytime blood sugar levels, and relatively low Hgb A1C, suggest overtreatment.
  • Substitution of regular insulin with an immediate-acting insulin analog, such as Humulin lispro,6,7 may be of some help. This has not been firmly established.

Consultations

Consider endocrine or diabetes consultation for difficult or unusual cases.

Follow-up

Further Outpatient Care

  • Continue glucose monitoring with special attention to hypoglycemia in patients with Somogyi phenomenon.
  • Monitor weight, Hgb A1C, and fasting blood glucose levels.

Prognosis

  • With proper identification and management, the prognosis for Somogyi phenomenon is excellent.
  • No evidence of long-term sequelae exists.

Patient Education

  • Instruct patients in proper identification of symptoms of hypoglycemia, insulin dose, timing of meals, and insulin administration.
  • For excellent patient education resources, see eMedicine's patient education article Insulin Reaction.

Miscellaneous

Medicolegal Pitfalls

  • Failure to properly identify this action of insulin therapy can lead to severe hypoglycemia and its sequelae.
  • Failure to identify Somogyi phenomenon delays proper diabetes control, and mismanagement worsens the situation.
  • Distinguishing morning hyperglycemia as a result of poor control from the Somogyi phenomena and the dawn effect is imperative.

Multimedia

Normal hypoglycemic counterregulation.

Media file 1: Normal hypoglycemic counterregulation.

Mechanisms of insulin secretion.

Media file 2: Mechanisms of insulin secretion.

References

  1. Somogyi M. Insulin as a cause of extreme hyperglycemia and instability. Bull St Louis Med Soc. 1938;32:498-500.

  2. Bolli GB, Gerich JE. The "dawn phenomenon"--a common occurrence in both non-insulin- dependent and insulin-dependent diabetes mellitus. N Engl J Med. Mar 22 1984;310(12):746-50. [Medline].

  3. Campbell PJ, Bolli GB, Cryer PE. Pathogenesis of the dawn phenomenon in patients with insulin-dependent diabetes mellitus. Accelerated glucose production and impaired glucose utilization due to nocturnal surges in growth hormone secretion. N Engl J Med. Jun 6 1985;312(23):1473-9. [Medline].

  4. Shanik MH, Xu Y, Skrha J, et al. Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse?. Diabetes Care. Feb 2008;31 Suppl 2:S262-8. [Medline]. [Full Text].

  5. McCrimmon R. The mechanisms that underlie glucose sensing during hypoglycaemia in diabetes. Diabet Med. May 2008;25(5):513-22. [Medline].

  6. [Best Evidence] Singh SR, Ahmad F, Lal A, et al. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ. Feb 17 2009;180(4):385-97. [Medline]. [Full Text].

  7. Lind M, Fahlen M, Happich M, et al. The effect of insulin lispro on glycemic control in a large patient cohort. Diabetes Technol Ther. Jan 2009;11(1):51-6. [Medline].

  8. Bolli GB, Gottesman IS, Campbell PJ. Glucose counterregulation and waning of insulin in the Somogyi phenomenon (posthypoglycemic hyperglycemia). N Engl J Med. Nov 8 1984;311(19):1214-9. [Medline].

  9. Raskin P. The Somogyi phenomenon. Sacred cow or bull?. Arch Intern Med. Apr 1984;144(4):781-7. [Medline].

  10. Somogyi M. Exacerbation of diabetes by excess insulin action. Am J Med. Feb 1959;26(2):169-91. [Medline].

Keywords

Somogyi phenomenon, diabetes, insulin, diabetes mellitus, type 2 diabetes, hypoglycemia, hyperglycemia, type 1 diabetes, diabetics, glucose levels, blood sugar levels, low blood sugar, high blood sugar, hypoglycemic, complications of diabetes, diabetes complications, diabetes insulin, diabetes hypoglycemia, Somogyi, insulin dependent diabetes, diabetes hyperglycemia, diabetic hypoglycemia, hypoglycemia insulin, Somogyi effect, dawn phenomenon insulin-induced hypoglycemic hyperglycemia, Somogyi’s phenomenon, hypoinsulinemia, diabetes mellitus type 1, diabetes mellitus type 2

Contributor Information and Disclosures

Author

Michael Cooperman, MD, Clinical Associate Professor of Endocrinology, Temple University; Chair, Department of Internal Medicine, Division of Endocrinology, Jeanes Hospital
Michael Cooperman, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, and Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Gregory William Rutecki, MD, Associate Professor, Program Director, Department of Internal Medicine, Feinberg School of Medicine, Northwestern University
Gregory William Rutecki, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Nephrology, National Kidney Foundation, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kent Wehmeier, MD, Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine
Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

Further Reading

Clinical guidelines:
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Glycemic management. American Association of Clinical Endocrinologists - Medical Specialty Society
American College of Endocrinology - Medical Specialty Society. 2000 Jan (revised 2007). 19 pages. NGC:005853

Clinical trials:
Insulin Analogues and Severe Hypoglycaemia
Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of T1DM

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