Somogyi Phenomenon

Background

In the 1930s, Somogyi speculated that hypoglycemia induced by insulin could cause a counter-regulatory hormone response that produces hyperglycemia. Unappreciated nocturnal hypoglycemia could lead to morning hyperglycemia, and the physician or patient may increase the evening insulin, exacerbating 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.

Pathophysiology

The ability to suppress insulin release is an important physiologic response that people with insulin-requiring diabetes cannot carry out. Defense against hypoglycemia involves counter-regulatory hormones, which stimulate gluconeogenesis and glycogenolysis and counteract the anabolic effects of insulin. This mechanism is dependent on an intact glucose sensor system in the CNS, pancreas, and afferent nerves. Counter-regulatory hormones include the following:

• Glucagon acts on the liver to stimulate glycogenolysis and gluconeogenesis and is probably the earliest and most important hormone in the Somogyi phenomenon.
• Epinephrine 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 may aid in prolonged and severe cases of Somogyi phenomenon by blocking glucose use and stimulating hepatic glucose output.
• Growth hormone is similar to cortisol.

Recent studies cast doubt on the importance of counter-regulatory hormones in mediating glycemic rebound. Hypoinsulinemia (waning of the insulin dose), insulin resistance, and hypersensitivity to the effects of the counter-hormones also may play a role.

Mortality/Morbidity

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

Sex

No sex predilection exists.

Age

No age predilection exists.

CLINICAL

History

• Patients 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.

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• 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 to people with either type 1 or type 2 diabetes.

Physical

The physical examination findings are unaffected.

Causes

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

DIFFERENTIALS

Other Problems to be Considered

Dawn phenomenon
Uncontrolled diabetes

WORKUP

Lab 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 A1 C (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 Hbg 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 where 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 increasing insulin doses.

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• 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, 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.
• Monitor weight, Hgb A1C, and fasting blood glucose levels.

Prognosis

• The prognosis is excellent with proper identification and management.
• 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

Medical/Legal 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.

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. 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].
5. Raskin P. The Somogyi phenomenon. Sacred cow or bull?. Arch Intern Med. Apr 1984;144(4):781-7. [Medline].
6. Somogyi M. Exacerbation of diabetes by excess insulin action. Am J Med. 1959;26:169