The Myth of the Somogyi & How I Adjust Insulin
World Small Animal Veterinary Association Congress Proceedings, 2017
Jacquie Rand1, BVSc, DVSc, MACVS, DACVIM; Kristen Roomp2
1School of Veterinary Science, University of Queensland, QLD, Australia and Australian Pet Welfare Foundation, Brisbane, QLD, Australia; 2Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg

Many clinicians believe that the Somogyi effect or rebound hyperglycemia following hypoglycemia commonly occurs in diabetic cats treated with insulin, but there is only one study of 6 cats from 1986 purportedly documenting this. In contrast, numerous studies in human diabetic patients over the last quarter century have rejected the common occurrence of the Somogyi phenomenon. Most such cases in humans are now thought to be associated with inadequate duration of insulin action in the early morning. In some patients, an early morning surge of growth hormone, termed the “dawn phenomena”, resulting in insulin resistance was thought to exacerbate the hyperglycemia. However, human patients with apparent rebound hyperglycemia were found not to have higher levels of growth hormone, cortisol, or glucagon than those who had little or no rebound hyperglycemia. A close inverse correlation was found between blood glucose and free insulin concentrations. Therefore, it was concluded that hyperglycemia, when present, was more likely to be due to relative insulin deficiency in the latter part of the night than a response to antagonist hormones. Similarly, a study in human diabetic patients using continuous blood glucose measurements found that mean morning blood glucose concentrations after hypoglycemic nights were lower than after nights without hypoglycemia, indicating that nocturnal hypoglycemia did not subsequently cause hyperglycemia. Another study investigating the association between preceding nocturnal hypoglycemia and daytime hyperglycemia, found that nocturnal hypoglycemia did not appear to cause clinically important daytime hyperglycemia. Daytime plasma glucose concentrations were unrelated to peak nocturnal plasma glucagon, epinephrine, norepinephrine, growth hormone, or cortisol concentrations. Therefore, most apparent cases of rebound hyperglycemia in humans are now thought to be associated with inadequate duration of insulin action in the early morning, unrelated to any preceding nocturnal hypoglycemia.

Despite these findings in humans, many clinicians treating diabetic cats make insulin dose adjustments believing that the Somogyi effect is contributing to hyperglycaemia. They subsequently reduce insulin dose even when there is no evidence of preceding hypoglycaemia. In the case series of cats reported to have the Somogyi effect, all cats were treated with once daily with NPH or PZI (protamine zinc insulin). These cats has insulin-induced hypoglycemia (<70 mg/dL [<3.9 mmol/L]) within 4 to 8 hours, followed by hyperglycemia for up to 24 hours after injection. However, a number of other explanations other than the Somogyi effect account for this blood glucose pattern and the observed improvement following changes to the cats’ management. NPH typically has its nadir four hours after insulin injection, and after 7–8 hours there is little exogenous insulin action, and blood glucose concentrations are often at pre-insulin injection values. Resolution of the rebound pattern in 5/6 cats is consistent with findings in humans that hyperglycemia after resolution of hypoglycemia reflects inadequate insulin concentration to adequately control blood glucose concentration. Cats improved after they were changed to insulin dosing protocols expected to give more sustained glucose lowering effect. Use of intermediate-acting insulin and/or once daily insulin dosing likely resulted in inadequate duration of insulin action to control blood glucose concentrations after the hypoglycemic nadir.

Supporting the findings in humans that the Somogyi effect is rare, a study of 55 cats under intensive blood glucose control with glargine found that blood glucose curves which were consistent with insulin-induced rebound hyperglycemia were very rare, despite the frequent occurrence of biochemical hypoglycemia. Rebound hyperglycemia associated with persistent marked insulin resistance was extremely rare in glargine­treated cats, with less than 4 events in 10,000 daily blood glucose curves. Rebound hyperglycemia without persistent insulin resistance was more common, occurring in 25% of cats, albeit infrequently, and in affected cats is evident in less than one in 50 daily blood glucose curves. Overall, rebound hyperglycemia without insulin resistance occurred in less than one in 200 daily curves. Further investigation of the cause of marked morning hyperglycemia in diabetic cats treated with glargine is indicated to determine if inadequate duration of insulin and/or a growth hormone surge is the underlying cause.

Clinicians managing diabetic cats treated with lente and exhibiting marked morning hyperglycemia or insulin resistance should either swap to a longer-acting insulin or increase frequency of insulin dosing. Continuous glucose monitoring is one method of determining if hypoglycemia is preceding hyperglycemia. However, continuous glucose monitoring documenting hypoglycemia followed by hyperglycemia still does not indicate if the hyperglycemia is due to inadequate insulin concentrations to prevent hyperglycemia. This requires concurrent measurement of circulating insulin concentrations.

In summary, in humans, the frequent occurrence of the Somogyi effect has been refuted, and in a study of glargine-treated diabetic cats, blood glucose curves consistent with insulin-induced rebound hyperglycemia were very rare, despite the frequent occurrence of biochemical hypoglycemia. It is important to recognize that the fluctuations of blood glucose concentration occur commonly in the first weeks, and more rarely months, following the initiation of treatment with glargine, and can be mistaken for the Somogyi effect. However, these fluctuations generally resolve with time using consistent dosing.

As a rule of thumb for clinicians, the dose of glargine or detemir should be reduced if the cat develops asymptomatic or clinical hypoglycemia, but not when blood glucose concentration is high and poorly responsive to insulin. In cats with intermediate acting insulin and experiencing hyperglycemia, with or without preceding hypoglycaemia, it is strongly recommend that the cat be switched to a longer acting insulin. When this is not possible, consider increasing the frequency of dosing. Insulin dose should be reduced if hypoglycaemia occurs, especially if it results in clinical signs.


1.  Somogyi M. Exacerbation of diabetes by excess insulin action. Am J Med. 1959;26:169–191.

2.  Gale EA, Kurtz AB, Tattersall RB. In search of the Somogyi effect. Lancet. 1980;2:279–282.

3.  Tordjman KM, Havhn CE, Levandoski LA, White NH, Santiago JV, Cryer PE. Failure of nocturnal hypoglycemia to cause fasting hyperglycemia in patients with insulin-dependent diabetes mellitus. N Engl J Med. 1987;317:1552–1559.

4.  Hoi-Hansen T, Pedersen-Bjergaard U, Thorsteinsson B. The Somogyi phenomenon revisited using continuous glucose monitoring in daily life. Diabetologia. 2005;48:2437–2438.

5.  Hirsch IB, Smith LJ, Havlin CE, Shah SD, Clutter WE, Cryer PE. Failure of nocturnal hypoglycemia to cause daytime hyperglycemia in patients with IDDM. Diabetes Care. 1990;13:133–142.

6.  McMillan FD, Feldman EC. Rebound hyperglycemia following overdosing of insulin in cats with diabetes mellitus. J Am Vet Med Assoc. 1986;188:1426–1431.

7.  Havlin CE, Cryer PE. Nocturnal hypoglycemia does not commonly result in major morning hyperglycemia in patients with diabetes mellitus. Diabetes Care. 1987;10:141–147.

8.  Pramming S, Thorsteinsson B, Bendtson I, Rønn B, Binder C. Nocturnal hypoglycaemia in patients receiving conventional treatment with insulin. Br Med J (Clin Res Ed). 1985;291:376–379.

9.  Raskin P. The Somogyi phenomenon. Sacred cow or bull? Arch Intern Med. 1984;144:781–787.

10.  Choudhary P, Davies C, Emery CJ, Heller SR. Do high fasting glucose levels suggest nocturnal hypoglycaemia? The Somogyi effect - more fiction than fact? Diabet Med. 2013;30:914–917.

11.  Bolli GB, Gerich JE. The “dawn phenomenon” - a common occurrence in both non-insulin-dependent and insulin-dependent diabetes mellitus. N Engl J Med. 1984;310:746–750.

12.  Carroll MF, Schade OS. The dawn phenomenon revisited: implications for diabetes therapy. Endocr Pract. 2005;11:55–64.

13.  Roomp K, Rand J. Rebound hyperglycemia in diabetic cats. J Feline Med Surg. 2016;18(8):587–596.


Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Jacquie Rand, BVSc, DVSc, MACVS, DACVIM
School of Veterinary Science
University of Queensland
QLD, Australia

Australia and Australian Pet Welfare Foundation
Brisbane, QLD, Australia

Kirsten Roomp
University of Luxembourg

MAIN : Internal Medicine II : Myth of the Somogyi
Powered By VIN