Dawn Phenomenon


Article Author:
Teri O'Neal


Article Editor:
Euil Luther



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Updated:
11/10/2019 6:36:45 PM

Introduction

The “dawn phenomenon” refers to periodic episodes of hyperglycemia occurring in the early morning hours before, and to some extent after, breakfast. Originally described in the early 1980s by Schmidt et al. [1], the dawn phenomenon differs from the Somogyi effect in that it is not preceded by an episode of hypoglycemia. Understanding and differentiating between these two clinical entities become critical in the optimal management of diabetes.[2]

Etiology

Diurnal variation in hepatic glucose metabolism has been well documented.  The transient increase in both glycogenolysis and gluconeogenesis in the early morning hours can be responsible for hyperglycemia if unopposed by insulin.[3][4][5]

Epidemiology

The dawn phenomenon, and more recently, the extended dawn phenomenon (persistence of hyperglycemia into the later morning hours), have been studied extensively with numerous articles published on the subject. Both entities are responsible for morning glucose elevations, which are difficult to control. The dawn phenomenon has been documented in both type 1 and type 2 diabetes and has been demonstrated in all age groups, even patients with type 2 diabetes over 70 years of age. For both type 1 and type 2 diabetes mellitus, prevalence is estimated to exceed 50 percent. [6] This affects a large patient population over a wide age range, and the dawn phenomenon will be an important consideration for any clinician who manages patients with diabetes.

Pathophysiology

Studies in populations without diabetes have shown that blood glucose, and plasma insulin levels remain steady through the night, with only a small increase in insulin secretion before dawn, which serves to depress hepatic glucose production.  Hyperglycemia is prevented by this physiologic surge of insulin. Hence, the dawn phenomenon does not occur in patients without diabetes subjects because they can secrete normal amounts of insulin to prevent it.  In patients without diabetes growth hormone exerts insulin-antagonistic effects. [7] Furthermore, exogenous insulin activity frequently begins to wane during the early morning hours (depending on the type of insulin and route of administration), so there is not enough opposition to hepatic activity to prevent hyperglycemia. Patients with type 2 diabetes are more likely affected by early morning dysregulation of hepatic glucose production because of the inability to produce compensatory insulin secretion. [2]

History and Physical

Patients with diabetes will manifest the dawn phenomenon clinically with persistent and worsening early morning hyperglycemia, which is difficult to control. Often found early in the disease process, this is associated with worsening HbA1c levels.  The dawn phenomenon is not associated with nocturnal hypoglycemic episodes, and no specific physical findings are present.

Evaluation

Diagnosis of the dawn phenomenon is most effectively achieved by the use of continuous glucose monitoring (CGM), which in recent years has become more widely available to clinicians. [8] In addition to documenting elevated early morning glucose levels, CGM ensures no associated nocturnal episodes of hypoglycemia have occurred, which could indicate a Somogyi effect rather than a true dawn phenomenon. The dawn phenomenon is quantified by subtracting the overnight glucose nadir from the glucose value observed just before breakfast. An alternative to CGM has been described by Monnier et al., utilizing intermittent glucose monitoring to quantify the magnitude of the dawn phenomenon.  A strong correlation between pre-meal glucose values and the change in glucose with the dawn phenomenon has been identified. This has enabled the development of a formula to calculate the magnitude of early morning hyperglycemia without CGM.[9] By measuring blood glucose pre-breakfast, pre-lunch, and pre-dinner, then taking the difference between the pre-breakfast glucose and the average of the pre-lunch and pre-dinner glucose values to determine “X”, the presence of the dawn phenomenon in an individual, which has been defined as an upward variation in glucose of 20 mg/dl, can be detected with 71% sensitivity and 68% specificity. The magnitude of the dawn phenomenon can then be calculated by using the equation 0.49X +15. [9]

Treatment / Management

When the presence of the dawn phenomenon is detected, especially when associated with the extended dawn phenomenon, an individual patient should be considered for earlier and more aggressive control of glucose.  The prevention of long-term sequelae by minimizing exposure to hyperglycemia is key early in the disease process. Optimal insulin therapy is important in type 1 diabetes, but also in type 2 diabetes.  Oral hypoglycemic agents have failed to show adequate control of the dawn phenomenon, while insulin therapy has been shown much more effective. 

Choosing an insulin regimen must, of course, be individualized for each patient, but research has indicated that the presence of the dawn phenomenon must be considered in selecting the type of insulin and the mechanism of delivery.  In studies that have demonstrated superior glycemic control with continuous insulin infusion as opposed to long-acting glargine formulations, the dawn phenomenon is likely the reason. The ability for a continuous infusion to provide a bolus in the early morning hours to counteract the dawn phenomenon is a possible explanation, as long-acting glargine preparations have no ability to provide this. For type 1 diabetes, tight control with insulin must take into account the dawn phenomenon to avoid nocturnal hypoglycemia before the onset of early morning glucose elevations. If insulin adjustments are made based on early morning fasting glucose levels, a larger dose of insulin might be administered than would be appropriate if the dawn phenomenon magnitude was considered. [10]

Management of morning hyperglycemia should be a part of the overall diabetes control strategy.  Lifestyle modification is an important component to be considered.  Better control of morning glucose levels has been demonstrated by increasing the amount of exercise in the evening and increasing the protein to carbohydrate ratio of the evening meal. Consuming breakfast is also very important. While it seems counterintuitive, an early morning meal serves to decrease the secretion of insulin-antagonistic hormones. [11] [2]

Differential Diagnosis

The dawn phenomenon is known for early morning hyperglycemia.  Other considerations for this clinical presentation must include the Somogyi effect as well as poor glycemic control. [2] 

The Somogyi effect (still a matter of debate for some authorities) is the development of rebound hyperglycemia after an episode of hypoglycemia, often induced by excess insulin or inadequate calorie intake with insulin therapy.  Exclusion of overnight hypoglycemia by the use of continuous glucose monitoring is an effective way of ruling this out when evaluating early morning hyperglycemia.

Poor glycemic control in the overall picture of diabetes is evident by the persistent elevation of blood glucose levels, without an obvious prominence of early morning hyperglycemia.  

Prognosis

The importance of recognition and control of the dawn phenomenon in type 2 diabetes lies in preventing additional exposure to elevated blood glucose levels, thereby preventing increasing insulin resistance. The increasing defect in insulin secretion and sensitivity has been shown to produce a steady decline in the quality of normal glucose metabolism over the life course of the disease. [12] Additional data from Monnier et al., has indicated that the dawn phenomenon could affect overall glycemic control in type 2 diabetes, elevating the HbA1c levels by as much as 0.4%.[8]

Complications

Epidemiological analyses have provided information that a 1% increase in A1c can be associated with a 15%-20% increased risk of cardiovascular complications.[13] Additionally, a 2012 study reported by researchers from Sweden indicated that a 0.8% reduction in A1c could produce a cardiovascular death risk reduction as high as 45%.[14] Controlling the dawn phenomenon alone could achieve as much as half the A1c improvement needed for this benefit, and since it is felt to be one of the earlier disorders in the natural progression of type 2 diabetes, and should be taken into consideration as an indicator for more aggressive therapy early in the disease.

Deterrence and Patient Education

Patients with diabetes should receive extensive education in all aspects of the disease, with emphasis on dietary and medication management, as well as the importance of exercise and awareness of the potential consequences of the disease.  Specific information regarding the dawn phenomenon should be provided if the patient is suspected or has been diagnosed with this entity.  The importance of using dietary interventions to minimize the dawn phenomenon should be discussed at length.  Recommendations should include increasing protein to carbohydrate ratio for the evening meal and encouraging the patient to have breakfast regularly.  Increased physical activity during the evening hours has also demonstrated some effectiveness in minimizing early morning hyperglycemia. [2]

Pearls and Other Issues

 

 

Enhancing Healthcare Team Outcomes

Nurse diabetes educators, dieticians, and clinicians must be skilled at the recognition of the dawn phenomenon. an interprofessional team approach in managing patients with this problem will result in the best outcomes. [Level V]  Communication between all members of the team is important to maximize benefit from needed lifestyle changes, self-monitoring of the disease, and medication adjustments.  Presenting a "united front", the interprofessional team can convey a strong message to the patient about the importance of controlling the dawn phenomenon in the context of their diabetes.  


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Dawn Phenomenon - Questions

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What would one expect to find in a patient with diabetes mellitus with the dawn phenomenon?



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Which is true with regards to the dawn phenomenon?



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Which is true about the dawn phenomenon?



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How is the dawn phenomenon diagnosed?



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In the absence of continuous glucose monitoring, how can the dawn phenomenon be estimated?



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A 16-year-old male with type 1 diabetes presents to the clinic with early morning hyperglycemic episodes. His glucose has been between 200 and 300 mg/dL before breakfast and has required increased doses of regular insulin by sliding scale. Readings for the remainder of the day have been within normal limits for him. There have been no recent changes in his medication, activity, or diet. Continuous glucose monitoring confirms no overnight hypoglycemia, but a significant rise in glucose levels in the early morning hours. Which of the following mechanisms is most likely responsible for poor glycemic control of this type?



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A 30-year-old female diagnosed one year ago with type 2 diabetes mellitus, has exhibited persistent hyperglycemia in the morning in spite of appropriate doses of three oral medications. Her HbA1c is 9.2%. Continuous glucose monitoring indicates a rise of 30 mg/dl in serum glucose in the early morning hours with no periods of hypoglycemia. She is compliant with medications as well as recommendations for diet and exercise. Which of the following is the most appropriate intervention to minimize the development of long term cardiovascular sequelae of uncontrolled diabetes?



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Dawn Phenomenon - References

References

The dawn phenomenon, an early morning glucose rise: implications for diabetic intraday blood glucose variation., Schmidt MI,Hadji-Georgopoulos A,Rendell M,Margolis S,Kowarski A,, Diabetes care, 1981 Nov-Dec     [PubMed]
The dawn phenomenon revisited: implications for diabetes therapy., Carroll MF,Schade DS,, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2005 Jan-Feb     [PubMed]
The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes., Monnier L,Colette C,Dunseath GJ,Owens DR,, Diabetes care, 2007 Feb     [PubMed]
Magnitude of the dawn phenomenon and its impact on the overall glucose exposure in type 2 diabetes: is this of concern?, Monnier L,Colette C,Dejager S,Owens D,, Diabetes care, 2013 Dec     [PubMed]
Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production., Boden G,Chen X,Urbain JL,, Diabetes, 1996 Aug     [PubMed]
Evidence of increased systemic glucose production and gluconeogenesis in an early stage of NIDDM., Perriello G,Pampanelli S,Del Sindaco P,Lalli C,Ciofetta M,Volpi E,Santeusanio F,Brunetti P,Bolli GB,, Diabetes, 1997 Jun     [PubMed]
Diurnal rhythm in endogenous glucose production is a major contributor to fasting hyperglycaemia in type 2 diabetes. Suprachiasmatic deficit or limit cycle behaviour?, Radziuk J,Pye S,, Diabetologia, 2006 Jul     [PubMed]
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., Campbell PJ,Bolli GB,Cryer PE,Gerich JE,, The New England journal of medicine, 1985 Jun 6     [PubMed]
The dawn phenomenon in type 2 diabetes: how to assess it in clinical practice?, Monnier L,Colette C,Dejager S,Owens D,, Diabetes & metabolism, 2015 Apr     [PubMed]
Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII., Hirsch IB,Bode BW,Garg S,Lane WS,Sussman A,Hu P,Santiago OM,Kolaczynski JW,, Diabetes care, 2005 Mar     [PubMed]
The dawn phenomenon and the Somogyi effect - two phenomena of morning hyperglycaemia., Rybicka M,Krysiak R,Okopień B,, Endokrynologia Polska, 2011     [PubMed]
Inzucchi SE,Bergenstal RM,Buse JB,Diamant M,Ferrannini E,Nauck M,Peters AL,Tsapas A,Wender R,Matthews DR, Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015 Mar;     [PubMed]
Riddle MC,Ambrosius WT,Brillon DJ,Buse JB,Byington RP,Cohen RM,Goff DC Jr,Malozowski S,Margolis KL,Probstfield JL,Schnall A,Seaquist ER, Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes care. 2010 May;     [PubMed]
Eeg-Olofsson K,Cederholm J,Nilsson PM,Zethelius B,Svensson AM,Gudbjörnsdóttir S,Eliasson B, New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR). Journal of internal medicine. 2010 Nov;     [PubMed]

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