Dawn Phenomenon

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, its prevalence is estimated to exceed 50 percent.[6] This affects a large patient population over a wide age range, and the dawn phenomenon should 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 achieve supression of the hepatic glucose production. Hyperglycemia is prevented by this physiologic surge of insulin. Hence, the dawn phenomenon does not occur in patients without diabetes 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][8]

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.[9][10] 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.[11] 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.[11]

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 to be 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 insulin 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 insulin preparations have no ability to achieve 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.[12](A1)

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 by 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.[13][2] In recent study the use of acarbose helped with dawn phenomenon treatment, but not the use of sulfonylurea.[14](B3)

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 (CGM) is an effective way of ruling this out when evaluating early morning hyperglycemia. When CGM is not available, a fingerstick in early morning hours (between 2-3 am) is recommended and it can provide guidance on the trend of the glucose levels.

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.[15] Additional data from Monnier et al., has indicated that the dawn phenomenon could affect the overall glycemic control in type 2 diabetes, elevating the HbA1c levels by as much as 0.4%.[9]

Complications

Epidemiological analyses have provided information that a 1% increase in A1c can be associated with a 15%-20% increased risk of cardiovascular complications.[16] 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%.[17] 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 earliest disorders in the natural progression of type 2 diabetes, it should be taken into consideration as an indicator for more aggressive therapy early in the disease.