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 1980’s by Schmidt, et al., 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.
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.
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 type 2 diabetics over 70 years of age. For both type 1 and type 2 diabetes mellitus, prevalence is estimated to exceed 50 percent. This obviously affects a large patient population over a wide age range, and the dawn phenomenon will be an important consideration for any clinician who manages diabetic patients.
Studies in nondiabetic populations 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 nondiabetic subjects because they can secrete normal amounts of insulin to prevent it. In type 1 diabetics, nocturnal spikes of growth hormone are the most likely mechanism to explain the dawn phenomenon, as growth hormone exerts insulin-antagonistic effects. 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. Type 2 diabetics are more likely affected by early morning dysregulation of hepatic glucose production because of the inability to produce compensatory insulin secretion.
Diabetic patients 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.
Diagnosis of the dawn phenomenon is most effectively achieved by use of continuous glucose monitoring (CGM), which in recent years has become more widely available to clinicians. 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 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. 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.
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 which 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.
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.
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 lifetime course of the disease. 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%. Epidemiological analyses have provided information that a 1% increase in A1c can be associated with a 15-20% increased risk of cardiovascular complications. 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%. 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.