Dawn Phenomenon Affects Half of Type 2 Diabetes Patients

November 07, 2013

The so-called "dawn phenomenon" has a significant impact on many of those with type 2 diabetes and is already present in some patients treated only with diet alone, new research shows. In addition, this effect is not blunted by oral hypoglycemic agents, the study by Louis Monnier, MD, from University Montpellier, France, and colleagues reveals.

The dawn phenomenon refers to a spontaneous rise in blood glucose that occurs at the end of the night in patients with both type 1 and type 2 diabetes; this does not occur in individuals without diabetes, because endogenously produced insulin prevents this.

The findings indicate that in selected type 2 diabetes patients, specifically those with HbA1c approaching 7% who are demonstrating evidence of the dawn phenomenon, insulin use should be considered earlier than it is traditionally, because insulin can eliminate this effect, said Geremia B Bolli, MD, from the University of Perugia, Italy.

"We have defined the frequency of the dawn phenomenon in type 2 diabetes, which in the present paper occurs in around 50% of patients, and this definition is more accurate than previous ones due to our use of continuous glucose monitoring [CGM] systems," Dr. Monnier told Medscape Medical News.

In addition, he and his colleagues quantify the effect of this phenomenon, showing that the mean impact on HbA1c was around a 0.4% rise. "This may seem small," said Dr. Monnier, "but when one considers that treatment with, for example, [dipeptidyl peptidase-4] DPP-4 inhibitors [gliptins], results in a mean drop in HbA1c of only around 0.7% to 0.8% [as well as] that a drop of 1.0% in HbA1c can reduce macrovascular complications by 40% and microvascular ones by 37%," then one can gauge the significance.

Dr. Monnier agrees with Dr. Bolli that the new findings indicate that insulin use should be considered earlier for type 2 diabetes patients showing evidence of the dawn phenomenon. "We are unable to control the dawn phenomenon with our current armamentarium of oral hypoglycemic agents, even though metformin is probably the one that has the highest potency for reducing [it]. My position is that insulin should be considered for the treatment of type 2 diabetes as soon as the HbA1c becomes greater than 7% when patients are already treated with maximal tolerated doses of oral agents," he told Medscape Medical News.

Dr. Monnier and colleagues' study is published online October 29 in Diabetes Care.

Oral Antidiabetics Don't Affect Dawn Phenomenon

The spontaneous progressive rise in blood glucose values that represents the dawn phenomenon in type 2 diabetes follows a nadir in blood sugar levels, at around 3 to 4 am in the morning, and is a consequence of the production of glucose by the liver at the end of the night, Dr. Monnier explained. This does not occur in nondiabetic individuals since their bodies will automatically adjust the production of endogenous insulin to counteract this hepatic glucose production.

In their study, he and his colleagues examined 248 non–insulin-treated patients with type 2 diabetes who underwent CGM for 2 consecutive days and were divided into 3 groups based on treatment: diet alone (n = 53), insulin sensitizers alone (metformin and/or thiazolidinediones; n = 82), and insulin secretagogues (sulfonylureas, glinides, or DPP-4 inhibitors) alone or in combination with an insulin sensitizer; n = 113).

Overall, the median magnitude of the dawn glucose increase was 16 mg/dL, and this was not significantly different when the differing groups by categories of treatment were compared.

The participants were then divided according to whether or not they exhibited the dawn phenomenon — defined as a greater-than-20-mg/dL increase in blood glucose based on prior research — which approximately half of them did.

Both the HbA1c levels and the 24-hour mean glucose values were significantly greater (P = .007 and P = .0009, respectively) in those who exhibited the dawn phenomenon compared with those who did not. The mean differences were 4.3 mmol/mol for HbA1c (0.39%) and 12.4 mg/dL for average glucose concentrations.

The mean impact on 24-hour glucose was not significantly different for those on diet alone compared with the 2 subsets treated with oral antihyperglycemic agents.

Thus, "it appears that the dawn phenomenon is already present in those who are free of any pharmacological treatment with antidiabetic agents," say the authors.

And "the dawn phenomenon has a remnant impact in subjects treated with our current oral antidiabetic armamentarium," they observe.

Treat Dawn Phenomenon Early, With Basal Insulin

Dr. Bolli said this new research confirms that the dawn phenomenon is a common occurrence among type 2 diabetes patients, independent of oral therapy and in a real-world setting.

The work also reaffirms what should be a primary objective of type 2 diabetes therapy, he says, that is, treatment of the dawn phenomenon — the normalizing of blood sugar around breakfast time.

And it's important that this problem is addressed early on in the course of the disease before significant HbA1c rises occur, he stresses, because otherwise a vicious circle is established whereby hyperglycemia begets hyperglycemia.

And importantly, oral medications do not adequately control the dawn phenomenon even when given in combination, he observed.

"I think if A1c is greater than 7.0% and the postprandial blood glucose is okay, one has to work on the fasting blood glucose, and the best approach is basal insulin in the evening," he told Medscape Medical News.

Dr. Monnier and colleagues report have reported no relevant financial relationships. Dr. Bolli has received honoraria from Sanofi, MannKind, and Eli Lilly for scientific advising and consulting.

 

Diabetes Care. Publish online October 29, 2013. Abstract

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