Dawn phenomenon

In 1981, Schmidt et al. described the passive insulin resistancethat leads to morning hyperglycemia as the so-called dawn phenomenon. Campbell et al. demonstrated in 1985 that this form of hyperglycemia is due to the nocturnal secretion of growth hormones (Hürter 1997).

Dawn phenomenon refers to the episodes of hyperglycemia occurring in diabetic patients in the early morning hours (O'Neal 2021).

The Dawn phenomenon is a common complication in diabetics (Reinhardt 2004). It can occur in type 1 and type 2 DM, in insulin-dependent and non-insulin-dependent diabetics and has been demonstrated in all age groups (O'Neal 2021).

The prevalence is estimated to be >50% for type 1 and type 2 DM (O'Neal 2021).

Type 1 diabetics are most commonly affected (Herold 2020) and here children or adolescents are particularly affected due to nocturnal secretion of growth hormones. These growth-related morning hyperglycaemias occur about 3 - 4 times per week during the growth phases and cannot be predicted (Hürter 1997).

In the Dawn phenomenon, increased secretion of the growth hormone (GH) leads to an increased insulin requirement in the second half of the night (Herold 2020). A preceding hypoglycemia is not found here (Hien 2007).

The Dawn phenomenon also depends on any meal break. As soon as there is a break of > 5 h between two meals, the insulin requirement for the second meal is almost as high as that for breakfast (Hien 2007).

In patients without diabetes mellitus, plasma insulin and blood glucose levels remain constant overnight. Only shortly before dawn is there a slight increase in insulin secretion, which serves to suppress hepatic glucose production and prevent hyperglycemia. Hence, the Dawn phenomenon occurs exclusively in diabetics.

In type 1 diabetics, the activity of exogenous insulindecreases in the early morning hours. This means that there is not enough hepatic activity to prevent hyperglycaemia.

In type 2 diabetics, morning dysregulation of hepatic glucose production is found as these patients are unable to activate compensatory insulin production.

(O'Neal 2021)

The nocturnal release of growth hormones decreases the excretion of nitrogen and promotes the uptake of amino acids into the cell. Growth hormones act synergistically to insulin - with respect to amino acid metabolism - and inhibit glucose uptake in the periphery (Siegenthaler 2006).

According to recent studies, morning hyperglycemia is due to hypoinsulinemia.

The secretion of insulinfollows a circadian rhythm and is oppositional to melatonin secretion: between 0.00 am and 6.00 am the lowest concentration is secreted, between 12.00 am and 6.00 pm the highest (Reyhanoglu 2021).

A moderate increase in blood glucose does not usually cause any symptoms.

If, in addition to the morning hyperglycaemia, headaches, fatigue (Reinhardt 2004) and night sweats are also present, a Somogyi effect is the most likely differential diagnosis (Wehling 2006).

In the Dawn phenomenon, increased secretion of the growth hormone (GH) leads to an increased insulin requirement in the second half of the night (Herold 2020). Pre-existing hypoglycemia is not present in Dawn syndrome, in contrast to the Somogyi effect (Hien 2007).

The release of growth hormones begins with the phase of falling asleep. There is no direct link to the time of day, i.e. if the patient does not go to sleep until around 4.00 a.m., the Dawn phenomenon is brought forward to the late morning hours. The Dawn phenomenon does not occur after a night of drinking without sleep (Hien 2007).

CGM

Continuous glucose monitoring (CGM) is the most effective diagnostic measure (O'Neal 2021). It should be used in any case when it is unclear whether a Dawn phenomenon or a Somogyi effect is present (Kolossa 2014).

Calculation of the Dawn phenomenon

An alternative to CGM was described by Monnier et al. 2015, in which BG values are measured before breakfast, lunch and dinner. Then, the difference in BG- value between the value before breakfast and the average value before lunch and dinner is calculated to determine "X".

With an upward variation of glucose of 20 mg / dl, the presence of the Dawn phenomenon can be detected with a sensitivity of 71% and a specificity of 68%.

The magnitude of the Dawn phenomenon can be calculated using the equation 0.49X +15.

(O'Neal 2021)

Increasing hyperglycemia in the early morning hours, which is difficult to control (O'Neal 2021).

Typically no ketone bodies are found in the morning urine (Furger 2003).

• Somogyi effect (O'Neal 2021)

The Dawn phenomenon can be masked by the Somogyi effect (Kolossa 2014).

In epidemiological analyses, a 1% increase in HbA1c level was associated with a 15%-20% higher risk of cardiovascular complications.

In a study by Swedish researchers, a reduction in cardiovascular mortality of up to 45% was shown for a 0.8% decrease in HbA1c (O'Neal 2021).

After exclusion of a Somogyi effect (Furger 2003), the evening insulin dose should be adjusted with intermediate or long-acting insulin (Herold 2020). The last insulin dose should be injected into the thigh as late as possible. As there is always a risk of nocturnal hypoglycaemia after changing the evening insulin dose, it is essential to measure the nocturnal BG values in the first period after the changeover (Hien 2007).

If increasing the evening dose is not sufficient, there are further therapeutic measures:

• Use of long-acting analogue insulins such as Lantus or Levemir (Hien 2007).
• Use of an insulin pump = CSII (continuous subcutaneous insulin infusion), which should then be adjusted to an increased basal rate of insulin in the early morning hours (Herold 2020).

Example: If one goes to sleep around 10pm, the pump is set for a gradual increase in basal rate starting around 3am. If one goes to sleep around 0.00 a.m., the gradual increase should start from 5.00 a.m. (Hien 2007).

It is important for the further prognosis of the patient with regard to the long-term consequences,

to achieve optimal glycemic control early in the course of the disease. If oral antidiabetics are not sufficient to prevent a dawn phenomenon, insulin should be switched to at an early stage (O'Neal 2021).

Similarly, recognition of Dawn phenomenon is important to prevent increasing insulin resistance (O'Neal 2021).

The implantation of an insulin pump inchildhood and adolescence is carried out in up to 48.8 % to prevent a Dawn phenomenon (Kapellen 2006).

1. Bolli G B et al. (1984) The "dawn phenomenon"-a common occurrence in both non-insulin-dependent and insulin-dependent diabetes mellitus. N Engl J Med Mar 22; 310 (12): 746 -750 doi: 10.1056/NEJM198403223101203.
2. Furger P (2003) Internal quick: the facts turbo. Thieme Publishers 579
3. Herold G et al (2020) Internal medicine. Herold Publishers 738
4. Hien et al (2007) Diabetes- Handbuch: A guide for practice and clinic. Springer publishing house Heidelberg
5. Howorka K (1988) Functional, near-normoglycemic insulin substitution. Springer Verlag Heidelberg 105 - 106
6. Hürter P et al (1997) Diabetes in children and adolescents: clinic - therapy - rehabilitation. Springer Verlag Berlin / Heidelberg / New York 260 - 262
7. Hürter P et al (2013) Children and adolescents with diabetes. Springer Verlag Berlin / Heidelberg 164
8. Kapellen T et al. (2006) The insulin pump in childhood and adolescence: differences in age groups with regard to therapy goals and their realization. Diabetology and Metabolism 1 - A 75 DOI: 10.1055/s-2006-943800
9. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 241
10. Kolossa R (2014) Insulin pump therapy. Diabetologist (10) 472 - 476
11. Monnier L et al. (2015) The dawn phenomenon in type 2 diabetes: how to assess it in clinical practice? Diabetes Metab. (2) 132 - 137
12. Reinhardt D (2004) Therapy of diseases in childhood and adolescence. Springer Verlag Berlin / Heidelberg 153
13. O'Neal T B et al (2021) Dawn- Phenomenon. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;Bookshelf ID: NBK430893. PMID: 28613643
14. Reyhanoglu G et al (2021) Somogyi Phenomenon. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID: 31855369, Bookshelf ID: NBK551525.
15. Siegenthaler W et al (2006) Clinical pathophysiology. Georg Thieme Verlag Stuttgart / New York 1173

16. Wehling M et al (2006) Clinical pharmacology. Georg Thieme Verlag Stuttgart / New York 273, 275