The textbook says so

The second edition of the eight-year textbook on pathophysiology of the human health edition (P133): "Insulin can directly stimulate Na + -K + -ATPase activity and promote cellular potassium uptake", "Serum potassium ion concentration can directly stimulate insulin secretion, thereby promoting cellular potassium uptake". As for the specific mechanism, the book does not describe it.

Five-Year Physiology Eighth Edition (P405): "Insulin promotes the entry of potassium ions into cells". This description makes no difference whether it is said or not.

So, what is the specific mechanism by which insulin can lower blood potassium?

Many clinicians do not delve into this basic research issue, and it is OK to use it and be effective. However, knowing what it is but not knowing why, the heart is always at ease.

The specific mechanism of insulin lowering blood potassium

After insulin binds to the receptor, it activates the IRS1-PI3K-PDK1 cascade signaling. Starting from PDK1, the signaling pathway is divided into two, and finally exerts two effects [1,2]:

• Activates and promotes the transport of Na + -K + -ATPase from intracellular vesicles to cell membranes, resulting in the uptake of more potassium ions into the cell and the exclusion of sodium ions from the cell;
• Activation prompts the transport of glucose transporter (GLUT4) from intracellular vesicles to cell membranes, accelerating glucose uptake.

It can be seen from the above that lowering blood sugar and lowering blood potassium are two simultaneous but opposite processes after the activation of the insulin signaling pathway. This is the fundamental reason why glucose must be supplemented at the same time when insulin is used to treat hyperkalemia.

Glucose + insulin to reduce potassium, how to do it?

Before answering this question, the first thing to mention is the classification of the severity of hyperkalemia.

UK and European guidelines recommend blood potassium concentrations of 5.5 to 5.9 mmol/L for mild hyperkalemia, 6.0 to 6.4 mmol/L for moderate, and ≥ 6.5 mmol/L for severe [3].

In addition to directly measuring the concentration, the blood potassium level can usually be judged according to the electrocardiogram: mild and moderate high potassium usually have shortened QT interval and tent-like T-wave high-tip basal stenosis; moderate and severe high potassium usually have prolonged PR interval, widened QRS wave, arrhythmia, and even cardiac arrest.

The UK guidelines recommend [3]

• For severe hyperkalemia with blood potassium ≥ 6.5 mmol/L, intravenous infusion of insulin 10U + glucose 25g (converted from liquid concentration) is recommended;
• For moderate hyperkalemia with a blood potassium level of 6.0 to 6.4 mmol/L, intravenous infusion of 10 U + 25 g glucose may be considered.

According to foreign research data [4-7], when using glucose-insulin infusion for about 15 minutes, blood potassium begins to decline, with a maximum decrease of 0.65 to 1.0 mmol/L, and the maximum effect appears at 30 to 60 minutes of infusion. The effect can be maintained for 2 hours, and then blood potassium will rebound.

Do diabetics who use insulin need regular potassium supplementation?

The blood potassium balance of the human body is regulated by two internal and external systems:

The exogenous system regulates the balance of total potassium in the body, which is checked and balanced by dietary potassium intake and potassium excretion from the body's metabolism. The excretion route is mainly excreted through the kidneys, and the kidneys have a strong compensatory ability. In non-serious diseases, the total potassium balance in the body can be maintained by increasing or decreasing the excretion of urinary potassium.

The endogenous regulatory system mainly regulates the balance of potassium ions inside and outside the cell. Only about 2% of the potassium in the human body is distributed in the extracellular fluid, so the transport of potassium ions inside and outside the cell has a huge impact on the concentration of potassium in the blood, and various hormones in the body can affect the balance of potassium in the blood, such as insulin and catecholamines.

Animal experiments have shown [9] that subcutaneous and intramuscular insulin injections (peak insulin concentrations up to 3-4 times normal) do not cause significant changes in blood potassium, while intravenous insulin injections of the same dose (peak insulin concentrations up to 200 times normal) can cause significant decreases in blood potassium.

A similar phenomenon also occurs in diabetic patients. The reason may be that when subcutaneous or intramuscular injection, insulin absorption is relatively slow, the peak concentration is low, and the body can compensate; while when intravenous administration, insulin enters the blood immediately, the peak concentration is high, and the body cannot compensate in time.

Therefore, diabetic patients do not require regular potassium supplementation when injecting insulin subcutaneously; while when intravenous insulin is required, such as ketoacidosis and hyperglycemia, potassium supplementation is required as appropriate.

Intravenous use of insulin, how to supplement potassium?

1. In the state of ketoacidosis and hyperglycemia and hyperosmolality, the principle of potassium supplementation is [10]

• When blood potassium is less than 5.2 mmol/L, potassium should be replenished intravenously;
• Pre-treatment hypokalemia, with urine volume ≥ 40 mL/h, potassium supplementation is necessary during fluid replacement and insulin therapy;
• If blood potassium <3.3 mmol/L is found, potassium supplementation should be given priority. When blood potassium rises to 3.5 mmol/L, insulin therapy should be started to avoid arrhythmia, cardiac arrest and respiratory muscle paralysis.

2. When the average diabetic patient must use a glucose solution: