The Role of Insulin in Diabetes Management
Insulin is a critical hormone that regulates blood glucose levels by allowing cells to absorb sugar from the blood for energy [1.2.1]. In people with diabetes, the body either doesn't produce enough insulin or can't use it effectively. According to the CDC, in 2021, 29.7 million people in the U.S. had diagnosed diabetes [1.7.2]. Many of these individuals depend on manufactured insulin to manage their condition. Insulins are categorized based on how quickly they work, when they peak, and how long they last. These categories include rapid-acting, short-acting, intermediate-acting, and long-acting insulins [1.2.4]. While most insulins are clear solutions, some are intentionally manufactured to be cloudy suspensions.
What is Cloudy Insulin and Why Does it Look That Way?
Cloudy insulin is typically an intermediate-acting insulin, with Neutral Protamine Hagedorn (NPH) insulin being the most common example [1.2.1]. NPH insulin includes added substances, specifically protamine and zinc, which cause it to form a suspension of crystalline insulin [1.2.1, 1.2.5]. These particles are not dissolved but suspended in the liquid, giving it a milky or cloudy appearance [1.3.6]. The purpose of these additives is to slow down the rate at which the insulin is absorbed into the bloodstream. This results in a slower onset of action (1 to 3 hours), a peak effect between 4 and 10 hours, and a duration of up to 18 hours [1.2.3, 1.6.4, 1.2.6]. This prolonged action helps control blood sugar levels between meals and overnight [1.2.7].
Types of Insulin That Should Be Cloudy
It's crucial to know which insulins are supposed to appear cloudy to avoid improper use.
- Intermediate-Acting Insulins: NPH insulins, such as Humulin N and Novolin N, are the primary examples of insulins that are naturally cloudy [1.2.7].
- Pre-mixed Insulins: These insulins combine a rapid- or short-acting insulin with an intermediate-acting NPH insulin. Because they contain NPH, they are also cloudy [1.2.4]. Examples include Humulin 70/30, Novolin 70/30, and Humalog Mix 75/25 [1.2.1, 1.2.5]. These formulations provide both a quick burst of insulin to cover meals and a longer-lasting effect [1.2.4].
The Importance of Proper Handling and Mixing
Because cloudy insulins are suspensions, the particles can settle at the bottom of the vial or pen [1.3.1]. If not mixed properly before each injection, the dose administered can be inaccurate, leading to either too much or too little insulin, which will significantly affect blood glucose readings [1.3.5].
How to Prepare Cloudy Insulin:
- Wash your hands thoroughly.
- Roll the vial gently between your palms 10-20 times [1.4.4].
- Invert or tip the vial up and down 10 times [1.3.6].
- Inspect the insulin. It should be uniformly milky white. Do not use it if you see clumps, solid white particles stuck to the sides (a 'frosted' look), or if it remains clear [1.3.5, 1.3.6].
- Never shake the vial vigorously, as this can create air bubbles that lead to inaccurate dosing [1.2.4].
When mixing clear and cloudy insulin in the same syringe, the rule is always "clear before cloudy" [1.6.5]. This means you draw the clear (rapid- or short-acting) insulin into the syringe first, and then draw the cloudy (NPH) insulin [1.3.4]. This prevents the NPH particles from contaminating the clear insulin vial and altering its fast-acting properties [1.3.1].
When Cloudiness Is a Danger Sign
While some insulins are meant to be cloudy, if an insulin that is normally clear appears cloudy, discolored, or contains particles, it should not be used [1.5.2]. This change in appearance can indicate that the insulin has been compromised due to:
- Improper Storage: Exposure to extreme heat or freezing temperatures can cause the insulin protein to break down, or denature, forming clumps or a precipitate [1.3.2].
- Contamination: Accidentally mixing cloudy insulin into a clear vial, or contamination with skin particles or blood, can alter its appearance and effectiveness [1.3.2].
- Expiration: Using insulin past its expiration date can result in reduced potency.
Using compromised insulin can lead to unpredictable blood sugar control, including hyperglycemia (high blood sugar), and is unsafe [1.5.2].
Comparison: Cloudy vs. Clear Insulin
| Feature | Cloudy Insulin (NPH) | Clear Insulin (Rapid-Acting) |
|---|---|---|
| Appearance | Uniformly cloudy or milky after mixing [1.3.6] | Clear and colorless [1.2.7] |
| Primary Type | Intermediate-acting [1.2.4] | Rapid-acting or Short-acting [1.2.4] |
| Onset of Action | 1–3 hours [1.6.4] | 10–20 minutes [1.2.7] |
| Peak Effect | 4–10 hours [1.2.6] | Varies, but much shorter than NPH [1.2.1] |
| Duration | 10–18 hours [1.2.6] | 2–4 hours [1.2.7] |
| Primary Use | Provides basal (background) glucose control between meals and overnight [1.2.7]. | Covers blood sugar spikes from meals (bolus insulin) [1.2.4]. |
| Mixing Rule | Drawn into the syringe after clear insulin ("clear before cloudy") [1.6.6]. | Drawn into the syringe before cloudy insulin [1.6.6]. |
Conclusion
Understanding what cloudy insulin is and how to use it correctly is a fundamental skill in diabetes self-management. NPH and pre-mixed insulins are intentionally cloudy due to added substances that prolong their action. Correctly resuspending this insulin by rolling and inverting it before every dose is essential for accuracy and safety. Equally important is recognizing when an insulin has changed appearance unexpectedly. If a typically clear insulin turns cloudy, it is a sign of spoilage and must be discarded. By following proper handling, mixing, and injection site rotation procedures, patients can ensure their insulin therapy is both safe and effective in controlling blood glucose levels.
For more detailed information on insulin types, you can visit Diabetes UK [1.2.4].
