Fun fact: Will people who were afraid of injections when they were young still be afraid of them when they grow up?

Maybe everyone has noticed that many people have been sick recently, so some netizens asked, those who were afraid of injections when they were young, will they still be afraid when they grow up? I felt ridiculous when I first saw this question, but after thinking about it, it seems that injections are rarely seen now, and I haven't had an injection for many years. The last time was when I was injured at work while doing an experiment. I went to the hospital to have the wound sutured and got a tetanus shot. I was in pain for several days, which made me still very shy about injections.

The injection also made me realize the difficulties faced by another group of people, that is, the diabetic group. Due to research related to this group, I have some contact with them, so I also understand this group. Unlike us who only get injections occasionally, they have to get injections frequently because of their diseases, and some even need multiple injections a day...

01. Diabetes: a huge invisible group

Except for those who know someone with diabetes, most people only know diabetes as a blood sugar-related disease that requires long-term medication and injections. However, the size of this group exceeds many people's expectations.

The figure below is a map of the global diabetes distribution and possible future growth based on IDF statistics. As you can see, the number is actually quite terrifying, with tens of millions of patients in different regions.

The Western Pacific region is the hardest hit by diabetes, accounting for more than one-third of the world's diabetes patients.

As the most populous country in the Western Pacific, China also has a huge number of diabetes patients. According to an epidemiological survey of Chinese diabetes patients published in JAMA, the dire situation is that it is estimated that the diabetes rate in China is as high as 11.6%, and the proportion of the population in the pre-diabetes stage is as high as 50.1%. Perhaps another way of saying it is more intuitive is that there are currently about 114 million diabetes patients in China, one in every 11 people has diabetes, and among adults, nearly 500 million are in the pre-diabetes stage. This is an extremely scary number, which means that whether from the perspective of the current number of patients or the number of potential diabetes patients in the future, China’s diabetes status quo and future growth trend are extremely severe (ref2)

In fact, the number of people who die from diabetes in China is also the highest in the world.

Next, let us introduce some basic knowledge about diabetes.

02. What is diabetes?

Diabetes is a metabolic disease, which is typically characterized by long-term chronic high blood sugar, accompanied by frequent urination, thirst, polyphagia, hunger, weight loss, etc. (ref3). The causes of diabetes are generally divided into two categories: the amount of insulin produced by pancreatic islet cells decreases, or the cells cannot properly respond to insulin, resulting in insulin's inability to reasonably regulate blood sugar. In general, diabetes is divided into the following four categories:

1. Type 1 diabetes is caused by the failure of pancreatic β cells and the absolute lack of insulin secretion. It usually develops early and is also called juvenile diabetes.

2. Type 2 diabetes. This is the most common form of diabetes, accounting for the vast majority of Chinese diabetics. The main cause is insufficient insulin secretion or insulin resistance. Insufficient insulin secretion refers to a decrease in quantity, and insulin resistance refers to a decrease in effect. In other words, insulin resistance means that although the body can secrete insulin normally, the body's cells cannot respond to it reasonably, so insulin sensitivity decreases.

3. Gestational diabetes, which occurs in pregnant women with no history of diabetes.

4. A special type of diabetes, which is a state of high blood sugar caused by genetic defects, drugs, inflammation of the pancreas or tumors.

Type 2 diabetes accounts for more than 90% of diabetes patients (ref4), so it has attracted much attention. Type 2 diabetes usually develops after middle age, but the incidence of type 2 diabetes patients in China is getting younger and younger. If not treated in time, it will lead to a variety of complications, such as cardiovascular disease, stroke, chronic kidney disease, foot ulcers and eye damage. In severe cases, it may even lead to ketoacidosis or death (ref5).

Therefore, dealing with diabetic complications has always been an important clinical issue.

03. How to treat diabetes?

The treatment of diabetes is mainly to lower blood sugar. Regarding the treatment of diabetes, I believe many people must have heard that diabetes requires injections. This is the objective reality of diabetes treatment. So far, common diabetes drugs are generally divided into oral and injection types, and the two often need to be used in combination.

Oral drugs are mainly used to treat diabetic patients with pancreatic islet function, such as sulfonylureas, glinides and metformin, which often need to be taken multiple times a day. However, it is interesting that since metformin objectively reduces energy intake, it may promote human longevity. The FDA has approved the experimental study of metformin longevity drug, which may become the first longevity drug in the future.

In fact, oral short-acting hypoglycemic drugs often affect treatment compliance due to the high frequency of administration. For example, a survey found that the higher the frequency of drug use, the more likely it is to cause changes in compliance.

What is hypoglycemic injection therapy? There are many advantages to subcutaneous injection of drugs into the human body. On the one hand, it allows the drug to take effect as quickly as possible, rather than going through the human digestive system. On the other hand, it is also a last resort. For example, the component of insulin is protein. After entering the human digestive system, this substance will be directly digested and lose its effect.

Therefore, how to find a long-acting drug has become an urgent need. Glucagon-like peptide-1 receptor agonist is such a drug. Let's talk about this drug.

04. Glucagon-like peptide-1 receptor agonist

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid polypeptide secreted by enteroendocrine cells in the ileum. This peptide can enhance the secretion of insulin, thereby lowering blood sugar levels in a glucose-dependent manner. Therefore, it has always been a target for many drugs to treat diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a general term for this type of drug (ref7).

This is a study of this class of drugs in the New England Journal of Medicine

Compared with the risks of insulin, such as the risk of hypoglycemia and weight gain, which further aggravates the vicious cycle of insulin resistance, GLP-1RA has better blood sugar and weight loss effects and can avoid the shortcomings of conventional insulin treatment. Therefore, GLP-1RA has become a new option for the treatment of diabetes. This type of drug can significantly reduce diabetes (ref8)

05. Microsphere encapsulation technology

How can GLP-1RA better play its hypoglycemic effect? ​​Researchers thought of using microsphere encapsulation technology to encapsulate the active ingredient exenatide through polylactide-glycolide (PLG) to form a microsphere, and such a microsphere hydrates to form an aggregate at the injection site. After entering the human body, PLG slowly degrades and is eventually hydrolyzed into carbon dioxide and water; and the drug is gradually released as the microsphere degrades, exerting a lasting hypoglycemic effect.

Since the drug diffuses gradually, it is released in the human body in steps. Compared with conventional injections, this microsphere technology can make a single injection of the active ingredient exenatide last for about 10 weeks in the body. This is a huge breakthrough because it means that patients no longer need to inject drugs every day, but can choose to inject once a week, which greatly reduces their pain.

It should be noted that high-frequency injections not only increase the mental burden of patients, but also lead to poor treatment compliance, resulting in drug shortages, missed medications, and failure to take medications on time. If not promptly remedied, it can easily cause significant fluctuations in blood sugar, which in turn affects the stable control of blood sugar. For some patients with type 2 diabetes who still have pancreatic islet function and poor HbA1c and blood sugar control, this new microsphere technology can achieve sustained release through physical means to obtain steady-state blood drug concentrations. It is superior to OAD and insulin in terms of blood sugar lowering efficacy, and can achieve comprehensive blood sugar lowering once a week. While safely controlling blood sugar, it greatly reduces the frequency of injections (the traditional injection frequency can be up to 28 times a week), which significantly improves treatment compliance.

Therefore, this drug that can reduce the frequency of injections and maintain the therapeutic effect has attracted much attention. In 2005, the FDA approved this drug for the clinical treatment of diabetes. Subsequently, the drug was launched in many countries and regions around the world. In early 2018, the China Food and Drug Administration (CFDA) officially approved the drug for domestic marketing, providing a new treatment option for improving blood sugar control in patients with type 2 diabetes.

So, if you think getting an injection is painful, think about the suffering of those who need injections every day. Fortunately, with the advancement of medicine, their pain can be reduced by at least seven times.

I believe that with the emergence of better drugs in the future, diabetes will eventually be conquered by humans.

1. International Diabetes Federation. IDF Diabetes Atlas, 8th edn. Brussels, Belgium: International Diabetes Federation, 2017.

2. Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults[J]. Jama, 2013, 310(9): 948-959.

3. http://www.who.int/news-room/fact-sheets/detail/diabetes

4. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. (December 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the

5. Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96.

Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN (July 2009). "Hyperglycemic crises in adult patients with diabetes". Diabetes Care. 32 (7): 1335–43.

6. Hauber AB, Han S, Yang JC, et al. Effect of pill burden on dosing preferences, willingness to pay, and likely adherence among patients with type 2 diabetes[J]. Patient preference and adherence, 2013, 7: 937.

7. Marathe CS, Rayner CK, Jones KL, et al. (2013). "Glucagon-like peptides 1 and 2 in health and disease: A review". Peptides. 44: 75–86.

8. Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes[J]. New England Journal of Medicine, 2017, 377(13): 1228-1239.

9. DeYoung MB, MacConell L, Sarin V, et al. Encapsulation of exenatide in poly-(D, L-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes[J]. Diabetes technology & therapeutics, 2011, 13(11): 1145-1154.

Final statement:

The diabetes drugs mentioned in this article, such as metformin, sulfonylureas and the injectable drug exenatide, are all clinical drugs. Please do not use them without authorization, but use them according to your own pathological condition and the doctor's advice.

In addition, although metformin has entered FDA-approved clinical trials and may become a longevity drug in the future, it is not recommended for ordinary people to try it at present.