To advance our project on anti-glycemic foods, we engaged with various stakeholders and reviewed relevant data. Diabetes, affecting over 537 million adults globally, is a serious health issue causing complications like blindness and heart disease. Our survey revealed strong public interest in anti-glycemic foods, with 88% acknowledging the impact of diet on health.

We chose resistant starch due to its benefits for blood sugar control and gut health. High-amylose sweet potatoes were selected as the carrier due to their dietary fiber content and potential for managing diabetes. Although high-amylose grains exist, their poor texture limits their use, making sweet potatoes a more viable option.

Regulatory considerations are crucial as China enforces strict GMO regulations. Recent policy changes, including the issuance of biosafety certificates for gene-edited plants, offer hope for the future of our genetically edited sweet potatoes.

Diabetes is a long-term health condition that occurs when the pancreas either fails to produce adequate insulin or when the body cannot use the insulin it produces efficiently [1]. Insulin is a crucial hormone responsible for regulating blood sugar levels. Hyperglycemia, which refers to elevated blood glucose levels, is a common consequence of unmanaged diabetes and can cause significant damage to various bodily systems over time, particularly the nerves and blood vessels [2].

According to the latest report from the International Diabetes Federation (IDF), approximately 537 million adults (aged 20-79) worldwide were living with diabetes in 2021, meaning that 1 in 10 people had the condition. This number is expected to rise to 643 million by 2030 and to 783 million by 2045. During this period, the global population is projected to increase by 20%, while the number of people with diabetes is estimated to grow by 46% [3]. The condition of diabetes is insidious in its early stages and progresses slowly, but its consequences are very serious, being the leading cause of blindness, kidney failure, heart attack, stroke, and lower limb amputation [1].

Figure 1. Estimated total number of adults (20-79 years) with diabetes in 2021 (http://www.diabetesatlas.org/)

Given the rapid rise of diabetes worldwide, particularly in countries such as China, India, and the United States, we have developed a significant interest and sense of urgency regarding this issue. To assess the real-world demand for our study, we conducted a survey with 416 participants. Most respondents were over the age of 40, accounting for 66%, which is also the primary demographic affected by diabetes. From the survey, we found that 53% of participants knew someone in their social circle with diabetes. In reality, this figure may be underestimated, as 8% of respondents indicated they were unsure of the health status of those around them (since diabetes is often a private matter). Therefore, the prevalence of diabetes in everyday life should not be underestimated.

Interview 1: Dr. Yin

Interview 1

1. Diabetes management is often described as a "five-horse carriage," which includes dietary control, physical exercise, medication, diabetes education, and patient self-monitoring of blood glucose levels. Among these, dietary control serves as the cornerstone of management, being essential regardless of the severity.
2. When developing anti-glycemic foods, it is essential to consider three key aspects: quantification, cost, and taste. Dr. Yin mentioned that while we currently advise diabetic patients to consume anti-glycemic foods with every meal, achieving this in practice is quite difficult. The challenges are as follows:
   1. Can we standardize the intake? How much should be consumed at each meal to ensure adequate caloric intake without imposing an additional glycemic burden?
   2. There is the issue of cost. A single breakfast made with anti-glycemic foods can cost around ten yuan, which may be unaffordable for many patients.
   3. The taste is not particularly appealing. Anti-glycemic foods tend to have a coarse texture due to their high content of resistant starch and dietary fiber. This rough texture often makes it difficult for most people to maintain long-term consumption.
3. Anti-glycemic foods are more suitable for relatively younger individuals, as they tend to absorb nutrients more efficiently. This group may include those who are overweight or prone to elevated postprandial blood sugar levels, such as diabetic patients. However, long-term consumption by pregnant women may lead to nutritional imbalances, and thus is not recommended. Additionally, individuals with poor gastrointestinal absorption should avoid excessive intake, as it may result in malnutrition.

Public's awareness
In addition to understanding the necessity of anti-glycemic foods from a medical perspective, we also conducted a survey to assess the public's awareness and acceptance of such products. This helps us gain insight into the market and solidify our goals. 88% of respondents believe that their daily eating habits have a significant impact on their health. Additionally, 63% of participants have some level of awareness about anti-glycemic foods, and 92% are willing to pay a higher price for them. These results indicate a high level of public acceptance and willingness to bear the additional cost of anti-glycemic foods, suggesting that our products have substantial market potential.

Interview 2: Dr. Xu

Interview 2

After deciding to develop an anti-glycemic food, we were uncertain about the primary ingredient. Therefore, we consulted Dr. Xu from the gastroenterology department, who provided us with some recommendations and insights:

1. A. Resistant starch (also known as enzyme-resistant or indigestible starch) is not easily digested in the small intestine but can be fermented in the large intestine, producing volatile fatty acids that help regulate gut microbiota and prevent issues such as constipation. Resistant starch is found in some natural foods, such as potatoes, bananas, and rice, but the content is relatively low in these foods.
2. B. In genetically modified high-amylose corn, the resistant starch content can reach up to 60%. Amylose, which is harder to break down than other starches, is a type of resistant starch that is digested more slowly, resulting in a slower absorption of glucose into the bloodstream.
3. The benefits of resistant starch for the gastrointestinal system include:
   1. Promoting gut microbiota balance: Resistant starch provides nutrition for beneficial bacteria in the gut, such as bifidobacterium, supporting their growth and reproduction, while bypassing absorption in the small intestine.
   2. Lowering blood sugar levels: Resistant starch is not digested or absorbed in the small intestine and is slowly broken down into glucose in the large intestine, thus preventing sharp spikes in postprandial blood sugar levels.
   3. Improving lipid metabolism: Resistant starch can reduce the synthesis of low-density lipoprotein (LDL) cholesterol while promoting the secretion of high-density lipoprotein (HDL) cholesterol, contributing to lowering blood lipid levels.
   4. Increasing satiety: Since resistant starch is not directly absorbed, it slows gastric emptying, thereby increasing the feeling of fullness.
   5. Maintaining gut health: Resistant starch ferments in the large intestine, producing gases that help regulate gut microbiota and prevent issues like constipation.
4. It is important to note that while resistant starch offers multiple health benefits, it is difficult for the gastrointestinal system to digest and absorb. Excessive intake may increase the risk of digestive discomfort, potentially causing bloating, nausea, abdominal pain, or constipation.

From Dr. Xu, we learned about what resistant starch is, its benefits, and the issues that need attention.

Although we decided to focus on resistant starch as the target for developing anti-glycemic foods, the question remained—what species should serve as the carrier? In previous discussions with Dr. Yin, it was noted that the price and taste of anti-glycemic foods are critical factors to consider during development. In addition, Professor Li from Yangzhou University explained that although high-amylose rice, wheat, and corn have been successfully bred both domestically and internationally, their application in the food industry is quite limited. This is primarily due to their poor texture, which is often described as being similar to cardboard. As a result, these high-amylose starches have considerable untapped potential. However, to fully realize this potential, it is essential to find suitable methods to overcome their drawbacks as food products. If this challenge can be addressed, these high-amylose crops could play a significant role in the prevention and management of diabetes.

As a result, we turned our attention to sweet potatoes. To further assess feasibility, we consulted Dr. Xu Meimei.

Dr. Xu explained that the Diabetes Expert Guidelines mention that:

1. Sweet potatoes are rich in dietary fiber, which helps stimulate appetite and is beneficial for diabetic patients. However, sweet potatoes also promote the secretion of gastric acid, so patients with excessive stomach acid or frequent symptoms of acid reflux or heartburn should avoid consuming them. Diabetic patients can eat sweet potatoes in moderation, with a daily recommended intake of 100g to avoid affecting blood sugar control and causing gastrointestinal discomfort.
2. For diabetic patients, individuals needing to control blood sugar, and those trying to lose weight, sweet potatoes with a high resistant starch content (over 50%) are a favorable choice, as they help regulate blood sugar levels and minimize fluctuations. These resistant starch-rich sweet potatoes are not only suitable for specific populations but can also be a part of a healthy diet for the general public. They can be used as a main course or side dish, providing essential energy and nutrients while helping to control blood sugar and weight.

Sources and Methods for Increasing Resistant Starch Content in Sweet Potatoes

To understand the sources of resistant starch in sweet potatoes and methods for increasing its content, we reviewed literature and consulted Professor Li Enpeng from Yangzhou University.

From our literature review, we learned that amylose is one of the two main components of starch, the other being amylopectin. Due to its relatively linear structure, amylose molecules are long and tightly packed, forming crystalline regions within the starch granules. These regions are more resistant to enzymatic digestion, making amylose a significant source of resistant starch [4].

Interview 3: Professor Li

Professor Li explained the starch biosynthesis pathway in sweet potatoes.

Interview 2

1. Starch biosynthesis is a complex process that involves the coordinated action of several enzymes, including granule-bound starch synthase (GBSS), ADP-glucose pyrophosphorylase (ADPG), starch synthase (SS), starch branching enzymes (SBE), and starch debranching enzyme (DBE). Amylose is primarily synthesized by GBSS, while amylopectin is produced through the combined actions of SS, SBE, and DBE. During starch biosynthesis, SBE catalyzes the α-1,6-glycosidic bonds in amylopectin and contributes to the formation of short chains within amylopectin clusters, making SBE crucial for amylopectin formation.
2. Currently, the predominant method for increasing amylose content in crops is through genetic engineering. High amylose varieties are typically derived from mutants, as naturally occurring high-amylose plants are not found. Genetic modification mainly targets SBE and SS, as deficiencies or alterations in these enzymes can significantly enhance amylose content.

Bakeries, supermarkets and confectionery processing factories

In terms of product applications, we visited several bakeries, supermarkets and confectionery processing factories (ISYOU Bakery). They shared similar market perspectives with us:

1. Consumers are increasingly concerned about foods with a low glycemic index (GI), low calorie content, and no preservatives, meaning they are more inclined to choose healthier options.
2. Shortbread-type cookies are a popular baked good, but they tend to have high fat content. They would be very interested in any potential improvements in this area.
3. There are already snacks specifically targeted at people with diabetes available on the market, and they are open to producing such items, as they believe this market has significant potential.

When we proposed using high-amylose sweet potatoes to make anti-glycemic cookies and cakes, they responded that it is technically feasible from a production standpoint. However, the actual GI value of the finished product would need to be measured, as the resistant starch content could change during the production process.

Public survey

Interestingly, aside from snacks and treats, our survey also revealed that 54% of people prefer unprocessed starch products. Therefore, in addition to developing high-value-added snacks and treats aimed at people with diabetes, we still plan to sell natural, high-amylose sweet potatoes to reach the widest possible audience.

Interview 4: Professor Cheng

Since our sweet potatoes are genetically edited crops, we need to be mindful of China's policies regarding genetically edited products. To better understand this, we consulted with Professor Cheng from China Agricultural University. He mentioned that China enforces strict regulations on genetically modified organisms (GMOs), with all genetically modified species or products requiring lengthy approval processes before entering the market. However, the government is showing signs of relaxing restrictions on GMOs, and genetically modified grains may soon be allowed in certain regions.

Professor Cheng,
College of food science and nutritional engineering, China Agricultural University

Policy documents

We also reviewed relevant policy documents and found that in 2023, the Ministry of Agriculture and Rural Affairs released the "Review Guidelines for Agricultural Gene-Edited Plants (Trial)" as well as the "2023 List of Approved Biosafety Certificates for Gene-Edited Agricultural Products (Production and Application)" [5]. The issuance of the nation's first biosafety certificate for a gene-edited plant marked a significant step forward, providing hope for the future of GMO production and application.

1. World Health Organization. Diabetes Fact Sheet. Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes
2. Deutsch AJ, Ahlqvist E, Udler MS. Phenotypic and genetic classification of diabetes. Diabetologia. 2022 Nov;65(11):1758-1769.
3. International Diabetes Federation. Diabetes Atlas: China. Available from: https://diabetesatlas.org/data/en/country/42/cn.html
4. Zhong Y, Tai L, Blennow A, Ding L, Herburger K, Qu J, Xin A, Guo D, Hebelstrup KH, Liu X. High-amylose starch: Structure, functionality and applications. Crit Rev Food Sci Nutr. 2023;63(27):8568-8590.
5. Ministry of Agriculture and Rural Affairs. Review Guidelines for Agricultural Gene-Edited Plants (Trial). Available from: https://www.moa.gov.cn/ztzl/zjyqwgz/sbzn/202304/P020230428340520546687.pdf