Type-2 Diabetes and the Mediterranean Diet

Diabetes Mellitus (DM), abbreviated to diabetes, is commonly known as sugar disease. Diabetes is a metabolic disease characterized by elevated blood sugar levels (hyperglycemia). The number of people with diabetes, currently reaching 425 million, is estimated to reach 592 million by 2035. The development and progression of diabetes are closely related to nutrition. The Mediterranean diet is one of the most effective dietary patterns for preventing diabetes. US News and World Report’s “Healthiest Diets 2020” list ranks diets according to their effects on different diseases, and we see that the dietary pattern most beneficial for diabetes is the Mediterranean Diet pattern. In this comprehensive review, we present the relationship between diabetes and the Mediterranean Diet.

What is diabetes and how does it develop?

Diabetes is a chronic metabolic disease characterized by high blood sugar that affects the conversion of food consumed into energy.

The foods we consume raise blood sugar. For the sugar in the blood to be used as energy, it must pass from the blood into the body's cells (muscle cells, fat cells, and liver cells). Therefore, when blood sugar reaches high levels in the circulation, the beta cells of the pancreas release a hormone into the blood called “insulin”. Insulin enables sugar to leave the blood and enter the cells.

In diabetes, the body cannot produce enough insulin or cannot use the insulin it has produced, which we call the development of insulin resistance. As a result, blood sugar reaches high levels. If this continues for a long time without being controlled, it can lead to skin ulcers and non-healing wounds, nerve damage called diabetic neuropathy, eye problems and vision loss, kidney disease, stroke, and cardiovascular disease, among other serious health problems.

There are several types of diabetes; the most common are Type 1, Type 2 and gestational diabetes. Type 1 diabetes is a condition that occurs when the body becomes unable to produce insulin as a result of an autoimmune disorder.

• Type 1 diabetes can develop with viruses and infections playing a role alongside genetic factors. In this type of diabetes, the person depends on insulin therapy, and a physician starts insulin treatment to achieve blood sugar control.
• Type 2 diabetes is much more common than Type 1 diabetes and accounts for approximately 90% of all diabetes. Type 2 diabetes is characterized mainly by progressive impairment of insulin secretion and/or insulin deficiency against a background of insulin resistance predisposed by genetic factors. Lifestyle plays an important role in the development of Type 2 diabetes.
• Gestational diabetes occurs in women who become less sensitive to insulin during pregnancy. It usually resolves after pregnancy, but is one of the risk factors for Type 2 diabetes. It must therefore be controlled for the health of both the baby and the mother.

- Related topic: What are diabetes, prediabetes, and insulin resistance? Symptoms and treatment 

Why does Type 2 diabetes develop? Risk factors

Type 2 diabetes has main symptoms including excessive thirst, frequent urination, fatigue, slow wound healing, blurred vision, unexplained sudden weight loss, and darkening of the neck and armpit areas.  

The frequency of Type 2 diabetes is increasing worldwide every day. Increasing obesity resulting from a Western lifestyle and changing eating habits plays a major role. There are several main risk factors involved in the development of Type 2 diabetes:

• Weight: Being overweight and obesity are the most important risk factors for developing Type 2 diabetes. However, people within the normal weight range can also develop Type 2 diabetes. 
• Unhealthy nutrition: Western-style diets high in sugar and fat increase the risk of Type 2 diabetes.
• Sedentary lifestyle: Physical activity helps maintain a normal weight range, use glucose as energy, and make cells more sensitive to insulin. 
• Abdominal fat accumulation: Fat accumulation around the waist is the most dangerous type of fat accumulation for health. For men, 102 cm, and for women, 89 cm are waist circumference thresholds above which the risk of Type 2 diabetes increases.
• Older age: People's risk of developing Type 2 diabetes increases as they age. However, the incidence (frequency) of Type 2 diabetes is also increasing in children, adolescents, and young adults because of unhealthy lifestyle habits.
• Hereditary predisposition: People whose mother, father, brother, or sister has a history of type 2 diabetes have a higher risk of developing the disease.
• Prediabetes: Prediabetes is a health condition in which blood sugar is higher than normal (fasting blood sugar between 100 and 125 mg/dl), but not yet high enough for a type 2 diabetes diagnosis. Prediabetes may also be called the period before diabetes or hidden diabetes. If not controlled, prediabetes can progress to type 2 diabetes.
• Gestational diabetes: Gestational diabetes usually resolves after pregnancy. However, cases in which it progresses to Type 2 diabetes are also seen if it does not resolve and remains untreated. Mothers who have delivered a macrosomic baby (≥ 4 kg) are at particularly higher risk of developing Type 2 diabetes.
• Polycystic Ovary Syndrome: Polycystic Ovary Syndrome (PKOS), which is common in women and has symptoms such as menstrual irregularities, excessive hair growth, and obesity, increases the risk of Type 2 diabetes.

When we examine all the risk factors, we can say that certain factors (weight, abdominal fat accumulation, prediabetes) are directly related to healthy nutrition. It is therefore possible to say that correcting eating habits will also reduce diabetes risk.

In recent years, studies of Type 2 diabetes and the relationship between general health and certain dietary patterns have increased in number. These dietary patterns include the Mediterranean diet, vegetarian diet, vegan diet, other plant-based diets, low-fat diets, and low-carbohydrate diets. However, its healthy and balanced inclusion of all food groups makes the Mediterranean dietary pattern one of the most effective diets for both reducing Type 2 diabetes risk and improving general health. Indeed, the Mediterranean Diet was selected in US News and World Report's “Healthiest Diets 2020” list as the “Healthiest” diet.

• Related topic: Best diets 2020

The relationship between Type 2 Diabetes and the Mediterranean Diet

In addition to healthy eating habits, the Mediterranean dietary pattern recommends daily physical activity. It also recommends eating healthy, seasonal, locally produced foods while socializing.

In summary, the Mediterranean dietary pattern recommends:

• Primarily: fruit, vegetables, olive oil, fish, whole grains, pulses, nuts, low-fat milk and dairy products,
• In moderate amounts: eggs and skinless white meat,
• In limited amounts: red meat consumption is recommended.

Scientific research findings on the Mediterranean diet and type-2 diabetes

Many studies have investigated the effects of the Mediterranean dietary pattern on Type 2 diabetes.

In 2020, “Nutrients” published a review evaluating studies from the preceding 5 years on the relationship between the Mediterranean Diet and Diabetes. Studies comparing other dietary patterns used to reduce diabetes risk with the Mediterranean dietary pattern were also evaluated. These included systematic reviews and meta-analyses. Studies included in this review generally assessed adherence to the Mediterranean dietary pattern using the “Mediterranean diet score”. A substantial proportion of the studies concluded that the Mediterranean diet has beneficial effects on Type 2 diabetes (Source 1).

Among these studies, in 2014, “Metabolism” published a meta-analysis study that included a total of 136,846 participants across 10 different studies. The groups with the highest and lowest adherence to the Mediterranean dietary pattern were compared. The comparison concluded that people adhering to the Mediterranean dietary pattern had a Type 2 diabetes risk 23% lower than the other group (Source 2).  

Another study was published in 2014 in “Public Health Nutrition”. This study covered research published between 2007-2014 and involving 122,810 participants across 9 studies that were evaluated. Similar to the preceding study's result, adherence to the Mediterranean Diet was concluded to reduce diabetes risk by 19% according to the findings (Source 3).  

In 2017, “The Journal of Nutrition” published a meta-analysis and systematic review involving a total of 1.5 million participants across 48 studies that were analyzed. The studies analyzed were conducted to assess the effects of different dietary patterns on Type 2 diet. These dietary patterns included the DASH diet and the AHEI scale. The “Dietary Approaches to Stop Hypertension” diet, known as DASH, has the Turkish equivalent “Hipertansiyonu önlemek için Diyet Yaklaşımları”. The DASH diet is broadly similar to the Mediterranean diet. The main difference between the Mediterranean and DASH diets is that the DASH diet restricts salt consumption to 1,500-2,300 mg. The AHEI scale was developed to define adherence to the dietary guidance developed to help people older than 2 years eat healthily and in a balanced way, the Dietary Guidelines for Americans, also described as the “Dietary Guide for Americans”. The study concluded that, although the Mediterranean diet, DASH diet, and AHEI scale differ in certain aspects of their content, each plays an effective role in the risk of developing Type 2 diabetes (Source 4).

In addition to the DASH diet and AHEI scale, the Mediterranean diet is compared with low-fat or low-carbohydrate paleo, vegetarian and vegan dietary patterns. All these patterns have beneficial effects on the risk of developing Type 2 diabetes because they limit foods that negatively affect health and cause sudden rises in blood sugar or weight gain.

Many more scientific publications have investigated the relationship between components of the Mediterranean dietary pattern and Type 2 diabetes. For example, in 2015, “American Journal of Clinical Nutrition” published a study examining the effects of olive oil within the Mediterranean dietary pattern on Type 2 diabetes. The study's age range was 25-65, with 145,087 participants. The participants were observed for 22 years. Their food consumption was verified every 4 years using a food frequency questionnaire. After 22 years of observation, 9,652 people were diagnosed with diabetes. It was concluded that using olive oil instead of margarine, butter, and mayonnaise could reduce Type 2 diabetes risk by, respectively, 5%, 8% and 15% according to the findings (Source 5).  

American Diabetes Association, also called the “American Diabetes Association” (ADA), states that keeping the lipid profile (cholesterol levels), weight, blood sugar, HbA1c values (the amount of sugar bound to hemoglobin in red blood cells over the last 3 months), and blood pressure within ideal ranges is important for reducing diabetes risk or supporting treatment. It states that people must acquire healthy eating and lifestyle habits to keep these values within normal ranges.   

Studies argue that the beneficial effects of the Mediterranean Diet on diabetes markers, namely HbA1c, fasting blood sugar, fasting insulin, and HOMA-IR (insulin resistance test), help reduce people's risk of developing Type 2 diabetes or support treatment. Let us examine studies on the relationship between the Mediterranean diet and glycemic control:

In 2014, “European Journal of Clinical Journal” published a meta-analysis evaluating 9 randomized controlled studies. These studies investigated the Mediterranean dietary pattern's effects in people with Type 2 diabetes on glycemic control, weight, and cardiovascular risk factors using comparisons with low-fat, non-calorie-restricted control diets or control diets in which the usual dietary pattern was unchanged. The meta-analysis results show that the Mediterranean Diet was more effective than other dietary patterns. When the Mediterranean Diet's effects on HbA1c, fasting blood sugar, and fasting insulin were compared with other dietary patterns,

• HbA1c, fasting blood sugar, and fasting insulin values were reduced by, respectively, 0.3%, 13 mg/dL, 0.55 μU/ml more than with the other diets (Source 6).

"Journal of the American College of Nutrition" published a study in 2007 involving participants aged 18-89, with a total of 3042 participants (Men: 1514; Women:1528). The study aimed to assess the effects of the Mediterranean dietary pattern on fasting blood sugar, insulin levels, and HOMA-IR (insulin resistance test). Participants had no history of cardiovascular disease. However, the rate of Type 2 diabetes in women was 6%, and in men 7.9%. The study found that participants with high adherence to the Mediterranean diet, compared with those with low adherence, had

• fasting blood sugar and insulin levels 15% lower; their HOMA-IR levels were 27% lower (Source 7).  

Research on diabetes shows that the different mechanisms involved in its development are interconnected. The pathophysiological process in diabetes is essentially elevated blood sugar resulting from insufficient insulin secretion by pancreatic beta cells or an inability to use the insulin secreted (insulin resistance). Both conditions cause disturbances in carbohydrate, protein, and fat metabolism. Insufficient pancreatic insulin secretion can result from factors such as genetics and age, as well as lipotoxicity, glucotoxicity, reactive oxygen species, inflammation, and cellular stress caused by insulin resistance. Understanding these terms involved in diabetes development is important for understanding its mechanism. Let us examine what these terms mean:

• Lipotoxicity: Excessive triglyceride storage in muscle, liver, and pancreas impairs the functions of these cells. This is called lipotoxicity.
• Glucotoxicity: Glucotoxicity is also called sugar poisoning. Excessively elevated blood glucose impairs production of the hormone insulin, and insulin secretion decreases substantially.
• Reactive oxygen species (ROT): Reactive oxygen species can have highly harmful effects, particularly when the body receives insufficient antioxidants. ROT accumulation in the human body causes oxidative damage to the cell membrane. Consequently, oxidative-stress-mediated dysfunctions such as diabetes occur.
• Inflammation: Inflammation, also commonly described as inflammatory swelling, is the totality of physiological responses of tissues supplied by blood vessels to all types of damage (living or non-living foreign agents, or internal/external tissue injury). Intra-abdominal adipose tissue, particularly in abdominal obesity, is an important determinant of inflammation. Inflammatory processes are associated with factors such as glucotoxicity, lipotoxicity, and oxidative stress (increased levels of free radicals in the body). These factors, resulting from unhealthy nutrition, a sedentary lifestyle, excessive alcohol use, and tobacco use, increase the release of pro-inflammatory factors in tissues, causing insulin resistance, cellular dysfunction, and therefore an increased risk of developing Type 2 diabetes.
• Cellular stress resulting from insulin resistance: In insulin resistance, the pancreas can produce insulin but cannot use it. In this situation, glucose and insulin cannot be used despite their very high levels in the blood.

Eliminating these factors involved in the development mechanism mentioned above can reduce the risk of Type 2 diabetes. Let us evaluate the effects of the Mediterranean diet, the dietary pattern whose effects on the development mechanism of Type 2 diabetes have been studied most extensively, on these mechanisms.

Mechanisms related to anti-inflammatory / antioxidant effects

Adipose (fat) tissue releases IL-1, IL-6, CRP and TNF-a as inflammatory markers, thereby causing inflammation by stimulating oxidative stress. Inflammation plays an active role in the progression of insulin resistance and development of Type 2 diabetes. Habits such as obesity, unhealthy nutrition, excessive alcohol use, tobacco use, and a sedentary lifestyle therefore increase inflammation and consequently Type 2 diabetes risk. Healthy nutrition, an active life, and good lifestyle habits reduce oxidative stress by suppressing mediators that cause inflammation, known as pro-inflammatory mediators.

One reason the Mediterranean dietary pattern has beneficial effects on Type 2 diabetes is its naturally high and balanced antioxidant content. Its antioxidant effects come from phenolic compounds (particularly flavonoids) in foods. Phenolic compounds found in foods such as olive oil, fresh vegetables, fruit, and pulses can reduce oxidative stress by suppressing pro-inflammatory mediators. For example, extra virgin olive oil contains oleuropein, hydroxytyrosol and tyrosol, phenolic compounds that can have antioxidant and anti-inflammatory effects. In addition to phenolic compounds, foods such as extra virgin olive oil, fish, walnuts, avocados, and almonds contain Polyunsaturated Fatty Acids and Monosaturated Fatty Acids (particularly oleic acid), which support anti-inflammatory effects. Found in oily fish, omega-3 helps lower high triglyceride levels, which are dangerous for Type 2 diabetes, and contributes to suppressing inflammatory activity. In contrast, foods such as fatty red meat, butter, and packaged foods contain saturated fats, which promote pro-inflammatory processes. Examining the Mediterranean dietary pattern shows that foods rich in saturated fat are restricted. Consequently, because unsaturated fatty acids are consumed at a much higher proportion than saturated fatty acids, oxidative stress is suppressed and beta-cell function improves. 

Whole grains, vegetables, fruit, and pulses provide high fiber intake, which plays an effective role in reducing serum levels of IL-6, TNF-a, CRP and similar inflammatory markers.

 Mechanisms related to glucagon-like peptide compounds

Glucagon-like peptide (GLP-1) is an incretin hormone that supports insulin production and secretion. It also inhibits the release of the blood-sugar-raising hormone secreted by the pancreatic islets of Langerhans, glucagon, and delays gastric emptying. These properties make GLP-1 highly important in Type 2 diabetes management. GLP-1 strengthens antioxidant defense mechanisms in endothelial tissue (the tissue forming the inner surface of blood and lymph vessels) and contributes to suppressing oxidative stress. As a result, it helps endothelial tissue perform its function. It also reduces appetite by influencing satiety at the central nervous system level. Thus, by controlling daily calorie intake, it helps prevent adipose tissue accumulation. Hyperglycemia is thought to increase GLP-1 resistance by increasing oxidative stress. Resistance of beta cells to GLP-1 can lead to progressive impairments in beta-cell production. Foods in the Mediterranean dietary pattern increase G-protein-coupled receptors such as GPR120, increasing GLP-1 release from L-cells. Increased GLP-1 release results in more insulin secretion from beta cells and helps prevent post-meal hyperglycemia.

Mechanisms related to branched-chain amino acid management

Branched-chain amino acids (DZAA) play an active role in energy homeostasis, nutritional metabolism, gut health, the immune system, and disease. Increased circulating DZAA may be seen in insulin resistance. This occurs because reduced / impaired DZAA breakdown increases serum DZAA levels. Therefore, increased DZAA (valine, leucine, isoleucine) is associated with the development of Type 2 diabetes. Increased BCAA levels can promote insulin resistance through activation of mTOR complex 1 (mTORC1). In addition, DZAA stimulates activation of the transcription factor NF-κB, triggering the release of pro-inflammatory cytokines (IL-6, TNF-α, intracellular adhesion molecule-1, CD40L). Consequently, pro-inflammatory cytokines contribute to the development of insulin resistance. Foods such as extra virgin olive oil in the Mediterranean dietary pattern help lower plasma DZAA levels, contributing to preventing the development of insulin resistance.

Mechanisms based on changes in gut microbiota

Gut microbiota, although composed primarily of bacteria, also contains organisms such as fungi, viruses, archaea, and protists. There are 4 main bacterial families living in the gut (Firmicutes, Bacteroidetes, Actinobacteria, and Proteobateria), each with many different species. When these bacteria exist in balance in the gut, they perform important functions in human physiology and metabolism. In healthy people, beneficial and opportunistic bacteria are balanced. When beneficial bacteria are in the minority, the risk of disease increases. Disruption of the microbiota's balance so that it begins harming the body is called 'dysbiosis'. Dysbiosis plays a role in the development of many diseases, including Type 2 diabetes. For example, Type 2 diabetes is associated with a decrease in Firmucites and other butyrate producing bacteria, and an increase in opportunistic and sulfate-producing bacteria. As in many areas of life, balance in the gut microbiota is very important for protecting gut and general health.

Dysbiosis increases intestinal permeability and Toll-like receptor (TLR) activation through bacterial components and pathogen-associated molecular patterns (PAMP), such as flagellin, lipoteichoic acid, peptidoglycan, and lipopolysaccharide (LPS). This causes the formation of inflammatory cytokines. For example, people with diabetes have higher LPS levels than people without diabetes. Foods and dietary patterns play an active role in microbiota composition and function. Complex interactions between foods and microorganisms can have beneficial or harmful effects on health. Many studies argue that the Mediterranean diet benefits gut microbiota. The Mediterranean diet is rich in fiber and complex carbohydrates. Fermentation of dietary fiber produces Short-Chain Fatty Acids (KZYA). KZYA contributes to regulating glucose and lipid metabolism by activating KZYA receptors in the liver, adipose tissue, brain, and pancreas. In addition, by stimulating GLP-1 and GLP-2 secretion, KZYA may increase insulin sensitivity, pancreatic β-cell proliferation, and satiety. For example, lower KZYA levels (particularly butyrate) have been observed in people with diabetes compared with healthy people. Therefore, following a Mediterranean dietary pattern and increasing KZYA levels will both contribute to preventing diabetes and help people with diabetes control their blood sugar.

In 2020, “JAMA” published a study investigating the extent to which the risk factors involved in Type 2 diabetes development, mentioned in our article, contribute to the development of this disease.  The study investigating the role of the Mediterranean dietary pattern in Type 2 diabetes and its related development mechanisms involved a mean age of 59 among 25,317 participants. Participants were observed for an average of 19.8 years. Adherence to the Mediterranean diet was determined using the “Mediterranean Diet Scale”. Mediterranean Diet adherence scores were 0-3, 4-5 and 6-9, divided into 3 categories. During the study, of 25,317 participants, only 9% developed Type 2 diabetes. Diabetes risk also varied even among those adhering to the Mediterranean diet. The study found that participants with higher adherence to the Mediterranean diet had a risk of developing Type 2 Diabetes 30% lower than those with lower adherence. In other words, the results indicate that the risk of developing Type 2 diabetes decreases as adherence to the Mediterranean dietary pattern improves. In addition, the results showed that the reduction in insulin resistance was the risk factor playing the most effective role in reducing Type 2 diabetes risk. Insulin resistance was followed by these risk factors, respectively:

• Reduction in Body Mass Index: BMI is calculated by dividing weight (kg) by the square of height (m2). It is used to classify people as underweight, normal weight, overweight, or obese.
• Increase in HDL: HDL (high-density lipoprotein), also known as good cholesterol, transports cholesterol from tissues and vessels to the liver. By contributing to preventing cholesterol plaque buildup in vessels, it helps reduce the risk of many diseases.
• Reduction in LDL: LDL (low-density lipoprotein), also known as bad cholesterol, transports cholesterol to tissues and vessels, in contrast to HDL. High LDL levels cause cholesterol plaques to accumulate in vessels, contributing to an increased risk of many diseases.
• Reduction in VLDL: VLDL (very-low-density lipoprotein), another type of bad cholesterol, also accumulates in vessels like LDL. It differs from LDL in containing more triglyceride than cholesterol; triglyceride is another type of fat with the property of accumulating in vessels.
• Reduction in inflammation: It is the body's physiological response to every type of damage (living or non-living foreign agents, or internal/external tissue injury).
• Increase in Branched-Chain Amino Acids: The essential amino acids DZAA are known as valine, leucine, and isoleucine. Because the body cannot produce DZAA, they must be obtained from food. They contribute to increasing glucose uptake and reducing insulin resistance.
• Reduction in Blood Pressure: Blood pressure is the pressure of blood inside the arteries of the circulatory system. High blood pressure can pave the way for many diseases.
• Reduction in HbA1c: HbA1c is the test most commonly used to diagnose diabetes. HbA1c reflects the average glucose value over the previous 2-3 months.

Overall, the study results show that following a Mediterranean diet can help eliminate risk factors involved in type 2 diabetes and many other diseases, such as cardiovascular disease and cancer, thereby contributing to reducing disease risk.

Conclusion

Many scientific studies argue that the Mediterranean diet helps reduce Type 2 diabetes risk and supports treatment. We therefore recommend following a Mediterranean dietary pattern both to improve general health and to protect against Type 2 diabetes. Following the Mediterranean dietary pattern can reduce the risk not only of type 2 diabetes but also of many diseases such as cancer, intestinal diseases, cardiovascular disease, and Alzheimer's.