Abstract

1. Introduction

Type 2 diabetes is a global epidemic, with approximately 422 million cases worldwide and a rapidly rising prevalence in middle- and low-income countries.^[1] In the United States in 2011–2012, 12%–14% of adults had type 2 diabetes and 38% had prediabetes.^[2] Prediabetes is even more common among those aged ≥ 65 in the United States, with a prevalence of 50%.^[3]Diabetes accounts for $176 billion of direct medical costs in the US, including annual per capita costs of $7900, a number 2.3 times higher than costs for adults without diabetes.^[4] In 2015, type 2 diabetes was the 7^thleading cause of death in the United States.^[5] Diabetes in older patients is associated with an increased risk of mortality, reduced functional status, and increased risk of institutionalization.^[6] Older patients also have the highest rates of macro- and micro-vascular complications from diabetes, including myocardial infarction, major lower extremity amputations, end stage renal disease, and visual impairment.^[3] Moreover, geriatric patients are at increased risk of medication-related complications, particularly hypoglycemia; the elderly have twice the number of emergency room visits for hypoglycemia than the general population with diabetes.^[6]

Dietary choices are a key driver of insulin resistance, especially in an aging, more sedentary population. Increases in consumption of calorie-dense foods, including fast foods, meats and other animal fats, highly refined grains, and sugar-sweetened beverages, are thought to play a critical role in the rising rates of type 2 diabetes worldwide.^[7] Lifestyle changes, particularly diet, can be highly effective in preventing, treating, and even reversing type 2 diabetes.^[8]–[11] Among the 20% of participants in the landmark Diabetes Prevention Program who were ages 60 and over, lifestyle changes conferred a 71% reduction in risk of type 2 diabetes, demonstrating that older adults reaped the greatest benefit from lifestyle interventions compared to other age groups.^[8]Lifestyle changes address the root causes of type 2 diabetes and can ameliorate comorbidities while reducing the risk of polypharmacy, particularly in the elderly. Plant-based diets―i.e., eating patterns that emphasize legumes, whole grains, vegetables, fruits, nuts, and seeds and discourage most or all animal products―are especially potent in preventing type 2 diabetes and have been associated with much lower rates of obesity, hypertension, hyperlipidemia, cardiovascular mortality, and cancer.^[12] We will review the evidence supporting the use of plant-based diets for the prevention and treatment of type 2 diabetes and its complications, and explore mechanisms by which plant-based diets reduce insulin resistance.

2. Plant-based diets for the prevention of type 2 diabetes

Observational studies strongly support the role of plant-based diets, and components of plant-based diets, in reducing the risk of type 2 diabetes.

3. Plant-based diets for the treatment of type 2 diabetes

As far back as the 1950s, studies have been published on treating hyperglycemia with a high-carbohydrate, low-fat diet,^[50]–[52] documenting the effectiveness of employing a predominantly vegetarian diet to treat diabetes. Barnard et al.,^[53] performed the first major randomized clinical trial on diabetic patients treated purely with a plant-based (vegan) diet, comparing it to a conventional diet based on the 2003 American Diabetes Association (ADA) guidelines. A total of 99 individuals, ages 27–82 years, were randomized to counseling on a low-fat vegan diet or the ADA diet and followed for 22 weeks. The recommended vegan diet comprised approximately 10% of energy from fat, 15% from protein, and 75% from carbohydrates and consisted of vegetables, fruits, grains, and legumes. Participants in the vegan group were asked to avoid animal products and added fats and to favor low-glycemic index foods, such as beans and green vegetables. By the end of the trial, 43% (21 of 49) of the vegan group and 26% (13 of 50) of the ADA group participants reduced their diabetes medications. Excluding those who changed medications, hemoglobin A1c fell 1.23 points in the vegan group compared with 0.38 points in the ADA group (P = 0.01). Body weight decreased 6.5 kg in the vegan group and 3.1 kg in the ADA group (P < 0.001). Among those who did not change lipid-lowering medications, LDL cholesterol fell 21.2% in the vegan group and 10.7% in the ADA group (P = 0.02). After adjustment for baseline values, even the reduction in urinary albumin was significantly greater in the vegan group (15.9 mg/24 h) than in the ADA group (10.9 mg/24 h).

When these individuals were followed for a total of 74 weeks, a sustained and equivalent weight loss was noted in both groups, but there was a significant absolute reduction in hemoglobin A1c of −0.40 points in the vegan group versus +0.01 in the ADA group (using the last available hemoglobin A1c value prior to any medication changes).^[54] In addition, there was a significant reduction in total cholesterol (−20.4 mg/dL vs. −6.8 mg/dL) and LDL cholesterol (−13.5 mg/dL vs. −3.4 mg/dL) in the vegan versus ADA diet, respectively. Dietary modification is an integral part of the lifestyle recommendations for persons with diabetes; it is worth noting that while the vegan diet required greater changes in macronutrient intake than the ADA-guided diet, there was no difference in acceptability or adherence to the diets,^[55] a finding that has also been demonstrated in other trials.^[56],[57] While this may be surprising given the potential degree of change required to adopt a vegan diet, the authors hypothesized that not limiting portion sizes, not counting calories or carbohydrates, and experiencing of a variety of new flavors in the vegan diet likely offset any hardship imposed by restricting animal products or added oils.^[55]

High-carbohydrate, low-fat, predominantly vegetarian diets are often associated with weight loss, making it difficult to ascertain what proportion of the improvement in glycemic control is due to weight loss versus dietary changes. To evaluate this question, Anderson et al.,^[52] performed a study on a metabolic ward enrolling lean men with type 2 diabetes who were taking insulin, and placing them on high-carbohydrate, high-fiber (HCF) diet (< 10% calories from fat, 70% from carbohydrates, and 65 g of fiber/day). Body weights were kept stable by simply having participants eat more if they lost weight on the HCF diet. Half of the participants were able to discontinue insulin, and the remainder were able to significantly reduce their insulin; overall, the average insulin dose decreased from 26 units on the baseline (control) diet to 11 units on the HCF diet. Fasting and 3 h postprandial plasma glucose values were lower in most patients on the HCF diets than on the control diets despite lower insulin doses. These results argue for the efficacy of low-fat, plant-based diets (which are naturally high in carbohydrates and fiber) in reversing the insulin resistance that is at the root of type 2 diabetes—though it remains unclear what component of a plant-based diet is most effective: the high carbohydrate and fiber content, the low fat and low-animal protein content, or both.

A 2014 review and meta-analysis of controlled clinical trials of vegetarian diets in the treatment of type 2 diabetes found a significant reduction in hemoglobin A1c of −0.39 points compared to control diets.^[58] This effect is approximately half of that seen with the addition of the first-line oral hypoglycemic agent, metformin, which in a recent meta-analysis was reported to reduce hemoglobin A1c by 0.9 points.^[59] A more recent randomized controlled trial conducted in Korea compared a brown-rice-based vegan diet with a conventional diabetic diet in patients ages 30–70 years with type 2 diabetes.^[60] Participants assigned to the vegan diet were asked to eat brown rice, favor low-glycemic index foods (e.g., legumes, legumes-based foods, green vegetables, and seaweed), and avoid polished/white rice, processed food made of rice flour or wheat flour, and all animal food products. Portions, calories, and frequency of meals were not restricted. Hemoglobin A1c levels decreased by 0.5 points in the vegan group compared with 0.2 points in the conventional group, a significant difference that was even more pronounced when the analysis was restricted to participants who were highly adherent to their respective diets (−0.9 vs. −0.3). The inclusion of individuals older than age of 60 in this trial, and in the majority of vegetarian trials mentioned in the meta-analysis above, supports recommending plant-based diets to all age groups with type 2 diabetes, including older adults.

4. Reduction of diabetes-related complications

The benefits of tight glycemic control with pharmacotherapy have been called into question, based on a lack of evidence for it preventing major clinical endpoints, including all-cause mortality, cardiovascular mortality, dialysis, renal death, blindness, and neuropathy.^[61] In contrast, plant-based diets have demonstrated improvements in glycemic control while also reducing macro- and micro-vascular risks of type 2 diabetes.

5. Current guidelines and macronutrients

In their 2017 “Standards of Medical Care in Diabetes,” the ADA states that a variety of eating patterns are acceptable for the management of type 2 diabetes and pre-diabetes, including Mediterranean, DASH, and plant-based diets.^[91] These guidelines recommend carbohydrate intake from legumes, whole grains, fruits, vegetables, and dairy products, with an emphasis on nutrient-dense, high-fiber, low-glycemic load foods. They also include a recommendation that people with diabetes follow the guidelines for the general population for intakes of saturated fat, dietary cholesterol, and trans fat. Plant-based diets are consistent with these guidelines. The Academy of Nutrition and Dietetics states that vegetarian and vegan diets are appropriate for all stages of life, from infancy to adulthood, and may provide benefits for the prevention and treatment of diabetes, obesity and ischemic heart disease.^[92]

There has been a wealth of research on macronutrient ratios and subtypes in relation to insulin resistance. Current ADA guidelines state that the optimal mix of macronutrients in type 2 diabetes has not been established.^[91] In general, sources of foods (e.g., animal vs. plant, refined versus unrefined) are equally important as, if not more important than, specific ratios of carbohydrate, protein, and fats when it comes to glycemic control and the prevention of type 2 diabetes. Moreover, in the most practical terms, people eat foods and combinations of foods, not individual macronutrients or macronutrient ratios. However, it is worth highlighting research on macronutrients and food sources that supports the use of plant-based foods in treating insulin resistance, improving overall health, and reducing mortality.

6. Mechanisms of plant-based diets in treating insulin resistance

Diets based in whole and minimally processed plant foods reduce insulin resistance and improve glycemic control by a variety of proposed mechanisms. Plant-based diets are high in fiber, antioxidants, and magnesium, all of which have been shown to promote insulin sensitivity.^[7],[17] Antioxidants such as polyphenols may inhibit glucose absorption, stimulate insulin secretion, reduce hepatic glucose output, and enhance glucose uptake.^[111] Fiber, which is found only in plant foods, modulates postprandial glucose response, and is fermented by intestinal bacteria to produce short-chain fatty acids, which also improve the glucose response, insulin signaling, and insulin sensitivity.^{[112]–[115]} Furthermore, fiber reduces the energy density of foods, promotes satiety, and has been associated with weight loss, which in turn reduces insulin resistance.^[113] Dietary fiber has been linked to decreased markers of inflammation, which may also ameliorate insulin resistance.^[17] Finally, a diet high in plant-based foods and low in meat is likely to exert beneficial metabolic effects by promoting shifts in the gut microbial profile, decreasing the production of trimethylamine N-oxide, a compound that has been tied to insulin resistance.^{[17],[39],[115]}

Plant-based diets also tend to be low in saturated fat, advanced glycation endproducts, nitrosamines, and heme iron dietary elements that have been associated with insulin resistance in epidemiologic and metabolic studies. Saturated fat, which is found primarily in animal-based foods, contributes to lipotoxicity, a phenomenon in which toxic fat metabolites (e.g., species of diacylglycerol and ceramide) accumulate in hepatic and skeletal muscle cells, impairing insulin signaling and thus decreasing glucose uptake.^{[116]–[119]}Saturated fat has been associated with oxidative stress, mitochondrial dysfunction, and insulin resistance in numerous metabolic and epidemiologic studies as well.^{[42]–[44],[98],[100],[120]} In addition, diets high in saturated fat are associated with a predominantly gram-negative, lipopolysaccharide-rich gut microbial pattern, which also leads to insulin resistance and inflammation.^[118] A plant-based diet has been shown to reduce visceral fat and improve markers of oxidative stress more than a conventional diet in individuals with type 2 diabetes.^[121]

Advanced glycation endproducts are oxidant compounds that are high in meat (especially when grilled, broiled, roasted, seared, or fried), and low in plant-based foods such as fruits, vegetables, legumes, and whole grains.^[122]Advanced glycation endproducts have been implicated in the pathogenesis of type 2 diabetes,^[39] and a diet low in these compounds has been shown to improve insulin resistance in people with type 2 diabetes.^[123] Nitrosamines, which are created when nitrite and nitrate preservatives in processed meat bind to amino compounds in those foods, have been shown to accelerate DNA damage and generation of reactive oxygen species and pro-inflammatory cytokines, leading to oxidative stress and insulin resistance.^[39]Iron from heme (animal) sources is a pro-oxidant molecule that promotes insulin resistance through various likely mechanisms: increased oxidative stress leading to impaired insulin signaling, direct pancreatic beta cell toxicity, decreased translocation of glucose transporter type 4 channels to the cell membrane, and increased hepatic glucose output.^[39] Several meta-analyses have demonstrated a strong link between serum ferritin or dietary heme iron and the risk of type 2 diabetes.^{[124]–[127]}

Finally, plant-based diets tend to promote weight loss and lower adiposity,^{[13],[128]–[131]} factors that are highly protective against insulin resistance. In contrast, meat consumption (including poultry) is highly predictive of obesity and weight gain over time.^{[15],[132]–[137]} Thus, meat increases type 2 diabetes risk not only by promoting weight gain, but also by mechanisms independent of body mass index, as aforementioned. Furthermore, when a hypocaloric high-protein diet is used for weight loss, the high protein content itself may negate key metabolic benefits of weight loss. Smith et al.,^[138] found that in obese postmenopausal women, a low-calorie, high-protein diet prevented the therapeutic effect of weight loss on skeletal muscle insulin sensitivity—likely due to worsening oxidative stress, as well as alterations in muscle cell structure and organization, induced by the high-protein diet.

Refined grains and added sugars have also been implicated in weight gain and insulin resistance.^{[29],[139],[140]} A whole-foods, plant-based dietary approach excludes animal products, refined grains, and added sugars, thus encouraging insulin sensitivity through loss of excess weight and maintenance of a healthier body weight. However, as noted previously, metabolic and epidemiologic studies confirm that plant-based diets improve insulin resistance even when there is no weight loss, and/or with statistical adjustment for body weight.

7. Implementation in clinical practice

Several reviews have presented practical strategies for using plant-based diets in clinical scenarios, including type 2 diabetes management.^{[141]–[143]} The key elements of the eating pattern include avoidance of animal products, highly refined grains, added sugars, and oils, and consumption of an abundance of legumes, leafy greens, cruciferous vegetables, starchy vegetables, whole grains, and fruits. In key randomized clinical trials of plant-based diets, low-glycemic index foods have been encouraged.^[53],[54]

Some clinicians may assume that their patients will not be open to adopting a plant-based diet. However, a plant-based diet has been shown to be similarly acceptable to an ADA diet among people with diabetes;^[55] plant-based diets have also been found to be highly acceptable in other medical contexts.^{[144]–[146]} Common questions about specific macro- and micronutrients in plant-based diets have been addressed elsewhere.^{[141],[143],[147],[148]} Patients who adopt a plant-based diet can experience decreases in blood sugar and blood pressure relatively quickly after changing their diet, especially if they are taking medications for these conditions. Close monitoring and anticipation of hypoglycemia is critical; medications may require adjustment.^[141] Ongoing support, education, and follow-up can help patients achieve and maintain dietary changes.

8. Conclusions

There is a general consensus that the elements of a whole-foods plant-based diet—legumes, whole grains, fruits, vegetables, and nuts, with limited or no intake of refined foods and animal products—are highly beneficial for preventing and treating type 2 diabetes. Equally important, plant-based diets address the bigger picture for patients with diabetes by simultaneously treating cardiovascular disease, the leading cause of death in the United States, and its risk factors such as obesity, hypertension, hyper-lipidemia, and inflammation. The advantages of a plant-based diet also extend to reduction in risk of cancer, the second leading cause of death in the United States; the World Cancer Research Fund and the American Institute for Cancer Research recommend eating mostly foods of plant origin, avoiding all processed meats and sugary drinks, and limiting intake of red meats, energy dense foods, salt, and alcohol for cancer prevention.^[149] Large healthcare organizations such as Kaiser Permanente are promoting plant-based diets for all of their patients because it is a cost effective, low-risk intervention that treats numerous chronic illnesses simultaneously and is seen as an important tool to address the rising cost of health care.^[147] Plant-based eating patterns also carry significant environmental benefits. The World Health Organization and the United Nations have promoted diets higher in plant foods as not only effective for preventing chronic diseases and obesity, but also more environmentally sustainable than diets rich in animal products,^[150] a position also supported in the scientific report of the 2015 United States Dietary Guidelines Advisory Committee.^[151] While larger interventional studies on plant-based diets carried out for longer periods of time would add even more weight to the already mounting evidence, the case for using a plant-based diet to reduce the burden of diabetes and improve overall health has never been stronger.

Footnotes

References