LATEST DIETARY APPROACHES TO DIABETES

Background

Diabetes represents one of the most important unmet prevention and treatment challenges. Despite an armamentarium of medications, diabetes and its complications have reached epidemic proportions and are rapidly increasing. The prevalence of diabetes is now more than 10% in the U.S. and Canada^1,2 and diabetes remains the leading cause of blindness, end-stage kidney disease, non-traumatic lower limb amputation, and a leading cause of premature cardiovascular disease (CVD) and death.^1-3 The economic impact has been described as an “economic tsunami”⁴ which threatens to bankrupt healthcare systems and damage economies; a problem compounded by the current COVID-19 pandemic where hospital and ICU admissions and mortality are among the highest in people with diabetes and its associated co-morbidities.^5,6

Diet and lifestyle are universally considered the cornerstones of therapy for the prevention and treatment of diabetes.^7,8 Clinical practice guidelines for nutrition therapy have undergone a major modernization over the last decade -- moving away from a focus on single nutrients (e.g., “low fat,” “low carb,” or “high protein”) to a focus on food and dietary patterns.⁹ Historically, guidelines were very macronutrient-centric, recommending a narrow acceptable macronutrient distribution range (e.g., 55% calories from carbohydrate and 30% calories from fat), but have become progressively broader and more inclusive (e.g., 45-65% calories from carbohydrate, <35% calories from fat, and 15-20% calories from protein) as more emphasis is placed on quality over quantity of the carbohydrate, fat, and protein in the diet.⁹ With the recognition that a focus on single nutrients misses important nutrient-nutrient and nutrient-food interactions that better explain chronic disease risk than single nutrients alone,⁹ there has been a shift to more dietary pattern-based recommendations.

The best available evidence from randomized trials and prospective cohort studies has been reviewed by expert committees of major clinical practice guidelines in the U.S. and Canada^7,8 and translated into recommendations for several dietary patterns, all of which contain soy. A selection of these dietary patterns is included below.

Low GI/GL High-Carbohydrate Dietary Pattern

The glycemic index (GI) provides an assessment of the quality of carbohydrate-containing foods based on their ability to raise postprandial blood glucose levels. Low-GI carbohydrate-rich foods (including low-GI soyfoods such as soymilk, tofu, tempeh, and edamame) are exchanged for high-GI foods to create a low-GI dietary pattern. Systematic reviews and meta-analyses have shown that low-GI/glycemic load (GL) dietary patterns lead to improvements in hemoglobin A1c (HbA1c) (the main target of glycemic control for diabetes) of approximately -0.5% (a reduction that meets the threshold set by the Food and Drug Administration (FDA) for new drug development¹⁰ and is at the lower limit of efficacy of the available anti-hyperglycemic agents¹¹) as well as improvements in body weight, blood lipids (including the established lipid target low-density lipoprotein cholesterol [LDL-C]), and blood pressure in randomized controlled trials.^12-19 Systematic reviews and meta-analyses of prospective cohort studies have shown that these advantages for intermediate risk factors appear to translate to associated reductions in incident diabetes and CVD.^12,20-27 Evidence of a causal relationship with clinical cardiometabolic disease outcomes is supported by an important biological analogy with the oral prandial agent acarbose, an alpha-glucosidase inhibitor which effectively converts the diet to a low-GI/GL dietary pattern and has been shown to decrease incident diabetes, hypertension, and, in some cases, CVD in individuals with diabetes and prediabetes.^28-31

Low-Carbohydrate Dietary Pattern

Low-carbohydrate dietary patterns represent a heterogeneous group of approaches (e.g., Ketogenic diet, Atkins diet, Zone diet, etc.) which have in common low carbohydrate content (variably defined as carbohydrate <40% calories³² to <26% calories³³ for low carbohydrate diets and <10% calories for very low carbohydrate diets that induce ketosis).³³ Network meta-analyses of randomized trials of diets of varying macronutrient distributions have shown weight loss and improvements in blood pressure and glycemic control with low-carbohydrate diets, but have failed to show their superiority over moderate or high-carbohydrate diets.^34,35 Systematic reviews and meta-analyses of randomized trials conducted specifically in people with diabetes have also shown that improvements in glycemic control are seen at 6 months but not at 12 months.³² Additionally, improvements seen in triglycerides and high-density lipoprotein cholesterol (HDL-C) come at the expense of increases in the more atherogenic aspects of the lipid profile, and established lipid targets for cardiovascular risk reduction, LDL-C, non-HDL-C, and apolipoprotein B (apoB).³² The quality of the protein and fat substituted for the carbohydrate in low carbohydrate diets, however, is an important consideration based on the Eco-Atkins randomized trial which showed that a plant-based, low-carbohydrate diet comprised of unsaturated fat from nuts, canola oil, and plant protein (mainly soy) reduced LDL-C compared to a high carbohydrate diet.^36,37

Mediterranean Dietary Pattern

The Mediterranean dietary pattern refers to a plant-based diet emphasizing high consumption of fruits, vegetables, legumes (soy), nuts, seeds, cereals, and whole grains; moderate to high consumption of olive oil (as the principal source of fat); low to moderate consumption of dairy products, fish, and poultry; low consumption of red meat, and low to moderate consumption of wine, mainly during meals.³⁸ The Prevencion con Dieta Mediterranea (PREDIMED) trial, a large Spanish multicenter randomized cardiovascular outcome trial, showed that a Mediterranean dietary pattern, supplemented with either extra virgin olive oil or mixed nuts, reduced major cardiovascular events by ~30%, diabetes incidence by 53% (single-center finding), and increased reversion of metabolic syndrome by ~30%.^39-42 Systematic reviews and meta-analyses have confirmed the cardiovascular benefits in the available randomized controlled trials and prospective cohort studies.⁴³ Systematic reviews and meta-analyses of randomized controlled trials, the PREDIMED trial, and other individual well-powered longer term randomized controlled trials of intermediate cardiometabolic risk factors have also shown improvements in HbA1c, fasting plasma glucose, body weight, and triglycerides that support the reductions in cardiometabolic events.^44-50

Dietary Approaches to Stop Hypertension (DASH) Dietary Pattern

The DASH dietary pattern was originally developed through research sponsored by the U.S. National Heart, Lung, and Blood Institute (NHLBI) to treat hypertension without medication.^51,52 It emphasizes fruits, vegetables, fat-free/low-fat dairy, whole grains, nuts and legumes, and limits processed meats, sweets, and sugar-sweetened beverages with the aim of increasing potassium, calcium, magnesium, dietary fiber, and protein, and decreasing saturated fat and cholesterol.^51,52 An umbrella review of systematic reviews and meta-analyses showed that the DASH dietary pattern led to clinically meaningful reductions in systolic (~5mmHg) and diastolic (~2.5mmHg) blood pressure as well as reductions in HbA1c, LDL-C, total cholesterol, fasting blood insulin, and body weight in randomized controlled trials. This same umbrella review showed that these effects on intermediate risk factors appeared to translate to associated reductions in incident diabetes, CVD, coronary heart disease (CHD), and stroke in prospective cohort studies.⁵³

Vegetarian Dietary Pattern

Vegetarian dietary patterns represent a family of diets that exclude some or all animal foods and range from lacto-ovo vegetarian to vegan. Systematic reviews and meta-analyses have shown that “healthy” vegetarian dietary patterns reduce HbA1c, body weight, body mass index (BMI), waist circumference, and the established lipid targets (LDL-C and non-HDL-C) in randomized controlled trials⁵⁴ and are associated with reductions in CHD incidence and mortality in prospective cohort studies.⁵⁵

Portfolio Dietary Pattern

The Portfolio dietary pattern (also known as the “Dietary Portfolio” or “Portfolio Diet”) is a plant-based dietary pattern that was first developed in the early 2000s as a “portfolio” of cholesterol-lowering foods, each of which has a FDA, Health Canada, and/or European Food Safety Authority (EFSA) approved health claim for the reduction of cholesterol.^56-62 The dietary pattern is built on a foundation of a low-saturated fat NCEP Step II diet (≤7% saturated fat , ≤ 200mg dietary cholesterol) with the addition of 4 cholesterol-lowering foods: 45g nuts (tree nuts or peanuts); 50g plant protein (soy or pulses); 20g viscous soluble fiber (oats, barley, psyllium, eggplant, okra, apples, oranges, or berries); and 2g plant sterols (plant sterol-enriched margarine or supplements),^63-67 plus “heart healthy” monounsaturated fats (extra virgin olive oil, cold-pressed canola/soybean oils, or avocados) in replacement of high GI carbohydrate⁶⁸ It was shown in an early head-to-head randomized trial of the Portfolio diet versus statin therapy (first line lipid-lowering therapy) that the components when taken together resulted in a ~30% reduction in LDL-C, similar to results from 20mg lovastatin.⁶⁴ A recent systematic review and meta-analysis of the available randomized trials⁶⁹ confirmed this “drug-like” effect in the intended combination with low saturated fat intake with reductions of ~29% (33% in efficacy trials to 15% in a multicenter effectiveness trial) while demonstrating further benefits to other atherogenic aspects of the lipid profile (non-HDL-C, apoB, triglycerides), inflammation (with a clinically meaningful reduction in high sensitivity C-reactive protein (CRP) of ~30%), blood pressure, and 10-year CHD risk score. Although the Portfolio dietary pattern has not been formally tested in people with diabetes, each component has been shown individually to lower LDL-C in systematic reviews and meta-analyses of randomized controlled trials inclusive of people with diabetes.^70-78 The results of the Combined Portfolio Diet and Exercise Study (PortfolioEx trial), a 3-year, multicenter randomized controlled trial of the effect of the Portfolio diet plus exercise on the progression of atherosclerosis (assessed by vascular MRI) in high cardiovascular risk individuals (ClinicalTrials.gov Identifier, NCT02481466), will provide important new data in people with diabetes, as approximately half of the participants will have type 2 diabetes.

Approach to Nutrition Therapy for Diabetes

Although the evidence may be stronger for some dietary patterns than others when considering certain indications (e.g., Mediterranean dietary pattern for cardiovascular risk reduction, the DASH dietary pattern for blood pressure reduction, the Portfolio dietary pattern for LDL-C reduction, etc.), not one dietary pattern has been identified as best for all individuals. The approach to nutrition therapy is moving away from a prescriptive one-size-fits-all set of recommendations. As adherence is the most important determinants of achieving the benefits of any dietary pattern, the overarching clinical practice recommendation across guidelines is to individualize nutrition therapy by using the available evidence of advantages and disadvantages of the different dietary patterns to select the dietary pattern that best aligns with the values, preferences, and treatment goals of the individual in order to achieve the greatest adherence over the longterm and thus achieve the intended benefits.^7,9

Conclusions

Clinical practice guidelines for nutrition therapy of diabetes have shifted from nutrient-based recommendations to food- and dietary pattern-based recommendations. The dietary patterns outlined in this article combine the advantages of different foods (including soy) and can result in clinically meaningful improvements in glycemic control, blood lipids, blood pressure, and inflammation, and are associated with reductions in diabetes and CVD. By allowing for flexibility in the proportion of macronutrients in the diet with a focus on quality over quantity and dietary patterns over single nutrients, these dietary patterns provide an opportunity to individualize therapy based on the values, preferences, and treatment goals of the individual to prevent new cases of diabetes and improve care for those living with diabetes.

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