Mediterranean Diet Delays Need for Glucose Lowering Medications

The recent PREDIMED trial randomized over 7,000 participants between three diet plans: two variations of Mediterranean diet and a low-fat control diet.

According to a recent study, a Mediterranean eating plan can delay the need of patients for glucose lowering medications. This was revealed on June 14th, published ahead of print in ADA Diabetes Care, in a subgroup analysis of the PREDIMED Trial (Primary Prevention of Cardiovascular Disease with a Mediterranean Diet).

The traditional Mediterranean diet consists of a high intake of olive oil, fruits, vegetables, nuts, and cereals; a moderate amount of fish and poultry, and a low intake of red meat, whole-fat dairy, and sweets. The known benefits of the traditional Mediterranean diet include: lipid-lowering effects; protection against oxidative stress, inflammation, and platelet aggregation; amino acid restricted nutrient sensing pathways that decrease the risk of cancer and increase lifespan; modified hormones and growth factors that decrease the risk of cancer; and alteration of the gut microbiota that may decrease the risk for obesity and type 2 diabetes.

The PREDIMED trial remains the largest dietary intervention trial to analyze the effects of the Mediterranean diet on cardiovascular disease prevention. This trial randomized over 7,000 participants between three diet plans: Mediterranean diet supplemented with extra virgin olive oil (EVOO), Mediterranean diet supplemented with mixed nuts, and a low-fat control diet. After a median follow up of 4.8 years, the primary endpoint (stroke, myocardial infarction or death from cardiovascular cause) occurred in 288 participants. Results indicated that both Mediterranean diets resulted in a significantly lower rate of cardiovascular disease.

Currently, people with diabetes or pre-diabetes are encouraged to practice caloric restriction to promote weight loss, but there is a need for studies that can display whether any certain eating plan without energy restriction can slow progression of diabetes. The purpose of this subgroup analysis is to examine the effects of both Mediterranean eating plans (with EVOO or mixed nuts) on a patient with diabetes’ need for glucose-lowering medications. In multivariable time-to-event survival models, two outcomes were assessed: introduction of the first glucose-lowering medication (oral or injectable) and the initiation of insulin.

From the PREDIMED trial, patients with diabetes at baseline that were not using insulin were assessed for the outcome of insulin initiation (1158 in Mediterranean + EVOO, 1017 in Mediterranean + mixed nuts, and 1055 in the control group) and patients with diabetes at baseline not yet receiving glucose-lowering medication were included in the glucose-lowering medication initiation analyses (447 in Mediterranean + EVOO, 394 in Mediterranean + mixed nuts, and 369 in the control group). Participants received individual and group training sessions from dietitians at baseline and quarterly. At each session, a validated 14-item dietary questionnaire was used to determine adherence to the diet plan. Participants received extra virgin olive oil (1 L/week, instructed to take at least 4 tablespoons/day), mixed nuts (30 g/day, including walnuts, hazelnuts, and almonds), or a small nonfood gift for the control group.

After a 3.2-year median follow-up, 686 participants with diabetes and only lifestyle management for treatment at baseline started glucose-lowering medications (576 participants started an oral agent, 37 participants started long-term insulin, and 73 participants started both an oral agent and insulin at the same time). The hazard ratios for starting a glucose-lowering medication compared to control were 0.83 for Mediterranean + EVOO and 0.92 for Mediterranean + nuts. The multivariable adjusted hazard ratios of starting glucose-lowering medications were 0.78 and 0.89 for Mediterranean + EVOO and Mediterranean + nuts, respectively. The hazard ratios for starting insulin therapy were 0.90 for Mediterranean + EVOO and 0.91 for Mediterranean + nuts, compared with the control. The multivariable-adjusted hazard ratios of starting insulin therapy were 0.87 and 0.89 for Mediterranean + EVOO and Mediterranean + nuts, respectively.

The Mediterranean + EVOO eating plan resulted in a decrease in requirement of initiation of glucose-lowering medications in people with diabetes and no history of cardiovascular disease. Neither eating plan made a significant difference in need for insulin therapy in people with diabetes, compared to control. The Mediterranen + EVOO diet can therefore be considered as an eating plan, without caloric restriction, that can help people with diabetes attain increased glycemic control.

These results may not be generalized to all patients with diabetes since the recruited population was all white adults, age 55-80 years old, without cardiovascular disease. Further studies may be beneficial to clinicians and patients with diabetes to further strengthen the correlation between the Mediterranean diet or alterations of the Mediterranean diet and improved outcomes for patients with diabetes.

Practice Pearls:

• The Mediterranean diet consists of a high intake of olive oil, fruits, vegetables, nuts, and cereals; a moderate amount of fish and poultry, and a low intake of red meat, whole-fat dairy, and sweets.
• The Mediterranean diet is beneficial for cardiovascular health and may also reduce the need for initiation of glucose-lowering medications in patients with diabetes.
• This study was exploratory and further studies need to be conducted to strengthen the relationship between the Mediterranean diet and benefits for patients with diabetes.

References:

Basterra-Gortari, F. Javier, et al, “Effects of a Mediterranean Eating Plan on the Need for Glucose-Lowering Medications in Participants With Type 2 Diabetes: A Subgroup Analysis of the PREDIMED Trial.” Diabetes Care, 2019, p. dc182475., doi:10.2337/dc18-2475.

Tosti, Valeria, et al, “Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms.” The Journals of Gerontology: Series A, vol. 73, no. 3, 2017, pp. 318–326., doi:10.1093/gerona/glx227.

Amber Satz, PharmD Candidate, LECOM School of Pharmacy