Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases

Abstract

Insulin resistance (IR), defined as an attenuated biological response to circulating insulin, is a fundamental defect in obesity and type 2 diabetes (T2D), and is also linked to a wide spectrum of pathological conditions, such as non-alcoholic fatty liver disease (NAFLD), cognitive impairment, endothelial dysfunction, chronic kidney disease (CKD), polycystic ovary syndrome (PCOS), and some endocrine tumors, including breast cancer. In obesity, the unbalanced production of pro- and anti-inflammatory adipocytokines can lead to the development of IR and its related metabolic complications, which are potentially reversible through weight-loss programs. The Mediterranean diet (MedDiet), characterized by high consumption of extra-virgin olive oil (EVOO), nuts, red wine, vegetables and other polyphenol-rich elements, has proved to be associated with greater improvement of IR in obese individuals, when compared to other nutritional interventions. Also, recent studies in either experimental animal models or in humans, have shown encouraging results for insulin-sensitizing nutritional supplements derived from MedDiet food sources in the modulation of pathognomonic traits of certain IR-related conditions, including polyunsaturated fatty acids from olive oil and seeds, anthocyanins from purple vegetables and fruits, resveratrol from grapes, and the EVOO-derived, oleacein. Although the pharmacological properties and clinical uses of these functional nutrients are still under investigation, the molecular mechanism(s) underlying the metabolic benefits appear to be compound-specific and, in some cases, point to a role in gene expression through an involvement of the nuclear high-mobility group A1 (HMGA1) protein.

Cardio-Metabolic Effects of High-Fat Diets and Their Underlying Mechanisms—A Narrative Review

“…At the level of dietary components, there are several nutraceuticals present in the Mediterranean diet that have been shown to have beneficial health effects (reviewed in detail recently by Mirabelli et al [128]). For example, resveratrol, a potent anti-oxidant present in red wine, skin of grapes, berries, and peanuts, has been demonstrated to reduce fasting glycemia and insulinemia, improve insulin sensitivity (reduced homeostatic model assessment of insulin resistance index), and decrease systolic and diastolic blood pressure in patients with type 2 diabetes [129].…”

The Role of Diet on Insulin Sensitivity

“…Growing evidence shows that dietary composition has a marked impact on the risk of developing obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), certain types of endocrine cancer and many other intertwined metabolic and reproductive disorders, all featured by insulin resistance (IR) [ 1 ]. IR is an increasingly common pathological condition in Westernized populations [ 2 ], as well as in ethnic minorities [ 3 ], resulting from an attenuated response to insulin action in peripheral target organs and tissues, which include mainly, but not exclusively, skeletal muscle, fat and liver.…”

“…In this context, increasing evidence is linking adiposity to the impaired brain structure and decreased insulin sensitivity of this target organ in patients with excessive body weight. Additionally, obese individuals suffering either from T2D or milder forms of hyperglycemia are exceedingly prone to cognitive decline and dementia, showing progressive deficits over time [ 1 ]. Although this was not assessed with ex vivo histological analyses, results from in vivo behavioral and cognitive testing procedures suggest that ranolazine might effectively counteract the metabolic and structural brain disturbances induced by a high-fat diet and T2D [ 10 ].…”

“…When compared to a low-fat diet, adherence to a Mediterranean-based regimen, particularly rich in unsaturated fats from EVOO or nuts, was associated with a significant reduction of CVD events and related mortality (approximately 30%) [ 25 ]. Other than basic nutrition and unsaturated fatty acids, the Mediterranean Diet provides several plant-based functional foods and nutrients that have been shown to have beneficial effects on insulin sensitivity and metabolic health, reversing IR states and certain hard-curative disease traits in patients with obesity, T2D, CVD, steatohepatitis, cognitive decline, endocrine-related cancers and polycystic ovary syndrome (PCOS) [ 1 ]. We had the opportunity to gather epidemiological and mechanistic evidence about the role of the Mediterranean Diet and selected nutritional supplements on the abovementioned IR-related diseases in a detailed review.…”

“…We had the opportunity to gather epidemiological and mechanistic evidence about the role of the Mediterranean Diet and selected nutritional supplements on the abovementioned IR-related diseases in a detailed review. Unsaturated fatty acids, flavonoids, anthocyanins and other polyphenols were inevitably in the spotlight [ 1 ].…”