Nutrients and Dietary Approaches in Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: A Narrative Review.

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality in developed countries. The prevalence of CVD is much higher in patients with type 2 diabetes mellitus (T2DM), who may benefit from lifestyle changes, which include adapted diets. In this review, we provide the role of different groups of nutrients in patients with T2DM and CVD, as well as dietary approaches that have been associated with better and worse outcomes in those patients. Many different diets and supplements have proved to be beneficial in T2DM and CVD, but further studies, guidelines, and dietary recommendations are particularly required for patients with both diseases.

Role of dietary modifications in the management of type 2 diabetic complications.

Diabetes is a chronic metabolic disorder with a high rate of morbidity and mortality. Insufficient insulin secretion and insulin action are two major causes for the development of diabetes, which is characterized by a persistent increase in blood glucose level. Diet and sedentary life style play pivotal role in development of vascular complications in type 2 diabetes. Dietary modification is associated with a reprogramming of nutrient intake, which are proven to be effective for the management of diabetes and associated complications. Dietary modifications modulate various molecular key players linked with the functions of nutrient signalling, regulation of autophagy, and energy metabolism. It activates silent mating type information regulation 2 homolog1 (SIRT1) and AMP-activated protein kinase (AMPK). AMPK mainly acts as an energy sensor and inhibits autophagy repressor Mammalian target of rapamycin (mTOR) under nutritional deprivation. Under calorie restriction (CR), SIRT1 gets activated directly or indirectly and plays a central role in autophagy via the regulation of protein acetylation. Dietary modification is also effective in controlling inflammation and apoptosis by decreasing the level of pro-inflammatory cytokines like nuclear factor kappa- beta (NF-kß), tissue growth factor-beta (TGF-ß), tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). It also improves glucose homeostasis and insulin secretion through beta cell regeneration. This indicates calorie intake plays a crucial role in the pathogenesis of type 2 diabetes-associated complications. The present review, emphasizes the role of dietary modifications in diabetes and associated complications.

Reduced reticulum-mitochondria Ca2+ transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy.

Type 2 diabetic cardiomyopathy features Ca2+ signaling abnormalities, notably an altered mitochondrial Ca2+ handling. We here aimed to study if it might be due to a dysregulation of either the whole Ca2+ homeostasis, the reticulum-mitochondrial Ca2+ coupling, and/or the mitochondrial Ca2+ entry through the uniporter. Following a 16-week high-fat high-sucrose diet (HFHSD), mice developed cardiac insulin resistance, fibrosis, hypertrophy, lipid accumulation, and diastolic dysfunction when compared to standard diet. Ultrastructural and proteomic analyses of cardiac reticulum-mitochondria interface revealed tighter interactions not compatible with Ca2+ transport in HFHSD cardiomyocytes. Intramyocardial adenoviral injections of Ca2+ sensors were performed to measure Ca2+ fluxes in freshly isolated adult cardiomyocytes and to analyze the direct effects of in vivo type 2 diabetes on cardiomyocyte function. HFHSD resulted in a decreased IP3R-VDAC interaction and a reduced IP3-stimulated Ca2+ transfer to mitochondria, with no changes in reticular Ca2+ level, cytosolic Ca2+ transients, and mitochondrial Ca2+ uniporter function. Disruption of organelle Ca2+ exchange was associated with decreased mitochondrial bioenergetics and reduced cell contraction, which was rescued by an adenovirus-mediated expression of a reticulum-mitochondria linker. An 8-week diet reversal was able to restore cardiac insulin signaling, Ca2+ transfer, and cardiac function in HFHSD mice. Therefore, our study demonstrates that the reticulum-mitochondria Ca2+ miscoupling may play an early and reversible role in the development of diabetic cardiomyopathy by disrupting primarily the mitochondrial bioenergetics. A diet reversal, by counteracting the MAM-induced mitochondrial Ca2+ dysfunction, might contribute to restore normal cardiac function and prevent the exacerbation of diabetic cardiomyopathy.

Resveratrol and Diabetic Cardiomyopathy: Focusing on the Protective Signaling Mechanisms.

Diabetic cardiomyopathy (DCM) is a common cardiovascular complication of diabetic mellitus that is characterized by diastolic disorder in the early stage and clinical heart failure in the later stage. Presently, DCM is considered one of the major causes of death in diabetic patients. Resveratrol (RSV), a naturally occurring stilbene, is widely reported as a cardioprotective substance in many heart diseases. Thus far, the specific roles of RSV in DCM prevention and treatment have attracted great attention. Here, we discuss the roles of RSV in DCM by focusing its downstream targets from both in vivo and in vitro studies. Among such targets, Sirtuins 1/3 and AMP-activated kinase have been identified as key mediators that induce cardioprotection during hyperglycemia. In addition, many other signaling molecules (e.g., forkhead box-O3a and extracellular regulated protein kinases) are also regulated in the presence of RSV and exert beneficial effects such as opposing oxidative stress, inflammation, and apoptosis in cardiomyocytes exposed to high-glucose conditions. The beneficial potential of an RSV/stem cell cotherapy is also reviewed as a promising therapeutic strategy for preventing the development of DCM.

A Diet Rich in Medium-Chain Fatty Acids Improves Systolic Function and Alters the Lipidomic Profile in Patients With Type 2 Diabetes: A Pilot Study.

CONTEXT: Excessive cardiac long-chain fatty acid (LCFA) metabolism/storage causes cardiomyopathy in animal models of type 2 diabetes. Medium-chain fatty acids (MCFAs) are absorbed and oxidized efficiently. Data in animal models of diabetes suggest MCFAs may benefit the heart. OBJECTIVE: Our objective was to test the effects of an MCFA-rich diet vs an LCFA-rich diet on plasma lipids, cardiac steatosis, and function in patients with type 2 diabetes. DESIGN: This was a double-blind, randomized, 2-week matched-feeding study. SETTING: The study included ambulatory patients in the general community. PATIENTS: Sixteen patients, ages 37-65 years, with type 2 diabetes, an ejection fraction greater than 45%, and no other systemic disease were included. INTERVENTION: Fourteen days of a diet rich in MCFAs or LCFAs, containing 38% as fat in total, was undertaken. MAIN OUTCOME MEASURES: Cardiac steatosis and function were the main outcome measures, with lipidomic changes considered a secondary outcome. RESULTS: The relatively load-independent measure of cardiac contractility, S', improved in the MCFA group (P < .05). Weight-adjusted stroke volume and cardiac output decreased in the LCFA group (both P < .05). The MCFA, but not the LCFA, diet decreased several plasma sphingolipids, ceramide, and acylcarnitines implicated in diabetic cardiomyopathy, and changes in several sphingolipids correlated with improved fasting insulins. CONCLUSIONS: Although a diet high in MCFAs does not change cardiac steatosis, our findings suggest that the MCFA-rich diet alters the plasma lipidome and may benefit or at least not harm cardiac function and fasting insulin levels in humans with type 2 diabetes. Larger, long-term studies are needed to further evaluate these effects in less-controlled settings.