Crucial Interactions between Altered Plasma Trace Elements and Fatty Acids Unbalance Ratio to Management of Systemic Arterial Hypertension in Diabetic Patients: Focus on Endothelial Dysfunction.

The coexistence of SAH with T2DM is a common comorbidity. In this study, we investigated the link between altered plasma antioxidant trace elements (ATE: manganese, selenium, zinc, and copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile, which is modified during SAH-T2DM association compared to the healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of total SFA, palmitic acid, arachidonic acid, and PUFA ω6/PUFA ω3; drop in tandem of PUFA/SFA and EPA + DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA rise, concurrent drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitant enhancement of Cu, Mn, and Fe); endothelial dysfunction (endotheline-1 increase); athero-thrombogenesis risk (concomitant rise of ApoB100/ApoA1, Ox-LDL, tHcy, and Lp(a)), and inflammation (higher of Hs-CRP, fibrinogen and ferritin). Our study opens to new therapeutic targets and to better dietary management, such as to establishing dietary ATE and PUFA ω6/PUFA ω3 or PUFA/SFA reference values for atherosclerotic risk prevention in hypertensive/diabetic patients.

Lipid Profile Modulates Cardiometabolic Risk Biomarkers Including Hypertension in People with Type-2 Diabetes: A Focus on Unbalanced Ratio of Plasma Polyunsaturated/Saturated Fatty Acids.

Type 2 diabetes mellitus (T2DM) is associated with lipid metabolism disorder, particularly elevated plasma levels of non-esterified free fatty acids (NEFFA) and an increased cardiovascular disease risk, such as essential hypertension (H). The plasma unbalance of saturated fatty acid (SFA)/polyunsaturated fatty acid (PUFA) ratio is a likely contributor, but the mechanisms involved are not clearly elucidated. The aim of this study is to explore the association between plasma SFA/PUFA ratio and the clusters of cardiometabolic syndrome (CMS), including the atherogenic biomarkers, inflammatory status, feeding patterns, and physical activity in people with T2DM with or without essential hypertension. The study was conducted on 784 adult male and female participants, aged between 30 and 50 years, and divided into 3 groups: 100 T2DM without hypertension (D); 368 T2DM with hypertension (DM); and 316 hypertensive participants without T2DM (H). All Participants were phenotyped regarding CMS clusters according to the NCEP/ATPIII criteria. Insulin resistance was assessed by Homeostasis model assessment (HOMA model). Metabolic, atherogenic, and inflammatory parameters were analyzed by biochemical methods; NEFFA by microfluorimetry; SFA, PUFA-n6 and PUFA-n3 by gas phase chromatography. Dietary lipids and physical activity were analyzed through the use of validated questionnaires. The clusters of CMS were found in all groups. Dyslipidemia was correlated with accretion NEFFA levels in all groups, but more accentuated in the DH group (r = +0.77; p < 0.001). Similarly, plasma PUFA/SFA ratio and PUFA-3 level was lower, concomitantly with a higher plasma ApoB100/ApoA1 (p < 0.001), lipoprotein (a), homocysteine (p < 0.001), and pro-inflammatory cytokines (TNFα, IL-6, IL1-ß) in the DH group. Likewise, the depletion of PUFA-n3/PUFA-n6 ratio is associated with the decrease of omega 3-DHA (docosahexaenoic acid) and omega 3-EPA (eicosapentaenoic acid) (p < 0.001). It appears that the PUFAs-n3 ratio modulates cardiometabolic risk, inflammatory state and atherogenic biomarkers. The plasma unbalanced ratio of SFA/PUFA reflects dietary fatty acids intake. The contribution of dietary lipids is undisputed. Nutritional recommendations are required to determine the fatty acids ratio (saturated and unsaturated) provided in the diet.

The desert gerbil Psammomys obesus as a model for metformin-sensitive nutritional type 2 diabetes to protect hepatocellular metabolic damage: Impact of mitochondrial redox state.

INTRODUCTION: While metformin (MET) is the most widely prescribed antidiabetic drug worldwide, its beneficial effects in Psammomys obesus (P. obesus), a rodent model that mimics most of the metabolic features of human diabetes, have not been explored thoroughly. Here, we sought to investigate whether MET might improve insulin sensitivity, glucose homeostasis, lipid profile as well as cellular redox and energy balance in P. obesus maintained on a high energy diet (HED). MATERIALS AND METHODS: P. obesus gerbils were randomly assigned to receive either a natural diet (ND) consisting of halophytic plants (control group) or a HED (diabetic group) for a period of 24 weeks. MET (50 mg/kg per os) was administered in both animal groups after 12 weeks of feeding, i.e., the time required for the manifestation of insulin resistance in P. obesus fed a HED. Parallel in vitro experiments were conducted on isolated hepatocytes that were shortly incubated (30 min) with MET and energetic substrates (lactate + pyruvate or alanine, in the presence of octanoate). RESULTS: In vivo, MET lowered glycemia, glycosylated haemoglobin, circulating insulin and fatty acid levels in diabetic P. obesus. It also largely reversed HED-induced hepatic lipid alterations. In vitro, MET increased glycolysis but decreased both gluconeogenesis and ketogenesis in the presence of glucogenic precursors and medium-chain fatty acid. Importantly, these changes were associated with an increase in cytosolic and mitochondrial redox states along with a decline in respiration capacity. CONCLUSIONS: MET prevents the progression of insulin resistance in diabetes-prone P. obesus, possibly through a tight control of gluconeogenesis and fatty acid ß-oxidation depending upon mitochondrial function. While the latter is increasingly becoming a therapeutic issue in diabetes, the gut microbiota is another promising target that would need to be considered as well.

[The link between trace elements and metabolic syndrome/oxidative stress in essential hypertension with or without type 2 diabetes]. / Association du profil des minéraux traces au syndrome métabolique et au stress oxydant dans l'hypertension artérielle essentielle avec ou sans diabète de type 2.

The relationship between trace elements (TE) and essential hypertension (EH) is subtle and complex. This relationship is mediated by endothelial dysfunction, insulin resistance, oxidative stress (OS) and athero-inflammatory state. The aim of this study was to examine the TE impact; particularly selenium (Se), zinc (Zn), copper (Cu) and manganese (Mn) as predictive type 2 diabetes biomarkers in a hypertensive subject. The study was undertaken on 400 adult patients (40-60 years), who were divided in 4 groups: hypertensive (H), type 2 diabetes (T2D), hypertensive-diabetic (HD) and healthy group. Patients were phenotyped regarding their metabolic syndrome profile using the NCEP/ATPIII criteria. Hypertension was defined as systolic (SBP) and diastolic (DBP) blood pressure ≥ 140/90 mmHg, respectively. The SBP and DBP measurements by electronic blood pressure using Omron 705 CP(®) type. Insulin resistance was assessed by Homa-IR model. Metabolic and inflammatory parameters were determined by Cobas Integra(®); the TE investigated by mass spectrometric atomic absorption; the OS markers evaluated by Randox kits. Serum Se concentrations are reduced in all groups, concomitantly with a marked depletion GPx activity in the HD group. However, Zn levels were decreased than in H and HD groups, but unchanged in T2D group. In contrast, Mn levels are increased in all groups; whereas the Cu levels increased only in H and HD groups, concomitantly with cytosolic SOD-Cu/Zn and mitochondrial SOD-Mn depletion. The Zn/Cu ratio decreases significantly in hypertensive group but not in diabetics groups. It appears that Zn/Cu ratio reflects the transition from hypertension phase to hypertension associated with T2D. Ultimately, TE plays an important role in the hypertension pathophysiology and can be considered as predictive T2D biomarkers in hypertensive patients.