Affinity kinetics of leptin-reactive immunoglobulins are associated with plasma leptin and markers of obesity and diabetes.

Obese subjects display elevated plasma levels of leptin reflecting the phenomenon of leptin resistance. Here, we aimed to determine whether leptin-reactive immunoglobulins (Ig) are present in obese and type 2 diabetes (T2D) patients and whether their plasma levels and affinity kinetics may correlate with obesity and diabetes markers. We show that leptin levels are increased in obese patients with and without T2D. Although mean plasma levels of leptin-reactive IgG were similar between study groups, IgG in obese non-diabetic patients had increased dissociation rate and lower affinity (increased dissociation equilibrium constant value; KD). In controls and diabetic patients, the association rates of leptin IgG correlated negatively with obesity and diabetes markers, respectively. In contrast, KD values correlated positively with plasma leptin levels and obesity traits in our cohort, and with diabetes markers in both the total cohort and in the obese T2D group. Taken together, our data reveal that leptin-reactive IgG are present in healthy subjects, obese, and diabetic patients but display altered affinity kinetics in obesity. Increased IgG binding to leptin in healthy subjects associated with lower body mass index (BMI) suggests an enhancing role of IgG in leptin signaling. Accordingly, a decreased affinity of IgG for leptin, found in obese patients, can be relevant to leptin resistance.

Potential role of liver enzyme levels as predictive markers of glucose metabolism disorders in a Tunisian population.

The relationship between liver enzymes and T2D risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders, as well as their discriminatory power, for T2D prediction. This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetic, newly diagnosed diabetics, and diagnosed diabetics. All participants underwent anthropometric and biochemical measurements. The relationship between hepatic enzymes and glucose metabolism markers was evaluated by analyses of covariance. The associations between liver enzymes and incident carbohydrate metabolism disorders were analyzed through logistic regression and their discriminatory capacity to predict T2D by ROC analysis. High AP, ALT, γGT, and AST levels were independently related to decreased insulin sensitivity. Interestingly, a higher AP level was significantly associated with an increased risk of prediabetes (p = 0.017), newly diagnosed diabetes (p = 0.004), and T2D (p = 0.007). An elevated γGT level was an independent risk factor for T2D (p = 0.032) and undiagnosed T2D (p = 0.010) in prediabetic and normoglycemic subjects, respectively. In ROC analysis, AP was a powerful predictor of incident diabetes and significantly improved T2D prediction. Liver enzymes within the normal range, specifically AP levels, are associated with increased risk of carbohydrate metabolism disorders and significantly improved T2D prediction.

Potential Predictive Role of Lipid Peroxidation Markers for Type 2 Diabetes in the Adult Tunisian Population.

OBJECTIVES: We evaluated the potential clinical relevance of malondialdehyde (MDA) and autoantibodies to copper oxidized low-density lipoprotein (CuOx-LDL) in type 2 diabetes occurrence. METHODS: This cross-sectional study enrolled 69 normoglycemic subjects, 18 prediabetic patients and 108 type 2 diabetes patients. MDA concentration was assessed spectrophotometrically. Plasma IgG, IgA and IgM levels to CuOx-LDL were determined by ELISA. RESULTS: Plasma MDA levels were considerably higher in obese, prediabetic and type 2 diabetes subjects compared to controls. In multiple linear regression analysis, both MDA and IgA to CuOx-LDL were significantly associated with glucose metabolism markers (p<0.05). Multiple logistic regression analyses showed that high plasma MDA and IgA to CuOx-LDL were independent risk factors for type 2 diabetes (OR 1.196, 95% CI: 1.058 to 1.353; p=0.004; OR 1.626, 95% CI: 1.066 to 2.481; p=0.024; respectively). Importantly, elevated IgA to CuOx-LDL predicted incident diabetes in patients with prediabetes (OR 2.321, 95% CI:1.063 to 5.066; p=0.035). From stratified analyses by body mass index (BMI), both MDA and IgA to CuOx-LDL remained independent predictors of type 2 diabetes occurrence in non-obese subjects (p<0.05). More interesting, elevated IgA to CuOx-LDL levels could be predictors of type 2 diabetes in obese prediabetic subjects (p=0.044). Conversely, neither IgG nor IgM to CuOx-LDL was associated with glucose metabolism markers, obesity or type 2 diabetes. CONCLUSIONS: Plasma MDA and IgA to CuOx-LDL were significantly associated with blood markers of glucose metabolism. High levels of MDA and IgA to CuOx-LDL could independently predict type 2 diabetes development in normoglycemia and prediabetic subjects.

Role of disturbed fatty acids metabolism in the pathophysiology of diabetic erectile dysfunction.

BACKGROUND: Vasculogenic erectile dysfunction (VED) is considered as a common complication among people with type 2 diabetes (T2D). We tested whether changes in fatty acid (FAs) classes measured in erythrocytes are associated with increased risk of diabetic VED along with related risk factors. METHODS: We assessed erythrocyte FAs composition, lipid peroxidation parameters and inflammatory cytokines among 72 T2D men with VED, 78 T2D men without VED and 88 healthy volunteers with similar age. Biochemical, hepatic, lipid and hormonal profiles were measured. RESULTS: T2D people with VED had significant decrease in the indexes of Δ6-desaturase and elongase activities compared to the other studied groups. The same group of participants displayed lower erythrocytes levels of dihomo-γ-linolenic acid (C20:3n-6) (P < .001), precursor of the messenger molecule PGE1 mainly involved in promoting erection. Moreover, absolute SFAs concentration and HOMA IR levels were higher in T2D people with VED when compared to controls and associated with impaired NO concentration (1.43 vs 3.30 ng/L, P < .001). Our results showed that IL-6 and TNF-α were significantly increased and positively correlated with MDA levels only in T2D people with VED (r = 0.884, P = .016 and r = 0.753, P = .035; respectively) suggesting a decrease in the relative availability of vasodilator mediators and an activation of vasoconstrictors release. CONCLUSION: Our findings show that the deranged FAs metabolism represents a potential marker of VED in progress, or at least an indicator of increased risk within men with T2D.

Deltamethrin induced oxidative stress in kidney and brain of rats: Protective effect of Artemisia campestris essential oil.

Artemisia campestris (Asteraceae) is widely used in traditional medicine in Southern Tunisia as a decoction for its antivenom, anti-inflammatory, antirheumatic, and antimicrobial activities. A. campestris essential oil (ACEO) was obtained by hydrodistillation from the aerial parts, since it has beneficial and therapeutic effects. Deltamethrin is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to deltamethrin leads to nephrotoxic and neurotoxic side effects for human and many species including birds and fish. The present study was conducted to investigate the potential nephroprotective, neuroprotective and antioxidant effects of ACEO against sub-acute deltamethrin toxicity in male rats. Deltamethrin intoxicated rats revealed a significant increase in serum kidney and brain indicators as well as creatinin, urea and uric acid levels, and AChE activity as compared to control rats. In addition, kidney and brain lipid peroxidation and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were altered significantly in deltamethrin treated rats. These biochemical disturbances were confirmed by histological and histomorphometric changes in brain and kidney tissues. However, ACEO normalized the altered serum levels of creatinin, urea, uric acid, and AChE. Moreover, ACEO reduced deltamethrin-induced lipid peroxidation and oxidative stress profile. Furtheremore, it reduced deltamethrin-induced histopathology and histomorphometric degeneration. It can be concluded that the protective effect of ACEO may be attributed to its antioxidant properties.

Segregation of S292F TPO gene mutation in three large Tunisian families with thyroid dyshormonogenesis: evidence of a founder effect.

UNLABELLED: We aimed to identify causal mutation(s) in 13 patients with thyroid dyshormonogenesis (TD) from three consanguineous Tunisian families. A 12-year clinical follow-up showed phenotypic variability ranging from the presence to the absence of goiter, sensorineural deafness, and mental retardation. Genetic analysis using microsatellite markers within two candidate genes (TPO and PDS) gave evidence of linkage with the TPO gene. Sequencing of its 17 exons and their flanking intron-exon junctions revealed the previously described c.875C>T (p.S292F) mutation in homozygous state. No additional mutations were found in either a 900 bp of the TPO gene promoter or PDS gene. In silico analysis showed that p.S292F mutation might reduce the catalytic cavity of the TPO which would restrict access of a potential substrate to the catalytic pocket. Using 4SNPs and one microsatellite marker in the TPO gene, an associated haplotype: G-C-G-G-214 was found, giving evidence of a founder mutation. CONCLUSION: This is the first description of a TD causing mutation in Tunisia and thus may help to develop a genetic screening protocol for congenital hypothyroidism in the studied region. Although structural modeling suggested a pathogenic effect of this mutation, functional studies are needed. Additional causing and/or modifier genes, together with late diagnosis could explain the clinical variability observed in our patients.