High Risk First Degree Relatives of Type 1 Diabetics: An Association with Increases in CXCR3 +

We analyzed the level of (a) CXCR3+ (Th1) and CCR4+ (Th2) T memory cells (b) interferon-γ inducible chemokine (IP-10)(Th1) and thymus and activation-regulated chemokine (TARC)(Th2), in 51 first degree relatives (FDRs) of type 1 diabetics (T1D) (17 high risk FDRs (GADA+, IA-2+) and 34 low risk FDRs (GADA−, IA-2−)), 24 recent-onset T1D (R-T1D), and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., P<0.001). Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, P<0.05). Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response

Relation of the Mediterranean diet with the incidence of gestational diabetes

Background/objectives: Some studies document relationships of the incidence of gestational diabetes mellitus (GDM) with individual components of the diet, but studies exploring relationships with patterns of eating are lacking. This observational study aimed to explore a possible relationship between the incidence of GDM and the Mediterranean diet (MedDiet) pattern of eating. Subjects/methods: In 10 Mediterranean countries, 1076 consecutive pregnant women underwent a 75-g OGTT at the 24th-32nd week of gestation, interpreted both by the ADA-2010 and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)-2012 criteria. The dietary habits were assessed by a previously validated questionnaire and a Mediterranean Diet Index (MDI) was computed, reflecting the degree of adherence to the MedDiet pattern of eating: a higher MDI denoting better adherence. Results: After adjustment for age, BMI, diabetes in the family, weight gain and energy intake, subjects with GDM, by either criterion, had lower MDI (ADA-2010, 5. 8 vs 6. 3, P=0. 028; IADPSG-2012, 5. 9 vs 6. 4, P<0. 001). Moreover, the incidence of GDM was lower in subjects with better adherence to the MedDiet (higher tertile of MDI distribution), 8. 0% vs 12. 3%, OR=0. 618, P=0. 030 by ADA-2010 and 24. 3% vs 32. 8%, OR=0. 655, P=0. 004 by IADPSG-2012 criteria. In subjects without GDM, MDI was negatively correlated with both fasting plasma glucose and AUC glucose, P<0. 001 for both. Conclusions: Adherence to a MedDiet pattern of eating is associated with lower incidence of GDM and better degree of glucose tolerance, even in women without GDM. The possibility to use MedDiet for the prevention of GDM deserves further testing with intervention studies.peer-reviewe

Relationship between serum tumor necrosis factor receptor-2 concentration and periodontal destruction in patients with type 2 diabetes: Cross-sectional study

Introduction: The role of tumor necrosis factor-α (TNFα) is well documented in pathogenesis of chronic periodontitis (CP) and type 2 diabetes (T2D). Considering short half-life of TNFα, tumor necrosis factor receptor-2 (TNFR2) is used as prosperous surrogate marker of TNFα activity. Objective The aim was to detect TNFR2 serum concentration and correlate it with periodontal destruction in patients with diagnosed T2D and nondiabetics. Methods The study included 85 patients divided into three groups: T2D + CP (group T2D, n = 34); nondiabetics + CP (Group PD, n = 27); and healthy controls (group HC, n = 24). T2D was diagnosed according to WHO criteria (2013) and periodontitis was diagnosed using International Workshop for a Classification of Periodontal Diseases and Conditions criteria (1999). TNFR2 level was measured by enzyme-linked immunosorbent assay (ELISA). Results There was no difference in TNFR2 level among the groups (Kruskal-Wallis, p = 0.482). Significant correlation (Pearson's correlation coefficient) was observed between clinical attachment loss (CAL) and TNFR2 concentration in PD group (rp = -0.460, p = 0.016). In T2D group, correlations were observed between TNFR2 concentration and CaL (rp = 0.363, p = 0.005) and periodontal inflamed surface area (PISA) (rp = 0.345, p = 0.046) and periodontalepithelial surface area (PESA) (rp = 0.578, p = 0.000). Conclusion Higher concentration of TNFR2 was associated with higher CAL, PESA, and PISA scores in T2D group. Contrary to that, nondiabetics with higher values of CAL exhibited lower concentration of TNFR2, presenting potential protective effect on periodontal destruction. These results imply that diabetes may alter TNFR2 secretion originated from periodontium.Uvod: Uloga faktora nekroze tumora-alfa (TNFα) dokazana je u patogenezi hronične parodontopatije (HP) i dijabetesa melitusa tipa 2 (DM tip 2). S obzirom na to da je poluživot TNFα veoma kratak, receptor 2 faktora nekroze tumora (TNFR2) koristi se kao marker aktivnosti TNFα. Cilj rada Cilj ovog rada je određivanje koncentracije TNFR2 u serumu i koreliranje sa parametrima destrukcije parodoncijuma kod zdravih i ispitanika sa dijagnostikovanim DM tip 2. Metode rada U studiju je uključeno 85 pacijenata podeljenih u tri grupe: DM tip 2 + HP (DM grupa, n = 34), zdravi ispitanici + HP (PD grupa, n = 27) i zdrave kontrole (ZK grupa, n = 24). Dijagnoza DM tip 2 postavljena je na osnovu kriterijuma SZO (2013), dok je dijagnoza HP postavljena na osnovu kriterijuma Internacionalne radionice za klasifikaciju stanja i oboljenja parodoncijuma (1999). Koncentracija TNFR2 merena je ELISA metodom. Rezultati Koncentracija serumskog TNFR2 nije se razlikovala među grupama (Kraskal-Volis, p = 0,482). Postoji značajna korelacija (Pirson) između nivoa pripojnog epitela (NPE) i koncentracije TNFR2 u PD grupi (rp = -0,460, p = 0,016). U DM tip 2 grupi, statistički značajna korelacija uočena je između koncentracije TNFR2 i NPE (rp = 0,363, p = 0,005), kao i parametara uticaja inflamacije iz parodoncijuma na sistemsko zdravlje - PISA (rp = 0,345, p = 0,046) i PESA (rp = 0,578, p = 0,000). Zaključak Kod pacijenata sa dijabetesom veće koncentracije TNFR2 odgovaraju većim vrednostima NPE, PESA i PISA. Nasuprot tome, kod sistemski zdravih ispitanika sa HP veće vrednosti NPE su povezane sa manjim koncentracijama TNFR2, što bi moglo govoriti o potencijalnoj zaštitnoj ulozi ovog citokina na destrukciju parodoncijuma. Rezultati govore da dijabetes može uticati na sekreciju TNFR2 iz parodoncijuma

Relationship between Obesity, Adipocytokines and Inflammatory Markers in Type 2 Diabetes: Relevance for Cardiovascular Risk Prevention

This study aimed to analyse the impact of obesity in type 2 diabetes (T2D) on adipocytokines (adiponectin, leptin and resistin) and inflammatory markers (TNF-α, IL-6 and hsCRP) as cardiovascular risk factors. A cross-sectional study comparing the basal levels of adipocytokines and inflammatory markers was done in 18 obese (BMI ≥ 30 kg/m2) (group A), 21 overweight (25 kg/m2 ≤ BMI &lt; 30 kg/m2) (group B), 25 non-obese T2D patients (group C) and 15 non-obese controls (group D). The lowest levels of adiponectin and the highest levels of leptin, resistin, TNF-α, IL-6 and hsCRP were found in group A. Adiponectin levels were significantly lower, and resistin, TNF-α, and hsCRP levels were elevated in group C vs. D. However, leptin and IL-6 levels differed significantly between groups A and B, but not between groups C and D. Moreover, we found a significant negative correlation between adiponectin and TNF-α, but not with other markers, which was independent of the presence of obesity. In contrast, leptin and resistin correlated with the inflammatory markers, and this correlation was obesity-dependent. Our results suggest that obesity influences cardiovascular risk primarily through changes in leptin and resistin and less efficiently at the level of adiponectin

Targeting Mitochondria in Diabetes

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes

Biological and biochemical characteristics of a Mediterranean population with Gestational Diabetes Mellitus

The interplay of various nutrients provided to the developing foetus determines the growth potential of the conceptus. This study assessed the inter-relationship between these nutrients in a Mediterranean population including 1062 pregnant, previously non-diabetic women. These underwent an oral glucose tolerance test (oGTT) and were accordingly classified into gestational hyperglycaemic and normoglycaemic groups. Fasting insulin, HbA1c, and lipid profiles were further assessed, and the anthropomorphic characteristics of the mother and child at birth were measured. Lipid profiles were compared between the two groups and related to the biological characteristics of the mother and child at birth. Gestational hyperglycaemia was significantly associated with elevated triglycerides (P<0.0001) and decreased low density lipoprotein cholesterol (LDL-C) (P=0.02). There were no significant changes in total cholesterol and high density lipoprotein cholesterol (HDL-C) levels. Maternal BMI correlated positively with the various glycaemic indices (P<0.0001) and triglycerides (P<0.0001), but inversely with cholesterol (P<0.0001), HDL-C (P<0.0001) and LDL-C (P<0.0001). The infant birth weight correlated positively with maternal body weight (P<0.0001), LDL-C (P<0.0001) and the glycaemic indices (P<0.0001), but negatively with cholesterol (P<0.0001), triglycerides (P<0.0001), HDL-C (P<0.0001) and FBG (P<0.0001). This study confirms that the maternal body mass index (BMI), insulin resistance, and LDL-C levels positively contribute towards foetal growth, whereas a negative correlation was noted with cholesterol, triglycerides, and HDL-C

Hypertension in Obese Type 2 Diabetes Patients is Associated with Increases in Insulin Resistance and IL-6 Cytokine Levels: Potential Targets for an Efficient Preventive Intervention

Increased body weight as well as type 2 diabetes (T2D) are found to be associated with increased incidence of hypertension, although the mechanisms facilitating hypertension in T2D or nondiabetic individuals are not clear. Therefore, in this study we compared the levels of insulin resistance (IR:OGIS), plasma insulin (PI:RIA) levels, and pro-inflammatory cytokines (IL-6 and TNF-α: ELISA), being risk factors previously found to be associated with hypertension, in T2D patients showing increased body weight (obese and overweight, BMI ≥ 25 kg/m2) with hypertension (group A, N = 30), or without hypertension (group B, N = 30), and in nonobese (BMI &lt; 25 kg/m2), normotensive controls (group C, N = 15). We found that OGIS index was the lowest (A: 267 ± 35.42 vs. B: 342.89 ± 32.0, p &lt; 0.01) and PI levels were the highest (A: 31.05 ± 8.24 vs. B: 17.23 ± 3.23, p &lt; 0.01) in group A. In addition, IL-6 levels were higher in group A (A: 15.46 ± 5.15 vs. B: 11.77 ± 6.09; p &lt; 0.05) while there was no difference in TNF-α levels. Our results have shown that appearance of hypertension in T2D patients with increased body weight was dependent on further increase in IR which was associated with the rise in pro-inflammatory IL-6 cytokine. The results imply that lifestyle intervention aimed to decrease IR might be beneficial in reducing the risk for hypertension in those T2D individuals