Aim To analyse the long-term impact of altered metabolism on the level of mediators of inflammatory response in female patients with type 2 diabetes. Methods This study included 97 female patients with type 2 diabetes and 107 female, nondiabetic control subjects, who were recruited at the Clinical Centre University of Sarajevo and the General Hospital Tešanj. The effects of glycaemic control on markers of inflammatory response represented by C-reactive protein (CRP), fibrinogen, leukocytes, sedimentation rate, and cytokine IL-6 were tested. All subjects were free of evidence of infections, surgery, thyroid disease, polycystic ovarian syndrome, active liver and kidney damage. All biochemical analyses were performed according to standard International Federation of Clinical Chemistry (IFCC) protocols. Results A significant increase of fibrinogen (p<0.001), CRP (p=0.001), interleukin-6 (p=0.013), leukocytes (p<0.001) and sedimentation rate (p=0.008) in diabetic female population compared to control subjects was found. A significant correlation between CRP and haemoglobin A1c (p=0.035), interleukin-6 and glucose (p=0.032), IL-6 and body mass index (p=0.007) was found. Conclusion Our data suggest that inflammation plays an important role in the pathogenesis of diabetes in female diabetic population. A more detailed study on a far larger number of subjects is needed if they were to be used effectively as biomarkers in the primary prevention of type 2 diabetes in this population.

The growing field of metabolomics has opened up new opportunities for prediction of type 2 diabetes (T2D) going beyond the classical biochemistry assays. We aimed to identify markers from different pathways which represent early metabolic changes and test their predictive performance for T2D, as compared to the performance of traditional risk factors (TRF). We analyzed 2776 participants from the Erasmus Rucphen Family study from which 1571 disease free individuals were followed up to 14-years. The targeted metabolomics measurements at baseline were performed by three different platforms using either nuclear magnetic resonance spectroscopy or mass spectrometry. We selected 24 T2D markers by using Least Absolute Shrinkage and Selection operator (LASSO) regression and tested their association to incidence of disease during follow-up. The 24 markers i.e. high-density, low-density and very low-density lipoprotein sub-fractions, certain triglycerides, amino acids, and small intermediate compounds predicted future T2D with an area under the curve (AUC) of 0.81. The performance of the metabolic markers compared to glucose was significantly higher among the young (age < 50 years) (0.86 vs. 0.77, p-value <0.0001), the female (0.88 vs. 0.84, p-value =0.009), and the lean (BMI < 25 kg/m2) (0.85 vs. 0.80, p-value =0.003). The full model with fasting glucose, TRFs, and metabolic markers yielded the best prediction model (AUC = 0.89). Our novel prediction model increases the long-term prediction performance in combination with classical measurements, brings a higher resolution over the complexity of the lipoprotein component, increasing the specificity for individuals in the low risk group.

Objective: Tobacco cigarette smoking is one of the major leading causes of death throughout the world. Smoking has both acute and chronic effect on haematological parameters. The aim of the present study was to assess the extent of adverse effects of cigarette smoking on biochemical characteristics in healthy smokers. Subjects and Method: One hundred and fifty six subjects participated in this study, 56 smokers and 100 non-smokers. The smokers were regularly consuming 10-20 cigarettes per day for at least 3 years. Complete blood cell count was analyzed by CELL-DYN 3700 fully automatic haematological analyzer. Results: The smokers had significantly higher levels of white blood cell (p<0,001), hemoglobin (p=0,042), mean corpuscular volume (p=0,001) and mean corpuscular hemoglobin concentration (p<0,001). All other measured parameters did not differ significantly. Cigarette smoking caused a significant increase (p<0,001) in red blood cells, white blood cells (p=0,040), hemoglobin (p<0,001), hematocrit (p=0,047) and mean corpuscular hemoglobin (p<0,001) in males in comparison to female smokers. Conclusion: In conclusion, our study showed that continuous cigarette smoking has severe adverse effects on haematological parameters (e.g., hemoglobin, white blood cells count, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cells count, hematocrit) and these alterations might be associated with a greater risk for developing atherosclerosis, polycythemia vera, chronic obstructive pulmonary disease and/or cardiovascular diseases.

Therapeutic response to metformin, a first‐line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large‐scale meta‐analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2‐K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.

Our aim was to determine the incidence of prediabetes and risk of developing cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS). This prospective, observational study included 148 women with PCOS, without Type 2 diabetes mellitus (T2DM) and CVD present at baseline. In the fasting blood samples, we measured lipids, glucose, and insulin levels during oral glucose tolerance test, levels of C-reactive protein (CRP), steroids, 25-hydroxyvitamin D (25-OHD), prolactin, thyroid-stimulating hormone, and parathyroid hormone. The follow-up period was 3 years. At baseline, prevalent prediabetes was present in 18 (12%) of PCOS cases and it progressed to T2DM in 5 (3%) of the cases. Incident prediabetes during the follow-up was noted in 47 (32%) women or 4.7 per 1000 persons/year. Prediabetes was associated with elevated body mass index (BMI) (odds ratio [OR] = 1.089, confidence interval [CI]: 1.010; 1.174, p = 0.026), high baseline levels of CRP (OR = 3.286, CI: 1.299; 8.312, p = 0.012), homeostatic model assessment - insulin resistance (IR) (OR = 2.628, CI: 1.535; 4.498, p < 0.001), and high lipid accumulation product (LAP) (OR = 1.009, CI: 1.003; 1.016, p = 0.005). Furthermore, prediabetes was associated with low 25-OHD (OR = 0.795, CI: 0.724; 0.880, p ≤ 0.05). In addition, cardiovascular risk in PCOS women with prediabetes was high (hazard ratio = 1.092, CI: 1.036; 1.128, p < 0.001). We showed association of prediabetes with high BMI, IR, markers of inflammation, LAP, and low serum 25-OHD concentration. IR appears to be more relevant than the other predictors of prediabetes risk in this study. PCOS women are considered as a high-risk population for prediabetes.

Metformin is the first-line antidiabetic drug with over 100 million users worldwide, yet its mechanism of action remains unclear. Here the Metformin Genetics (MetGen) Consortium reports a three-stage genome-wide association study (GWAS), consisting of 13,123 participants of different ancestries. The C allele of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose transporter GLUT2, was associated with a 0.17% (P = 6.6 × 10−14) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry. rs8192675 was the top cis expression quantitative trait locus (cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for hepatic GLUT2 in regulation of metformin action. Among obese individuals, C-allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c reduction than T-allele homozygotes. This was about half the effect seen with the addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.

Introduction: Because of increasing prevalence of T2MD worldwide, it’s very important to recognize risk factors for diabetic complications, as soon as possible. Symptoms of complications appear a few or many years after tissue damage. So, it’s imperative to establish surveillance of diabetics with laboratory and other diagnostic procedures for early recognition of diabetic complications. Follow up of clinical curs of diabetes, by using databases of patients, provide possibility for permanent analysis of important laboratory parameters and any changes could be registered. Although an emerging evidence suggests a strong association of ALT (alanine aminotransferase) and γGT (gamma glutamyl transferase) activity with type 2 diabetes mellitus (T2DM), only a limited number of studies have analyzed the association of AST (aspartate aminotransferase), ALT, γGT, and ALP (alkaline phosphatase) activities in controlled T2DM. Material and Methods: Gender differences are of special interest in trying to follow diabetes progression and development of its complications. Here the activities of ALT, AST, γGT, ALP were analyzed as well as levels of glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in 40 T2DM patients and 40 age-matched healthy subjects. Blood samples were collected from all participants in regular 3-months intervals up to 6 months period. Standard IFCC enzyme protocols were used to determine enzyme activities. Results and discussion: In first measured interval, significantly higher activities of ALT (p= 0,050) and glucose levels (p=0,045) were shown in male. A significant correlation was shown between ALT and AST activity with FPG and HbA1c levels in first and third measured interval. ALT activity was much higher in the group of patients with poor glycemia control. Average levels of activities of enzymes stay nearly in normal limits, but changes of enzymes activities should be recognized as soon as possible, earlier than tissue changes and diabetic complications become irreversible.