Myostatin and carbohydrate disturbances.

Purpose/aim of the study: Myostatin is a myokine that has been shown to inhibit muscle growth and to have potentially deleterious effects on metabolism. The aim of the current study was to compare its circulating serum levels in subjects from the whole spectrum of carbohydrate disturbances leading to diabetes. MATERIALS AND METHODS: A total of 159 age-, sex-, and BMI-matched subjects participated in the study - 50 had normal glucose tolerance (NGT), 60 had prediabetes (PreDM), and 49 had type 2 diabetes mellitus (T2D). Oral glucose tolerance testing was used to determine glucose tolerance. Serum myostatin was quantified by means of ELISA. RESULTS: Circulating serum myostatin levels were highest in patients with T2D, lower in subjects with prediabetes, and lowest in subjects with normoglycemia (all p < 0.05). Myostatin was shown to be positively associated with fasting plasma glucose, HOMA-IR, hepatic enzymes, uric acid, and FINDRISC questionnaire scores in both sexes. ROC analyses determined circulating myostatin levels to be of value for differentiating subjects with T2D (AUC = 0.72, p = 0.002 in men; AUC = 0.70, p = 0.004 in women) in the study population. After adjustment for potential confounders, in a multiple binary logistic regression model, serum myostatin added further information to traditional risk estimates in distinguishing subjects with T2D. CONCLUSIONS: Serum myostatin levels are higher with deterioration of carbohydrate tolerance. Furthermore, circulating myostatin is positively associated with traditional biochemical estimates of poor metabolic health. These data add to evidence of the involvement of this myokine in the pathogenesis of T2D.

Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control.

Type 2 diabetes (T2D) is one of the most common chronic metabolic disorders in adulthood worldwide, whose pathophysiology includes an abnormal immune response accompanied by cytokine dysregulation and inflammation. As the T2D-related inflammation and its progression were associated with the balance between pro and anti-inflammatory cytokines, anticytokine treatments might represent an additional therapeutic option for T2D patients. This review focuses on existing evidence for antihyperglycemic properties of disease-modifying antirheumatic drugs (DMARDs) and anticytokine agents (anti-TNF-α, anti-interleukin-(IL-) 6, -IL-1, -IL-17, -IL-23, etc.). Emphasis is placed on their molecular mechanisms and on the biological rationale for clinical use. Finally, we briefly summarize the results from experimental model studies and promising clinical trials about the potential of anticytokine therapies in T2D, discussing the effects of these drugs on systemic and islet inflammation, beta-cell function, insulin secretion, and insulin sensitivity.

Serum AGEs and sRAGE levels are not related to vascular complications in patients with prediabetes.

BACKGROUND: While hyperglycemia has a key role in the pathogenesis of microvascular complications of diabetes, it is just one of the many factors contributing to macrovascular damage. The aim of the present study is to investigate the link between serum pentosidine and sRAGE levels and vascular complications in patients with prediabetes compared to normal glucose tolerance controls with obesity. METHODS: In this study were included 76 patients with mean age 50.7 ±â€¯10.7 years, divided into two age and BMI-matched groups - group 1 with obesity without glycemic disturbances (n = 38) and group 2 with obesity and prediabetes (n = 38). RESULTS: There was no significant difference in pentosidine and sRAGE levels between patients with obesity and prediabetes. Patients with hypertension had lower levels of sRAGE compared to nonhypertensive subjects. sRAGE showed a weak negative correlation to blood glucose on 60th min of OGTT and HOMA index. There was no correlation between sRAGE and pentosidine levels and the markers of micro- and macrovascular complications. There was no difference in sRAGE and pentosidine levels between patients with and without endothelial dysfunction. CONCLUSIONS: sRAGE and pentosidine levels are similar in patients with obesity with and without prediabetes and do not correlate to the markers of micro- and macrovascular complications.

Higher levels of thioredoxin interacting protein (TXNIP) in patients with prediabetes compared to obese normoglycemic subjects.

BACKGROUND: Thioredoxin interacting protein (TXNIP) is one of the mediators of oxidative stress induced beta-cell glucotoxisity. TXNIP might play a key role in impaired glucose homeostasis preceding overt T2DM. The aim of the present study was to compare TXNIP levels between patients with prediabetes and obese normoglycemic controls and to evaluate the link between TXNIP and metabolic risk factors. PATIENTS AND METHODS: In the present study we included 79 patients with mean age 50.3 ±â€¯10.6 years, divided into two age and BMI matched groups -control group with obesity without glycemic disturbances (NGT) (n = 40) and prediabetes (n = 39). RESULTS: We found significantly higher levels of TXNIP in patients with prediabetes compared to normoglycemic obese controls (54.2 ± 69.9 vs. 23.9 ± 47.1 pg/ml; p = 0.03). The levels of TXNIP gradually increased from normal glucose tolerance trough IFG/IGT only to IFG + IGT (27,1; 44.0; 49.9 and 95.7 pg/ml respectively; p = 0.025 between NGT and IFG + IGT). TXNIP levels correlated weakly only with fasting blood glucose (r = 0.235; p = 0.04) but not with glucose during OGTT or the markers of insulin resistance. CONCLUSIONS: The levels of TXNIP are higher in patients with prediabetes compared to normoglycemic controls as they increase gradually from NGT trough IFG/IGT only to IFG + IGT.