Nutritional Management and Physical Activity in the Treatment of Sarcopenic Obesity: A Review of the Literature.

BACKGROUND: The prevalence of sarcopenic obesity among adults aged ≥65 years is increasing worldwide. It is a condition that describes the concomitant presence of sarcopenia and obesity, but it appears to be associated with greater increases in the risks for disability, morbidity, and mortality than the two conditions combined. The current review aims to summarize the available literature data on the effectiveness of lifestyle modification for the management of this high-risk geriatric syndrome. METHODS: We conducted a comprehensive search across multiple databases, including PubMed, Scopus, Web of Science, and Cochrane Library, for publications published from January 1950 to June 2024. RESULTS: The detection of early preventive and therapeutic approaches to combat sarcopenic obesity is essential for healthy aging. There is ample evidence that suggests that poor dietary habits and physical inactivity are the main reasons for the development of sarcopenic obesity and should thus be the main targets for intervention. In the absence of effective pharmacological interventions, the best effect on sarcopenic obesity is achieved by combination with proper dietary intervention and regular physical activity according to the individual's health condition. CONCLUSIONS: Further research is needed to discover the most effective strategy for the prevention and treatment of sarcopenic obesity, as well as potential pharmacological options to improve muscle mass and function in older populations with physical restrictions.

Common carotid artery intima media thickness (CIMT) in patients with prediabetes and newly diagnosed type 2 diabetes mellitus.

AIM: To evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven cardiovascular disease and some classic cardio-metabolic risk factors. PATIENTS AND METHODS: The study included 461 obese patients with an average age of 53.2 ± 10.7 years, divided into three groups - group 1 without carbohydrate disturbances (n = 182), group 2 with prediabetes (n = 193) and group 3 with newly diagnosed diabetes mellitus (n = 86). RESULTS: The patients with new-onset diabetes had significantly higher mean CIMT values compared to those with prediabetes or without carbohydrate disturbances and a higher frequency of abnormal IMT values. CIMT correlated significantly with age, systolic BP, diastolic BP and fasting blood glucose and showed a high predictive value for the presence of diabetic neuropathy and sudomotor dysfunction. Patients with abnormal CIMT values had a higher incidence of arterial hypertension, dyslipidemia, metabolic syndrome, peripheral neuropathy, and sudomotor dysfunction. Patients who developed type 2 diabetes during follow-up had a significantly higher initial mean CIMT, which showed the highest predictive value for the risk of new-onset diabetes, with CIMT≥0.7 mm having 53 % sensitivity and 83 % specificity for the risk of progression to diabetes mellitus. CONCLUSION: Patients with new-onset diabetes mellitus had significantly greater intima media thickness of the common carotid artery and a greater frequency of abnormal CIMT values compared to those with normoglycemia and prediabetes. CIMT has a high predictive value for the presence of diabetic neuropathy, sudomotor dysfunction and the risk of new onset diabetes.

Long-term effectiveness, outcomes and complications of bariatric surgery.

Dietary imbalance and overeating can lead to an increasingly widespread disease - obesity. Aesthetic considerations aside, obesity is defined as an excess of adipose tissue that can lead to serious health problems and can predispose to a number of pathological changes and clinical diseases, including diabetes; hypertension; atherosclerosis; coronary artery disease and stroke; obstructive sleep apnea; depression; weight-related arthropathies and endometrial and breast cancer. A body weight 20% above ideal for age, gender and height is a severe health risk. Bariatric surgery is a set of surgical methods to treat morbid obesity when other treatments such as diet, increased physical activity, behavioral changes and drugs have failed. The two most common procedures currently used are sleeve gastrectomy and gastric bypass. This procedure has gained popularity recently and is generally considered safe and effective. Although current data show that perioperative mortality is low and better control of comorbidities and short-term complications is achieved, more randomized trials are needed to evaluate the long-term outcomes of bariatric procedures. This review aims to synthesize and summarize the growing evidence on the long-term effectiveness, outcomes and complications of bariatric surgery.

Islet transplantation-immunological challenges and current perspectives.

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes (T1D) by transplanting pancreatic beta cells. Overall, pancreatic islet transplantation has improved to a great extent, and cellular replacement will likely become the mainstay treatment. We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced. Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h. Approximately 54% of the patients gained insulin independence at the end of the first year, while only 20% remained insulin-free at the end of the second year. Eventually, most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation, which imposed the need to improve immunological factors before transplantation. We also discuss the immunosuppressive regimens, apoptotic donor lymphocytes, anti-TIM-1 antibodies, mixed chimerism-based tolerance induction, induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes, pretransplant infusions of donor apoptotic cells, B cell depletion, preconditioning of isolated islets, inducing local immunotolerance, cell encapsulation and immunoisolation, using of biomaterials, immunomodulatory cells, etc.

Circulating Asprosin Concentrations in Patients with Obesity and Carbohydrate Disturbances.

Asprosin is a fasting-induced glucogenic hormone, secreted by white adipose tissue in response to starvation. The aim of the current study was to determine the levels of asprosin in subjects from the entire spectrum of the carbohydrate metabolism. A total of 153 Causcasian subjects participated in this study: group 1, healthy volunteers; group 2, obese subjects without glycemic disturbances; group 3, subjects with prediabetes and group 4, patients with newly identified type 2 diabetes. Subject with body mass index≥30 kg/m2 and dysglycemia (prediabetes and diabetes) showed significantly high levels of asprosin (1.40 ng/ml [IQR=0.98-1.94]; 1.27 ng/ml [IQR=0.86-2.12]; 1.09 ng/ml [IQR=0.89-1.58]) compared to the control group (0.71 ng/ml [IQR=0.54-0.92]; p<0.001). Correlation analysis showed that serum asprosin also had significant positive associations with some anthropometric parameters, liver enzymes, fasting and post load glucose and insulin, LDL and triglycerides. Furthermore, we estimated a marked relationship between asprosin concentrations and intima media thickness of the common carotid artery as well as neuropathy disability and vibration sensitivity. The circulating asprosin levels for differentiating subjects with carbohydrate disturbances and those with obesity were determined by ROC analysis. The AUC for disturbances of the glucose metabolism was 0.672 (p<0.001; 95% CI=0.581-0.751) and for obesity AUC was 0.849 (p<0.001; 95% CI=0.785-0.919). Circulating asprosin could be used as a predictive factor for early carbohydrate disorders and might be a potential new therapeutic target for the treatment of dysglycemia and obesity. Further prospective studies are needed to confirm this observation.

Usefulness of different adiposity indexes for identification of metabolic disturbances in patients with obesity.

CONTEXT: Despite the role of BMI as a classical obesity index, other indexes reflecting mainly abdominal obesity, usually outperform BMI in terms of metabolic complications prediction. OBJECTIVE: The aim of the present study is to compare the usefulness of different adiposity indexes for the identification of metabolic disturbances in patients with obesity. METHODS: In the study, we included 461 patients - group 1 with obesity (n = 182), group 2 with prediabetes (n = 193), and group 3 with newly diagnosed type 2 diabetes (n = 86). Different anthropometric and adiposity indexes were calculated - WHR, WSR, VAI, ABSI, BRI, Hip index, WWI, LAP. RESULTS: VAI and LAP had the highest predictive value for the presence of carbohydrate disturbances. VAI also showed the strongest correlation with Framingham and SCORE compared to other adiposity indexes. CONCLUSIONS: VAI and LAP are most useful for the identification of metabolic disturbances and cardiovascular risk in patients with obesity.

IL-18 Serum Levels in Patients with Obesity, Prediabetes and Newly Diagnosed Type 2 Diabetes.

BACKGROUND: Obesity and diabetes are related to chronic low-grade inflammation. As a pro-inflammatory cytokine, IL-18 stimulates various cell types and has pleiotropic functions. OBJECTIVE: To assess the levels of IL-18 in subjects from the entire spectrum of glycemic disorders. METHODS: This study included 387 Caucasians divided into four groups: healthy controls, obese subjects without carbohydrate issues, prediabetic patients, and recently discovered type 2 diabetics. RESULTS: Subject with body mass index ≥30kg/m2 and glycemic disorders showed significantly high levels of IL-18 (249.77 ± 89.96 pg/ml; 259.01 ± 95.70 pg/ml; and 340.98 ± 127.65 pg/ml) compared with that of the control group (219.47 ± 110.53 pg/ml, p < 0.05). IL-18 also had significant positive associations with some anthropometric parameters, liver enzymes, fasting, post-load glucose, insulin, uric acid, and triglycerides while negative with HDL. The circulating IL-18 levels for differentiating subjects with carbohydrate disturbances and those with metabolic syndrome were determined by ROC analysis. The AUC for the disturbances of the carbohydrate metabolism was 0.597 (p = 0.001; 95% CI = 0.539 - 0.654) and for MS AUC was 0.581 (p = 0.021; 95 % CI = 0.516 - 0.647). CONCLUSION: Our data indicate that as the levels of IL-18 are increased the carbohydrate tolerance is deteriorated. However, the significance of IL-18 in the progression of diabetes mellitus and subsequent consequences requires further exploration.

Fibroblast Growth Factor 21 as a Marker of Prediabetes in Patients with Non-alcoholic Fatty Liver Disease.

BACKGROUND: Fibroblast growth factor 21 is a peptide primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α activation which plays an important role in regulating carbohydrate and lipid metabolism. This study investigated the association between fibroblast growth factor 21 and prediabetes in obese patients with non-alcoholic fatty liver disease in adult population. METHODS: A total of 85 obese non-alcoholic fatty liver disease patients without (n = 49) and with prediabetes (n = 36) were included. Serum fibroblast growth factor 21 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Higher fibroblast growth factor 21 serum levels were observed in patients with prediabetes, metabolic syndrome, dyslipidemia, and insulin resistance. There were significant correlations between fibroblast growth factor 21 and waist-to-stature ratio, visceral adiposity index, triglycerides, very low-density lipoproteins, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), Quantitative Insulin Sensitivity Check Index, and Stumvoll index of insulin sensitivity. Fibroblast growth factor 21 level ≥320 pg/mL was associated with a 4.2-fold higher risk of prediabetes and ≥270 pg/mL for metabolic syndrome approximately 4 times. CONCLUSION: Fibroblast growth factor 21 is associated with increased risk for prediabetes, metabolic syndrome, and insulin resistance in obese patients with non-alcoholic fatty liver disease.

Increased Serum Pentraxin 3 Is Associated with Prediabetes and Type 2 Diabetes in Obese Patients with Nonalcoholic Fatty Liver Disease.

Background: Pentraxin 3 (PTX3) is an acute-phase protein, which resembles C-reactive protein in both structure and function, and belongs to the same family. PTX3 is associated with cardiovascular diseases, obesity, and metabolic syndrome (MetS). This study evaluated the relationship between serum PTX3 levels, prediabetes, newly diagnosed type 2 diabetes mellitus (T2DM), and other biochemical and clinical parameters in obese patients with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 77 obese patients with NAFLD were included. Forty-seven of them were with normal glucose levels and 30 were with glycemic disorders, including prediabetes and newly diagnosed T2DM. Serum PTX3 was measured using ELISA method. Results: Higher PTX3 serum levels were found in patients with prediabetes and T2DM compared with those with normal blood glucose (2321.29 ± 926.63 vs. 1877.03 ± 895.45 pg/mL, P = 0.028). There were significant correlations between PTX3 and alanine aminotransferase (P = 0.018), gamma-glutamyl transferase (P = 0.005), and neuropathy disability score (P < 0.05). The presence of hypertension, dyslipidemia, insulin resistance, and MetS, as well as the number of components of the MetS did not affect PTX3 levels. Conclusions: PTX3 serum levels were higher in an obese subject with NAFLD with prediabetes and T2DM.

Stress Hyperglycemia, Diabetes Mellitus and COVID-19 Infection: Risk Factors, Clinical Outcomes and Post-Discharge Implications.

The novel severe acute respiratory distress syndrome-coronavirus 2 (SARS-CoV-2) has caused one of the most substantial pandemics that has affected humanity in the last century. At the time of the preparation of this review, it has caused the death of around 5 million people around the globe. There is ample evidence linking higher mortality risk rates from Coronavirus disease-19 (COVID-19) with male gender, advancing age and comorbidities, such as obesity, arterial hypertension, cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and cancer. Hyperglycemia has been found to be accompanying COVID-19 not only in individuals with overt diabetes. Many authors claim that blood glucose levels should also be monitored in non-diabetic patients; moreover, it has been confirmed that hyperglycemia worsens the prognosis even without pre-existing diabetes. The pathophysiological mechanisms behind this phenomenon are complex, remain controversial, and are poorly understood. Hyperglycemia in the setting of COVID-19 could be a consequence of deterioration in pre-existing diabetes, new-onset diabetes, stress-induced or iatrogenic due to substantial usage of corticosteroids within the context of a severe COVID-19 infection. It is also plausible that it might be a result of adipose tissue dysfunction and insulin resistance. Last but not least, SARS-CoV-2 is also claimed to trigger sporadically direct ß-cell destruction and ß-cell autoimmunity. Pending further validations with longitudinal data are needed to legitimize COVID-19 as a potential risk factor for the development of diabetes. Hereby, we present an emphasized critical review of the available clinical data in an attempt to unravel the complex mechanisms behind hyperglycemia in COVID-19 infection. The secondary endpoint was to evaluate the bidirectional relationship between COVID-19 and diabetes mellitus. As the worldwide pandemic is still expanding, demand for answering these questions is arising. It will be of immense help for the management of COVID-19 patients, as well as for the implementation of post-discharge policies for patients with a high risk of developing diabetes.

Relationship between circulating netrin-1 levels, obesity, prediabetes and newly diagnosed type 2 diabetes.

BACKGROUND: Netrin-1 is presumed to have regenerative, angiogenic and anti-inflammatory properties, thus it could play a substantial role in the development of insulin resistance and T2DM. OBJECTIVE: The aim of this study was to evaluate the relationship between serum netrin-1 levels and carbohydrate disturbances in patients with obesity. METHODS: Sample size consisted of 163 patients, divided into four groups: obesity without carbohydrate disturbances prediabetes and diabetes and healthy controls Netrin-1 level was determined using ELISA method. RESULTS: Circulating serum Netrin-1 was significantly lower in patients only with obesity, as well as with those with prediabetes and diabetes in comparison to the control group. Correlation analysis revealed that netrin-1 correlates negatively with BMI, waist, WSR, LDL and positive with sudomotor function. Netrin-1 ≤ 0.17 ng/ml has about 3 fold higher risk for carbohydrate disturbances (OR 3.06, 95% CI 1.48-6.34, p = .003). CONCLUSION: Netrin-1 is associated with an increased risk for glycaemic disorders in patients with obesity.

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.

Neopterin in the Evolution from Obesity to Prediabetes and Newly Diagnosed Type 2 Diabetes.

Background: Neopterin, marker of cellular immunity and oxidative stress, is mainly produced by activated macrophages. It could play a crucial role in the development of insulin resistance (IR) and type 2 diabetes (T2D). The aim of this study was to investigate the circulating levels of neopterin in different stages of glucose dysregulation from obesity through prediabetes to newly diagnosed diabetes. Methods: Neopterin levels were determined using a commercially available human enzyme-linked immunosorbent assay kit. The homeostasis model assessment of IR was used as an index to assess IR. Results: The sample consisted of 163 subjects with mean age 52.5 ± 11.3 years, divided in three age- and body mass index (BMI)-matched groups-obesity, prediabetes, and diabetes. The control group consisted of 42 healthy individuals. Neopterin levels were significantly higher in patients with obesity and/or prediabetes and newly diagnosed diabetes than those in the control group, respectively (4.14 ± 2.51; 4.04 ± 2.80 and 2.17 ± 1.93 vs. 0.87 ± 0.84; P < 0.05). Correlation analysis showed that the level of neopterin positively correlated with BMI, waist, waist-to-stature ratio, waist-to-hip ratio, fasting glucose, and triglycerides. Receiver operating characteristic analysis established neopterin suitable for distinguishing subjects with obesity [area under the curve (AUC) = 0.83; P < 0.001] and carbohydrate disturbances (AUC = 0.59; P < 0.05) from those without these conditions. Neopterin ≥0.47 ng/mL have an odds ratio (OR) of 2.71 for development of dysglycemia, whereas threshold value of neopterin ≥0.56 ng/mL shows an OR of 5.94 for development of obesity. Conclusion: The levels of neopterin were increased in patients with obesity and carbohydrate disturbances. Further studies will elucidate the role of the biomarker in development of T2D and its complications.

Lumican in Obese Patients with Nonalcoholic Fatty Liver Disease With or Without Prediabetes.

Background: Lumican is a small leucine-rich proteoglycan that regulates the assembly of collagen fibers in the extracellular matrix of different tissues. Excess collagen production in the liver is key in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and might contribute to the risk of type 2 diabetes mellitus and cardiovascular diseases. The aim of this study was to evaluate the relationship between serum lumican and prediabetes, and other biochemical and clinical parameters in obese subjects with NAFLD. Methods: The study group included 79 subjects with obesity and NAFLD of which 41 had normal carbohydrate tolerance and 38 had prediabetes. Serum lumican was measured by means of enzyme-linked immunosorbent assay. Results: Higher lumican serum levels were found in patients with prediabetes compared with those with normal carbohydrate tolerance (0.117 ± 0.074 vs. 0.080 ± 0.048 ng/mL, P = 0.010) as well as in subjects with metabolic syndrome (MetS) versus those without MetS (0.113 ± 0.071 vs. 0.079 ± 0.048 ng/mL, P = 0.034). There was also a modest positive association between lumican levels and fasting glucose (r = 0.228, P < 0.05). Lumican levels ≥0.07 ng/mL determine a 3.9-fold higher risk of prediabetes (odds ratio: 3.945, 95% confidence interval: 1.518-10.254, P = 0.005). Conclusions: Lumican levels were higher in obese subjects with NAFLD with prediabetes and MetS. Lumican bears an increased risk for prediabetes in the study population.

Impact of testosterone treatment on circulating irisin in men with late-onset hypogonadism and metabolic syndrome.

OBJECTIVES: The beneficial effects of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH) on the body composition and metabolic outcomes are well-established. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". The aim of this study was to evaluate the effects of TRT on the levels of serum irisin in subjects with LOH. STUDY DESIGN: A total 40 men with metabolic syndrome (MS) and LOH (measured serum testosterone concentration < 12 nmol/l). TRT with Testosterone Undecanoate (Nebido™) was performed at baseline and at week 6. Irisin serum concentration was determined at baseline and at week 18 by means of ELISA. RESULTS: Circulating irisin was positively associated with serum testosterone (r = 0.283, p < 0.05). TRT has led to a statistically significant rise in circulating serum irisin levels (7.12 ± 0.76 mcg/ml versus 7.76 ± 0.75 mcg/ml; paired-samples t-test p < 0.001). ROC-analyses determined irisin to be predictive of treatment response (AUC = 0.741, p = 0.014). CONCLUSIONS: Irisin is positively associated with serum testosterone in a population of men with MS and LOH. TRT in these subjects has led to a significant improvement in associated clinical symptoms as well as to a significant rise in serum irisin levels.

The role of Sudoscan feet asymmetry in the diabetic foot.

The aim of this study was to investigate the role of Sudoscan asymmetry parameters in the diabetic foot. PATIENTS AND METHODS: In this study we included 165 participants: 84 type 2 diabetes patients divided into three HbA1c matched groups - group 1: newly diagnosed diabetics (n = 31), group 2: people with longer diabetes duration and established neuropathy (n = 33), group 3: patients with diabetic foot ulcer (n = 20), and a control group of 81 people with prediabetes. All subjects underwent peripheral sudomotor evaluation using Sudoscan device (Impeto Medical, Paris). RESULTS: Patients with diabetic foot had significantly higher Sudoscan feet asymmetry (19.6%) compared to those with only diabetic neuropathy (7.9%), compared to the group with newly diagnosed diabetes (7.44%), and compared to controls (2.5%). This test has shown a good discriminative value (with a threshold of 9.5%) for diabetic foot with area under the ROC curve of 0.955 (p = 0.001). Additionally, in a regression model feet asymmetry proved its predictive value for participants with diabetic foot. CONCLUSION: In this study Sudoscan feet asymmetry proved to be a novel discriminator and predictor for diabetic foot patients. It might be considered as a marker for early damage in the neuropathy evaluation protocol.

Higher levels of IL-18 in patients with prediabetes compared to obese normoglycaemic controls.

Background: Overweight and obesity are linked to low-grade chronic inflammation that can impair normal insulin function and induce insulin resistance. The aim of this study was to compare IL-18 levels between patients with prediabetes and obese normoglycaemic controls.Patients and methods: In this study, we included 131 patients with mean age 54.9 ± 9.1 years, divided into two groups - group 1 with obesity without glycaemic disturbances (n = 66) and group 2 with prediabetes (n = 65). IL-18 was measured using enzyme-linked immunosorbent assay (ELISA) method.Results: Patients with prediabetes had significantly higher levels of IL-18 compared to obese controls (304.0 ± 220.4 vs. 233.6 ± 103.6 pg/l, p=.029). When patients with prediabetes were divided into IFG only, IGT only and IFG + IGT the highest levels of IL-18 were found in IGT only patients.Conclusions: Patients with prediabetes have higher levels of IL18 compared to obese normoglycemic controls.

PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. METHODS: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. RESULTS: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). CONCLUSIONS: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.

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.