osteoprotegerin and Prediabetic-State

To examine the relationship between hormones involved in bone remodeling and glucose metabolism alterations in prediabetes.. OPN was higher in IGR compared to NGT (5.3 ± 0.5 vs. 3.3 ± 0.2 μg/mL; p = 0.008) and in isolated IGT compared to IFG and IFG-IGT (6.3 ± 0.5 vs. 4.5 ± 0.3 and 5.4 ± 0.5 μg/mL; p = 0.02). OCN was similar in IFG and NGT but lower in IGT and IFG-IGT compared to NGT (7.2 ± 0.3 and 5.4 ± 0.2 vs. 8.3 ± 0.3 ng/mL; p < 0.01). OPN was positively correlated with HbA1c, fasting and 2 h plasma glucose and PTH. OCN was negatively correlated with body fat, 2 h plasma glucose, insulin and positively correlated with Stumvoll index. OPG correlated with TGD/SSPI (r = - 0.29; p < 0.05), EGP, and hepatic insulin resistance index in IGR (r = 0.51, r = 0.43; p < 0.01). There was no correlation between PTH and insulin sensitivity or Beta-cell function parameters.. In prediabetes, hormones known to be involved in bone remodeling may affect glucose metabolism before overt T2DM occurs with tissue-specific mechanisms.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Fasting; Female; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Prediabetic State

Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPN) are soluble members of the tumor necrosis factor superfamily. Growing evidence suggest that there is link between inflammation, insulin resistance and OPG, soluble RANKL (sRANKL). We aimed to ascertain whether OPG and sRANKL levels are altered in prediabetic subjects and there is association between OPG/sRANKL and metabolic parameters.. Forty prediabetic subjects and 40 age- and BMI-matched controls were recruited for this cross-sectional study. Circulating OPG, sRANKL were measured using ELISA. Anthropometric and metabolic parameters were also determined.. Circulating sRANKL (97.74±17.67 vs. 55.00±11.19 pg/mL, P=0.010) and OPG (261.54±74.55 vs. 159.23±52.91 pg/mL, P=0.020) levels were found to be significantly higher in diabetic subjects compared with control subjects. There was a positive correlation between sRANKL and OPG. sRANKL also positively correlated with BMI, insulin resistance marker HOMA-IR, inflammatory marker hs-CRP. Logistic regression analyses revealed that the odds ratio was increased for prediabetes in subjects with having elevated sRANKL levels.. Increased sRANKL and OPG levels were associated with prediabetic subjects. sRANKL and OPG may play a role in the pathogenesis of diabetes as well as metabolic disturbance.

Topics: Adipose Tissue; Adult; Aged; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Male; Middle Aged; Osteoprotegerin; Prediabetic State; RANK Ligand

Osteoprotegerin has been shown to be increased in cardiovascular disorders and type 2 diabetes mellitus. Prediabetes represents a high risk condition for diabetes and diabetic complications. Therefore, we aimed to find the relationship between prediabetes and osteoprotegerin with nuclear factor-B ligand, carotid intima media thickness, and metabolic markers. A total of 54 participants with prediabetes including impaired fasting glucose (n = 21), impaired glucose tolerance (n = 8), impaired fasting glucose and impaired glucose tolerance (n = 25), and 60 healthy individuals as a control were admitted to the study. Metabolic and anthropometric parameters, insulin resistance variables, osteoprotegerin, and nuclear factor-B ligand markers, carotid intima media thickness were examined at baseline for all participants. To evaluate the effect of therapy we determined the same parameters after the end of the study. Measurements of waist circumference, body mass index, body fat percentage and levels of fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance, triglyceride levels and hsCRP and carotid intima media thickness were significantly higher in patients with prediabetes (p < 0.05). We also found higher osteoprotegerin and lower nuclear factor-B ligand levels in patients than in controls however, the value was non-significant (p > 0.05). Patients with prediabetes were under lifestyle interventions with (group 1, n = 33) or without metformin (group 2, n = 21) therapy. Baseline anthropometric and metabolic characteristics were not found statistically different in group 1 and group 2. Mean follow up period of the patients were 7.9 ± 2.2 month (min-max: 6-12 months). After the follow up period we evaluated the same parameters and found significant differences between waist circumference, body mass index, body fat percentage, fasting insulin, homeostatic model assessment of insulin resistance, and osteoprotegerin levels (p < 0.05). However, carotid intima media thickness, and nuclear factor-B ligand levels significantly different only in the group treated with metformin (p < 0.05). We also compared the variables after the treatment period with the control group and found significantly lower levels in terms of fasting insulin, homeostatic model assessment of insulin resistance, waist circumference, body mass index, body fat percentage, carotid intima media thickness, osteoprotegerin, and nuclear factor-B ligand values (p < 0.05). C

Topics: Adult; Blood Glucose; Body Mass Index; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Life Style; Male; Metformin; Middle Aged; Osteoprotegerin; Prediabetic State; RANK Ligand; Treatment Outcome; Waist Circumference

High osteoprotegerin (OPG) has been reported in association with insulin resistance and type 2 diabetes. We aimed to evaluate the association of serum OPG with impaired glucose regulation (IGR) and microalbuminuria among middle-aged and older Chinese.. Serum OPG was measured in 599 individuals with normal glucose regulation, 730 with impaired glucose regulation and 327 newly diagnosed patients with diabetes. Serum OPG was measured using ELISA methods and urine albumin/creatinine ratio was used to determine the urinary albumin excretion.. Serum OPG levels were significantly higher in subjects with isolated impaired fasting glucose, isolated impaired glucose tolerance, combined impaired fasting glucose/impaired glucose tolerance and diabetes than in those with normal glucose regulation, whereas serum OPG levels were not different in the four groups with dysregulation of glucose metabolism. OPG was associated with a higher risk for IGR (OR 1.108 for each 0.1 μg/l increase in OPG, 95% CI 1.009-1.117, p = 0.01) after adjustment for gender, age, BMI, current smoking and alcohol intake, family history of diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile; the corresponding OR of combined impaired glucose regulation and type 2 diabetes was 1.121 (95% CI 1.101-1.141, p = 0.0005). OPG was associated with the risk of microalbuminuria (OR 1.025, 95% CI 1.006-1.044, p = 0.02) after adjustment for gender, age, current smoking, current alcohol intake, family history of diabetes, BMI, waist/hip ratio, HOMA-IR, eGFR and lipid profile.. Serum OPG level is closely and independently associated with IGR and is an independent risk factor for microalbuminuria.

Topics: Aged; Albuminuria; Biomarkers; C-Reactive Protein; China; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Longitudinal Studies; Male; Middle Aged; Osteoprotegerin; Prediabetic State

Today the prevalence of type 2 diabetes reached an epidemic level. It is known that type 2 diabetes could only be prevented before the manifestation, during the "prediabetic" state, urging the development of diagnostic tests to recognize the group at risk in time.. The authors explored metabolic differences between healthy, normal glucose tolerant, normal insulin resistant females having first degree relatives with and without type 2 diabetes.. Healthy, normal insulin sensitive females without (n = 26) and with (n = 18) type 2 diabetic relatives were investigated.. Healthy females with first degree diabetic relatives had lower low density lipoproteins and higher high density lipoproteins as well as higher glucose and insulin levels at the 120 min of oral glucose test as compared to those without first degree diabetic relatives.. These results suggest that the appearance of insulin resistance is preceded by hepatic insulin resistance and impaired lipid metabolism in the symptom-free prediabetic period of genetically susceptible females.. Bevezetés: A 2-es típusú cukorbetegség ma már „világjárvány”, megelőzése csak a „praediabetes” idején eredményes, ezért olyan szűrővizsgálatokra van szükség, amelyek a cukorbetegség várományosait időben felfedik. Célkitűzés: A szerzők célul tűzték ki egészséges, negatív családi anamnézisű (genetikailag nem diabeteses) és elsőfokú cukorbeteg rokonokkal rendelkező (genetikailag diabeteses), normális szénhidrát-toleranciájú és inzulinérzékenységű nőkben a diagnosztikai értékű anyagcsere-eltérések feltárását. Módszer: A klemp vizsgálatok során normális inzulinérzékenységű, genetikailag nem diabeteses (n = 26) és genetikailag diabeteses (n = 18) önkéntesek adatait elemezték. Eredmények: Genetikailag diabeteses, egészséges nőkben az orális cukorterhelés 120. percében magasabb glükóz- és inzulinkoncentrációt, valamint nagyobb magas denzitású és kisebb alacsony denzitású lipidszintet találtak a genetikailag nem diabeteses egészséges nőkben mért értékekhez képest. Következtetések: Az eredmények szerint genetikailag diabeteses, egészséges nőkben a kialakuló inzulinrezisztenciát megelőzi a hepaticus inzulinrezisztencia és a zsíranyagcsere zavara. A szerzők nem kaptak választ arra a kérdésre, hogy a cukorbetegséghez és az elhízáshoz vezető energiafelesleg miért okoz genetikailag diabeteses nőkben korán zsíranyagcsere-zavart és hyperinsulinaemiát, továbbá arra sem, hogy az elhízás miért nem társul mindig inzulinrezisztenciával. Orv. Hetil., 2013, 154, 1747–1753.

Topics: Adipokines; Adult; Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Diabetes Mellitus, Type 2; Family; Female; Follicle Stimulating Hormone; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Interleukin-6; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Obesity; Osteocalcin; Osteoprotegerin; Prediabetic State; Triglycerides; Tumor Necrosis Factor-alpha

Diabetic patients experience a higher risk for severe periodontitis; however, the underlying mechanism remains unclear. We investigated the contribution of antibacterial T-cell-mediated immunity to enhanced alveolar bone loss during periodontal infection in nonobese diabetic (NOD) mice by oral inoculation with Actinobacillus actinomycetemcomitans, a G(-) anaerobe responsible for juvenile and severe periodontitis. The results show that 1) inoculation with A. actinomycetemcomitans in pre-diabetic NOD mice does not alter the onset, incidence, and severity of diabetes; 2) after A. actinomycetemcomitans inoculation, diabetic NOD mice (blood glucose >200 mg/dl and with severe insulitis) exhibit significantly higher alveolar bone loss compared with pre-diabetic and nondiabetic NOD mice; and 3) A. actinomycetemcomitans-reactive CD4+ T-cells in diabetic mice exhibit significantly higher proliferation and receptor activator of nuclear factor kappaB ligand (RANKL) expression. When diabetic mice are treated with the RANKL antagonist osteoprotegerin (OPG), there is a significant reversal of alveolar bone loss, as well as reduced RANKL expression in A. actinomycetemcomitans-reactive CD4+ T-cells. This study clearly describes the impact of autoimmunity to anaerobic infection in an experimental periodontitis model of type 1 diabetes. Thus, microorganism-reactive CD4+ T-cells and the RANKL-OPG axis provide the molecular basis of the advanced periodontal breakdown in diabetes and, therefore, OPG may hold therapeutic potential for treating bone loss in diabetic subjects at high risk.

Topics: Actinobacillus Infections; Aggregatibacter actinomycetemcomitans; Alveolar Bone Loss; Animals; Bacteria, Anaerobic; Carrier Proteins; CD4-Positive T-Lymphocytes; Diabetes Mellitus, Type 1; Glycoproteins; Humans; Membrane Glycoproteins; Mice; Mice, Inbred NOD; Osteoprotegerin; Prediabetic State; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor