Serum osteoglycin is stable during various glycemic challenges in healthy men.

PURPOSE: Osteoglycin is hypothesized to be metabolically active and may enhance insulin action. We hypothesized that osteoglycin levels increase during hyperglycemia as a physiological response to enhance the effects of insulin. METHODS: Eight healthy males were included in a cross-over study consisting of three study days following an 8 h fast. First, we performed an oral glucose tolerance test (OGTT); second, an isoglycemic intravenous glucose infusion (IIGI); and third, a control period consisting of a three hour fast. We analyzed blood samples for circulating osteoglycin levels during the study days. Repeated measures ANOVA was performed to compare levels of s-osteoglycin between OGTT, IIGI, and the fasting control. RESULTS: There were no differences in baseline osteoglycin levels among study days (p > 0.05). We observed no significant changes neither in absolute s-osteoglycin levels by time (p = 0.14) nor over time by study day (p = 0.99). Likewise, we observed no significant changes in percentage s-osteoglycin levels neither by time (p = 0.11) nor over time by study day (p = 0.89). CONCLUSION: We found that s-osteoglycin levels were stable for three hours during OGTT, IIGI, and fasting in healthy males. Based on the present study, circulating s-osteoglycin levels may be measured independently of fasting or non-fasting conditions. Furthermore, circulating physiological levels of glucose and insulin did not affect s-osteoglycin levels.

Glucose Tolerance Tests and Osteocalcin Responses in Healthy People.

Aim: Osteocalcin and undercarboxylated osteocalcin are suggested to be endocrine messengers from the bones and have been shown to stimulate insulin secretion from pancreatic ß-cells. Insulin is hypothesized to increase the osteoblastic production of osteocalcin. The aim of the study was to investigate whether the route of glucose administration influence the circulating levels of osteocalcin and undercarboxylated osteocalcin. Methods: Twelve healthy males were enrolled in an acute cross-over study where they underwent an oral glucose tolerance test (OGTT), an isoglycemic intravenous glucose infusion (IIGI) and a fasting period (control). Blood samples were collected throughout 180 min and analyzed for osteocalcin and undercarboxylated osteocalcin and compared to insulin, glucose, and gastro-intestinal hormone responses. Results: Neither osteocalcin levels nor undercarboxylated osteocalcin levels over time differed between the OGTT, IIGI, and fasting. Baseline insulin levels and glucose levels were not associated with osteocalcin or undercarboxylated osteocalcin levels. Increases in insulin and glucose levels were neither associated with altered osteocalcin nor undercarboxylated osteocalcin levels. Conclusion: The route of glucose administration does not influence the circulating levels of osteocalcin and undercarboxylated osteocalcin despite the differential insulin and incretin responses. In the acute setting this suggests that insulin does not increase osteoblastic production of osteocalcin in healthy human males.

Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects.

Background: To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role in this compartment remains unclear. Objective: The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge. Design: Twelve healthy males were recruited for an acute crossover study that consisted of two tests each following an 8-hour fasting period. An oral glucose tolerance test (OGTT) was performed, and blood samples were collected over a 3-hour period. Following a period of at least 1 week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood-collection protocol. Results: The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected, systemic insulin levels were lower during the IIGI compared with the OGTT (P < 0.05). miR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide (GLP)-1, GLP-2, and glucose-dependent insulinotropic polypeptide. Conclusions: The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.

Differential impact of glucose administered intravenously or orally on bone turnover markers in healthy male subjects.

BACKGROUND: Patients with type-1 (T1D) and type-2 diabetes mellitus (T2D) have an increased risk of hip fracture. The underlying mechanisms may involve disturbances in the incretin hormones. Our aim was to clarify if glucose administration i.e. orally or intravenously differentially affects bone turnover markers in healthy males. METHODS: 12 healthy males were included in a cross-over study consisting of three tests following an 8hour fast. First, an oral glucose tolerance test (OGTT) was performed. Subsequently, we carried out an isoglycemic intravenous glucose infusion (IIGI) that closely mimicked the glucose response curve to the oral glucose load. We analyzed blood samples for the bone turnover markers serum C-terminal telopeptide of type I collagen (s-CTX) and serum procollagen type I N propeptide (s-P1NP), as well as insulin, glucose, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2). Finally, eight of the twelve participants underwent a control experiment where they fasted for 3h (Control). RESULTS: While OGTT induced a 50% reduction in s-CTX, only a ~30% reduction was seen during the IIGI and the Control. Neither intervention influenced s-P1NP. The concentration of insulin was highest during the OGTT. However, insulin was also increased significantly during the IIGI compared to the Control. Plasma concentrations of GIP, GLP-1 and GLP-2 were higher under the OGTT than during the IIGI and Control. A linear regression indicated that peak p-GIP significantly predicts nadir s-CTX (p=0.03), and that peak p-GIP could explain 34% of the variability in nadir s-CTX (adjusted R2=0.34). CONCLUSION: This study indicates that glucose per se does not acutely affect bone turnover markers. However, gastrointestinal hormones, especially GIP, possibly in combination with hyperglycemia, may have an acute, uncoupling effect on bone turnover leading to a decrease in bone resorption but no change in bone formation.

Predictors of mortality subsequent to a fracture in diabetes mellitus patients.

BACKGROUND: Type-1 and type-2 diabetes mellitus (DM) are associated with an increased fracture risk and possibly an increased risk of death following a fracture. AIM: To investigate the association between diabetes-related drugs and mortality following a fracture. METHODS: A nested case-control study was conducted. Cases were patients with DM who died following a fracture; controls were DM patients not dying after a fracture. We identified DM patients using the Danish National Hospital Discharge Register (1977-2011) and included information on date of DM diagnosis, date of fracture, and comorbidities. From the Danish Cause of Death Register, the date of death was collected (2008-2011). From the Central Region of Jutland, Denmark, medication use was collected (2008-2011). Analysis was performed by unconditional logistic regression. RESULTS: Two thousand six hundred twenty one diabetes patients with a fracture following the diabetes diagnosis and with information on medication use were included. Of these, 229 died. In a multivariate analysis, statin use [n = 1,106 (42%) statin users, odds ratio (OR) = 0.60, 95% confidence interval, p = 0.012] decreased the risk of dying subsequent to a fracture. Male gender (OR = 1.57, p = 0.005), increasing age (OR = 1.08, p < 0.001), a diagnosis of retinopathy (OR = 2.12, p = 0.008), heart failure (OR = 1.68, p = 0.004), and use of glucocorticoids (OR = 2.22, p = 0.001) were associated with an increased risk of death. None of the antidiabetics: biguanides, glucagon-like receptor agonists, ß-cell stimulants, glitazones, and insulin were associated with mortality. CONCLUSION: Co-morbidity reflected by late onset complications, heart failure, and glucocorticoid use was associated with an increased risk of mortality subsequent to a fracture. Statin use may reduce mortality subsequent to a fracture in diabetes patients. Clinical trials are needed to determine whether diabetes patients with a fracture should initiate statin treatment.