Effects of exogenous GIP and GLP-2 on bone turnover in individuals with type 2 diabetes.

CONTEXT: Individuals with type 2 diabetes (T2D) have an increased risk of bone fractures despite normal or increased bone mineral density (BMD). The underlying causes are not well understood but may include disturbances in the gut-bone axis, in which both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are regulators of bone turnover. Thus, in healthy fasting participants, both exogenous GIP and GLP-2 acutely reduce bone resorption. OBJECTIVE: The objective of this study was to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D. METHODS: We included 10 men with T2D. Participants met fasting in the morning on three separate test days and were injected subcutaneously with GIP, GLP-2, or placebo in a randomized crossover design. Blood samples were drawn at baseline and regularly after injections. Bone turnover was estimated by circulating levels of collagen type 1 C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), sclerostin, and PTH. RESULTS: GIP and GLP-2 significantly reduced CTX to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared with after placebo (p = 0.001). In addition, P1NP and sclerostin increased acutely after GIP whereas a decrease in P1NP was seen after GLP-2. PTH levels decreased to 67 ± 2.5% of baseline after GLP-2 and to only 86 ± 3.4% after GIP. CONCLUSION: Subcutaneous GIP and GLP-2 affect CTX and P1NP in individuals with T2D to the same extent as previously demonstrated in healthy individuals.

Self-Reported Asthma Is Associated with Reduced Sperm Count-A Cross-Sectional Study of More than 6000 Young Men from the General Population.

Asthma is driven by an inflammatory response that may impact testicular function. In this cross-sectional study, we investigated the association between self-reported asthma and testicular function (semen parameters, reproductive hormone levels), and determined whether potential further inflammation due to self-reported allergy modified this association. A total of 6177 men from the general population completed a questionnaire including information on doctor-diagnosed asthma or allergy, had a physical examination, delivered a semen sample, and had a blood sample drawn. Multiple linear regression analyses were performed. A total of 656 (10.6%) men reported having ever been diagnosed with asthma. Generally, self-reported asthma was consistently associated with a poorer testicular function; however, few estimates were statistically significant. Specifically, self-reported asthma was associated with statistically significant lower total sperm count [median: 133 vs. 145 million; adjusted ß (95% CI): -0.18 (-0.33 to -0.04) million on cubic-root-transformed scale] and borderline statistically significant lower sperm concentration compared with no self-reported asthma. The association between asthma and total sperm count was of similar magnitude among men with and without allergy. In conclusion, men with self-reported asthma had poorer testicular function than men without asthma. However, the cross-sectional design of the study limits ascertainment of causality.

Acarbose diminishes postprandial suppression of bone resorption in patients with type 2 diabetes.

AIMS: The alpha-glucosidase inhibitor acarbose is an antidiabetic drug delaying assimilation of carbohydrates and, thus, increasing the amount of carbohydrates in the distal parts of the intestines, which in turn increases circulating levels of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1). As GLP-1 may suppress bone resorption, acarbose has been proposed to potentiate meal-induced suppression of bone resorption. We investigated the effect of acarbose treatment on postprandial bone resorption in patients with type 2 diabetes and used the GLP-1 receptor antagonist exendin(9-39)NH2 to disclose contributory effect of acarbose-induced GLP-1 secretion. METHODS: In a randomised, placebo-controlled, double-blind, crossover study, 15 participants with metformin-treated type 2 diabetes (2 women/13 men, age 71 (57-85 years), BMI 29.7 (23.6-34.6 kg/m2), HbA1c 48 (40-74 mmol/mol)/6.5 (5.8-11.6 %) (median and range)) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a six-week wash-out period. At the end of each period, circulating bone formation and resorption markers were assessed during two randomised 4-h liquid mixed meal tests (MMT) with infusions of exendin(9-39)NH2 and saline, respectively. Glucagon-like peptide 2 (GLP-2) was also assessed. RESULTS: Compared to placebo, acarbose impaired the MMT-induced suppression of CTX as assessed by baseline-subtracted area under curve (P = 0.0037) and nadir of CTX (P = 0.0128). During acarbose treatment, exendin(9-39)NH2 infusion lowered nadir of CTX compared to saline (P = 0.0344). Neither parathyroid hormone or the bone formation marker procollagen 1 intact N-terminal propeptide were affected by acarbose or GLP-1 receptor antagonism. Acarbose treatment induced a greater postprandial GLP-2 response than placebo treatment (P = 0.0479) and exendin(9-39)NH2 infusion exacerbated this (P = 0.0002). CONCLUSIONS: In patients with type 2 diabetes, treatment with acarbose reduced postprandial suppression of bone resorption. Acarbose-induced GLP-1 secretion may contribute to this phenomenon as the impairment was partially reversed by GLP-1 receptor antagonism. Also, acarbose-induced reductions in other factors reducing bone resorption, e.g. glucose-dependent insulinotropic polypeptide, may contribute.

The role of GLP-1 in the postprandial effects of acarbose in type 2 diabetes.

AIMS: The alpha-glucosidase inhibitor acarbose is believed to reduce plasma glucose by delaying hydrolysis of carbohydrates. Acarbose-induced transfer of carbohydrates to the distal parts of the intestine increases circulating glucagon-like peptide 1 (GLP-1). Using the GLP-1 receptor antagonist exendin(9-39)NH2, we investigated the effect of acarbose-induced GLP-1 secretion on postprandial glucose metabolism in patients with type 2 diabetes. METHODS: In a double-blinded, placebo-controlled, randomized, crossover study, 15 participants with metformin-treated type 2 diabetes (age: 57-85 years, HbA1c: 40-74 mmol/mol) were subjected to two 14-day treatment periods with acarbose or placebo, respectively, separated by a 6-week wash-out period. At the end of each period, two randomized 4-h liquid mixed meal tests with concomitant infusion of exendin(9-39)NH2 and saline, respectively, were performed. RESULTS: Compared to placebo, acarbose increased postprandial GLP-1 concentrations and decreased postprandial glucose. We observed no absolute difference in the exendin(9-39)NH2-induced increase in postprandial glucose excursions between placebo and acarbose periods, but relatively, postprandial glucose was increased by 119 ± 116% (mean ± s.d.) during exendin(9-39)NH2 infusion in the acarbose period vs a 39 ± 27% increase during the placebo period (P = 0.0163). CONCLUSIONS: We confirm that acarbose treatment stimulates postprandial GLP-1 secretion in patients with type 2 diabetes. Using exendin(9-39)NH2, we did not see an impact of acarbose-induced GLP-1 secretion on absolute measures of postprandial glucose tolerance, but relatively, the effect of exendin(9-39)NH2 was most pronounced during acarbose treatment.

Follow-Up After Cardiac Surgery Should be Extended to at Least 120 Days When Benchmarking Cardiac Surgery Centers.

OBJECTIVE: Short-term (30 days) mortality frequently is used as an outcome measure after cardiac surgery, although it has been proposed that the follow-up period should be extended to 120 days to allow for more accurate benchmarking. The authors aimed to evaluate whether mortality rates 120 days after surgery were comparable to general mortality and to compare causes of death between the cohort and the general population. DESIGN: A multicenter descriptive cohort study using prospectively entered registry data. SETTING: University hospital. The cohort was obtained from the Western Denmark Heart Registry and matched to the Danish National Hospital Register as well as the Danish Register of Causes of Death. A weighted, age-matched general population consisting of all Danish patients who died within the study period was identified through the central authority on Danish statistics. PARTICIPANTS: A total of 11,988 patients (>15 years) who underwent cardiac-surgery at Aarhus, Aalborg and Odense University Hospitals from April 1, 2006 to December 31, 2012 were included. INTERVENTIONS: Coronary artery bypass grafting, valve surgery and combinations. MEASUREMENTS AND MAIN RESULTS: Mortality after cardiac surgery matches with mortality in the general population after 140 days. Mortality curves run almost parallel from this point onwards, regardless of The European system for cardiac operative risk evaluation (EuroSCORE) and intervention. The causes of death in the cohort differed statistically significantly from the background population (p<0.0001; one-sample t-test) throughout the first postoperative year. The leading cause of death in the cohort was cardiac (38%); 53% of which was categorized as heart failure. A total of 54% of these patients were assessed preoperatively as having normal or mildly impaired heart function (EuroSCORE). CONCLUSIONS: This study supported an extended follow-up period after cardiac surgery when benchmarking cardiac surgery centers. Regardless of preoperative heart function, heart failure was the consistent leading cause of death.

Gender differences in diabetes mellitus and effects on self-care activity.

BACKGROUND: Effective self-care, including adherence to diet, exercise, and medication regimens, is an essential component of health care for individuals with diabetes mellitus (DM). OBJECTIVE: The goals of this study were to examine sex-based differences in DM and to explore the effects of gender on self-care. METHODS: This study was conducted retrospectively using data from the 2001 Medical Expenditure Panel Survey (MEPS). People with DM were identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code; analyses were stratified by sex. Variables included age, race/ethnicity, education, income, body mass index (BMI), number of comorbidities, physical and cognitive limitations, smoking status, and depression. Outcome measures were assessed by Short Form-12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS) scores. Univariate analyses were determined using t, chi(2), or Fisher exact tests, as appropriate. Multivariate analyses examined associations between sex and SF-12 MCS/PCS scores adjusted for other variables. RESULTS: A total of 1653 MEPS respondents (883 women, 770 men) with DM were identified for the current study. The women were significantly older than the men (61.2 vs 59.1 years), had less education (11.1 vs 12.0 years), and had lower incomes. Women had higher calculated BMI (31.4 vs 30.3), more comorbidities (7.8 vs 6.4), more depression, and more physical and cognitive limitations than did men. Women also scored lower than men on the SF-12 MCS and PCS (47.8 vs 49.9 and 38.2 vs 41.4, respectively). All these measures were statistically significant (P < 0.01). In multivariate analyses, physical limitations, BMI, and number of comorbidities were negatively correlated, and income and education were positively correlated, with MCS and PCS scores. CONCLUSIONS: Compared with their male counterparts, diabetic women scored lower on measures of health status and functioning-factors that are likely to affect self-care activities. Sex-based differences should be considered when developing screening and treatment programs for people with DM.