Association of adipokines and estradiol with bone and carotid calcifications in postmenopausal women.

OBJECTIVES: Carotid artery calcifications (CAC) and high carotid artery intima-media thickness (cIMT) are associated with low bone mineral density (BMD) by unknown mechanisms in postmenopausal women. Leptin, adiponectin and estradiol may mediate these associations. Our aim was to study the relationships of the aforementioned factors to bone health (BMD) and carotid atherosclerosis (CAC and cIMT). METHOD: Participants (n = 290, mean age 73.6 years) for this cross-sectional OSTPRE-BBA study (Kuopio Osteoporosis Risk Factor and Prevention - Bone, Brain and Atherosclerosis) were randomly selected from the OSTPRE cohort in 2009. Femoral neck and total body BMDs, trunk and total body fat mass were measured with dual-energy X-ray absorptiometry, and cIMT (mm) and CAC (no/yes) were measured with B-type ultrasound. Free estradiol, adiponectin and leptin were measured from serum samples. RESULTS: Circulating estradiol levels were associated with leptin (ß = 0.131, p < 0.001), but not with adiponectin (p > 0.05), when adjusted for total body fat mass. There were no associations between estradiol tertiles and BMDs, or with cIMT or CAC. Adiponectin levels were inversely associated with femoral neck BMD (p = 0.019, ß = -0.138) and total body BMD (p = 0.009, ß = -0.142), adjusted for total body fat mass, age, current smoking and estradiol, but showed no relationship with CAC or cIMT. Leptin levels were not associated with BMDs or cIMT; but the odds ratio was 1.5 between the CAC and leptin quartiles (p = 0.014), adjusted for total body fat mass, age, statin use and calcium intake. CONCLUSION: The adipokines are associated with vascular calcification and low BMD. Moreover, estradiol was not independently associated with BMD or CAC.

Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION).

AIMS: To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control. METHODS: In this multinational, randomized, double-blind, phase IIIb/IV study (GENERATION; NCT01006603), patients aged ≥65 years were randomized (1 : 1) to receive saxagliptin 5 mg/day or glimepiride ≤6 mg/day, added to metformin, during a 52-week treatment period. The primary endpoint was achievement of glycated haemoglobin (HbA1c) <7.0% at week 52 without confirmed/severe hypoglycaemia. The key secondary endpoint was incidence of confirmed/severe hypoglycaemia. Safety and tolerability were also assessed. RESULTS: Of 720 patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%; glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% confidence interval 0.73, 1.34; p = 0.9415); however, a significant treatment-by-age interaction effect was detected (p = 0.0389): saxagliptin was numerically (but not significantly) superior to glimepiride for patients aged <75 years (39.2 vs 33.3%) and numerically inferior for patients aged ≥75 years (35.9 vs 45.5%). The incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride (1.1 vs 15.3%; nominal p < 0.0001). Saxagliptin was generally well tolerated, with similar incidences of adverse events compared with glimepiride. CONCLUSION: As avoiding hypoglycaemia is a key clinical objective in elderly patients, saxagliptin is a suitable alternative to glimepiride in patients with T2D aged ≥65 years.

Declining cholecystectomy rate during the era of statin use in Finland: a population-based cohort study between 1995 and 2009.

BACKGROUND AND AIMS: Aging with comorbidities, obesity, and rapid recovery from operation may increase the need for laparoscopic cholecystectomy, but long-term use of statins may be associated with a decreased risk of gallstones. This population-based cohort study presents the changing rate and causative factors of laparoscopic cholecystectomy in Finland during the era of statin use. MATERIALS AND METHODS: Age structure of the population, changes in body mass index and diabetes, and the number of all cholecystectomies in 1995-2009 were retrieved from the registers of National Institute for Health and Welfare. Additionally, these results were supplemented by a population-based retrospective cohort (1581 laparoscopic cholecystectomy) in one community-based hospital area. The risk factors for laparoscopic cholecystectomy, use of statins, and surgical outcome were analyzed. RESULTS: During the 15 years, 123,794 cholecystectomies were performed in Finland, of which 94,740 (76.5%) were performed using laparoscopic technique. The median rate of laparoscopic cholecystectomy varied between 110 and 140 operations per 100,000 inhabitants. In 1995-2009, the annual number of cholecystectomies decreased from 8600 to 7500, the number of laparoscopic cholecystectomies increased by 10%, and the number of open cholecystectomies declined by 60%. In a cohort of 1581 laparoscopic cholecystectomies, the proportion of elderly (>65 years of age), obese (body mass index > 30 kg/m(2)), and diabetic patients increased from 17% to 28%, 9% to 34%, and 4% to 8%, respectively. Use of statins increased more than fourfold during the 15 years. CONCLUSIONS: The rates of all cholecystectomies decreased despite marked increase in laparoscopic cholecystectomies performed. The increase in risk factors for gallstones in Finland implied more marked increase in laparoscopic cholecystectomies. The possible role of statins on gallstone disease is discussed.

Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide.

OBJECTIVE: Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years. DESIGN: A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers. SUBJECTS: A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909. RESULTS: From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids. CONCLUSION: Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.

Ageing and associations of fasting plasma glucose and 2 h plasma glucose with HbA(1C) in apparently healthy population. "FIN-D2D" study.

OBJECTIVE: In this FIN-D2D cross-sectional survey the relationship of age with HbA(1c) and fasting and 2h glucose in the oral glucose tolerance test (OGTT) was explored in apparently randomly selected healthy population. PATIENTS AND METHODS: The glycaemic parameters were measured in 1344 men and 1482 women (aged 45-74 years), and among them we excluded all subjects with known diabetes, hypertension or dyslipidaemia. The final analyses for HbA(1c) and the ratios of fasting glucose/HbA(1c) and 2h glucose/HbA(1c) included 649 men and 804 women. RESULTS: Mean age was 57 years and BMI 26.1kg/m(2) for both genders. HbA(1c) increased in both genders with age (p<0.001). For a particular fasting glucose level HbA(1c) level was higher in older age groups (p<0.001 for linearity). By contrast, a particular 2h plasma glucose value in OGTT implied significantly lower HbA(1c) in the elderly (p<0.001 for linearity). CONCLUSION: In apparently healthy population, screened with OGTT, in older individuals compared with younger ones a particular HbA(1c) value implies slightly lower fasting glucose, but relatively higher 2h glucose. These results need to be verified in different populations. The effects of age on relation between HbA(1c) and plasma glucose should be taken into account in classifying people into different dysglycaemia categories.

Health economic consequences of reducing salt intake and replacing saturated fat with polyunsaturated fat in the adult Finnish population: estimates based on the FINRISK and FINDIET studies.

BACKGROUND/OBJECTIVES: To predict the health economic consequences of modest reductions in the daily intake of salt (-1.0 g per day) and replacement of saturated fat (SFA, -1.0 energy percent (E%)) with polyunsaturated fat (PUFA, +1.0 E%) in the Finnish population aged 30-74 years. SUBJECTS/METHODS: A Markov model with dynamic population structure was constructed to present the natural history of cardiovascular diseases (CVDs) based on the most current information about the age- and sex-specific cardiovascular risk factors, dietary habits and nutrient intake. To predict the undiscounted future health economic consequences of the reduction of dietary salt and SFA, the model results were extrapolated for the years 2010-2030 by replacing the baseline population in the year 2007 with the extrapolated populations from the official Finnish statistics. Finnish costs (€2009, societal perspective) and EQ-5D utilities were obtained from published references. RESULTS: During the next 20 years, a population-wide intervention directed at salt intake and dietary fat quality could potentially lead to 8000-13,000 prevented CVD cases among the Finnish adults compared the situation in year 2007. In addition, the reduced incidence of CVDs could gain 26,000-45,000 quality-adjusted life years and save €150-225 million over the same time period. CONCLUSION: A modest reduction of salt and replacement of SFA with PUFA in food products can significantly reduce the burden of CVD in the adult Finnish population. This impact may be even larger in the near future due to the ageing of Finnish population.

Body fat distribution is associated with lumbar spine bone density independently of body weight in postmenopausal women.

OBJECTIVE: To assess the association between the body fat distribution and axial bone mineral density (BMD) in postmenopausal women with or without hormone replacement therapy (HRT). DESIGN: Cross-sectional population-based study. SETTING: University of Eastern Finland, Bone and Cartilage Research Unit, Kuopio, Finland. POPULATION: 198 postmenopausal women, mean age 67.5 (1.9 SD), mean BMI 27.1 (3.9 SD). METHODS: Regional body composition and BMD assessed by dual X-ray absorptiometry (DXA, Prodigy). MAIN OUTCOME MEASURES: Spinal and Femoral BMD. RESULTS: Out of the body composition parameters, FM was the main determinant of postmenopausal bone mass. Only the lumbar spine (L2-L4) BMD, not the femoral neck BMD, was positively associated with the trunk FM. Positive trends for association were revealed between the spinal BMD and the trunk FM regardless of the use of HRT. Adjustments did not change the results. CONCLUSIONS: Higher trunk fat mass was associated with the spinal BMD, but not with the hip BMD in postmenopausal women, irrespective of the HRT use. In addition to biological factors, uncertainties related to DXA measurements in patients with varying body mass may contribute to this phenomenon.

A clinical and health economic review of a prefilled insulin pen.

OBJECTIVE: Several different durable or disposable insulin pen delivery devices are currently available, and newer, improved devices are being introduced. One prefilled insulin device, FlexPen (FP), has recently been improved (known as the Next Generation FlexPen (NGFP) in Europe or the improved FlexPen in the United States). The aim of this review is to summarize the clinical and health economic data of FP and its modified version. METHODS: Relevant clinical and health economic terms relating to insulin pens were used to search Medline for studies and other publications involving FP and NGFP. RESULTS: Sixteen publications investigating FP and/or the NGFP were identified. Patients prefer FP and are more confident with its use in comparison to vial/syringe insulin administration: in a study of 105 patients with type 1 or type 2 diabetes, 85% of patients found FP to be more discreet for use in public than a syringe, 74% of patients found FP to be easier to use overall and 82% of patients had more confidence with setting the correct dose with FP. Four publications investigated the dosing accuracy of FP or NGFP: all studies found the study doses for both were within ISO-specified limits. Pharmacoeconomic issues with insulin pen devices were identified in four papers, and switching to FP from vial/syringe was found to increase treatment adherence from 59% to 68% (p < 0.01), as measured by medication possession ratio. Switching to FP is also a cost-effective option for patients. Mean all-cause annual treatment (-$1748/patient, p < 0.01), hypoglycaemia-attributable costs (-$908/patient, p < 0.01), and other diabetes-attributable costs (-$643/patient, p < 0.01) were reduced following the switch from vial/syringe. CONCLUSIONS: Some limitations of traditional insulin administration devices can be overcome with insulin pen devices. FP is a prefilled disposable pen that has been modified to further improve characteristics beneficial to patient insulin administration.

Health-related quality of life among subjects with long-term mental symptoms in a population-based sample.

Women have shown to have poorer health-related quality of life (HRQL) than men. The purpose of this study was to examine HRQL, its gender differences and correlates among subjects (n = 158) with long-term mental symptoms in a population-based sample. HRQL was assessed with the eight dimensions and the Physical (PCS) and Mental Component Summary (MCS) scales of RAND-36. Sociodemographic and lifestyle factors were recorded and psychometric scales were administered. Psychiatric diagnoses were confirmed with the Structured Clinical Interview for DSM-IV. HRQL was quite poor in all dimensions of RAND-36 regardless of gender. Men and women had similarly poor scores for PCS and MCS. Mental health-related factors were main correlates of HRQL and this knowledge could be used in nursing practice and in health promotion.

Serum adiponectin and resistin levels in major depressive disorder.

OBJECTIVE: To examine the role of the adipose-tissue-derived low-grade inflammation markers adiponectin and resistin in major depressive disorder (MDD) in a population-based sample. METHOD: Serum levels of adiponectin and resistin were measured from 70 DSM-IV MDD subjects and 70 healthy controls. Depression severity was assessed with the 29-item Hamilton Depression Rating Scale. RESULTS: The MDD group had lowered serum adiponectin levels. Regression modelling with adjustments for age, gender, overweight, several socioeconomic and lifestyle factors, coronary heart disease and metabolic syndrome showed that each 5.0 microg/ml decrease in serum adiponectin increased the likelihood of MDD by approximately 20% (P = 0.01). The resistin levels correlated with atypical (P = 0.02), but not with typical depressive symptoms (P = 0.12). CONCLUSION: Our findings suggest that the lowered adiponectin levels in MDD are depression-specific and not explained by conventional low adiponectin-related factors such as such as coronary heart disease and metabolic disorders.

Effect of diet-induced weight loss on plasma apelin and cytokine levels in individuals with the metabolic syndrome.

BACKGROUND AND AIMS: Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss. METHODS AND RESULTS: 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods. CONCLUSION: Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

Association of depressive symptoms and metabolic syndrome in men.

OBJECTIVE: To explore the relationship between several indicators of depression and metabolic syndrome (MetS). METHOD: A population-based sample with high (HMS group) or low (LMS group) levels of mental symptoms, including those of depression, in three follow-ups participated in a clinical examination in 2005 (n = 223). MetS was determined according to the NCEP criteria. RESULTS: The prevalence of MetS was 49% in men and 21% in women. Men with MetS had higher rates of major depressive disorder than other men. They also displayed higher Hamilton Rating Scale for Depression (HDRS) scores and more often signs of suicidality. In logistic regression analyses, higher HDRS scores (OR 1.31, 95% CI 1.04-1.64) and belonging to the HMS group (OR 10.1, 95% CI 1.98-51.3) were independent associates for MetS but only in men. CONCLUSION: The results highlight that there is an association between long-term depressive symptoms and the emergence of MetS, especially in men.

The effect of glycaemic control on the quantitative characteristics of retinopathy lesions in patients with type 2 diabetes mellitus: 10-year follow-up study.

BACKGROUND: Diabetic retinopathy (DR) represents a common complication of type 2 diabetes mellitus. Appearance of DR lesions such as microaneurysms, haemorrhages, hard and soft exudates, IRMA and neovascularisation reflect the severity of DR. The aim of our study was to investigate the association of selected glycaemic parameters with particular DR abnormalities and their characteristics in patients with type 2 diabetes. METHODS: Eighty-three middle-aged patients with newly diagnosed type 2 diabetes mellitus participated in this 10-year prospective study. The glycaemic parameters such as glycated haemoglobin A1c (HbA1c), fasting blood/plasma glucose as well as 1- and 2-hour post-load glucose values were recorded at baseline, 5-year and 10-year follow-up. The fundus photographs were taken at baseline and then at 5-year and 10-year follow-ups and used for quantitative evaluation. RESULTS: Statistically significant positive correlations were found between all investigated 5-year glucose values and the extent of DR lesions at 10-year follow-up (p < 0.003). The 1- and 2-hour post-load glucose values correlated with the DR lesions with the highest significance (p

Downregulation of genes involved in NFkappaB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome: the GENOBIN study.

AIMS/HYPOTHESIS: The transcription factor nuclear factor-kappa-B (NFkappaB) is implicated in inflammatory responses, obesity and the metabolic syndrome, while immune cells appear to play a central role in mediating insulin resistance and can be used as a model to study inflammation and its relationship with insulin resistance. In peripheral blood mononuclear cells of overweight participants with the metabolic syndrome, we evaluated (1) the effect of diet-induced weight loss on the expression of genes involved in NFkappaB activation and (2) their association with insulin sensitivity. The genes studied were: TNF receptors TNFRSF1A and TNFRSF1B, and IL1R1, TLR4, TLR2, ICAM1, CCL5 and IKBKB. METHODS: We analysed data from 34 overweight participants with abnormal glucose metabolism and the metabolic syndrome, who were randomised to a weight-reduction (n = 24) or control group (n = 10) for 33 weeks. The mRNA expression was measured using real-time PCR. Measures of insulin and glucose homeostasis were assessed by IVGTT and OGTT. RESULTS: In general, the genes studied were downregulated after weight loss intervention. The changes in TLR4, TLR2, CCL5 and TNFRSF1A mRNA expression were associated with an increase in insulin sensitivity index independently of the change in waist circumference (p < 0.05). The change in IKBKB expression correlated with most of the changes in gene expression in the weight-reduction group. CONCLUSIONS/INTERPRETATION: These results suggest that proteins encoded by CCL5, TLR2 and TLR4, and TNFRSF1A might contribute to insulin-resistant states that characterise obesity and the metabolic syndrome. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00621205.

Glucose regulation and chronic pain at multiple sites.

OBJECTIVE: To analyse how glucose regulation status is associated with chronic regional pain and chronic widespread pain (CWP) in the adult population. METHODS: A structured interview and health examination study with 480 participants aged 30-65 yrs was carried out in Lapinlahti municipality in eastern Finland. The number of painful sites in the right or left upper and lower extremities, shoulders and hips, and in neck and back was summated. Those subjects with chronic pain in at least four sites were defined as having CWP. Diabetes and glucose tolerance status diagnosis were based on self-reported diagnoses, reimbursed medication and laboratory tests. Subjects with impaired fasting plasma glucose and/or elevated 2-h glucose level were combined into a group of impaired glucose regulation (IGR). RESULTS: Of the total sample, 55 subjects (11%) had diabetes. The prevalence of CWP was 13% (n = 62) in all subjects. The corresponding percentages for subjects with normal glucose regulation, IGR and diabetes were 9, 18 and 28%. In the multivariate analysis, diabetes was associated with CWP (odds ratio = 2.99; 95% CI 1.19, 7.53; P = 0.020). CONCLUSIONS: These results point to a significant association between diabetes and CWP in the adult population.

Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study.

OBJECTIVE: Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. DESIGN: Randomized controlled and individualized weight reduction intervention. SUBJECTS: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60+/-7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks. MEASUREMENTS: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction > or =5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR. RESULTS: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S (I) and the change in body weight was found (r=-0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (-39+/-16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=-0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention. CONCLUSION: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.

Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and genotype phenotype correlation.

OBJECTIVE: The existence of genotype-phenotype correlation in multiple endocrine neoplasia type 1 (MEN1) is controversial. Two founder mutations of the MEN1 gene in Northern Finland gave us an opportunity to compare clinical features among heterozygotes of different mutations. DESIGN AND METHODS: Study cohort included 82 MEN1 heterozygotes who were tested for MEN1 during the years 1982-2001. Medical records were reviewed for manifestations of MEN1, other tumours and cause of death by the end of August 2003. Logistic regression analysis was used in evaluating the impact of age, gender and mutational status of affected heterozygotes on the likelihood of developing manifestations of MEN1. RESULTS: Founder mutations 1466del12 and 1657insC were found in 39 and 29 individuals, and D418N, G156R and R527X mutations in 9, 3 and 2 individuals respectively. Except for pituitary adenoma and nonfunctional pancreatic tumour (NFPT), age was a risk factor for all the disease manifestations. For NFPT, frameshift/nonsense mutations (1657insC, R527X) gave an odds ratio (OR) of 3.26 (95% confidence intervals (CI), 1.27-8.33; P = 0.014) compared with in-frame/missense mutations (1466del12, D418N, G156R); including the founder mutation carriers (n = 68) only, the 1657insC mutation gave an OR of 3.56 (CI, 1.29-9.83; P = 0.015). For gastrinoma, in-frame/missense mutations predicted the risk with an OR of 6.77 (CI, 1.31-35.0; P = 0.022), and in the founder mutations group the 1466del12 mutation gave an OR of 15.09 (CI, 1.73-131.9, P = 0.014). CONCLUSIONS: In this study population, NFPT was more common in the frameshift/nonsense or 1657insC mutation carriers, whereas gastrinoma was more common in the in-frame/missense or 1466del12 mutation carriers.

Is discordance in bone measurements affected by body composition or anthropometry? A comparative study between peripheral and central devices.

Screening of osteoporosis using peripheral bone measurements has become more common, even though diagnostic discrepancies are known to exist between peripheral dual-energy X-ray (pDXA) or quantitative ultrasound (QUS) and central DXA measurements. Values of diagnostic parameters such as bone mineral density, speed of (ultra)sound, and broadband ultrasound attenuation are affected by bone size and soft tissue composition. However, their significance for the discordance between peripheral and central techniques is unclear. In this study, bone status and total body composition of 139 women (mean age 68.3 yr [1.7 SD], mean body mass index 26.5 kg/m2 [3.6 SD]) were assessed by 3 GE Lunar devices. Heel pDXA and heel QUS were conducted using peripheral instantaneous X-ray imaging (PIXI) and Achilles, respectively, and central DXA measurements were taken at the posterior-anterior lumbar spine (L2-L4) and at the left femoral neck using Prodigy. Positive significant associations were found between body height or fat (%) and most DXA or QUS parameters. The discordance between the site-dependent DXA or QUS T-score values typically increased (p<0.05) as a function of body weight or fat (%), but not with body height. On an average, body adiposity accounted for less than 11% of the differences between the techniques; however, increase of total body fat from 20% to 45% led to a discrepancy of one T-score between DXA(HEEL) and QUS(HEEL). To avoid diagnostic bias, comparative assessment of the devices using the same population is recommended.

Glycemic responses of oat bran products in type 2 diabetic patients.

BACKGROUND AND AIM: Cereal products with low postprandial glycemic response are encouraged in the management of hyperglycemia. In this study, we determined the postprandial glycemic response of two different oat bran products in patients with type 2 diabetes. In addition, we investigated the effects of oat bran flour on postprandial glucose response following an oral glucose load. METHODS AND RESULTS: A randomized, controlled, repeated measures design with two test series was used. Twelve type 2 diabetic patients participated in five 2-h meal glucose tolerance tests on separate occasions. Volunteers were given in random order oat bran flour, oat bran crisp and glucose load providing 12.5 g glycemic carbohydrate (series 1), 25 g glucose load alone and 25 g glucose load with 30 g oat bran flour (series 2). Finger-prick capillary blood analysis was carried out fasting and then 15, 30, 45, 60, 90 and 120 min after the start of the meal. The oat bran flour had a lower 0-120 min area under the glucose response curve (AUC) (47+/-45 mmol min/L) than the glucose load (118+/-40 mmol min/L) (p<0.002), but there was no difference between the oat bran crisp (93+/-41 mmol min/L) and the glucose load in this respect. The oat bran flour decreased the glucose excursion from baseline by 1.6 mmol/l (2.4, 0.8) (mean (95% CI)) and 1.5 mmol/l (2.0, 1.1) at 30 and 45 min after the glucose load, respectively. CONCLUSIONS: Oat bran flour high in beta-glucan had a low glycemic response and acted as an active ingredient decreasing postprandial glycemic response of an oral glucose load in subjects with type 2 diabetes.