The Relationship between 25-hydroxyvitamin D Levels, Insulin Sensitivity and Insulin Secretion in Women 3 Years after Delivery.

OBJECTIVES: There is a direct correlation between 25-hydroxyvitamin D (25[OH]D) levels and insulin sensitivity. Furthermore, women with gestational diabetes (GDM) may have lower levels of 25(OH)D compared to controls. The present study intended to investigate 25(OH)D levels and their association with insulin sensitivity and insulin secretion in women with prior GDM and in controls 3.2 years after delivery. METHODS: A total of 87 patients with prior GDM and 45 randomly selected controls (age range, 22 to 44 years) with normal glucose tolerance during pregnancy nested within a cohort of all deliveries at Saint Margit Hospital, Budapest, between January 1 2005, and December 31 2006, were examined. Their 25(OH) D levels were measured by radioimmunoassay. Insulin sensitivity and fasting insulin secretion were estimated using the homeostasis model asssessment (HOMA) calculator and early insulin secretion by the insulinogenic index based on a 75 g oral glucose tolerance test. RESULTS: There was no significant difference in 25(OH)D levels between cases and controls (27.2±13.1 [±SD] vs. 26.9±9.8 ng/L). There was a positive association between HOMA insulin sensitivity and 25(OH)D levels (beta = 0.017; 95% CI 0.001 to 0.034/1 ng/mL) that was robust to adjustment for age and body mass index. There was a nonsignificant association between HOMA insulin secretion and 25(OH)D (p=0.099), while no association was found with the insulinogenic index. CONCLUSIONS: Prior GDM status was not associated with 25(OH)D levels; however, 25(OH) D levels were associated with HOMA insulin sensitivity. It is hypothesized that the association between HOMA insulin secretion and 25(OH)D levels is related to the autoregulation of fasting glucose levels because no association between 25(OH)D and insulinogenic index was found.

Large increase in the prevalence of self-reported diabetes based on a nationally representative survey in Hungary.

AIMS: To estimate and compare the prevalence of self-reported diabetes based on nationally representative surveys of the Hungarian adult population in 2002 (published data - Hungarostudy) and a survey in 2012. METHODS: A cross-sectional computer-assisted telephone interview survey on a stratified representative sample of community-dwelling adults (n=1000) in 2012. To describe self-reported diabetes prevalence and its temporal changes generalized linear models were used and results were compared to figures from Hungarostudy. RESULTS: Age standardized prevalence of self-reported type 2 diabetes was 11.7% (95%CI 10.0-13.8%) without gender or rural-urban differences in 2012. People with self-reported diabetes were older than controls (mean [SE]: 63.9 [0.9] vs. 45.9 [0.3] years, p<0.0001). The prevalence of diabetes sharply increased after 40 years of age and peaked at age 70 (27.7% [2.5], page*age<0.0001). The prevalence of self-reported diabetes increased by 89% (OR 1.89, 95%CI 1.53-2.32) from 6.2 to 11.7% between the two surveys with the most pronounced increase in the age group 55-64 years (from 11.6 to 24.4%). CONCLUSIONS: We reported an alarming increase in the prevalence of self-reported type 2 diabetes in the last decade that mostly affects working age people. If this trend continues, a major public health crisis in Hungary can be envisaged.

[The severity of gestational diabetes mellitus affects microvascular dysfunction measured three years after pregnancy that may be related to increased oxidative stress]. / A gestatiós diabetes mellitus súlyossága befolyásolja a három évvel a szülést követoen mért microvascularis diszfunkció mértékét, amely kapcsolatban állhat az emelkedett szisztémás oxidatív stresszel.

INTRODUCTION: Oxidative-nitrative stress and poly(ADP-ribose) polymerase activation observed in gestational diabetes may play role in the increased cardiovascular risk in later life. AIM: The present study aimed to examine the influence of the severity of previous gestational diabetes (insulin need) on vascular function three years after delivery. Furthermore, the authors investigated the relation of vascular function with oxidative-nitrative stress and poly(ADP-ribose) polymerase activation. METHOD: Macrovascular function was measured by applanation tonometry; microvascular reactivity was assessed by provocation tests during Laser-Doppler flowmetry in 40 women who had gestational diabetes 3 years before the study. Oxidative-nitrative stress and poly(ADP-ribose) polymerase activity in blood components were determined by colorimetry and immunohistochemistry. RESULTS: Three years after insulin treated gestational diabetes impaired microvascular function and increased oxidative stress was observed compared to mild cases. CONCLUSIONS: The severity of previous gestational diabetes affects microvascular dysfunction that is accompanied by elevated oxidative stress. Nitrative stress and poly(ADP-ribose) polymerase activity correlates with certain vascular factors not related to the severity of the disease.

[Factors limiting glycaemic control in insulin-treated type 2 diabetes]. / A normoglykaemia elérésének korlátai inzulinkezelt 2-es típusú cukorbetegekben.

Insulin therapy is the most effective treatment of diabetes. It is proven to prevent microvascular disease and likely to decrease the risk of cardiovascular complications. However, these benefits are associated with a 2-3 times increased risk of hypoglycaemia and a faster weight gain compared to other antidiabetic medications. In addition, one study found elevated all-cause mortality among patients on intensive therapy (requiring more frequent insulinisation). Insulin has growth factor properties that may translate to increased mitogenicity. These factors could prevent the medical team or the patient from initiation or intensification of insulin therapy. The authors describe evidence on long-term remission related to transient intensified insulin therapy at diabetes diagnosis. The currently recommended method of insulin initiation is once daily basal insulin treatment that offers different schedules for intensification. The authors review the pharmacokinetics of analogue insulins that translate to similar efficacy to human insulins with a 20-30% lower risk of hypoglycaemia.

[Assessment of risk factors for fractures in postmenopausal women with osteoporosis]. / A csonttörés kockázati tényezoinek vizsgálata postmenopausás, osteoporosisos nobetegek körében.

INTRODUCTION: The main consequence of osteoporosis is bone fracture. Bone fracture risk is determined by several risk factors beyond osteodensitometric results. Some of these factors could be estimated by simple clinical questionnaires. AIM: The aim of the present study (Score-HU) was to investigate the risk factors of bone fracture among osteoporotic postmenopausal women (n = 11,221), who were examined in an osteologic outpatient departments. METHOD: Risk factors of each patient were recorded with the use of a simple identical data sheet. RESULTS: The incidence of risk factors were the following: previous bone fracture (79.4%), medication (except antiporotic treatment, antihypertensive drugs 67.9%, sleeping pills 36%, antidepressants 26.5%, corticosteroids 13.5%), decreased mobility (44.6%), early menopause (31.9%), smoking (31.2%), frequent falls (29.1%), and poor health status (more than 3 chronic diseases; 24.1%). CONCLUSIONS: Estimating the above mentioned risk factors we could assess the bone fracture risk more accurately than taking alone the bone mineral density results into consideration.

Heterogeneous effect of gestational weight gain on birth weight: quantile regression analysis from a population-based screening.

PURPOSE: Classical regression models might give an incomplete picture of the associations between predictors and outcomes. We investigated associations between gestational weight gain (GWG) and birth weight along the entire birth weight distribution with quantile regression and estimated effects of hypothetical prevention strategies. METHODS: The GWG-birth weight association was analyzed using quantile and classical regression models on data from a population-based gestational diabetes screening (n = 4760) at the Szent Imre Teaching Hospital in Budapest, Hungary (2002-2005). Birth weight distributions were modeled based on hypothetical GWG changes. RESULTS: At a body mass index of 20 kg/m(2), a 1-kg difference in GWG was associated with a 14.2 g (95% confidence interval, 10.0-20.9) higher birth weight at the fifth percentile of the birth weight distribution and a 29.0 g (21.3-35.6) higher birth weight at the 95th percentile. The coefficient from linear regression was 20.7 (17.5-24.0). Estimates differed modestly between the two regressions at a body mass index of 30 kg/m(2). A population-wide 2-kg decrease in GWG would rather affect the risk of macrosomia (-1.8%) than that of low birth weight (+0.4%). In contrast, a 3-kg decrease in GWG among overweight and obese women would lower macrosomia more modestly (-0.8%). CONCLUSIONS: A population-wide lowering of GWG would lead to greater improvements in the right tail of the birth weight distribution.

Assessment of the mineral density and mineral content of the equine third metacarpal and first phalanx bone by dual energy x-ray absorptiometry.

In the first part of this methodological study eleven metacarpi of 9 skeletally normal horses were examined from 4 directions by dual energy x-ray absorptiometry (DXA). The differences between the dorsopalmar-palmarodorsal and lateromedial-mediolateral (opposite sites) bone mineral density (BMD) values were found to be nonsignificant. In the second part of the study the precision of the Norland XR-26 densitometer was tested by measuring 34 metacarpal bones and 34 proximal phalanges, each of them three times, from a single direction. The difference between the individual measurements of the first phalanges and of the metacarpal bones originating from the right or the left side of the same horse were not significant, nor did the age or breed have a significant effect on BMD or bone mineral content (BMC). However, both BMD and BMC are greater in the metacarpal bones than in the proximal phalanges and are higher in geldings than in mares or to stallions, while the BMD or BMC values of mares and stallions did not differ from each other significantly. These data point to the necessity of further BMD studies in a higher number of patients.

Calcaneous quantitative ultrasound measurements predicts vertebral fractures in idiopathic male osteoporosis.

OBJECTIVES: The aim of this study was to identify the differences in ultrasound bone variables (QUS) and to test the ability to discriminate male patients with and without vertebral fractures. METHODS: We therefore measured broadband ultrasound attenuation (BUA) and speed of sound (SOS) matched for bone mineral density (BMD) and vertebral deformity in idiopathic male osteoporosis. RESULTS: One hundred and seventeen men (age 56.6 range 27-78) were divided into three groups (osteoporosis n=25, osteopenia n=58 and age-matched control n=34) according to BMD T-score by WHO criteria. We found 66 patients (56%) with at least one vertebral deformity during the study. BMD and BUA did not differ, while SOS was lower in osteoporosis (p<0.001) and control group (p<0.001) between the patients with and without vertebral compression. Strong positive correlation was demonstrated between BUA and BMD (lumbar spine r=0.44, p<0.001, femoral neck r=0.56, p<0.001, radius r=0.40, p<0.001), while similar association between SOS and BMD values was not shown. There was no relationship between the BUA and vertebral fracture risk (Odds ratio: 1.14 95% CI: 0.80-1.61). However, the relative risk of vertebral fracture by SOS was 1.56 (95% CI: 1.08-2.62). Adjusting for age and BMI the risk of vertebral fracture did not change (odds ratio for SOS 1.50 95% CI: 1.02-2.22). After adjustment for BMD SOS was still associated with fracture risk at all measured sites (odds ratio: 1.43, 95% CI: 1.02-2.22; 1.41, 95% CI: 1.02-2.17 and 1.32, 95% CI: 1.02-2.0). CONCLUSION: Our results suggest that BUA values are more closely related to density and structure while SOS values are able to predict fractures.

Comparison of the femoral neck bone density, quantitative ultrasound and bone density of the heel between dominant and non-dominant side.

Our study was initiated to evaluate whether there are differences between the two sides, depending on hand dominance, in densitometry values and quantitative ultrasound parameters (QUS) of the lower limb. One hundred and six women and 44 men were involved. The hand dominance was determined by interview. The bone mineral density (BMD) of the left and the right femoral necks and the calcanei were measured by dual-energy X-ray absorptiometry (DXA). The QUS examination consisted of measuring the attenuation (BUA), the speed of the ultrasound (SOS) and quantitative ultrasound index (QUI) transversing the left and right calcanei. The density of the neck of femur of the non-dominant side did not differ from that of the dominant side. On the other hand, BMD, BUA and the QUI of the calcaneus were higher on the non-dominant side in both genders (p<0.05 for each parameter). No similar differences were seen for the SOS values. Our study has confirmed the side-to-side differences of the calcaneus in both genders, lower values were found on the dominant side. No similar differences were seen on the femur. The AUC values seemed to be higher on the dominant side, however, these differences were not strictly significant. In the case of peripheral site (heel) measurements, the practical significance of our observations is that they raise the possibility of performing peripheral DXA and QUS examinations of the calcaneus on the dominant side of the patient according to handedness.

[Effect of cigarette smoking on bone quality parameters in women]. / A dohányzás hatása a nok csontjának minoségi jellemzoire.

INTRODUCTION: Smoking is a risk factor for osteoporosis. In a previous study, the authors showed lower bone density among smokers in a group of postmenopausal women. AIMS: After this finding, the primary goal of current research was to investigate how smoking could influence bone quality. METHODS: Forty-five (age range: 25-72 ys) smoker women were compared with 45 nonsmoker women adjusted for age and anthropometric parameters. Quantitative ultrasound method was used to determine the speed of ultrasound and the ultrasound attenuation transmitting the left heel (Achilles In Sight, GE Lunar). Dual photon absorptiometry method was applied to investigate the bone mineral density of lumbar spine and left femoral neck (Prodigy, GE Lunar) and single photon absorptiometry was used to determine the bone mineral content of radius at the non dominant side (NK-364, Gamma). RESULTS: No difference was found between smokers and non-smokers among the premenopausal group, however, postmenopausal smoker women had slightly lower speed of ultrasound and ultrasound attenuation values than non-smoker women. Postmenopausal smoker women suffering from bone fracture had significantly lower speed of ultrasound than postmenopausal non-smoker women (1508.9 vs. 1525.3 m/s, respectively), despite their bone density did not differ from each other. CONCLUSION: These data augment the knowledge about the injurious effect of smoking. The increased risk for bone fracture among smokers could be explained not only with the decrease of bone mass, which was previously described, but also with a decreased bone elasticity.

Increased bone fracture prevalence in postmenopausal women suffering from pollen-allergy.

INTRODUCTION: Our aim was to investigate whether pollen-allergy can affect bone mass and fractures in postmenopausal women. METHODS: A total of 125 postmenopausal pollen-allergic women (mean age: 61.26 yr) were split into four groups: (1) treated with neither H1 histamine receptor (H1R) antagonist nor inhaled corticosteroid (n=43); (2) treated only with H1R antagonist (n=53); (3) treated with both H1R antagonist and inhaled corticosteroid (n=17); (4) treated with only inhaled corticosteroid (n=12). Treatment, in the appropriate groups, had occurred for at least 5 years, seasonally. One-hundred non-allergic postmenopausal subjects matched for age, body mass index (BMI), and age at menopause served as controls. RESULTS: Overweight and obesity (25 kg/m(2) < or =BMI) were common among the allergic women (76%). Allergic patients without treatment had a slightly lower bone density than their non-allergic counterparts. The rate (34.9%) of prevalent low-energy fractures (distal forearm, hip, and clinical vertebral fractures) in untreated allergic patients was almost triple that observed in non-allergic women (13%, chi(2) p=0.003). Bone fracture occurred more often in H1R-only treated patients (30.19%) than in controls (chi(2) p=0.01); however, clinical vertebral or hip fractures developed neither in those treated only with H1R antagonist nor in those who received both H1R antagonist and inhaled corticosteroid. Bone fractures were more frequent among patients with inhaled steroid treatment than among patients with a combined treatment of inhaled steroid and antihistamine (50 versus 29.4%). BMI predicted prevalent fractures at 1.278 (95% CI: 1.047-1.559, p=0.016) for a 1 kg/m(2) increase among untreated allergic patients. CONCLUSION: In conclusion, we found a high prevalence of low-energy fractures among pollen-allergic postmenopausal women which was associated with obesity. It is possible that the H1R antagonists compensate for both the negative effect of pollen-allergy and the adverse effect of inhaled corticosteroid treatment on bone fracture risk.

The effect of intranasal salmon calcitonin therapy on bone mineral density in idiopathic male osteoporosis without vertebral fractures--an open label study.

The aim of this study was to examine the effect of intranasal salmon calcitonin therapy on bone mineral density (BMD) in idiopathic male osteoporosis without vertebral fractures. We conducted a randomized, open label, controlled trial in 71 male patients (mean age 59 +/- 6 years) suffering from idiopathic osteoporosis (femoral neck T-score < -2.5) without vertebral deformity. Patients in the control group (n = 31) received 400 IU Vitamin D + 1000 mg elemental calcium daily while the treatment group (n = 40) received 400 IU Vitamin D, 1000 mg elemental calcium plus 200 IU calcitonin nasal spray daily during alternate months. The study period was 18 months. Compared to controls, nasal calcitonin was associated with significant increases in bone mineral density at the lumbar spine (+3.5 +/- (-4.3%) vs. +0.83 +/- 6.4%, P = 0.04) and the femoral neck (+3.2 +/- 3.9% vs. +0.68 +/- 5.7%, P = 0.004). No significant difference was observed at the radius between the treatment groups (+1.4 +/- 8.8% vs. +1.4 +/- 10.9%, P = 0.98). Treatment was well tolerated with no premature discontinuations or significant side effects compared to the control group. We conclude that 200 IU salmon calcitonin nasal spray used daily, intermittently proved to be an effective and safe therapy in male idiopathic osteoporosis.

Bone disorders in experimentally induced liver disease in growing rats.

AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats. METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride (CCl(4)), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (F(max)) of the femora were determined. The results in animals treated with DEN+PB+CCl(4) (DPC, n = 21) were compared to those in untreated animals (UNT, n = 14) and in control group treated only with DEN+PB (DP, n = 20). RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8, but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and F(max) values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16. CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.