First-trimester HbA1c in relation to plasma glucose concentrations in an oral glucose tolerance test at 12 to 16 weeks' gestation-a population-based study.

BACKGROUND: Early-onset GDM often requires pharmacological treatment and is associated with adverse perinatal outcomes, but data is insufficient regarding the best methods to identify high-risk women requiring early GDM screening. The aim of this study was to analyze the diagnostic accuracy of HbA1c in the prediction of (1) plasma glucose concentrations > 90th percentile in an oral glucose tolerance test (OGTT) at 12-16 weeks' gestation; and (2) pharmacologically treated early- or late-onset GDM. METHODS: HbA1c was measured at 8-14 weeks' gestation in a population-based cohort of 1394 Finnish women recruited for the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study between 3/2013 and 12/2016. Information on maternal risk factors were collected at recruitment. Subsequently, a 2-hour 75 g OGTT was performed at 12-16 weeks' gestation (OGTT1), and if normal, repeated at 24-28 weeks' gestation (OGTT2). Early- and late-onset GDM were diagnosed using the same nationally endorsed cut-offs for fasting, 1 h- and 2 h-plasma glucose: ≥5.3, ≥ 10.0mmol/l, and/or ≥ 8.6mmol/l, respectively. In total, 52/1394 (3.7%) women required metformin or insulin treatment for GDM, including 39 women with early-onset GDM diagnosed at OGTT1 and 13 women with late-onset GDM diagnosed at OGTT2. RESULTS: Maternal early-pregnancy HbA1c ≥ 35mmol/mol (≥ 5.4%) was the best cut-off to predict fasting or post-load plasma glucose > 90th percentile in OGTT1, but its diagnostic accuracy was low [AUC (95% CI) 0.65 (0.62 to 0.69), sensitivity 0.55 (0.49 to 0.60) and specificity 0.67 (0.64 to 0.70)] both alone and in combination with other maternal risk factors. However, HbA1c ≥ 35mmol/mol correlated positively with plasma glucose concentrations at all time points of OGTT1 and predicted pharmacologically treated GDM diagnosed at OGTT1 or OGTT2; AUC (95% CI) 0.75 (0.68 to 0.81), sensitivity 0.75 (0.61 to 0.86), specificity 0.64 (0.61 to 0.66). CONCLUSIONS: In our population-based cohort, early-pregnancy HbA1c ≥ 35mmol/mol was positively associated with fasting and post-load plasma glucose concentrations in an OGTT at 12-16 weeks' gestation and predicted pharmacologically-treated early- and late-onset GDM, suggesting potential utility in first-trimester identification of women at high risk of severe GDM subtypes.

Large maternal waist circumference in relation to height is associated with high glucose concentrations in an early-pregnancy oral glucose tolerance test: A population-based study.

INTRODUCTION: To explore the role of maternal anthropometric characteristics in early-pregnancy glycemia, we analyzed the associations and interactions of maternal early-pregnancy waist circumference (WC), height and pre-pregnancy body mass index (BMI) with plasma glucose concentrations in an oral glucose tolerance test (OGTT) at 12-16 weeks' gestation. MATERIAL AND METHODS: A population-based cohort of 1361 pregnant women was recruited in South Karelia, Finland, from March 2013 to December 2016. All participants had their WC, weight, height, HbA1c , and blood pressure measured at 8-14 weeks' gestation and subsequently underwent a 2-h 75-g OGTT, including assessment of fasting insulin concentrations, at 12-16 weeks' gestation. BMI (kg/m2 ) was calculated using self-reported pre-pregnancy weight. Maternal WC ≥80 cm was defined as large. Maternal height ≥166 cm was defined as tall. Data on gestational diabetes treatment was extracted from hospital records. RESULTS: In the total cohort, 901 (66%) of women had an early-pregnancy WC ≥80 cm, which was associated with higher early-pregnancy HbA1c, higher concentrations of  fasting plasma glucose and serum insulin, higher post-load plasma glucose concentrations, higher HOMA-IR indices, higher blood pressure levels, and higher frequencies of pharmacologically treated gestational diabetes, than early-pregnancy WC <80 cm. Maternal height ≥166 cm was negatively associated with 1- and 2-h post-load plasma glucose concentrations. Waist-to-height ratio (WHtR) >0.5 was positively associated with both fasting and post-load plasma glucose concentrations at 12-16 weeks' gestation, even when adjusted for age, smoking, nulliparity, and family history of type 2 diabetes. The best cut-offs for WHtR (0.58 for 1-h plasma glucose, and 0.54 for 2-h plasma glucose) were better predictors of post-load glucose concentrations >90th percentile than the best cut-offs for BMI (28.1 kg/m2 for 1-h plasma glucose, and 26.6 kg/m2 for 2-h plasma glucose), with areas-under-the-curve (95% confidence interval) 0.73 (0.68-0.79) and 0.73 (0.69-0.77), respectively, for WHtR, and 0.68 (0.63-0.74) and 0.69 (0.65-0.74), respectively, for BMI. CONCLUSIONS: In our population-based cohort, early-pregnancy WHtR >0.5 was positively associated with both fasting and post-load glucose concentrations at 12-16 weeks' gestation and performed better than BMI in the prediction of post-load glucose concentrations >90th percentile. Overall, our results underline the importance of evaluating maternal abdominal adiposity in gestational diabetes risk assessment.

1H NMR Urinary Metabolomic Analysis in Older Adults after Hip Fracture Surgery May Provide Valuable Information for Patient Profiling-A Preliminary Investigation.

In these times of precision and personalized medicine, profiling patients to identify their needs is crucial to providing the best and most cost-effective treatment. In this study, we used urine metabolomics to explore the characterization of older adults with hip fractures and to explore the forecasting of patient outcomes. Overnight urine specimens were collected from 33 patients (mean age 80 ± 8 years) after hip fracture surgery during their stay at a rehabilitation hospital. The specimens were analyzed with 1H NMR spectroscopy. We performed a metabolomics study regarding assessments of frailty status, Functional Independence Measure (FIM), and Short Physical Performance Battery (SPPB). The main metabolic variations concerned 10 identified metabolites: paracetamol derivatives (4 peaks: 2.15 ppm; 2.16 ppm; 7.13 ppm and 7.15 ppm); hippuric acid; acetate; acetone; dimethylamine; glycine; alanine; lactate; valine; TMAO. At baseline, the urinary levels of these metabolites were significantly higher (i) in frail compared with non-frail patients, (ii) in persons with poorer FIM scores, and (iii) in persons with poorer compared SPPB scores. Our findings suggested that patients with increased levels of urine metabolites associated with metabolic, inflammatory, and renal disorders presented clear signs of frailty, impaired functional independence, and poor physical performance. Metabolomics could be a valuable tool to further characterize older adults, especially after major medical events.

Oral glucose tolerance test results in early pregnancy: A Finnish population-based cohort study.

AIMS: To analyze early-pregnancy oral glucose tolerance test (OGTT) results and differences between early- and late-pregnancy OGTT results in a population-based cohort. METHODS: From 3/2013 to 12/2016, pregnant women in South Karelia, Finland, were invited to undergo a 2-hour 75 g OGTT at 12-16 weeks' gestation (OGTT1) and, if normal, repeat testing at 24-28 weeks (OGTT2). Early and late gestational diabetes (GDM) were diagnosed using the same nationally endorsed criteria (fasting [FPG], 1- or 2-hour plasma glucose ≥5.3, ≥10.0 or ≥8.6 mmol/L, respectively). RESULTS: In OGTT1 (n = 1401), the mean (SD) FPG, 1- and 2-hour values were 4.85 (0.34), 6.63 (1.73) and 5.60 (1.28) mmol/L, respectively. Early GDM was diagnosed in 209 (14.9%). In OGTT2 (n = 1067), late GDM was diagnosed in 114 (10.6%). In women without GDM (n = 953), the mean FPG values were higher and post-load values lower in OGTT1 vs. OGTT2. No interaction effects of gestational timepoint and maternal BMI on OGTT results were detected, except for the 2-hour value. In women with late GDM, both mean FPG and post-load values were lower in OGTT1 vs. OGTT2. Results were similar employing the IADPSG GDM criteria. CONCLUSIONS: Our findings suggest that gestational-age specific OGTT thresholds for early GDM diagnosis need to be generated.

Effect of long-term endurance and strength training on metabolic control and arterial elasticity in patients with type 2 diabetes mellitus.

Poor glucose control increases the risk of vascular complications and cardiovascular mortality in patients with diabetes mellitus (DM). Our aim was to evaluate the efficacy of a long-term exercise training program on metabolic control and arterial stiffness in patients with type 2 DM. Fifty men with DM (age 52.3 +/- 5.6 years) were randomly assigned to the exercise training (E) or standard treatment for DM (control [C]) group for 24 months. Supervised exercise training included both endurance and muscle strength training 4 times/week. All exercise sessions were controlled by heart rate and intensity. Glycated hemoglobin A1c, insulin, leptin, blood lipids, blood pressure, maximal oxygen consumption in spiroergometry, and muscle strength were measured every 6 months. Arterial stiffness was assessed by measuring pulse wave velocity. Maximal oxygen consumption in spiroergometry (E 31.9 to 34.8 vs C 32.6 to 31.8 ml/kg/min; p = 0.003), muscle strength (sit-up test, E 12.7 to 20.8 vs C 14.6 to 13.1 times; p <0.001), hemoglobin A1c (E 8.2% to 7.6% vs C 8.0% to 8.3%; p = 0.006), and leptin (E 7.4 to 6.7 vs C 7.4 to 7.9 microg/L; p = 0.013) improved significantly in the E group, but no change or worsening in these variables occurred in the C group. Body weight was not different between groups at 2 years. However, pulse wave velocity increased in both groups (E +0.600 vs C +1.300 m/s; p = 0.27). In conclusion, long-term endurance and strength training was effective and resulted in improved metabolic control of DM compared with standard treatment. Despite significant cardiovascular risk reduction, conduit arterial elasticity did not improve.

Clinical performance of six different serum tartrate-resistant acid phosphatase assays for monitoring alendronate treatment.

Two forms of tartrate-resistant acid phosphatase (TRACP) circulate in human blood, TRACP 5a derived from inflammatory macrophages and TRACP 5b derived from osteoclasts. We compared the clinical performance of the following TRACP immunoassays for monitoring alendronate treatment in postmenopausal women: 1) TRACP 5b activity using a selective pH; 2) TRACP 5b activity using a selective substrate; 3) Total TRACP activity; 4) Total TRACP protein amount; 5) TRACP 5a activity; 6) TRACP 5a protein amount. TRACP and other bone turnover markers were measured before the start of treatment and at 3 months. Alendronate treatment decreased TRACP values determined with assays 1, 2 and 3, and had no effect on the values determined with assays 4, 5 and 6. Clinical performance of assays 1, 2 and 3 was good, and these assays correlated with each other and with the other bone markers. This study showed that TRACP 5b specific methods are useful for monitoring changes in bone resorption during alendronate treatment, and alendronate treatment does not affect serum TRACP 5a levels.

The association of myeloperoxidase promoter polymorphism with carotid atherosclerosis is abolished in patients with type 2 diabetes.

OBJECTIVES: Type 2 diabetes mellitus (DM) enhances the development of atherosclerosis and reduces the activity of the oxidative myeloperoxidase (MPO) enzyme. MPO gene has a functional promoter polymorphism -463G/A which leads to high- (GG) and low-expression (AG, AA) genotypes. DESIGN AND METHODS: We studied the association of MPO polymorphism with carotid artery intima-media thickness (IMT) in 198 randomly selected Finnish men of Caucasian origin, 161 non-diabetics and 37 with type 2 DM. Their carotid IMT was measured by high-resolution ultrasonography, and the overall mean IMT value was calculated. MPO genotypes were determined by the PCR-RFLP method. RESULTS: We found significant MPO genotype-by-study-group (control/DM) interactions with the overall mean IMT and internal carotid IMT (p=0.05 and p=0.04, respectively). Among non-diabetic subjects, the overall carotid IMT was 7.3% higher in subjects with the low-activity genotype when compared to the high-activity (G/G) group. The results remained significant after adjustment for total cholesterol and smoking (p=0.015). No similar genotypic association was found for the subjects with type 2 DM. CONCLUSIONS: This data suggests that in subjects with normal glucose metabolism, MPO gene variation may modify the carotid artery IMT.

Exercise training does not improve myocardial diastolic tissue velocities in Type 2 diabetes.

BACKGROUND: Myocardial diastolic tissue velocities are reduced already in newly onset Type 2 diabetes mellitus (T2D). Poor disease control may lead to left ventricular (LV) systolic dysfunction and heart failure. The aim of this study was to assess the effects of exercise training on myocardial diastolic function in T2D patients without ischemic heart disease. METHODS: 48 men (52.3 +/- 5.6 yrs) with T2D were randomized to supervised training four times a week and standard therapy (E), or standard treatment alone (C) for 12 months. Glycated hemoglobin (HbA1c), oxygen consumption (VO2max), and muscle strength (Sit-up) were measured. Tissue Doppler Imaging (TDI) was used to determine the average maximal mitral annular early (Ea) and late (Aa) diastolic as well as systolic (Sa) velocities, systolic strain (epsilon) and strain rate (epsilon) from the septum, and an estimation of left ventricular end diastolic pressure (E/Ea). RESULTS: Exercise capacity (VO2max, E 32.0 to 34.7 vs. C 32.6 to 31.5 ml/kg/min, p = .001), muscle strength (E 12.7 to 18.3 times vs. C 14.6 to 14.7 times, p < .001), and HbA1c (E 8.2 to 7.5% vs. C 8.0 to 8.4%, p = .006) improved significantly in the exercise group compared to the controls (ANOVA). Systolic blood pressure decreased in the E group (E 144 to 138 mmHg vs. C 146 to 144 mmHg, p = .04). Contrary to risk factor changes diastolic long axis relaxation did not improve significantly, early diastolic velocity Ea from 8.1 to 7.9 cm/s for the E group vs. C 7.4 to 7.8 cm/s (p = .85, ANOVA). Likewise, after 12 months the mitral annular systolic velocity, systolic strain and strain rate, as well as E/Ea were unchanged. CONCLUSION: Exercise training improves endurance and muscle fitness in T2D, resulting in better glycemic control and reduced blood pressure. However, myocardial diastolic tissue velocities did not change significantly. Our data suggest that a much longer exercise intervention may be needed in order to reverse diastolic impairment in diabetics, if at all possible.

The relationship of sterol regulatory element-binding protein cleavage-activation protein and apolipoprotein E gene polymorphisms with metabolic changes during weight reduction.

Sterol regulatory element-binding protein cleavage-activating protein (SCAP) and apolipoprotein E (apo E) regulate cellular and plasma lipid metabolism. Therefore, variations in the corresponding genes might influence weight reduction and obesity-associated metabolic changes. We investigated the relationships of SCAP (Ile796Val) and apo E polymorphisms on metabolic changes during weight reduction by using a 12-week very low-energy diet. Body composition, serum lipids, plasma glucose, and insulin were assessed in 78 healthy premenopausal women (initial body mass index, 34 +/- 4 kg/m(2); age, 40 +/- 4 years) before and after the intervention. The SCAP genotype groups did not differ in the responses of any parameters measured during weight reduction. Apo E did not differentiate the weight loss, but the changes in total and low-density lipoprotein cholesterol for the genotype groups apo E epsilon2/3, epsilon3/3, as well as epsilon3/4 and epsilon4/4 combined were -0.94 +/- 0.56 and -0.59 +/- 0.32, -0.71 +/- 0.49 and -0.49 +/- 0.45, and -0.55 +/- 0.47 and -0.37 +/- 0.39 mmol/L, respectively (P < .05 for both). In conclusion, neither the SCAP Ile796Val nor the apo E polymorphism was associated with weight loss in obese premenopausal women. However, the apo E-but not SCAP genotype-seems to be one of the modifying factors for serum cholesterol concentrations during very low-energy diet in obese premenopausal women.

Association of the IL6-174(G/C) polymorphism with C-reactive protein concentration after weight loss in obese men.

Elevated plasma concentration of C-reactive protein has emerged as an important predictor of future cardiovascular diseases and metabolic abnormalities in apparently healthy individuals. Obese individuals tend to have elevated C-reactive protein concentrations. Weight loss induces a change in this protein, and single nucleotide polymorphisms in regulating genes might affect this change, since C-reactive protein concentration is known to be approximately 40-50% heritable. Our aim was to study the association between the IL6 -174(G/C), IL1B +3,954(C/T) and CRP +1,059(G/C) single nucleotide polymorphisms, and CRP concentrations in obese men during a weight reduction program. We genotyped 72 obese men who had participated in a weight reduction program. Their C-reactive protein concentrations, interleukin-6 levels and fat mass were determined at two time points: at baseline and after weight reduction (after 2 months). After weight reduction, the mean weight loss was 14.3 kg. Median C-reactive protein concentrations decreased, after weight reduction, from 1.72 to 1.22 mg/l (p < 0.02). The baseline C-reactive protein concentration did not differ between the IL6-174(G/C) genotypes, but after weight loss, concentrations differed (p = 0.03 Kruskal-Wallis test); the highest concentration was found in the CC genotype (CC 1.01 versus GG 1.93 mg/l, p = 0.007 ANOVA post-hoc test). This change in concentration was associated with the IL6-174(G/C) genotype (p = 0.01, Kruskal-Wallis test), being least in the CC genotype. The other single nucleotide polymorphisms studied were not associated with CRP concentrations. Our results show that, at baseline, there is no difference in C-reactive protein concentrations among the different IL6-174(G/C) genotypes, but after weight loss the CC genotype is associated with highest C-reactive protein concentrations, resulting from the fact that C-reactive protein seems not to decrease with weight loss in this genotype.

Impaired myocardial function in newly onset type 2 diabetes associates with arterial stiffness.

AIM: The aim of this study was to evaluate myocardial function using pulsed and color-coded tissue Doppler imaging (TDI) and vascular wall elasticity using whole-body impedance cardiography (ICG) in patients with newly diagnosed Type 2 diabetes mellitus (DM2), and to compare the measurements with those of healthy controls. METHODS: Systolic (SBP) and diastolic (DBP) blood pressure and glycosylated hemoglobin (HbA1c) were measured in 49 men (mean age 52.3+/-5.6 years, duration of DM2 1.8 years), and 15 healthy male control subjects (48.3+/-7.4 years). Mitral annular peak systolic (Svm), early (Evm), and late (Avm) diastolic velocities as well as myocardial peak systolic (Sv), early (Ev) and late diastolic (Av) velocity from middle segments of the anterior, inferior and lateral wall and the inferior septum were measured by TDI. ICG at rest was used to measure cardiac index (CI) and pulse wave velocity (PWV). RESULTS: The patients had higher body mass index (BMI 29.1+/-3.7 vs. 25.2+/-2.4 kg/m(2), p=0.000) and SBP (142+/-15 vs. 120+/-7 mmHg, p=0.005) than the controls, CI was comparable (2.8+/-0.5 vs. 2.8+/-0.6l/min/m(2)). The patients had lower age adjusted myocardial Sv (3.8+/-1.1 vs. 4.8+/-1.1cm/s, p=0.002) and Ev (4.6+/-1.6 vs. 6.2+/-1.7 cm/s, p=0.011), and also mitral annulus peak early diastolic velocity (Evm 7.8+/-1.9 vs. 10.4+/-2.6 cm/s, p=0.001). In diabetic patients PWV (14.2+/-2.7 vs. 10.0+/-1.7 m/s, p=0.002) was higher. Age (r=-0.39, p=0.001), BMI (r=-0.44, p=0.000) and PWV (r=-0.52, p=0.000) correlated significantly with Evm. PWV correlated with age (r=0.50, p=0.000), SBP (r=0.67, p=0.000), and HBA1c (r=0.36, p=0.010). In stepwise regression analysis, PWV (beta=-0.39, p=0.000) was the major determinant of Evm. CONCLUSION: Myocardial function is impaired in asymptomatic patients with newly detected DM2 consistent with diabetic heart muscle disease. Arterial stiffness is strongly related to myocardial dynamics, and both may have the same pathophysiologic background.

Blood leukocyte count is a risk factor for intima-media thickening and subclinical carotid atherosclerosis in middle-aged men.

Leukocytosis is known to predict future cardiovascular events even in subjects without coronary heart disease (CHD), but its association with early atherosclerotic changes has remained less certain. The aim of the present study was to investigate how the blood leukocyte count compares with several other risk factors for CHD in determining carotid artery intima-media thickness (IMT) and subclinical carotid atherosclerosis in a population sample. Both carotid arteries were investigated with high-resolution B-mode ultrasound in a community-based sample of 219 randomly selected men aged 50-59 years to calculate the mean maximum IMT (MMax IMT) of 12 standard sites. Risk factor assessment included several traditional biochemical risk factors, blood pressure, maximal oxygen consumption and work load on ergometry, life-style habits and hematologic parameters. As genetic determinants, apolipoprotein E and A-IV polymorphisms were studied. According to multivariate regression analysis, age (P<0.0001), blood leukocyte count (P<0.0001) and systolic blood pressure (P<0.042) were the only significant predictors of MMax IMT. MMax IMT increased linearly from the lowest tertile of blood leukocyte count (1.14+/-0.20mm) to the second (1.18+/-0.25 mm) and to the highest tertile (1.25+/-0.27 mm, P=0.019). This difference remained significant after adjustment with age, systolic blood pressure and smoking (P=0.032). Leukocytes seem to have an independent role in the early arterial damage and they may reflect subclinical disease. This implies that leukocyte count is undervalued in the diagnostics and prognostics of carotid atherosclerosis.

Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover.

UNLABELLED: We studied clinical performance of serum TRACP 5b and other bone turnover markers, including S-CTX, U-DPD, S-PINP, S-BALP, and S-OC, for monitoring alendronate treatment. TRACP 5b had higher clinical sensitivity, area under the ROC curve, and signal-to-noise ratio than the other markers. INTRODUCTION: The purpose of this study was to compare the clinical performance of serum TRACP 5b (S-TRACP5b) with that of other markers of bone turnover in the monitoring of alendronate treatment. MATERIALS AND METHODS: This double-blinded study included 148 healthy postmenopausal women that were randomly assigned into two groups: one receiving 5 mg alendronate daily (n=75) and the other receiving placebo (n=73) for 12 months. All individuals in both groups received calcium and vitamin D daily. The bone resorption markers S-TRACP5b, serum C-terminal cross-linked telopeptides of type I collagen (S-CTX), and total urinary deoxypyridinoline (U-DPD), and the serum markers of bone formation procollagen I N-terminal propeptide (S-PINP), bone-specific alkaline phosphatase (S-BALP), and total osteocalcin (S-OC) were assessed at baseline and at 3, 6, and 12 months after initiation of treatment. Lumbar spine BMD (LBMD) was measured at baseline and 12 months. RESULTS: Compared with the placebo group, LBMD increased, and all bone markers decreased significantly more in the alendronate group (p<0.001 for each parameter). The decrease of S-TRACP5b after first 3 months of alendronate treatment correlated significantly with the changes of all other markers except S-OC, the best correlation being with S-CTX (r=0.60, p<0.0001). The changes of LBMD at 12 months only correlated significantly with the changes of S-TRACP5b (r=-0.32, p=0.005) and S-CTX (r=-0.24, p=0.037) at 3 months. Based on clinical sensitivity, receiver operating characteristic (ROC) curves, and signal-to-noise ratio, S-TRACP5b, S-CTX, and S-PINP were the best markers for monitoring alendronate treatment. Clinical sensitivity, area under the ROC curve, and signal-to-noise ratio were higher for S-TRACP5b than for the other markers. CONCLUSION: These results show that S-TRACP5b, S-CTX, and S-PINP are useful markers for monitoring alendronate treatment.

Effects of a weight maintenance program with or without exercise on the metabolic syndrome: a randomized trial in obese men.

BACKGROUND: Weight maintenance (WM) after weight reduction (WR) is difficult, but increased physical activity may help. We studied whether adding exercise to diet counseling decreases the occurrence of the metabolic syndrome (MBO). METHODS: Ninety voluntary middle-aged men with a BMI range of 30-40 and a waist girth >100 cm were recruited to the research institute's clinic in 1997. After a very-low-energy diet for 2 months (WR), the men were randomized into a walking, resistance training or control group for 6 months (WM). All groups received similar dietary advice. After WM, there was a 23-month follow-up. Diagnosis of MBO was based on >or= 3 components. RESULTS: After WR, the mean weight loss was 14.2 kg. At the end, the weight decrease was 4.8 kg (n = 68) with no statistically significant difference between the groups. All groups had improved some components (insulin, HDL cholesterol, body composition) of MBO. When the groups were combined, the odds ratio for the occurrence of MBO (vs. baseline) was 0.10 after WR, 0.08 after WM and 0.29 at the end. CONCLUSIONS: Adding structured exercise to diet counseling did not alleviate MBO better than diet only. However, the occurrence of MBO was reduced in all groups at the end.

The association of the apolipoprotein E gene promoter polymorphisms and haplotypes with serum lipid and lipoprotein concentrations.

BACKGROUND: Apolipoprotein E (ApoE) is known to modulate lipoprotein transport and metabolism. The common APOE epsilon2/epsilon3/epsilon4 polymorphism explains part of the variation in plasma cholesterol levels. Polymorphisms of the APOE gene regulatory region are suggested to be involved in explaining variation of lipoprotein levels within the APOE epsilon2/epsilon3/epsilon4 genotypes. OBJECTIVES: To study the associations of the APOE gene promoter polymorphisms -219G/T and +113G/C and their haplotypes with serum lipid and lipoprotein concentrations, especially within the most common APOE epsilon3/epsilon3 genotype group. SUBJECTS AND METHODS: From 219 middle-aged Finnish men, APOE genotypes were determined and haplotypes estimated. Plasma lipoproteins were isolated by ultracentrifugation and their lipids were measured. RESULTS: The studied APOE promoter polymorphisms and haplotypes associated with certain lipid variables independently of the APOE epsilon2/epsilon3/epsilon4 genotype. Within the APOE epsilon3/epsilon3 group, both -219G/G and +113G/G genotypes associated statistically significantly with higher levels of very low-density lipoprotein (VLDL) cholesterol, apoB and triglycerides, and tended to associate with lower HDL-cholesterol concentrations than the other genotypes. Compared with the -219T/+113C/epsilon3 haplotype, the more common -219G/+113G/epsilon3 haplotype was found more frequently among the group having high (over median) VLDL-cholesterol and triglyceride concentrations (OR 2.6, p<0.001 and OR=2.1, p=0.009, respectively). CONCLUSIONS: In addition to the APOE epsilon2/epsilon3/epsilon4 polymorphism, the promoter polymorphisms -219G/T and +113G/C as well as their haplotype modulate lipid and lipoprotein concentrations in middle-aged Finnish men.

Exercise training improves baroreflex sensitivity in type 2 diabetes.

Type 2 diabetes is a strong risk factor for coronary heart disease and sudden cardiac death. It is associated with reduced baroreflex sensitivity (BRS) and heart rate variability (HRV), which are indicators of increased risk for mortality and morbidity in various patient populations. This study was designed to assess the effects of exercise training on BRS, HRV, and hemodynamics in patients with type 2 diabetes. Subjects (50 men, mean age 53.3 +/- 5.1 years) with type 2 diabetes were randomized into either a control group, in which they received conventional treatment only, or an exercise group, in which they received conventional treatment together with heart rate-controlled endurance training twice a week and supervised muscle strength training twice a week for 12 months. Measurements taken at baseline and follow-up included VO(2max), standard time and frequency domain measures of HRV during 24-h recording, and BRS by the phenylephrine method. Cardiac index, systemic vascular resistance index, stroke index, and pulse wave velocity were measured by whole-body impedance cardiography. Significant improvements in VO(2max) (exercise group: +2.3 ml x kg(-1) x min(-1); P < 0.005 vs. control group), muscle strength, and glycemic control (exercise group: HbA(1c) -0.9%; P < 0.001 vs. control group) were observed in the exercise group. BRS increased in the exercise group, from 6.8 to 8.6 ms/mmHg, and decreased in the control group, from 7.5 to 6.4 ms/mmHg (95% CI for the difference between 0.05 and 4.36 ms/mmHg; P < 0.05). No significant changes in the time or frequency domain measures of HRV or in systemic hemodynamics were observed. We concluded that exercise training improves BRS sensitivity in type 2 diabetes subjects in addition to increasing the exercise capacity and muscle strength and improving glucose control. These beneficial effects in reflectory autonomic regulation and glucose control caused by exercise may be associated with improved prognosis of type 2 diabetes patients.

Effect of 8-month vertical whole body vibration on bone, muscle performance, and body balance: a randomized controlled study.

Recent animal studies have given evidence that vibration loading may be an efficient and safe way to improve mass and mechanical competence of bone, thus providing great potential for preventing and treating osteoporosis. Randomized controlled trials on the safety and efficacy of the vibration on human skeleton are, however, lacking. This randomized controlled intervention trial was designed to assess the effects of an 8-month whole body vibration intervention on bone, muscular performance, and body balance in young and healthy adults. Fifty-six volunteers (21 men and 35 women; age, 19-38 years) were randomly assigned to the vibration group or control group. The vibration intervention consisted of an 8-month whole body vibration (4 min/day, 3-5 times per week). During the 4-minute vibration program, the platform oscillated in an ascending order from 25 to 45 Hz, corresponding to estimated maximum vertical accelerations from 2 g to 8 g. Mass, structure, and estimated strength of bone at the distal tibia and tibial shaft were assessed by peripheral quantitative computed tomography (pQCT) at baseline and at 8 months. Bone mineral content was measured at the lumbar spine, femoral neck, trochanter, calcaneus, and distal radius using DXA at baseline and after the 8-month intervention. Serum markers of bone turnover were determined at baseline and 3, 6, and 8 months. Five performance tests (vertical jump, isometric extension strength of the lower extremities, grip strength, shuttle run, and postural sway) were performed at baseline and after the 8-month intervention. The 8-month vibration intervention succeeded well and was safe to perform but had no effect on mass, structure, or estimated strength of bone at any skeletal site. Serum markers of bone turnover did not change during the vibration intervention. However, at 8 months, a 7.8% net benefit in the vertical jump height was observed in the vibration group (95% CI, 2.8-13.1%; p = 0.003). On the other performance and balance tests, the vibration intervention had no effect. In conclusion, the studied whole body vibration program had no effect on bones of young, healthy adults, but instead, increased vertical jump height. Future human studies are needed before clinical recommendations for vibration exercise.