Differences In Fasting Glucose Research Articles

Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin

Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important physiological differences between these cohorts.

Incretin effects, gastric emptying and insulin responses to low oral glucose loads in patients after gastric bypass and lean and obese controls

BackgroundAfter laparoscopic Roux-en-Y gastric bypass (LRYGB), many patients suffer from dumping syndrome. Oral glucose tolerance tests are usually carried out with 50–75 g of glucose. The aim of this study was to examine whether minimal glucose loads of 10 g and 25 g induce a reliable secretion of satiation peptides without dumping symptoms after LRYGB. In addition, lean and obese controls were examined. ObjectiveThe objective of this study was to determine the effects of low oral glucose loads on incretin release and gastric emptying. SettingAll surgical procedures were performed by the same surgeon (RP) at the St. Claraspital Basel in Switzerland. Oral glucose challenges were carried out at the University Hospital of Basel (Phase 1 Research Unit). MethodsEight patients 10±.4 weeks after LRYGB (PostOP; body mass index [BMI]: 38.6 kg/m2±1.7) as well as 12 lean controls (LC; BMI: 21.8 kg/m2±.6) and 12 obese controls (OC; BMI 38.7 kg/m2±1.3) received 10 g and 25 g of oral glucose. We examined clinical signs of dumping syndrome; plasma glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, and peptide tyrosine tyrosine concentrations; and gastric emptying with a 13 C-sodium acetate breath test. ResultsNo signs of dumping were seen in PostOP. Compared with OC, LC showed lower fasting glucose, insulin, and C-peptide, and lower homeostasis model assessment (HOMA) and AUC-180 for insulin and C-peptide. In PostOP, fasting insulin, HOMA and AUC-180 for insulin was lower and no difference was found in fasting C-peptide or AUC-180 for C-peptide compared to OC. There was no significant difference in fasting glucose, insulin, C-peptide, HOMA and AUC-180 for insulin in PostOP compared to LC, but AUC-180 for C-peptide was higher in PostOP. AUC-60 for gut hormones was similar in OC and LC and higher in PostOP compared to OC or LC. gastric emptying was slower in LC and OC compared with PostOP. ConclusionAfter LRYGB, 25 g oral glucose is well tolerated and leads to reliable secretion of gut hormones. Fasting glucose, insulin and C-peptide are normalized, while glucagon-like peptide 1, glucose-dependent insulinotropic peptide and peptide tyrosine tyrosine are overcorrected. Pouch emptying is accelerated after LRYGB.

Effects of pistachios on the lipid/lipoprotein profile, glycemic control, inflammation, and endothelial function in type 2 diabetes: A randomized trial

ObjectiveThe health benefits of regular nut consumption have been well-documented; however, effects on cardiovascular risk in diabetes are emerging. This study examined the effects of daily pistachio consumption on the lipid/lipoprotein profile, glycemic control, markers of inflammation, and endothelial function in adults with type 2 diabetes. Materials/MethodsWe enrolled 30 adults (40–74years) with well-controlled type 2 diabetes (mean glycated hemoglobin 6.2%) in a randomized, crossover, controlled feeding study. After a 2-week run-in period, participants consumed nutritionally-adequate diets with pistachios (contributing 20% of total energy) or without pistachios for 4weeks each, separated by a 2-week washout. We assessed fasting lipids/lipoproteins, glycemic measures (while fasted and during a 75g oral glucose tolerance test), inflammatory markers, and endothelial function after each diet period. ResultsTotal cholesterol and the ratio of total to HDL cholesterol were significantly lower (p<0.05) following the pistachio diet (4.00mmol/L and 4.06mmol/L, respectively) compared to the control diet (4.15mmol/L and 4.37mmol/L, respectively). Triglycerides were significantly lower (p=0.003) following the pistachio diet (1.56mmol/L) compared to the control diet (1.84mmol/L). There were no treatment differences in fasting glucose and insulin, but fructosamine was significantly lower (p=0.03) following the pistachio diet (228.5μmol/l) compared to the control diet (233.5μmol/l). Inflammatory markers and endothelial function were unchanged. ConclusionDaily pistachio consumption can improve some cardiometabolic risk factors in adults with well-controlled type 2 diabetes. Our findings support recommendations that individuals with diabetes follow healthy dietary patterns that include nuts.

A Diet High in Protein Reduces Weight Gain, Food Intake and Liver Weight in Obese Zucker Rats

It has become a challenge to find effective treatments and preventive strategies to reduce obesity and diabetes (T2DM). There are several approaches to treating these diseases, including nutrition therapy. Diets high in protein are linked with weight reduction and improved insulin resistance. Therefore, the objective of this study was to examine the effects of a long‐term, high protein (pro) diet (40%) vs a moderate pro diet (20%) on body composition and metabolism using a genetic model of obesity/T2DM. Male, lean (L) and obese (O) Zucker rats (n = 8‐10 per group) were housed 2/cage and placed in one of four groups: L20, L40, O20 or O40. Animals were provided ad libitum access to diet and water for 12 weeks. At 12 weeks, animals were fasted for 8 hours, then trunk blood and tissues were collected. L had lower food intake (P &lt; 0.05) than O, and O40 had significantly lower food intake (P &lt; 0.05) than O20. Animals fed 40% pro had significantly lower weight gain (P &lt; 0.05) than those fed 20% pro. L had more muscle mass and lower fat mass than O (P &lt; 0.05). However, L40 had significantly lower fat mass than L20. O40 had lower liver weights (P &lt; 0.05) than O20. There was no difference in fasting glucose and O had higher fasting insulin. Fasting free fatty acids were higher in animals fed the 20% pro diet. There was no difference in basal phosphorylation of Akt, AMPK, mTOR or 4E‐BP1. There was no difference in basal BCAA between L20 and O20. L40 and O40 had significantly higher basal levels of BCAA (P &lt; 0.05). We conclude that higher protein diets have the potential to reduce weight gain and alter metabolism in obese rats. Funded by Arkansas Biosciences Institute.

Impaired Glucose Handling Is Revealed in Prostate Cancer Patients

Prostate cancer survivors have increased risk for diabetes and cardiovascular disease. Here, we evaluate glucose handling and lipid profiles in men with prostate cancer and compared them with 2 cancer-free reference groups to elucidate potential cancer-related changes in metabolism. Eight high-risk, newly diagnosed prostate cancer patients (>T3 or Gleason >8 or PSA >20ng/mL), 7 age-matched, cancer-free (HM) males and 10 young healthy (HY) males were included. Fasting blood samples were obtained for glucose- and lipid-related parameters followed by an oral glucose tolerance test (OGTT) to assess glucose handling, insulin and c-peptide response. There were no significant differences in fasting glucose between groups (patients: 4.87±1.18mM; HM: 3.65±0.21mM; HY: 3.70±0.46mM). However, patients demonstrated impaired 2-hr glucose concentrations (8.68±2.87mM where normal is defined as <7.8mM), which were significantly higher compared with HM and HY groups (HM: 5.21±1.92mM, p=0.002; HY: 3.24±1.05mM, p<0.001). Similarly, insulin and c-peptide responses demonstrated significantly greater 2-hr insulin and c-peptide concentration vs HM and HY groups. There were no significant differences in total cholesterol, HDL, LDL, triglycerides between the 3 groups. Thus, glucose handling, not the lipid profile, may be affected by prostate cancer, which may influence the risk of diabetes in survivorship. Funded by the Motorcycle Ride for Dad Foundation and the Canadian Institute of Health Research.

Reductions in glycemic and lipid profiles in hypertensive patients undergoing the Brazilian Dietary Approach to Break Hypertension: a randomized clinical trial

Hypertensive patients often have an unfavorable lipid and glucose profile. The main goal of dietary treatment for these patients is to achieve adequate control of blood pressure and reducing cardiovascular morbidity and mortality. The aim of this study was to evaluate whether the Brazilian Dietary Approach to Break Hypertension (BRADA) based on Dietary Approaches to Stop Hypertension but with both low sodium and glycemic index foods could reduce lipid and glycemic profiles in hypertensive patients who were seeing primary health care providers in a low-income region of Brazil. A randomized study of 206 individuals were followed up for the duration of 6 months. The experimental group received orientation and planned monthly menus from the BRADA diet. In the control group, counseling was based on standard care and mainly focused on salt intake reduction. Differences in all biochemical parameters were compared at the baseline and at the 6-month follow-up period. The mean age was 60.1 (±12.9) years old, and 156 subjects (119 females) completed the study. An intention-to-treat analysis showed that both groups reduced fasting plasma glucose, glycated hemoglobin, total cholesterol, and low-density lipoprotein cholesterol concentrations; however, statistically significant between-group differences were found for these parameters. The mean difference in fasting glucose was −7.0 (P < .01), −0.2 for HbA1c (P < .01), −28.6 for TC (P < .01), and −23.8 for LDL-c (P < .01) for the experimental group compared with the control group. This study showed the efficacy of the BRADA diet to treat hypertension on biochemical parameters tested in a primary health care service setting.

Effect of eplerenone on insulin action in essential hypertension: a randomised, controlled, crossover study.

An association exists between hyperaldosteronism, hypertension and impaired insulin action. Eplerenone is a selective mineralocorticoid receptor antagonist; however, little is known about its effects on insulin action. The aim of this study was to determine the effect of eplerenone on insulin action in hypertensive adults, using the hyperinsulinaemic euglycaemic clamp. A randomised, controlled, double-blind, crossover design was employed. After a 6-week washout period, hypertensive, non-diabetic patients were treated with either eplerenone 25 mg twice daily or doxazosin 2 mg twice daily for 12 weeks. After each treatment period, insulin action was assessed by a hyperinsulinaemic euglycaemic clamp, with isotope dilution methodology. After washout, treatment groups were crossed over. Fifteen patients completed the study. There were no differences in fasting glucose, or fasting insulin between treatment with eplerenone or doxazosin. The measure of overall insulin sensitivity, exogenous glucose infusion rates during the last 30 min of the clamp, was similar with both treatments; 23.4 (3.9) μmol kg(-1) min(-1) after eplerenone and 23.3 (3.6) μmol kg(-1) min(-1) after doxazosin (P=0.83). Isotopically determined fasting endogenous glucose production rates were similar after both treatments (eplerenone 9.4 (0.6) μmol kg(-1) min(-1) vs doxazosin 10.6 (0.7) μmol kg(-1) min(-1)). There was a trend for lower endogenous glucose production rates during hyperinsulinaemia following eplerenone compared with doxazosin (2.0 (0.8) μmol kg(-1) min(-1) vs 4.1 (0.9) μmol kg(-1) min(-1)). There was no difference in insulin stimulated peripheral glucose utilisation rates after treatment with eplerenone or doxazosin (25.4 (3.6) μmol kg(-1) min(-1) vs 27.0 (3.9) μmol kg(-1) min(-1)). This study gives reassuring evidence of the neutral effect of eplerenone on insulin action in hypertensive, non-diabetic patients.

The relationship of fasting glucose in basic state with the results of head-up tilt table test in children

Objective To explore the relationship of fasting glucose in basic state with the results of head-up tilt table test (HUTT) in children.Methods We choosed 157 cases of children (male 86 and female 71) with unexplained syncope,headache,dizziness and sigh,they were 3 ～ 18 (11.34 ± 3.29) years old and were outpatients or had been hospitalized in the Second Xiangya Hospital of Central South University from Sep 2012 to Feb 2013.The HUTT were carried on after eliminate organic disease of heart,head,bloodvessel and other reasons caused by the above symptoms and obtain written informed consent from participants or guardian.Before HUTI,trace fasting glucose of children would be monitored in based condition.Results (1) Between HUTT negative group (n =63) and HUTT positive group (n =94),there was no significant difference in fasting glucose [(5.40 ± 0.52) mmol/L vs (5.35 ± 0.61) mmoL/L,t =-0.590,P ＞ 0.05].(2) Only 1 case of heart inhibited type vasovagal syncope did not be included in 94 children with HUTT positive.There were no significant differences in fasting glucose between vascular inhibited type vasovagal syncope (n =67) and mixed vasovagal syncope (n =10) and orthostatic tachycardia syndrome (n =16)[(5.34 ±0.54) mmol/L vs (5.07 ±0.64) mmol/L vs (5.49 ±0.81) mmol/L,P ＞0.05].(3) Among 67 cases of vascular inhibitory type vasovagal syncope in children,two kinds induced way of based tilt table test (n =16) and sublingual nitroglycerin tilt table test (n =51) showed no significant differences in fasting glucose [(5.32 ±0.54) mmol/L vs (5.35 ±0.55) mmol/L,t =0.166,P ＞0.05].(4) In two groups of fasting glucose ＜5.5 mmol/L and ≥5.5 mmol/L,HUTT negative rate [37.63％ (35/93) vs 43.75％ (28/64)] and HUTT positive rate [62.37％ (58/93) vs 56.25％ (36/64)] showed no statistical significance (x2 =0.585,P ＞ 0.05).Conclusion Fasting glucose in basic state has no predictive value to HUTT results in children. Key words: Fasting glucose; Head-up tilt table test; Children

Impact of a new total Western diet for rodents on metabolic health and colorectal carcinogenesis

Our group developed a new total Western diet (TWD) for rodents that mimics typical human nutrition patterns with respect to macronutrient composition (amounts and types of sugar, fat, protein) and micronutrient content (vitamins and minerals) on a nutrient density basis. The goal of the present study was to determine the relative roles of macro‐ and micronutrients in dysregulating metabolism. Mice fed the TWD appeared to compensate for its high energy content by reducing food consumption, whereas animals fed a commercial DIO diet did not. However, food and energy intakes in mice fed a diet modified only for vitamin and mineral content was similar to the AIN93‐fed controls, whereas food and energy intakes by mice fed a diet modified for macronutrient composition were highly similar to DIO‐fed mice. These patterns were reflected in the average final body weight for each group, and body weight gain was entirely attributed to an increase in fat mass. Overall, based on our observations, the altered micronutrient composition of the TWD blocked the macronutrient driven increase in body weight. Significant differences in fasting glucose or oral glucose tolerance were observed only for mice fed the DIO diet. Our observations point to a complex interaction between macro‐ and micronutrients with respect to satiety and energy intake. We are currently examining the impact of these westernized rodent diets on colon carcinogenesis.

Inducible Deletion of UCP2 in Pancreatic β-Cells Enhances Insulin Secretion

In pancreatic β-cells, uncoupling protein 2 (UCP2) is thought to negatively regulate insulin secretion; however, its role is still debated, in part due to the confounding effects of long-term UCP2 deletion in current knockout mouse models. We have now generated an inducible β-cell-specific UCP2 deletion model by crossing loxUCP2 mice with those that express a Cre recombinase-estrogen receptor fusion protein driven by the mouse insulin promoter (MIPCreER). Because tamoxifen, which was used to induce UCP2 deletion, is an uncoupling agent, we initially determined whether tamoxifen affected glycemia. Initially, C57BL/6 control mice were injected intraperitoneally with tamoxifen or vehicle (corn oil [CO]) 3 times in 1 week, and the mice examined 2 weeks postinjection. Both groups of mice displayed similar glucose tolerance and in vivo and in vitro insulin secretion, suggesting no effects of tamoxifen on glucose homeostasis and β-cell function. MIPCreER×loxUCP2 male littermates were then injected with tamoxifen to induce β-cell-specific UCP2 deletion (ind.UCP2BKO) or with CO as described above. UCP2 deletion was confirmed by polymerase chain reaction (PCR) analysis of islets. There were no differences in fasting glucose, glucagon or insulin in ind.UCP2BKO mice and glucose (OGTT) and insulin tolerance tests revealed similar levels of glucose and insulin sensitivity. However, ind.UCP2BKO mice sustained significantly higher plasma insulin levels during an OGTT and isolated islets secreted more insulin in response to high glucose. Together, these results suggest that short-term deletion of β-cell UCP2 in adult mice leads to the direct enhancement of insulin secretion.

Abstract 241: Influence of Dietary Salt and Renin-angiotensin System activity on plasma Retinol-binding Protein 4 in Healthy Human Subjects

Introduction: Retinol-binding protein 4 (RBP-4) is a circulating adipokine associated with insulin resistance, obesity and cardiovascular risk. Previous evidence suggests a negative impact on insulin sensitivity via an interaction with the insulin-stimulated glucose transporter (GLUT-4), specifically in adipocytes. Since angiotensin-2 (ANG-2) impairs GLUT-4 presentation and insulin sensitivity, we hypothesized that renin-angiotensin system (RAS) activity might affect RBP-4 expression as well. Furthermore, both RAS activity and insulin sensitivity are affected by dietary salt, but the relationship between these factors and RBP-4 expression is unknown. We hypothesized that liberal salt diet, via suppression of RAS activity, would be associated with reduced RBP-4 levels compared to salt restriction. METHODS: Healthy subjects (7 men, 7 women, mean age 24 yr, BMI 22.6) were studied on low salt (LS 10 mmol Na/day) diet and then liberal salt (HS 200 mmol Na/day) diet for 1 week each. Samples were drawn after overnight rest in the supine position for plasma renin activity (PRA), serum Aldosterone (Aldo) and plasma RBP-4 and again after ANG-2 infusion (3ng/kg/min x 45 mins). Results: Salt manipulation predictably modified RAS activity (HS v. LS Aldo, 4.5 ± 3.8 v. 19.5 ± 8.5 ng/dl [p&lt;0.01]; HS v. LS PRA, 0.5 ± 0.4 v. 2.7 ± 1.4 ng/ml/hr [p&lt;0.01]). RBP-4 was significantly lower on a HS compared to LS diet (35.4 ± 6.6 v. 38.6 ± 7.9 mg/L, p= 0.017). No significant change was observed in RBP-4 level after ANG-2 infusion on either diet. Fasting insulin levels trended lower on HS compared to LS (3.9 ± 6.8 v. 4.4 ± 1.2 μIU/ml, p=0.09), but there was no difference in fasting glucose (81.9 ± 6.8 v. 82.1 ± 4.7 mg/dl, p=0.92). Conclusion: RBP-4 levels are modified by dietary salt intake. RBP-4 levels were lower under HS conditions (suppressed RAS) as compared to LS conditions. Acute administration of ANG-2 does not increase RBP-4 levels in this healthy population. Insulin response was similar to prior reports suggesting that the connection between RAS activity, dietary salt and insulin sensitivity may include RBP-4. Future work exploring the relationship between RBP-4, GLUT-4 and insulin sensitivity should take into consideration the effect of dietary salt intake.

Precocious Puberty, Elevated Steroidogenesis, and Leydig Cell Hyperplasia in Male Mice with a Gain of Function Mutation in the Luteinizing Hormone Receptor Gene.

The activation of the luteinizing hormone receptor (LHR) in the gonads by luteinizing hormone (LH) is critical for steroidogenesis and gametogenesis. Several activating mutations in human LHR have been identified in boys with sporadic or familial male limited precocious puberty (FMPP) or testotoxicosis. Boys with this mutation present with elevated levels of testosterone in the context of prepubertal LH levels, the onset of puberty by age four or earlier and Leydig cell hyperplasia. The majority of the activating mutations are in transmembrane helix 6 of the 7 transmembrane G protein-coupled receptor, the most common being a mutation of aspartic acid 578 to glycine. We have created a knock-in mouse (KiLHR) with an activating point mutation, caused by substitution of glycine for aspartic acid at position 582 (D582G) in mouse LHR, corresponding to the common D578G mutation in human LHR. In this study, we have examined the effects of the mutated LHR on reproductive and metabolic function in male KiLHR mice. RT-PCR analysis of RNA from multiple tissues of heterozygous KiLHR mice demonstrated expression of the WT and mutant alleles only in the gonads and brain. Male KiLHR mice exhibited precocious puberty as evidenced by premature balanopreputial separation at postnatal day 14.5 compared to 22.4 days for WT mice and presence of major urinary proteins (MUPs), which are secreted at the onset of puberty, in KiLHR mice at postnatal day 15 compared to day 22 in WT mice. KiLHR mice were fertile. Male KiLHR mice were analyzed at neonatal (7 and10d), prepubertal (2 and 3 weeks), pubertal (6 weeks) and adult (12 and 24 weeks) ages. Hormonal analysis indicated that the KiLHR mice had significantly elevated serum and testicular testosterone levels as early as postnatal day 7 and remained elevated through adulthood. No significant difference was seen in serum estradiol levels; however testicular estradiol levels were elevated in KiLHR mice compared to WT mice. Gonadotropin levels were decreased in KiLHR compared to WT mice. Expression of the steroidogenic enzyme genes was upregulated as early as 7 days consistent with the elevated testosterone levels. The levels of LHR mRNA were significantly upregulated at all ages, but not those of the follicle stimulating hormone or steroid hormone receptors. Histological analysis revealed premature Leydig cell proliferation and the presence of Leydig cell hyperplasia as early as 7 days of age. Gene expression analysis suggested the precocious development of adult Leydig cells. At 24 weeks, Leydig cell adenomas were apparent is some of the KiLHR mice. However, there were no apparent differences in testicular germ cell or Sertoli cell development. KiLHR mice at 24 weeks of age exhibited impaired glucose tolerance compared to WT mice although there was no difference in fasting glucose or insulin levels. No changes in body weight or body fat were measured between the genotypes. The overall phenotype of precocious puberty, elevated testosterone and Leydig cell hyperplasia in the KiLHR male mice is similar to that seen in humans with FMPP. These studies suggest that the KiLHR mice will be a novel model to understand the effects of premature LHR activation during early Leydig cell development as well as the consequences of chronic elevated testosterone levels on adult testicular and metabolic function. Supported by NIH HD044119.

Greater Whole-Grain Intake Is Associated with Lower Risk of Type 2 Diabetes, Cardiovascular Disease, and Weight Gain1–3

Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48–80 g whole grain/d (3–5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8–13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in post-intervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose: −0.93 mmol/L (95% CI: −1.65, −0.21), total cholesterol: −0.83 mmol/L (−1.24, −0.42); and LDL-cholesterol: −0.72 mmol/L (−1.34, −0.11)]. Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials.

The rs10830963 variant of melatonin receptor MTNR1B is associated with increased risk for gestational diabetes mellitus in a Greek population

To investigate the association between Gestational Diabetes Mellitus (GDM) and the variants rs10830963 and rs1387153 in the MTNR1B locus in a sample of the Greek population. One hundred seventy-five unrelated pregnant Greek women (77 with GDM and 98 non-diabetic control subjects) were enrolled and the SNaPshot method was employed in order to investigate the association between GDM and the variants rs10830963 and rs1387153 in the MTNR1B locus. Pregnant women were screened for GDM at the 26th week with the 75 g glucose oral glucose tolerance test according to the American Diabetes Association criteria. The GG genotype and the G-allele of the rs10830963 (C/G) variant was found to be positively associated with a significantly increased risk for GDM (p = 0.047 and p = 0.012, respectively). No differences in fasting glucose and insulin levels were found between GDM patients with and without the studied variants. The MTNR1B locus (rs10830963 C/G) seems to predispose for GDM in Greek pregnant women. Our study confirms the association of GDM with the rs10830963 (C/G) variant in a sample of the Greek population. Population based whole genome screening studies and larger studies with detailed phenotypic data in patients with GDM are needed to address the clinical significance of this finding.

Egg consumption and risk of type 2 diabetes in older adults

Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. We assessed the association between egg intake and incident diabetes in older adults. In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989-2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1-3 eggs/mo, 1-4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.

A variant in the fibrillin-3 gene is associated with TGF-β and inhibin B levels in women with polycystic ovary syndrome

In an attempt to evaluate the association between allele 8 (A8) of D19S884 in the fibrillin-3 gene and circulating transforming growth factor (TGF) β and inhibin levels in women with polycystic ovary syndrome (PCOS), we studied 120 similarly aged women from families with PCOS and compared 40 women with PCOS who did not have A8 (A8- PCOS) with 40 women with PCOS who had A8 (A8+ PCOS) and 40 normally menstruating women who did not have either PCOS or A8 (A8- Non-PCOS). A8- PCOS is associated with higher levels of TGF-β1 compared with A8+ PCOS or A8- Non-PCOS, similar levels of TGF-β2 compared with A8+ PCOS but lower levels of TGF-β2 compared with A8- Non-PCOS, and lower levels of inhibin B and aldosterone compared with A8+ PCOS.

Maternal supplementation with vitamin A or β-carotene and cardiovascular risk factors among pre-adolescent children in rural Nepal.

Vitamin A plays an important role in fetal renal and cardiovascular development, yet there has been little research on its effects on cardiovascular risk factors later in childhood. To examine this question, we followed the children of women who had been participants in a cluster-randomized, double blind, placebo-controlled trial of weekly supplementation with 7000 μg retinol equivalents of preformed vitamin A or 42 mg of β-carotene from 1994 to 1997 in rural Nepal. Women received their assigned supplements before, during and after pregnancy. Over a study period of 3 years, 17,531 infants were born to women enrolled in the trial. In 2006-2008, we revisited and assessed 13,118 children aged 9-13 years to examine the impact of maternal supplementation on early biomarkers of chronic disease. Blood pressure was measured in the entire sample of children. In a subsample of 1390 children, venous blood was collected for plasma glucose, Hb1Ac and lipids and a morning urine specimen was collected to measure the ratio of microalbumin/creatinine. Detailed anthropometry was also conducted in the subsample. The mean ± s.d. systolic and diastolic blood pressure was 97.2 ± 8.2 and 64.6 ± 8.5 mm Hg, respectively, and about 5.0% had high-blood pressure (⩾120/80 mm Hg). The prevalence of microalbuminuria (⩾30 mg/g creatinine) was also low at 4.8%. There were no differences in blood pressure or the risk of microalbuminuria between supplement groups. There were also no group differences in fasting glucose, glycated hemoglobin, triglycerides or cholesterol. Maternal supplementation with vitamin A or β-carotene had no overall impact on cardiovascular risk factors in this population at pre-adolescent age in rural Nepal.

Effects of estradiol–drospirenone hormone treatment on carotid artery intima-media thickness and vertigo/dizziness in postmenopausal women

To investigate the effects of Angeliq on hormonal, metabolic, biochemical and cardiovascular profile, carotid intima-media thickness (CIMT) and vertigo/dizziness symptoms in postmenopausal women. Angeliq is a drug used for hormone replacement therapy that composed of drospirenone 2 mg and estradiol 1 mg. Thirty-two postmenopausal women were recruited for the study. All women were evaluated using personal interview, medical examination and carotid artery ultrasound. They were questioned specifically about vertigo/dizziness experienced. Participants were randomly submitted to oral daily treatment with Angeliq. The duration of the study was 6 months and the participants were studied in basal condition and after 6 months of the therapy. Follicle-stimulating hormone was significantly higher and estradiol was significantly lower in before therapy (BT) than in after therapy (AT) (p < 0.001). No differences in fasting glucose, CRP and WBC values, and lipid-lipoprotein profile were detected between the groups. The systolic and diastolic blood pressures and heart rate were also significantly higher in BT than in AT (p < 0.05). A significant (p < 0.001) difference in CIMT (0.51 ± 0.04 vs. 0.49 ± 0.03 mm) was found between BT and AT. Seven of 32 patients (22%) had vertigo/dizziness symptoms before treatment. After 6 months, none of the patients showed complaints of vertigo/dizziness. Oral daily treatment with Angeliq reduces CIMT and climacteric complaints including vertigo/dizziness in postmenopausal women. They may relate to anti-androgenic and anti-mineralocorticoid effects of Angeliq, respectively.

Long-Term Growth Hormone Therapy Changes the Natural History of Body Composition and Motor Function in Children with Prader-Willi Syndrome

Children with Prader-Willi syndrome (PWS) have decreased muscle mass, hypotonia, and impaired linear growth. Recombinant human GH (hGH) treatment reportedly improves body composition and physical function in children with PWS, but these studies lack long-term control data. To assess the impact of hGH therapy begun early in life on the natural history of PWS, we compared height, body composition, and strength in similar-age children with PWS naïve to hGH with those treated with hGH for 6 yr. Forty-eight children with PWS were studied: 21 subjects (aged 6-9 yr) treated with hGH for 6 yr (beginning at 4-32 months, mean 13 +/- 6 months) were compared with 27 children of similar age (5-9 yr) prior to treatment with hGH. Percent body fat, lean body mass, carbohydrate/lipid metabolism, and motor strength were compared using analysis of covariance. PWS children treated with hGH demonstrated lower body fat (mean, 36.1 +/- 2.1 vs. 44.6 +/- 1.8%, P < 0.01), greater height (131 +/- 2 vs. 114 +/- 2 cm; P < 0.001), greater motor strength [increased standing broad jump 22.9 +/- 2.1 vs. 14.6 +/- 1.9 in. (P < 0.001) and sit-ups 12.4 +/- 0.9 vs. 7.1 +/- 0.7 in 30 sec (P < 0.001)], increased high-density lipoprotein cholesterol (58.9 +/- 2.6 vs. 44.9 +/- 2.3 mg/dl, P < 0.001), decreased low-density lipoprotein (100 +/- 8 vs. 131 +/- 7 mg/dl, P < 0.01), and no difference in fasting glucose or insulin. hGH treatment in children with PWS, begun prior to 2 yr of age, improves body composition, motor function, height, and lipid profiles. The magnitude of these effects suggests that long-term hGH therapy favorably alters the natural history of PWS to an extent that exceeds risks and justifies consideration for initiation during infancy.

Comparison of Cardiometabolic Syndrome Parameters, Obesity, Insulin Resistance, and Elevated Alanine Aminotransferase in Current Professional Baseball and Football Players

Purpose: Media news reports have suggested that professional football players (PFP) were twice as likely to die before the age of 50 as professional baseball players (PBP). To scientifically study this premise, we compared cardiometabolic syndrome parameters between PFP and PBP. Methods: Cardiometabolic syndrome markers [blood pressure (BP) ≥130/85 mmHg, fasting glucose (FG) ≥100 mg/dL, triglycerides (TG) ≥150 mg/dL, waist circumference (WC) ≥100 cm, high density lipoprotein (HDL) cholesterol ≤40 mg/dL] body mass index (BMI), parameters of obesity [BMI >30 mg/kg2, WC ≥100 cm, waist-to-height ratio (WHR) >0.5], insulin resistance [triglycerides/HDL (TG/HDL) >3.5], and elevated alanine aminotransferase (ALT) ≥40 IU/L were compared in 69 PFP to 155 PBP who gave written consent to participate. ALT ≥40 IU/L was chosen as the upper limit of normal as this was the value used in men aged 20-29 in the standard National Health and Nutrition Examination Study (NHANES III). Institutional review board approval was obtained. SAS 9.1 was used for statistical analysis, with a p value of significance defined as ≤0.05. Results: Comparing the study population of PFP to PBP, PFP have an increased FG >100 mg/dL, increased BMI >30 kg/m2, increased WC ≥100 cm, and increased WHR >0.5, but decreased BP ≥130/85. In the subset of 19 Linemen (guards, tackles, centers, and defensive ends) compared to PBP, there was a significant increase in FG ≥100 mg/dL, BMI >30 kg/m2, WC ≥100 cm, WHR >0.5, and an increased incidence of the cardiometabolic syndrome (≥3 of the markers). There was no difference in BP between linemen and PBP. In the subset of 50 non-linemen (all other PFP other than linemen) compared to PBP, there was a significant increase in BMI but a significant decrease in BP and ALT. There was no difference in FG ≥ 100 mg/dl between non-linemen and PBP. Conclusion: PFP have increased obesity markers and hyperglycemia compared to PBP. However, elevated fasting glucose levels, obesity (as measured by WC and WHR), and increased cardiometabolic syndrome incidence in PFP were confined to the linemen subset. PBP have increased hypertension compared to PFP, the etiology of which is unclear. The increased cardiometabolic markers and implied cardiovascular risk for PFP appears to be limited to the linemen subset.