6761 articles - 08.09.10
1: Psychoneuroendocrinology. 2010 Aug 30; [Epub ahead of print]
Silverman DH, Geist CL, Kenna HA, Williams K, Wroolie T, Powers B, Brooks J, Rasgon NL.
UCLA David Geffen School of Medicine, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Clinic, CHS AR-144, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095-6942, USA.
Differential cerebral metabolic effects of various hormone therapy formulations, and their associations with cognitive status, remain to be established. The principal aim of the current study was to assess relationships between regional cerebral metabolism and estrogen-based hormone therapies. Postmenopausal women (n=53) at elevated risk for Alzheimer's disease (AD) were on estrogen-containing hormone therapy for at least one year prior to enrollment in a prospective, randomized clinical trial. Subjects underwent an FDG-PET scan, along with neuropsychological, medical, and demographic assessments at time of enrollment, to be repeated one year following randomization to hormone therapy continuation versus discontinuation, and results from analyses of the baseline assessments are reported here. Across all subjects, years of endogenous estrogen exposure correlated most closely with metabolism in right superior frontal gyrus (p<0.0005). Women taking 17beta-estradiol (E) performed three standard deviations higher in verbal memory than women taking conjugated equine estrogen (CEE), and their verbal memory performance positively correlated with metabolism in Wernicke's (p=0.003) and auditory association (p=0.002) areas. Women taking progesterone-plus-estrogen had lower metabolism than women taking unopposed estrogen within the mesial and inferior lateral temporal regions (p<0.0005) and the inferior frontal cortex, contralateral to Broca's area (p<0.0005). In conclusion, particular areas of relatively preserved metabolism were seen in women with more years of endogenous estrogen exposure, as well as in women taking estradiol-based formulations or estrogen therapies unopposed by progesterone, together suggesting regionally specific neuroprotective estrogenic effects. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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PMID: 20810219 [PubMed - as supplied by publisher]2: Diabetologia. 2010 Aug 29; [Epub ahead of print]
Muhlhauser I.
Unit of Health Sciences and Education, University of Hamburg, Martin-Luther-King Platz 6, 20146, Hamburg, Germany, Ingrid_Muehlhauser@uni-hamburg.de.
ADA/EASD recommendations and diabetes expert consensus statements are not evidence-based. Reform of guideline development is urgently needed. Overriding governance and composition of the guideline committee is a key problem. Methodologists without important conflicts of interest should lead the development process and have primary responsibility. The rating of the quality of evidence should be separated from making the recommendations, transparency has to be increased and conflicts of interest must be tackled. Patient needs are not yet met in guidelines. Patients increasingly demand concise, easy-to-read summaries of the benefits and risks of medicines together with more comprehensive scientific data. However, patient participation in individual decision making is not considered in guidelines. Guidelines do not provide the information necessary for informed or shared decision making. Study fact-sheets and drug facts boxes should be included in practice guidelines. It is timely to consider patient needs from the outset of the development of future guidelines.
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PMID: 20803189 [PubMed - as supplied by publisher]3: Clin Endocrinol (Oxf). 2010 Sep;73(3):277-85.
Lips P, Bouillon R, van Schoor NM, Vanderschueren D, Verschueren S, Kuchuk N, Milisen K, Boonen S.
Department of Endocrinology and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands. P.Lips@vumc.nl
Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance. This study tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. Calcium and vitamin D therapy has been recommended for older persons, either frail and institutionalized or independent, with key risk factors including decreased bone mineral density (BMD), osteoporotic fractures, increased bone remodelling as a result of secondary hyperparathyroidism and increased propensity to falls. In addition, treatment of osteoporosis with a bisphosphonate was less effective in patients with vitamin D deficiency. Calcium and vitamin D supplementation is a key component of prevention and treatment of osteoporosis unless calcium intake and vitamin D status are optimal. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, BMD, bone turnover, lower extremity function and falls, we suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50-75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in successful fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest. As calcium balance is not only affected by vitamin D status but also by calcium intake, recommendations for adequate calcium intake should also be met. The findings of community-based clinical trials with vitamin D and calcium supplementation in which compliance was moderate or less have often been negative, whereas studies in institutionalized patients in whom medication administration was supervised ensuring adequate compliance demonstrated significant benefits.
Publication Types: Research Support, Non-U.S. Gov't
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PMID: 20796001 [PubMed - in process]4: Diabetes Care. 2010 Aug 19; [Epub ahead of print]
Karve A, Hayward RA.
George Washington University School of Medicine and Health Sciences, Washington, D.C.
AbstractObjectives: To estimate rates of prevalence, diagnosis, and treatment of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Research design and methods: A representative sample of the US population (the National Health And Nutrition Examination Survey from 2005-2006 including 1,547 nondiabetic adults (age >18) without a history of myocardial infarction was assessed to determine the proportion of adults who met criteria for IFG/IGT, and the proportion of IFG/IGT subjects who: 1) reported receiving a diagnosis from their physician; 2) were prescribed lifestyle modification or an antihyperglycemic agent; and 3) were currently on therapy. We used multivariable regression analysis to identify predictors of diagnosis and treatment. Results: Of the 1,547 subjects, 34.6% (CI 30.3-38.9%) had pre-diabetes; 19.4% had IFG only; 5.4% had IGT only, and 9.8% had both. Only 4.8% of those with prediabetes reported having received a formal diagnosis from their physicians. No subjects with pre-diabetes received oral antihyperglycemics, and rates of recommendation for exercise or diet were 31.7% and 33.5%, respectively. Among 47.7% pre-diabetes subjects who exercised, 49.4% reported exercising for at least 30 minutes daily. Conclusion: Three years after a major clinical trial demonstrated that interventions could greatly reduce progression from IFG/IGT to type 2 diabetes, the majority of Americans with IFG/IGT were undiagnosed and untreated with interventions. Whether this is due to physicians being unaware of the evidence, unconvinced by the evidence, or clinical inertia is unclear.
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PMID: 20724649 [PubMed - as supplied by publisher]5: Diabetes. 2010 Aug 19; [Epub ahead of print]
den Hoed M, Ekelund U, Brage S, Grontved A, Zhao JH, Sharp SJ, Ong KK, Wareham NJ, Loos RJ.
MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK.
AbstractObjective: Large-scale genome-wide association (GWA) studies have so far identified 16 loci incontrovertibly associated with obesity-related traits in adults. We examined associations of variants in these loci with anthropometric traits in children/adolescents. Research design and methods: Seventeen variants representing 16 obesity-susceptibility loci were genotyped in 1,252 children (mean+/-SD age: 9.7+/-0.4yrs) and 790 adolescents (15.5+/-0.5yrs) from the European Youth Heart Study (EYHS). We tested for association of individual variants and a genetic predisposition score (GPS-17), calculated by summing the number of effect-alleles, with anthropometric traits. For 13 variants, summary statistics for associations with BMI were meta-analysed with previously reported data (N(total)=13,071 children/adolescents). Results: In EYHS, 15 variants showed associations or trends with anthropometric traits that were directionally consistent with earlier reports in adults. The meta-analysis showed directionally consistent associations with BMI for all 13 variants of which 9 were significant (0.033-0.098SD/allele, P<0.05). The near-TMEM18 variant had the strongest effect (0.098SD/allele, P=8.5.10(-11)). Effect sizes for BMI tended to be more pronounced in children/adolescents than reported earlier in adults for variants in/near SEC16B, TMEM18 and KCTD15, (0.028-0.035SD/allele higher), and less pronounced for rs925946 in BDNF (0.028SD/allele lower). Each additional effect-allele in the GPS-17 was associated with an increase of 0.034SD in BMI (P=3.6.10(-5)), 0.039SD in sum of skinfolds (P=1.7.10(-7)) and 0.022SD in waist circumference (P=1.7.10(-4)), comparable with reported results in adults (0.039SD/allele for BMI, 0.033SD/allele for waist circumference). Conclusions: Most obesity-susceptibility loci identified by GWA studies in adults are already associated with anthropometric traits in children/adolescents. While the association of some variants may differ with age, the cumulative effect size is similar.
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PMID: 20724581 [PubMed - as supplied by publisher]6: Diabetes Res Clin Pract. 2010 Aug 17; [Epub ahead of print]
Ovalle F.
UAB Comprehensive Diabetes Center, Division of Endocrinology, Diabetes & Metabolism, University of Alabama at Birmingham School of Medicine, 510 20th Street South, FOT Suite 702, Birmingham, AL 35294, USA.
A number of patients with diabetes require very high (>2Ukg(-1)day(-1)), or extremely high (>3Ukg(-1)day(-1)), insulin doses for the management of their hyperglycemia. Unfortunately, many of the physicians who treat these patients limit themselves to prescribing ever higher doses of insulin, without questioning why. Furthermore, when the insulin requirements get to be extreme, demanding an explanation, clinicians are frequently lost in a sea of literature where there is not a single paper dealing with this problem systematically. A systematic approach to the evaluation of these patients is necessary to facilitate an appropriate diagnosis, select the most reasonable therapy, and hopefully improve the long-term outcome of these patients. This manuscript intends to provide the clinician with a review of the literature pertinent for the differential diagnosis, work-up, and management of these patients. We will review the definitions of insulin sensitivity during normality, the various degrees or categories of insulin resistance, and the expected insulin requirements during each of these states. Subsequently, we propose a simple alphabetic mnemonic approach to help remember the differential diagnosis, and a clinical algorithm to help guide the work-up of these patients. Lastly, we briefly discuss general management considerations in these conditions. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
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PMID: 20724017 [PubMed - as supplied by publisher]7: J Clin Endocrinol Metab. 2010 Aug 18; [Epub ahead of print]
Delahunty C, Falconer S, Hume R, Jackson L, Midgley P, Mirfield M, Ogston S, Perra O, Simpson J, Watson J, Willatts P, Williams F; the Scottish Preterm Thyroid Group.
Wishaw General Hospital (C.D.), Wishaw ML2 0DP, Scotland, United Kingdom; Clinical and Population Sciences and Education (S.F., R.H., M.M., S.O., O.P., J.W., F.W.), University of Dundee, Ninewells Hospital and Medical School Campus, Dundee DD2 4BF, Scotland, United Kingdom; Neonatal Unit (L.J.), Southern General Hospital, Glasgow G51 4TF, Scotland, United Kingdom; Neonatal Unit (P.M.), Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland, United Kingdom; Neonatal Unit (J.S.), Queen Mother's Hospital, Glasgow G3 8SJ Scotland, United Kingdom; and Department of Psychology (P.W.), University of Dundee, Dundee DD1 4HN, Scotland, United Kingdom.
Context: Transient hypothyroxinemia is the commonest thyroid dysfunction of premature infants, and recent studies have found adverse associations with neurodevelopment. The validity of these associations is unclear because the studies adjusted for a differing range of factors likely to influence neurodevelopment. Objective: The aim was to describe the association of transient hypothyroxinemia with neurodevelopment at 5.5 yr corrected age. Design: We conducted a follow-up study of a cohort of infants born in Scotland from 1999 to 2001 </=34 wk gestation. Main Outcome Measures: We measured scores on the McCarthy scale adjusted for 26 influences of neurodevelopment including parental intellect, home environment, breast or formula fed, growth retardation, and use of postnatal drugs. Results: A total of 442 infants </=34 wk gestation who had serum T4 measurements on postnatal d 7, 14, or 28 and 100 term infants who had serum T4 measured in cord blood were followed up at 5.5 yr. Infants with hypothyroxinemia (T4 level </= 10th percentile on d 7, 14, or 28 corrected for gestational age) scored significantly lower than euthyroid infants (T4 level greater than the 10th percentile and less than the 90th percentile on all days) on all McCarthy scales, except the quantitative. After adjustment for confounders of neurodevelopment, hypothyroxinemic infants scored significantly lower than euthyroid infants on the general cognitive and verbal scales. Conclusions: Our findings do not support the view that the hypothyroxinemic state, in the context of this analysis, is harmless in preterm infants. Many factors contribute both to the etiology of hypothyroxinemia and neurodevelopment; strategies for correction of hypothyroxinemia should acknowledge its complex etiology and not rely solely on one approach.
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PMID: 20719832 [PubMed - as supplied by publisher]8: Diabetologia. 2010 Aug 14; [Epub ahead of print]
Nouwen A, Winkley K, Twisk J, Lloyd CE, Peyrot M, Ismail K, Pouwer F; for the European Depression in Diabetes (EDID) Research Consortium.
School of Psychology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK, a.nouwen@bhm.ac.uk.
AIMS/HYPOTHESIS: An earlier meta-analysis showed that diabetes is a risk factor for the development and/or recurrence of depression. Yet whether this risk is different for studies using questionnaires than for those relying on diagnostic criteria for depression has not been examined. This study examined the association of diabetes and the onset of depression by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic. METHODS: EMBASE, MEDLINE and PsycInfo were searched for articles published up to September 2009. All studies that examined the relationship between type 2 diabetes and the onset of depression were included. Pooled relative risks were calculated using fixed and random effects models. RESULTS: Eleven studies met our inclusion criteria for this meta-analysis. Based on the pooled data, including 48,808 cases of type 2 diabetes without depression at baseline, the pooled relative risk was 1.24 (95% CI 1.09-1.40) for the random effects model. This risk was significantly higher for studies relying on diagnostic criteria of depression than for studies using questionnaires. However, this difference was no longer significant when controlled for year of publication. CONCLUSIONS/INTERPRETATION: Compared with non-diabetic controls, people with type 2 diabetes have a 24% increased risk of developing depression. The mechanisms underlying this relationship are still unclear and warrant further research.
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PMID: 20711716 [PubMed - as supplied by publisher]9: J Clin Endocrinol Metab. 2010 Aug 11; [Epub ahead of print]
Lorenzo C, Haffner SM, Stancakova A, Laakso M.
Department of Medicine (C.L.), University of Texas Health Science Center, San Antonio, Texas 78229; Department of Medicine (S.M.H.), Baylor College of Medicine, Houston, Texas 77030; and Department of Medicine (A.S., M.L.), University of Eastern Finland and Kuopio University Hospital, FI-70211 Kuopio, Finland.
Context: Methods to directly measure insulin resistance are invasive, complex, and costly. Surrogate indexes derived from the oral glucose tolerance test (OGTT) have been developed, but few studies have systematically analyzed these indexes. Objective: We examined the relation of surrogate and direct measures of insulin resistance to metabolic variables. Design and Setting: We conducted a cross-sectional analysis of the validation cohort of the Metabolic Syndrome in Men study. Participants: Participants included 272 nondiabetic Finnish offspring of type 2 diabetic individuals (age, 24-50 yr; 55% female). Intervention: Surrogate indexes of insulin resistance were computed according to published formulas. Insulin sensitivity was also directly measured by the euglycemic-hyperinsulinemic clamp. Results: The strength of the correlation of the Matsuda index with directly measured insulin sensitivity (r = 0.77) was similar to that of Avignon's insulin sensitivity index (r = 0.76; P = 0.581) and simple index assessing insulin sensitivity using OGTT measurements (r = 0.74; P = 0.060) and stronger than that of indexes derived from fasting measurements [e.g. fasting insulin (r = 0.72; P = 0.011) and homeostasis model assessment of insulin resistance (r = 0.71; P = 0.001)]. Surrogate indexes were similar to directly measured insulin sensitivity in their relationships with metabolic abnormalities including definitive measures of fat distribution. Some indexes, however, had distinctive correlations: McAuley index with lipoproteins and Avignon insulin sensitivity and Stumvoll indexes with adiposity and fibrinogen. Conclusions: Surrogate indexes are valid measures of insulin resistance. Multiple sampling times during an OGTT may not be mandatory to adequately estimate insulin resistance in clinical and epidemiological studies.
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PMID: 20702522 [PubMed - as supplied by publisher]10: Diabetologia. 2010 Aug 11; [Epub ahead of print]
Hutter N, Schnurr A, Baumeister H.
Department of Rehabilitation Psychology and Psychotherapy, Institute of Psychology, University of Freiburg, Engelbergerstr. 41, 79085, Freiburg, Germany, hutter@psychologie.uni-freiburg.de.
AIMS/HYPOTHESIS: We systematically reviewed the impact of comorbid mental disorders on healthcare costs in persons with diabetes. METHOD: We conducted a comprehensive search for studies investigating adult persons (>/=18 years old) with diabetes mellitus. All studies that allowed comparison of healthcare costs between diabetic patients with mental disorders and those without were included. RESULTS: We identified 4,273 potentially relevant articles from a comprehensive database search. Of these, 31 primary studies (39 publications) fulfilled inclusion criteria, of which 27 examined comorbid depression. Hospitalisation rates and hospitalisation costs, frequency and costs of outpatient visits, emergency department visits, medication costs and total healthcare costs were mainly increased with small to moderate effect sizes in patients with diabetes and comorbid mental disorders compared with diabetic patients without such problems. Frequency (standardised mean difference [SMD] = 0.35-1.26) and costs (SMD = 0.33-0.85) of mental health specialist visits were increased in the group with mental health comorbidity. Results regarding diabetes-related preventive services were inconsistent but point to a reduced utilisation rate in diabetic patients with comorbid mental disorders. Statistical heterogeneity between studies was high (I (2) range 64-98%). Pooled overall effects are therefore not reported. Studies included differ substantially regarding sample selection, assessment of diabetes and comorbid mental disorders, as well as in assessment of cost variables. CONCLUSIONS/INTERPRETATION: In light of the increased healthcare costs and inadequate use of preventive services, comorbid mental disorders in patients with diabetes must become a major focus of diabetes healthcare and research.
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PMID: 20700575 [PubMed - as supplied by publisher]11: Diabetes Care. 2010 Aug 12; [Epub ahead of print]
Nettleton JA, McKeown NM, Kanoni S, Lemaitre RN, Hivert MF, Ngwa J, van Rooij FJ, Sonestedt E, Wojczynski MK, Ye Z, Tanaka T; the CHARGE Whole Grain Foods Study Group.
Division of Epidemiology, Human Genetics, & Environmental Sciences, The University of Texas Health Sciences Center- Houston, Houston, TX, U.S.A.
AbstractObjective: Whole grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Research Design & Methods: Via meta-analysis of data from 14 cohorts comprising approximately 48,000 participants of European descent, we studied interactions of whole grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a p-value <0.0028 (0.05/18 tests) as statistically significant. Results: Greater whole grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (beta [95% CI] per 1-serving greater whole grain intake: -0.009 mmol/L glucose [-0.013, -0.005], p <0.0001 and -0.011 pmol/L (ln) insulin [-0.015, -0.007], p =0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole grain intake was rs780094 (GCKR) for fasting insulin (p = 0.006), where greater whole grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Conclusions: Our results support the favorable association of whole grain intake with fasting glucose and insulin and suggest potential interaction between variation in GCKR and whole grain intake in influencing fasting insulin concentrations.
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PMID: 20693352 [PubMed - as supplied by publisher]12: Diabetes Care. 2010 Aug 6; [Epub ahead of print]
Malik VS, Popkin BM, Bray GA, Despres JP, Willett WC, Hu FB.
1. Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA.
AbstractObjective: Consumption of sugar-sweetened beverages (SSBs), which include soft drinks, fruit drinks, iced tea, energy and vitamin water drinks has risen across the globe. Regular consumption of SSBs has been associated with weight gain and risk of overweight and obesity but its role in the development of related chronic metabolic diseases, such as metabolic syndrome (MetSyn) and type 2 diabetes (T2DM), has not been quantitatively reviewed. Methods: We searched the MEDLINE database up to May 2010 for prospective cohort studies of SSB intake and risk of MetSyn, and T2DM. We identified 11 studies (3 for MetSyn; 8 for T2DM) for inclusion in a random effects meta-analysis comparing SSB intake in the highest to lowest quantiles in relation to risk of MetSyn and T2DM. Results: Based on data from these studies, including 310,819 participants and 15,043 cases of T2DM, individuals in the highest quantile of SSB intake (most often 1-2 servings/day) had a 26% greater risk of developing T2DM than those in the lowest quantile (none or < 1 serving/month) (RR:1.26 (95% CI: 1.12, 1.41)). Among studies evaluating MetSyn, including 19,431 participants and 5,803 cases, the pooled RR was 1.20 (95% CI: 1.02, 1.42). Conclusions: In addition to weight gain, higher consumption of SSBs is associated with development of MetSyn, and T2DM. These data provide empirical evidence that intake of SSBs should be limited to reduce obesity-related risk of chronic metabolic diseases.
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PMID: 20693348 [PubMed - as supplied by publisher]13: J Clin Endocrinol Metab. 2010 Aug;95(8):3569-77.
Khosla S.
Endocrine Research Unit, Guggenheim 7, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. khosla.sundeep@mayo.edu
CONTEXT: The very clinical trial, the Women's Health Initiative, which definitely established the antifracture efficacy of estrogen therapy, led to the demise of estrogen treatment as a viable, long-term option for prevention of bone loss in postmenopausal women due to the well-publicized adverse effects of estrogen plus progestin therapy on a number of nonskeletal endpoints. Given the diminishing clinical use of estrogen, it is logical to question whether estrogen regulation of bone remains a relevant issue at a clinical or basic research level. EVIDENCE ACQUISITION: Findings of this update are based on a PubMed search and the author's knowledge of the field. EVIDENCE SYNTHESIS: Basic and clinical studies on the mechanisms of estrogen effects on bone will continue to provide potential novel drug targets for the prevention and treatment of osteoporosis. At a clinical level, it is clear that even the low levels of estrogen present in postmenopausal women have a significant impact on bone turnover, leading to a more aggressive approach to prevent bone loss in patients with breast cancer on aromatase inhibitors. Conversely, increasing these low estrogen levels with small doses of estrogen may have beneficial skeletal effects in postmenopausal women without adverse effects on reproductive tissues. Finally, the search continues for new selective estrogen receptor modulators with beneficial effects on bone and other tissues. CONCLUSIONS: Even in the post-WHI era, basic and clinical investigation on estrogen and bone will continue to yield important insights that not only expand our knowledge at a basic level but also impact the health of our aging population.
Publication Types: Research Support, N.I.H., Extramural Review
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PMID: 20685883 [PubMed - indexed for MEDLINE]14: J Clin Endocrinol Metab. 2010 Aug 4; [Epub ahead of print]
Meier C, Brauchli YB, Jick SS, Kraenzlin ME, Meier CR.
Division of Endocrinology, Diabetes, and Metabolism (C.M., M.E.K.) and Hospital Pharmacy (C.R.M.), University Hospital Basel, CH-4031 Basel, Switzerland; Basel Pharmacoepidemiology Unit (Y.B.B., C.R.M.), Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, CH-4056 Basel, Switzerland; and Boston Collaborative Drug Surveillance Program (S.S.J., C.R.M.), Boston University School of Medicine, and Department of Epidemiology, School of Public Health, Boston University, Lexington, Massachusetts 02421.
Context: Depot medroxyprogesterone acetate (DMPA), which has a high rate of use among teenagers in Europe and the United States, has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. Studies on the association between DMPA use and fracture risk are limited. Objective: We aimed at evaluating the relationship between use of hormonal contraceptives, specifically DMPA, and fracture risk. Design: We conducted a case-control analysis using the United Kingdom-based General Practice Research Database. Setting and Participants: Participants were females aged 20-44 yr with an incident fracture diagnosis between 1995 and 2008. Main Outcome Measures: Odds ratios (OR) with 95% confidence intervals (CI) of incident fracture in relation to exposure to DMPA or combined oral contraceptives were assessed. Adjustments were made for smoking, body mass index, and additional potential confounders. Results: We identified 17,527 incident fracture cases and 70,130 control patients (DMPA exposure: 11 and 8%, respectively). Compared with nonuse, current use of one to two, three to nine, or 10 or more DMPA prescriptions yielded adjusted OR for fractures of 1.18 (95% CI = 0.93-1.49), 1.36 (95% CI = 1.15-1.60), and 1.54 (95% CI = 1.33-1.78), respectively. Fracture risk was highest after longer treatment duration (>2-3 yr), and there was no difference in patients below and above the age of 30 yr. For users of combined estrogen-containing oral contraceptives, the OR were around 1. Conclusions: This population-based study suggests that use of DMPA is associated with a slightly increased risk of fractures.
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PMID: 20685865 [PubMed - as supplied by publisher]15: Diabetes Care. 2010 Aug 3; [Epub ahead of print]
Belalcazar LM, Reboussin DM, Haffner SM, Hoogeveen RC, Kriska AM, Schwenke DC, Tracy RP, Pi-Sunyer FX, Ballantyne CM; and the Look AHEAD Research Group.
From the Department of Medicine, University of Texas Medical Branch, Galveston, Texas.
AbstractObjective. We examined whether a 1-year intensive lifestyle intervention (ILI) for weight loss reduced elevated high-sensitivity C-reactive protein (hs-CRP) levels in obese persons with diabetes and identified metabolic and fitness predictors of hs-CRP change. Research Design and Methods. Look AHEAD is an ongoing multicenter clinical trial examining the effects of weight loss achieved through ILI on cardiovascular events and overall mortality in obese/overweight adults with type 2 diabetes. We report on 1,759 Look AHEAD participants who had hs-CRP and fitness data at baseline and 1 year. Subjects were randomized to ILI or to usual care (diabetes support and education [DSE]). ILI involved frequent counseling to increase moderate-intensity exercise to 175 minutes/week, reduce caloric and saturated fat intake and change macronutrient composition to improve glycemic control. Results. ILI reduced median hs-CRP by 43.6% from baseline to 1 year, compared with a 16.7% reduction with DSE (p<0.001). ILI decreased weight (8.8%), hemoglobin A1c (0.7%) and triglycerides (17%) and increased fitness (19%) and high-density lipoprotein cholesterol (7.5%) (p<0.0001 versus changes with DSE). Changes in adiposity and glucose control with ILI remained independent predictors of 1-year hs-CRP change (p<0.0001 for each) after adjusting for demographics, smoking, cardiovascular history, statin and thiazolidinedione use and changes in fitness and lipid control. Neither statin nor insulin therapy modified the association between ILI and hs-CRP. Conclusions. A 1-year lifestyle intervention for weight loss in obese persons with diabetes was associated with substantial reductions in hs-CRP. Improved glycemic control and reduced adiposity had comparable effects on hs-CRP change.
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PMID: 20682679 [PubMed - as supplied by publisher]16: Clin Endocrinol (Oxf). 2010 Aug 2; [Epub ahead of print]
Parsaik AK, Murad MH, Sathananthan A, Moorthy V, Erwin PJ, Chari S, Carter RE, Farnell MB, Vege SS, Sarr MG, Kudva YC.
Endocrinology, Mayo Clinic, Rochester, MN, 55902, USA.
Abstract Introduction: Total pancreatectomy (TP) has been associated with substantial metabolic abnormalities and poor glycemic control limiting its use. Because data reported to date are limited, we evaluated outcomes related to the diabetes mellitus obligated by TP. Methods: A case series study of all patients who underwent TP from 01/01/1985 to 12/31/2006 at Mayo Clinic was conducted. TP cases were summarized according to perioperative procedures, mortality and morbidity after TP. To complement this retrospective examination, a survey was developed to measure DM treatment modality, target organ failure and complications in patients alive in 2007. We performed a meta-analysis to compare our results with similar previous studies and provide overall estimates of outcomes. Results: A total of 141 cases were studied (97 malignant diseases, 44 benign diseases). The median survival was much less for malignant pathology (2.2 vs 8.7 years, Log rank p =0.0009). In 2007, there were 59 patients that were presumed alive, and 47 (80%) responded to the survey. Mean HbA1c at last follow up was 7.5% with 89% of respondents on a complex insulin program (mean daily insulin requirement 35 +/- 13 units). Episodic hypoglycemia was experienced by 37 (79%); 15 (41%) experienced severe hypoglycemia. In contrast, diabetic ketoacidosis developed in only 2 (4%). Target organ complications and chronic diarrhea developed in 13 patients (28%) each. Conclusion: The primary factor determining survival after TP is the etiology necessitating TP, i.e. pancreatic malignancy. Most respondents used complex insulin programs but hypoglycemia continues to be a problem.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20681992&dopt=ExternalLink
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PMID: 20681992 [PubMed - as supplied by publisher]17: Diabetes Care. 2010 Aug;33(8):1872-94.
Li R, Zhang P, Barker LE, Chowdhury FM, Zhang X.
Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. eok8@cdc.gov
OBJECTIVE: To synthesize the cost-effectiveness (CE) of interventions to prevent and control diabetes, its complications, and comorbidities. RESEARCH DESIGN AND METHODS: We conducted a systematic review of literature on the CE of diabetes interventions recommended by the American Diabetes Association (ADA) and published between January 1985 and May 2008. We categorized the strength of evidence about the CE of an intervention as strong, supportive, or uncertain. CEs were classified as cost saving (more health benefit at a lower cost), very cost-effective (<or=$25,000 per life year gained [LYG] or quality-adjusted life year [QALY]), cost-effective ($25,001 to $50,000 per LYG or QALY), marginally cost-effective ($50,001 to $100,000 per LYG or QALY), or not cost-effective (>$100,000 per LYG or QALY). The CE classification of an intervention was reported separately by country setting (U.S. or other developed countries) if CE varied by where the intervention was implemented. Costs were measured in 2007 U.S. dollars. RESULTS: Fifty-six studies from 20 countries met the inclusion criteria. A large majority of the ADA recommended interventions are cost-effective. We found strong evidence to classify the following interventions as cost saving or very cost-effective: (I) Cost saving- 1) ACE inhibitor (ACEI) therapy for intensive hypertension control compared with standard hypertension control; 2) ACEI or angiotensin receptor blocker (ARB) therapy to prevent end-stage renal disease (ESRD) compared with no ACEI or ARB treatment; 3) early irbesartan therapy (at the microalbuminuria stage) to prevent ESRD compared with later treatment (at the macroalbuminuria stage); 4) comprehensive foot care to prevent ulcers compared with usual care; 5) multi-component interventions for diabetic risk factor control and early detection of complications compared with conventional insulin therapy for persons with type 1 diabetes; and 6) multi-component interventions for diabetic risk factor control and early detection of complications compared with standard glycemic control for persons with type 2 diabetes. (II) Very cost-effective- 1) intensive lifestyle interventions to prevent type 2 diabetes among persons with impaired glucose tolerance compared with standard lifestyle recommendations; 2) universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old; 3) intensive glycemic control as implemented in the UK Prospective Diabetes Study in persons with newly diagnosed type 2 diabetes compared with conventional glycemic control; 4) statin therapy for secondary prevention of cardiovascular disease compared with no statin therapy; 5) counseling and treatment for smoking cessation compared with no counseling and treatment; 6) annual screening for diabetic retinopathy and ensuing treatment in persons with type 1 diabetes compared with no screening; 7) annual screening for diabetic retinopathy and ensuing treatment in persons with type 2 diabetes compared with no screening; and 8) immediate vitrectomy to treat diabetic retinopathy compared with deferred vitrectomy. CONCLUSIONS: Many interventions intended to prevent/control diabetes are cost saving or very cost-effective and supported by strong evidence. Policy makers should consider giving these interventions a higher priority.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20668156&dopt=ExternalLink
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PMID: 20668156 [PubMed - in process]18: J Clin Endocrinol Metab. 2010 Jul 28; [Epub ahead of print]
Kaptein EM, Sanchez A, Beale E, Chan LS.
Department of Medicine (E.M.K., A.S., E.B.), University of Southern California, Los Angeles, California 90033; and Department of Biostatistics and Outcomes Assessment (L.S.C.), Los Angeles County, University of Southern California Medical Center, Los Angeles, California 90033.
Context: Effects of thyroid hormone therapy on postoperative morbidity and mortality in adults remain controversial. Objective: The aim was to conduct a systematic review evaluating effects and risks of postoperative T3 therapy in adults. Data Sources: Electronic databases and reference lists through March 2010 were searched. Study Selection: Studies with comparable control groups comparing T3 to placebo therapy in randomized controlled trials were selected. Data Extraction: Two reviewers independently screened and reviewed titles, abstracts, and articles. Data were abstracted from 14 randomized controlled trials (13 cardiac surgery and one renal transplantation). In seven studies, iv T3 was given in high doses (0.175-0.333 mug/kg . h) for 6 to 9 h, in four studies iv T3 was given in low doses (0.0275-0.0333 mug/kg . h for 14 to 24 h), and in three studies T3 was given orally in variable doses and durations. Data Synthesis: Both high- and low-dose iv T3 therapy increased cardiac index after coronary artery bypass surgery. Mortality was not significantly altered by high-dose iv T3 therapy and could not be assessed for low-dose iv or oral T3. Effects on systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, new onset atrial fibrillation, inotrope use, serum TSH and T4 were inconclusive. Limitations: Numbers of usable unique studies and group sizes were small. Duration of T3 therapy was short, and dosages and routes of administration varied. Conclusions: Short duration postoperative iv T3 therapy increases cardiac index and does not alter mortality. Effects on other parameters are inconclusive.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20668034&dopt=ExternalLink
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PMID: 20668034 [PubMed - as supplied by publisher]19: Diabetes Care. 2010 Jul 27; [Epub ahead of print]
Lazo M, Solga SF, Horska A, Bonekamp S, Diehl AM, Brancati FL, Wagenknecht LE, Pi-Sunyer FX, Kahn SE, Clark JM; for the Fatty Liver Subgroup of the Look AHEAD Research Group.
Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Welch Center for Prevention, Epidemiology and Clinical Research.
AbstractObjective: Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD), however its efficacy in patients with type 2 diabetes is unproven. Research Design and Methods: Look AHEAD is a 16-center clinical trial with 5145 overweight or obese adults with type 2 diabetes, who were randomly assigned to an intensive lifestyle intervention (ILI) to induce a minimum weight loss of 7%, or a control group who received diabetes support and education (DSE). In the Fatty Liver Ancillary Study, 96 participants completed proton-magnetic resonance spectroscopy ((1)H-MRS) to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12-months. We defined steatosis > 5.5% as NAFLD. Results: Participants were 49% women and 68% white. The mean age was 61 years, mean BMI 35 kg/m(2), mean steatosis 8.0% and mean AST and ALT 20.5 and 24.2 U/L respectively. After 12 months, participants assigned to ILI (n=46), as compared to DSE (n=50), lost more weight (-8.5% vs. -0.05%; p<0.01), had a greater decline in steatosis (-50.8% vs. -22.8%; p=0.04) and in A1c (-0.7% vs. -0.2%; p=0.04).There were no significant 12-month changes in AST or ALT levels. Twenty-six percent (6 of 23) of DSE participants and 3% (1 of 31) of ILI participants without NAFLD at baseline developed NAFLD at 12 months (p<0.05). Conclusions: A 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20664019&dopt=ExternalLink
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PMID: 20664019 [PubMed - as supplied by publisher]20: J Clin Endocrinol Metab. 2010 Jul 21; [Epub ahead of print]
Dong Y, Stallmann-Jorgensen IS, Pollock NK, Harris RA, Keeton D, Huang Y, Li K, Bassali R, Guo DH, Thomas J, Pierce GL, White J, Holick MF, Zhu H.
Georgia Prevention Institute, Department of Pediatrics (Y.D., I.S.S.-J., N.K.P., R.A.H., D.K., Y.H., K.L., D.G., J.T., G.L.P., H.Z.); General Pediatrics, Department of Pediatrics (R.B.), and Endocrinology, Department of Medicine (J.W.), Medical College of Georgia, Augusta, Georgia 30912; and Endocrinology, Department of Medicine (M.F.H.), Boston University Medical Center, School of Medicine, Boston, Massachusetts 02118.
Context: Vitamin D insufficiency/deficiency is commonly observed in black youth. Objective: The aim was to determine 25-hydroxyvitamin D [25(OH)D] in response to 2000 IU vitamin D supplementation over time; to evaluate the relation between 25(OH)D concentrations and total body fat mass by dual-energy x-ray absorptiometry; and to determine whether vitamin D supplementation improves arterial stiffness measured by pulse wave velocity (PWV). Design: We conducted a randomized, blinded, controlled clinical trial. Setting and Participants: Forty-nine normotensive black boys and girls, aged 16.3 +/- 1.4 yr, were randomly assigned to either the control group (400 IU/d; n = 24) or the experimental group (2000 IU/d; n = 25). Results: Plasma 25(OH)D values at baseline and at 4, 8, and 16 wk were 34.0 +/- 10.6, 44.9 +/- 9.4, 51.2 +/- 11.1, and 59.8 +/- 18.2 nmol/liter, respectively, for the control group; and 33.1 +/- 8.7, 55.0 +/- 11.8, 70.9 +/- 22.0, and 85.7 +/- 30.1 nmol/liter, respectively, for the experimental group. The experimental group vs. the control group reached significantly higher 25(OH)D concentrations at 8 and 16 wk, respectively. Partial correlation analyses indicated that total body fat mass at baseline was significantly and inversely associated with 25(OH)D concentrations in response to the 2000-IU supplement across time. Furthermore, carotid-femoral PWV increased from baseline (5.38 +/- 0.53 m/sec) to posttest (5.71 +/- 0.75 m/sec) in the control group (P = 0.016), whereas in the experimental group carotid-femoral PWV decreased from baseline (5.41 +/- 0.73 m/sec) to posttest (5.33 +/- 0.79 m/sec) (P = 0.031). Conclusion: Daily 2000 IU vitamin D supplementation may be effective in optimizing vitamin D status and counteracting the progression of aortic stiffness in black youth. Plasma 25(OH)D concentrations in response to the 2000 IU/d supplementation are negatively modulated by adiposity.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20660028&dopt=ExternalLink
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PMID: 20660028 [PubMed - as supplied by publisher]