Lack of association between 25(OH)D levels and incident type 2 diabetes in older women

OBJECTIVE

To examine whether lower serum levels of serum 25-hydroxyvitamin (OH) D [25(OH)D] are associated with increased risk of developing type 2 diabetes.

RESEARCH DESIGN AND METHODS

A post hoc analysis of three nested case-control studies of fractures, colon cancer, and breast cancer that measured serum 25(OH)D levels in women participating in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study who were free of prevalent diabetes at baseline. Diabetes was defined as self-report of physician diagnosis or receiving insulin or oral hypoglycemic medication. We used inverse probability weighting to make the study population representative of the WHI population as a whole. Weighted logistic regression models compared 25(OH)D levels (divided into quartiles, clinical cut points [<50, 50–<75, ≥75 nmol/L], or as a continuous variable) using the distribution of control subjects and adjusted for multiple confounding factors.

RESULTS

Of 5,140 women (mean age 66 years) followed for an average of 7.3 years, 317 (6.2%) developed diabetes. Regardless of the cut points used or as a continuous variable, 25(OH)D levels were not associated with diabetes incidence in either age or fully adjusted models. Nor was any relationship found between 25(OH)D and incident diabetes when evaluated by strata of BMI, race/ethnicity, or randomization status in the Calcium Vitamin D trial.

CONCLUSIONS

Lower serum 25(OH)D levels were not associated with increased risk of developing type 2 diabetes in this racially and ethnically diverse population of postmenopausal women.Vitamin D has been shown to have numerous nonskeletal effects, including an important role in pancreatic insulin secretion and insulin action (1). Although several studies have reported a protective relationship between vitamin D and the risk of developing diabetes, the data are not consistent. A recent meta-analysis found that three of six observational studies (OS) found an association between low vitamin D status and increased risk of incident type 2 diabetes or metabolic syndrome (2). In contrast, eight clinical trials found vitamin D supplementation had no effect on glycemia or incident diabetes (1). It may be that higher doses of vitamin D than those tested in clinical trials may be required to affect diabetes risk. Alternatively, the associations of calcium and vitamin D intake with improved glucose metabolism reported in OS may be the result of confounding by other components of foods containing these nutrients (3), outdoor exercise associated with solar radiation, or other factors (4,5).We undertook this analysis to further evaluate the relationship between 25-hydroxyvitamin D [25(OH)D] levels and diabetes risk in a large cohort of postmenopausal women participating in the Women’s Health Initiative (WHI). Several nested case-control studies within the WHI measured 25(OH)D levels in over 5,000 women, providing a unique opportunity to evaluate an older, multiethnic population at high risk for both vitamin D insufficiency and diabetes (6,7). Our objectives were to examine whether decreased serum levels of 25(OH)D were associated with increased risk of incident type 2 diabetes and whether ethnicity or BMI modified the relationship.     

The longitudinal course of PTSD among disaster workers deployed to the World Trade Center following the attacks of September 11th

This study examined the long-term mental health outcomes of 2,960 nonrescue disaster workers deployed to the World Trade Center site in New York City following the September 11, 2001 (9/11) terrorist attacks. Semistructured interviews and standardized self-report measures were used to assess the prevalence of posttraumatic stress disorder (PTSD) and other psychopathology 4 and 6 years after the attacks. Clinician-measured rates of PTSD and partial PTSD 4-years posttrauma were 8.4% and 8.9%, respectively, in a subsample of 727 individuals. Rates decreased to 5.8% and 7.7% for full and partial PTSD 6 years posttrauma. For the larger sample, self-report scores revealed probable PTSD and partial PTSD prevalence to be 4.8% and 3.6% at 4 years, and 2.4% and 1.8% at 6 years. Approximately 70% of workers never met criteria for PTSD. Although PTSD rates decreased significantly over time, many workers remained symptomatic, with others showing delayed-onset PTSD. The strongest predictors of ongoing PTSD 6 years following 9/11 were trauma history (odds ratio (OR) = 2.27, 95% confidence interval (CI) [1.06, 4.85]); the presence of major depressive disorder 1-2 years following the trauma (OR = 2.80, 95% CI [1.17, 6.71]); and extent of occupational exposure (OR = 1.31, 95% CI [1.13, 1.51]). The implications of the findings for both screening and treatment of disaster workers are discussed.     

Disasters and mass casualties: II. explosive, biologic, chemical, and nuclear agents

Terrorists' use of explosive, biologic, chemical, and nuclear agents constitutes the potential for catastrophic events. Understanding the unique aspects of these agents can help in preparing for such disasters with the intent of mitigating injury and loss of life. Explosive agents continue to be the most common weapons of terrorists and the most prevalent cause of injuries and fatalities. Knowledge of blast pathomechanics and patterns of injury allows for improved diagnostic and treatment strategies. A practical understanding of potential biologic, chemical, and nuclear agents, their attendant clinical symptoms, and recommended management strategies is an important prerequisite for optimal preparation and response to these less frequently used agents of mass casualty. Orthopaedic surgeons should be aware of the principles of management of catastrophic events. Stress is less an issue when one is adequately prepared. Decontamination is essential both to manage victims and prevent further spread of toxic agents to first responders and medical personnel. It is important to assess the risk of potential threats, thereby allowing disaster planning and preparation to be proportional and aligned with the actual casualty event.     

Comparison of Traditional Phenotypic Identification Methods with Partial 5′ 16S rRNA Gene Sequencing for Species-Level Identification of Nonfermenting Gram-Negative Bacilli

Correct identification of nonfermenting Gram-negative bacilli (NFB) is crucial for patient management. We compared phenotypic identifications of 96 clinical NFB isolates with identifications obtained by 5′ 16S rRNA gene sequencing. Sequencing identified 88 isolates (91.7%) with >99% similarity to a sequence from the assigned species; 61.5% of sequencing results were concordant with phenotypic results, indicating the usability of sequencing to identify NFB.Nonfermenting Gram-negative bacilli (NFB) are ubiquitous in the environment and may cause opportunistic infections in immunocompromised patients and individuals with cystic fibrosis (2, 9). Accurate diagnosis and appropriate treatment require species-specific identification of clinically significant NFB isolates. Conventional phenotypic identification may involve a number of methods, including observation of growth and colony morphology on various media, analysis of manual biochemical reactions, and the use of automated and nonautomated commercially available biochemical panels. Unfortunately, commercial phenotypic databases are often outdated and lack current taxonomy (15). Moreover, phenotypic systems often cannot account for the variable characteristics observed among members of the same species, resulting in poor precision upon repeat testing (3).Identification of NFB by partial 5′ 16S rRNA gene sequencing using the MicroSeq 500 system (Applied BioSystems, Foster City, CA) is more accurate than conventional phenotypic methods and other commercial systems involving fatty acid and carbon utilization profiles (16). As for any identification method, limitations for 16S rRNA gene sequencing exist (11). Bacterial taxonomy and nomenclature continue to change as the genotypic features of organisms are analyzed in greater detail. Furthermore, these analyses have identified unique strains with distinct biochemical and genetic profiles that make definitive identification difficult until the strains are accepted as new species (8, 17). Even with a relatively complete sequence database, 16S rRNA gene sequences from different strains are often identical or closely matched (i.e., >99.5% similar), making expert judgment a requirement for identification (11).When 16S rRNA gene sequencing is used to identify bacteria, the availability and completeness of databases will affect the accuracy of identification. Previous studies have shown that the MicroSeq 500 16S rRNA gene sequence library is incomplete and outdated for the identification of clinical isolates of Mycobacterium species (4) and Nocardia species (5, 14). As sequencing technology has become more affordable (6), clinical laboratories are now utilizing sequencing methods in conjunction with freely accessible public databases for organism identification. GenBank (http://blast.ncbi.nlm.nih.gov/Blast.cgi) is one such database that has been evaluated and found to contain sequence errors, especially in sequences submitted prior to 1995 (10, 11). The use of commercial databases increases the cost of sequence-based identification, and these databases are often outdated (4, 14). Finally, no criteria for reporting sequence identities exist, likely due to high levels of phylogenetic variation among species (11).In the present study, implementation of 5′ 16S rRNA gene sequencing using the first 500 to 527 bp for the identification of clinical NFB isolates was assessed. PCR and sequencing methods were performed as described previously (13, 14). Sequence similarity analysis was accomplished using the MicroSeq 500 library (version 500-0125) in conjunction with a new sequence library used previously to assess NFB identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (13). Identifications of 96 clinical isolates by sequencing were compared to identifications established by conventional phenotypic and commercial methods (using the Vitek or API 20NE system [bioMérieux, Durham, NC] or the MicroScan sysem [Siemens Healthcare Diagnostics Inc., Newark, DE]) with the latest version of software available at the time of testing. Isolates were recovered from clinician-requested specimens from patients with suspected infection at four different institutions. Each of the institutions performed phenotypic identifications according to their protocols, which were not necessarily the same among the institutions. While this approach presented a potential limitation for the study, all institutions regularly participated in proficiency surveys and were accredited according to the Clinical Laboratory Improvement Amendments (CLIA). Reporting criteria for identifications based on similarity of sequences were established as follows: excellent species identification, 99.8 to 100% similarity to a database sequence from the assigned species; good species identification, 99.1 to 99.7% similarity; and unlikely species identification, 96.7 to 99.0% similarity. These criteria are consistent with the recommendations reported by Janda and Abbott (11). Of the 96 clinical isolates examined, 64 (66.7%) yielded excellent species identification, 24 (25.0%) yielded good identification, and 8 (8.3%) could be identified confidently only to the genus level by sequencing (Table ​(Table1).1). Fifteen isolates with discrepant identifications by sequencing and phenotypic methods exhibited sequence identity scores between 99.8 and 100%, in support of the sequencing results (Table ​(Table11).

TABLE 1.

Phenotypic identifications of NFB isolated from clinical samples compared with identifications obtained using partial 16S rRNA gene sequencing

Postmenopausal hormone therapy: new questions and the case for new clinical trials

Observational studies suggest that postmenopausal hormone therapy (HT) prevents coronary heart disease, whereas randomized clinical trials have not confirmed a cardioprotective effect. Although observational studies may have overestimated the coronary benefit conferred by postmenopausal hormone use, there are other plausible explanations for the apparent discrepancy between previous results and the less favorable findings from clinical trials such as the large Women's Health Initiative. There is now a critical mass of data to support the hypothesis that age or time since menopause may importantly influence the benefit-risk ratio associated with HT, especially with respect to cardiovascular outcomes, and that the method of administration, dose, and formulation of exogenous hormones may also be relevant. Although the weight of the evidence indicates that older women and those with subclinical or overt coronary heart disease should not take HT, estrogen remains the most effective treatment currently available for vasomotor symptoms, and its effects on the development of coronary disease in newly postmenopausal women remain unclear. Moreover, effects of HT on quality of life and cognitive function in recently postmenopausal women merit further study. These unresolved clinical issues provide the rationale for the design of the Kronos Early Estrogen Prevention Study, a 5-year randomized trial that will evaluate the effectiveness of low-dose oral estrogen and transdermal estradiol in preventing progression of atherosclerosis in recently postmenopausal women.