Fracture Prevention Clinic Targeting Patients with Fragility Fracture of the Distal Radius: A Pilot Study.

BACKGROUND: Identifying and treating patients with fragility fractures may be effective in prevention of subsequent fractures because a first fragility fracture often predicts a second fracture. OBJECTIVES: To evaluate a multidisciplinary anti-osteoporotic clinic for patients with prior distal radius fragility fractures (DRFF). To assess whether addressing this early fracture may prevent a second fracture. METHODS: A retrospective case-control study was performed. Cases included patients treated surgically for DRFF who were assessed at a tertiary, multidisciplinary, fracture-prevention clinic. Controls were a series of similarly treated patients who did not attend the clinic. The primary outcome measure was a second fracture. RESULTS: Average follow-up was 42 months for the treated group and 85 months for the untreated group. The treated group received more treatment for osteoporosis than controls; however, despite one new fracture in the treated group and six new fractures in the control group, there was no significant difference in fracture occurrence. CONCLUSIONS: This pilot study supports the effectiveness of our multidisciplinary anti-osteoporotic clinic in treating osteoporosis but not in reducing subsequent fractures. Further study with larger cohorts and longer follow-up is needed to improve our ability to implement effective prevention of fragility fractures.

Prognostic relevance of Ki67 expression in primary male breast cancer: determination of cut-off points by different evaluation methods and statistical examinations.

PURPOSE: 1% of all breast cancer cases occur in men. There are significant differences regarding clinical behaviour and genetic profiles between female (FBC) and male breast cancer (MBC). Parameters for decision-making on treatment and prognosis are derived from FBC. Ki67 has a high value as a prognostic and predictive factor in FBC, but accurate Ki67 cut-off points for MBC are missing. In this study, we aimed to evaluate adequate examination methods and reliable cut-off points for Ki67 to assess the highest prognostic value for patient's overall survival (OS). METHODS: In this multicentric retrospective study, histological specimens were obtained from 104 male patients who were diagnosed and treated for primary invasive breast cancer. We applied three methods of Ki67 analysis: Tumor average scoring (TA), tumor border scoring (TB) and hot-spot scoring (HS). Calculated Ki67 cut-off points for each method were assessed as a threshold for patients' overall survival (OS). RESULTS: Ki67 cut-off points were 13.5 for the TA group, 22.5 for the HS group and 17.5 for the TB group. Only Ki67 TA cut-off calculations demonstrated statistical significance (p = 0.04). Ki67 expression analysis of TA showed that more than 90% of patients with low Ki67 levels (< 13.5) were alive after 5-year follow-up. CONCLUSION: Our findings demonstrate that determination of Ki67 expression in TA is the most reliable to define a cut-off point with high prognostic value. A Ki67 cut-off point of 13.5 shows highest statistical power to define luminal A subgroup and OS.

Common Pitfalls in the Interpretation of Endocrine Tests.

Endocrine tests are the cornerstone of diagnosing multiple diseases that primary care physicians are frequently faced with. Some of these tests can be affected by situations that affect the proper interpretation, leading to incorrect diagnoses and unnecessary treatment, such as the interference of biotin with thyroid function test, falsely elevated prolactin values in presence of macroprolactinemia or falsely normal due to the "hook effect" in macroprolactinomas. Recognizing these situations is essential for the clinician to make an adequate interpretation of these tests as well as an accurate diagnosis that guarantees the best outcomes for the patient.

The metabolic syndrome in pediatrics: do we have a reliable definition? A systematic review.

OBJECTIVE: Metabolic syndrome is a cluster of cardio-metabolic risk factors associated with an increased risk of cardiovascular disease and type 2 diabetes. In the last two decades, several definitions of metabolic syndrome have been proposed for the pediatric population; all of them agree on the defining components but differ in the suggested criteria for diagnosis. This review aims to analyze the current diagnostic criteria of metabolic syndrome in pediatrics with reference to their feasibility and reliability in clinical practice. METHODS: The systematic research was conducted from January 2003 to June 2020 through MEDLINE via PubMed, Cochrane Library and EMBASE databases. RESULTS: After the selection phase, a total of 15 studies (182 screened) met the inclusion criteria and are reported in the present review. Twelve studies were cross-sectional, two were longitudinal and one was a consensus report. The sample population consisted of multiethnic group or single ethnic group, including Turkish, European, Asian and Hispanic subjects. CONCLUSIONS: To date, there is not a univocal, internationally accepted pediatric definition of metabolic syndrome, which guarantees a high sensitivity and stability of the diagnosis. The definition proposed by IDF results the most straightforward and easy to use in clinical practice, having the unquestionable advantage of requiring measurements quickly accessible in clinical practice, without the adoption of multiple reference tables. Further research is needed to validate a new version of such definition which includes the diagnostic cut-off points recently suggested by published guidelines.

Maximum adenoma diameter, regardless of uni- or bilaterality, is a risk factor for autonomous cortisol secretion in adrenal incidentalomas.

PURPOSE: To evaluate differences between patients with unilateral and bilateral adrenal incidentalomas (AIs) in the prevalence of autonomous cortisol secretion (ACS) and related comorbidities. METHODS: In this multicentre retrospective study, AIs ≥ 1 cm without overt hormonal excess were included in the study. ACS was defined by a post-dexamethasone suppression test (DST) serum cortisol ≥ 5.0 µg/dl, in the absence of signs of hypercortisolism. For the association of ACS with the prevalence of comorbidities, post-DST serum cortisol was also analysed as a continuous variable. RESULTS: Inclusion criteria were met by 823 patients, 66.3% had unilateral and 33.7% bilateral AIs. ACS was demonstrated in 5.7% of patients. No differences in the prevalence of ACS and related comorbidities were found between bilateral and unilateral AIs (P > 0.05). However, we found that tumour size was a good predictor of ACS (OR = 1.1 for each mm, P < 0.001), and the cut-off of 25 mm presented a good diagnostic accuracy to predict ACS (sensitivity of 69.4%, specificity of 74.1%). During a median follow-up time of 31.2 (IQR = 14.4-56.5) months, the risk of developing dyslipidaemia was increased in bilateral compared with unilateral AIs (HR = 1.8, 95% CI = 1.1-3.0 but, this association depended on the tumour size observed at the end of follow-up (HR adjusted by last visit-tumour size = 0.9, 95% CI = 0.1-16.2). CONCLUSIONS: Tumour size, not bilaterality, is associated with a higher prevalence of ACS. During follow-up, neither tumour size nor bilaterality were associated with the development of new comorbidities, yet a larger tumour size after follow-up explained the association of bilateral AIs with the risk of dyslipidaemia.

Reconsidering the HbA1c Cutoff for Diabetes Diagnosis Based on a Large Chinese Cohort.

INTRODUCTION: The HbA1c has been considered as the 'gold standard' in diabetes diagnosis and management, however, age, gender and body mass index (BMI) might have certain effects on HbA1c. We are aiming to further investigate the correlation between age and HbA1c, and whether it was affected by gender and BMI. METHODS: A cross-sectional survey including 135,893 nondiabetic individuals who took the physical examination between 2013 and 2017 was conducted. The subjects were grouped by gender, age and BMI, and the interactive and independent effects of the 3 factors on the HbA1c were detected. The median and 95% confidence interval (CI) of HbA1c levels were calculated. RESULTS: The HbA1c levels gradually increased along with age, both in female and male, and there is a positive association between BMI and the HbA1c. The difference on HbA1c in gender was associated with both age and BMI, the age-related increase in HbAlc was accentuated in the subgroup with higher BMI, and there was a marked accentuation of the positive association between BMI and HbA1c as age increased. In almost all the young and middle-aged (aged 20-59) subgroups, the 97.5th percentiles of HbA1c levels were lower than 6.5%, suggesting that the single HbA1c cutoff value is probably not applicable to the young and middle-aged population. CONCLUSIONS: We recommend that the effects of age, gender and BMI should be taken into consideration when using HbA1c for the diagnosis and management of diabetes, especially in the young and middle-aged population.

The Prevalence of Metabolically Healthy and Unhealthy Obesity according to Different Criteria.

OBJECTIVE: Obesity-related disease risks may vary depending on whether the subject has metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO). At least 5 definitions/criteria of obesity and metabolic disorders have been documented in the literature, yielding uncertainties in a reliable international comparison of obesity phenotype prevalence. This report aims to compare differences in MHO and MUO prevalence according to the 5 most frequently used definitions. METHODS: A random sample of 4,757 adults aged 35 years and older (male 51.1%) was enrolled. Obesity was defined either according to body mass index or waist circumference, and the definitions of metabolic abnormalities were derived from 5 different criteria. RESULTS: In MHO, the highest prevalence was obtained when using the homeostasis model assessment (HOMA) criteria (13.6%), followed by the Chinese Diabetes Society (11.4%), Adult Treatment Panel III (10.3%), Wildman (5.2%), and Karelis (4.2%) criteria; however, the MUO prevalence had an opposite trend to MHO prevalence. The magnitude of differences in the age-specific prevalence of MHO and MUO varied greatly and ranked in different orders. The proportion of insulin resistance for MHO and MUO individuals differed significantly regardless of which metabolic criterion was used. CONCLUSION: The prevalence of MHO and MUO in the Chinese population varies according to different definitions of obesity and metabolic disorders.

Assessing the severity of Type 2 diabetes using clinical data-based measures: a systematic review.

AIMS: To identify and critically appraise measures that use clinical data to grade the severity of Type 2 diabetes. METHODS: We searched MEDLINE, Embase and PubMed between inception and June 2018. Studies reporting on clinical data-based diabetes-specific severity measures in adults with Type 2 diabetes were included. We excluded studies conducted solely in participants with other types of diabetes. After independent screening, the characteristics of the eligible measures including design and severity domains, the clinical utility of developed measures, and the relationship between severity levels and health-related outcomes were assessed. RESULTS: We identified 6798 studies, of which 17 studies reporting 18 different severity measures (32 314 participants in 17 countries) were included: a diabetes severity index (eight studies, 44%); severity categories (seven studies, 39%); complication count (two studies, 11%); and a severity checklist (one study, 6%). Nearly 89% of the measures included diabetes-related complications and/or glycaemic control indicators. Two of the severity measures were validated in a separate study population. More severe diabetes was associated with increased healthcare costs, poorer cognitive function and significantly greater risks of hospitalization and mortality. The identified measures differed greatly in terms of the included domains. One study reported on the use of a severity measure prospectively. CONCLUSIONS: Health records are suitable for assessment of diabetes severity; however, the clinical uptake of existing measures is limited. The need to advance this research area is fundamental as higher levels of diabetes severity are associated with greater risks of adverse outcomes. Diabetes severity assessment could help identify people requiring targeted and intensive therapies and provide a major benchmark for efficient healthcare services.

Impact of the definition of osteoarthritis and of the timing of its onset on the association between type 2 diabetes mellitus and osteoarthritis: Clinical Practice Research Datalink.

AIMS: In a previous case-control study in a large primary care database, the Clinical Practice Research Datalink (CPRD), type 2 diabetes mellitus (T2DM) was associated with a decreased rate of total joint replacement (TJR). As this was in contrast to the hypothesis, selection bias due to the used definition of osteoarthritis (OA) or misclassification of the onset of OA were raised as possible explanations. We therefore aimed to explore the effect of the definition of OA, and hypothesized timing of its onset on the association between T2DM and OA. METHODS: All patients using a non-insulin anti-hyperglycaemic drug (NIAD) between 1989 and 2012 in the CPRD were included and matched to unexposed patients. Cox proportional hazard models were fitted estimating the risk of TJR or OA in T2DM patients compared to patients without T2DM. These analyses were repeated in sensitivity scenarios and joint-specific analyses. To assess whether misclassification of onset of OA may affect the association, analyses were repeated with addition of a latency period of up to 10 years after start of follow-up. RESULTS: The use of TJR as a proxy for OA (hazard ratio (HR) = 0.74; 95% Confidence Interval (CI) = 0.70-0.78) resulted in a HR that was approximately 0.2 lower than when OA diagnostic codes were used (HR = 0.93; 95% CI = 0.90-0.95). The joint-specific subgroup analyses, sensitivity scenarios, and latency analyses showed similar results. CONCLUSION: When examining the association between T2DM and OA, the use of TJR as a proxy for OA resulted in a 20% lower estimate than the OA diagnosis.

The repeatability of glucocorticoids: A review and meta-analysis.

Glucocorticoids are highly conserved hormones that mediate a suite of responses to changing conditions in vertebrates. Recent work has focused on understanding how selection operates on glucocorticoid secretion in natural populations. Because heritability is rarely estimated and difficult to measure in the wild, many studies report within-individual repeatability as an estimate of stable between individual differences in glucocorticoid secretion. We conducted a systematic review and meta-analysis on estimates of within-individual glucocorticoid repeatability to elucidate general patterns of repeatability, and to test for relationships between covariates and estimates of repeatability. To this end, we collected 203 estimates of within-individual glucocorticoid repeatability drawn from 71 separate studies and 55 species. Overall, we found moderate levels of repeatability (0.29). We also found that repeatability varied by sample type. Long-term measures (e.g., fecal and feather samples) and acute stress-induced plasma glucocorticoids had higher repeatability (long-term: 0.44, stress-induced: 0.38), than baseline glucocorticoid levels (0.18). Repeatability also decreased with increasing time between repeated sampling events. Despite significant overall repeatability, there was substantial heterogeneity in estimates from different studies, suggesting that repeatability of glucocorticoid secretion varies substantially across systems and conditions. We discuss the implications of our results for understanding selection on glucocorticoid traits and suggest that continuing work should focus on evaluating the repeatability of within-individual glucocorticoid reaction norms.

How to use and interpret hormone ratios.

Hormone ratios have become increasingly popular throughout the neuroendocrine literature since they offer a straightforward way to simultaneously analyze the effects of two interdependent hormones. However, the analysis of ratios is associated with statistical and interpretational concerns which have not been sufficiently considered in the context of endocrine research. The aim of this article, therefore, is to demonstrate and discuss these issues, and to suggest suitable ways to address them. In a first step, we use exemplary testosterone and cortisol data to illustrate that one major concern of ratios lies in their distribution and inherent asymmetry. As a consequence, results of parametric statistical analyses are affected by the ultimately arbitrary decision of which way around the ratio is computed (i.e., A/B or B/A). We suggest the use of non-parametric methods as well as the log-transformation of hormone ratios as appropriate methods to deal with these statistical problems. However, in a second step, we also discuss the complicated interpretation of ratios, and propose moderation analysis as an alternative and oftentimes more insightful approach to ratio analysis. In conclusion, we suggest that researchers carefully consider which statistical approach is best suited to investigate reciprocal hormone effects. With regard to the hormone ratio method, further research is needed to specify what exactly this index reflects on the biological level and in which cases it is a meaningful variable to analyze.

IS BIOCHEMICAL ASSESSMENT OF PHEOCHROMOCYTOMA NECESSARY IN ADRENAL INCIDENTALOMAS WITH MAGNETIC RESONANCE IMAGING FEATURES NOT SUGGESTIVE OF PHEOCHROMOCYTOMA?

OBJECTIVE: Currently, it is unclear whether pheochromocytomas can be ruled out based on low intensity on T2-weighted sequences and signal loss on out-of-phase magnetic resonance imaging (MRI) sequences. Hence, in this study, we investigated whether biochemical screening for pheochromocytoma in patients with adrenal incidentalomas (AIs) showing MRI features not suggesting pheochromocytoma would prove beneficial. METHODS: We performed MRI for 300 AIs in 278 consecutive patients. All patients were screened for pheochromocytoma with plasma metanephrine and normetanephrine. Patients with high plasma levels of metanephrine and/or normetanephrine were also assessed for pheochromocytoma by urinary metanephrines. RESULTS: Hyperintensity was detected on T2-weighted MRI sequences in 28 (9.3%) of the 300 AIs. Among these 28 incidentalomas, pheochromocytoma was diagnosed in 13 (46.4%) of the cases by histopathologic analysis. Hyperintensity on T2-weighted MRI was significantly higher in pheochromocytomas compared to the remaining AIs (P<.001). All 13 pheochromocytomas were characterized by hyperintensity on T2-weighted sequences and the absence of signal loss on out-of-phase MRI sequences. Pheochromocytoma was not detected in any of the 272 AIs that appeared hypointense or isointense on T2-weighted MRI sequences or in the 250 cases with signal loss on out-of-phase sequences. CONCLUSION: The results of this study suggest that AIs that appear hypointense or isointense on T2-weighted MRI sequences and those with signal loss on out-of-phase sequences may not require routine biochemical screening for pheochromocytoma. Further studies including a higher number of pheochromocytomas are required to confirm our results.

The shortened combined clonidine and arginine test for growth hormone deficiency is practical and specific: a diagnostic accuracy study.

BACKGROUND: The growth hormone (GH) stimulation protocols for clonidine and arginine tests are non-standardized and can be lengthy. We examined the specificity of both tests using a shorter duration of timed samples: 90 min for clonidine and 60 min for arginine. METHODS: We retrospectively studied all children who had GH stimulation with clonidine and arginine to test for GH deficiency (GHD). We compared the diagnostic accuracy of both reference and new shortened test (index). RESULTS: We reviewed 243 charts (11.4±4.1 years old; 74.5% males). The combined reference test was performed on 159 children, 29 (18.3%) tested positive for GHD on the combined index test, Kappa 0.98, false positive rate 1 (0.8%), specificity 0.99, 95th CI (0.96-1), and p=1.0. The specificity of both the clonidine and arginine single index tests was 0.98%. CONCLUSIONS: The shortened clonidine and arginine stimulation index tests have good specificity. This is a viable option for testing children for GHD.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1.

Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists (AACE) and the Androgen Excess and PCOS Society (AES) aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2015. PCOS has been defined using various criteria, including menstrual irregularity, hyperandrogenism, and polycystic ovary morphology (PCOM). General agreement exists among specialty society guidelines that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological) and polycystic ovaries. There is need for careful clinical assessment of women's history, physical examination, and laboratory evaluation, emphasizing the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Free testosterone (T) levels are more sensitive than the measurement of total T for establishing the existence of androgen excess and should be ideally determined through equilibrium dialysis techniques. Value of measuring levels of androgens other than T in patients with PCOS is relatively low. New ultrasound machines allow diagnosis of PCOM in patients having at least 25 small follicles (2 to 9 mm) in the whole ovary. Ovarian size at 10 mL remains the threshold between normal and increased ovary size. Serum 17-hydroxyprogesterone and anti-Müllerian hormone are useful for determining a diagnosis of PCOS. Correct diagnosis of PCOS impacts on the likelihood of associated metabolic and cardiovascular risks and leads to appropriate intervention, depending upon the woman's age, reproductive status, and her own concerns. The management of women with PCOS should include reproductive function, as well as the care of hirsutism, alopecia, and acne. Cycle length >35 days suggests chronic anovulation, but cycle length slightly longer than normal (32 to 35 days) or slightly irregular (32 to 35-36 days) needs assessment for ovulatory dysfunction. Ovulatory dysfunction is associated with increased prevalence of endometrial hyperplasia and endometrial cancer, in addition to infertility. In PCOS, hirsutism develops gradually and intensifies with weight gain. In the neoplastic virilizing states, hirsutism is of rapid onset, usually associated with clitoromegaly and oligomenorrhea. Girls with severe acne or acne resistant to oral and topical agents, including isotretinoin (Accutane), may have a 40% likelihood of developing PCOS. Hair loss patterns are variable in women with hyperandrogenemia, typically the vertex, crown or diffuse pattern, whereas women with more severe hyperandrogenemia may see bitemporal hair loss and loss of the frontal hairline. Oral contraceptives (OCPs) can effectively lower androgens and block the effect of androgens via suppression of ovarian androgen production and by increasing sex hormone-binding globulin. Physiologic doses of dexamethasone or prednisone can directly lower adrenal androgen output. Anti-androgens can be used to block the effects of androgen in the pilosebaceous unit or in the hair follicle. Anti-androgen therapy works through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) to prevent the conversion of T to its more potent form, 5α-dihydrotestosterone. The choice of antiandrogen therapy is guided by symptoms. The diagnosis of PCOS in adolescents is particularly challenging given significant age and developmental issues in this group. Management of infertility in women with PCOS requires an understanding of the pathophysiology of anovulation as well as currently available treatments. Many features of PCOS, including acne, menstrual irregularities, and hyperinsulinemia, are common in normal puberty. Menstrual irregularities with anovulatory cycles and varied cycle length are common due to the immaturity of the hypothalamic-pituitary-ovarian axis in the 2- to 3-year time period post-menarche. Persistent oligomenorrhea 2 to 3 years beyond menarche predicts ongoing menstrual irregularities and greater likelihood of underlying ovarian or adrenal dysfunction. In adolescent girls, large, multicystic ovaries are a common finding, so ultrasound is not a first-line investigation in women <17 years of age. Ovarian dysfunction in adolescents should be based on oligomenorrhea and/or biochemical evidence of oligo/anovulation, but there are major limitations to the sensitivity of T assays in ranges applicable to young girls. Metformin is commonly used in young girls and adolescents with PCOS as first-line monotherapy or in combination with OCPs and anti-androgen medications. In lean adolescent girls, a dose as low as 850 mg daily may be effective at reducing PCOS symptoms; in overweight and obese adolescents, dose escalation to 1.5 to 2.5 g daily is likely required. Anti-androgen therapy in adolescents could affect bone mass, although available short-term data suggest no effect on bone loss.

Interpretation of plasma PTH concentrations according to 25OHD status, gender, age, weight status, and calcium intake: importance of the reference values.

CONTEXT: Reference values for plasma PTH assessment were generally established on small samples of apparently healthy subjects, without considering their 25-hydroxyvitamin D (25OHD) status or other potential modifiers of PTH concentration. OBJECTIVE: Our objective was to assess ranges of plasma PTH concentration in a large sample of adults, stratifying by 25OHD status, age, gender, weight status, and calcium intake. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey is based on 1824 middle-aged Caucasian adults from the Supplémentation en Vitamines et Minéraux Antioxydants study (1994). MAIN OUTCOME MEASURES: Plasma PTH and 25OHD concentrations were measured by an electrochemoluminescent immunoassay. Extreme percentiles of plasma PTH concentrations were assessed specifically in subjects who had plasmatic values of 25OHD of 20 ng/mL or greater and 30 ng/mL or greater. RESULTS: Among subjects with 25OHD status of 20 ng/mL or greater, the 97.5th percentile of plasma PTH concentration was 45.5 ng/L. By using this value as a reference, 5% of the subjects with plasma 25OHD less than 20 nmol/L had a high plasma PTH level, reflecting secondary hyperparathyroidism. Among vitamin D-replete subjects (25OHD status of 20 ng/mL or greater), the 97.5th percentile of plasma PTH was higher in overweight/obese subjects (51.9 vs 43.5 ng/L among normal weight subjects). CONCLUSIONS: The reference value for plasma PTH defined in this vitamin D-replete population was far below the value currently provided by the manufacturer (65 ng/L) and varied according to overweight status. These results may contribute to improve the diagnosis of primary and secondary hyperparathyroidism and subsequent therapeutic indication.

Prevalence and cost of possibly unnecessary venous blood glucose measurements in primary care.

The American Diabetes Association issues annually its recommendations for diabetes mellitus screening. Although there is a high proportion of people with undiagnosed diabetes in the general population, it is suspected that many of these screening tests could be needless. An analysis was made of the number of venous blood glucose measurements that did not meet the American Diabetes Association requirements performed in 150 people seen in primary care. On average, an unnecessary venous blood glucose measurement is performed every 15 months. The number is significantly higher in people over 45 years of age, and also in women as compared to men (although with a p value slighty higher than 0.05).

Diagnostic performance of using one- or two-HbA1c cut-point strategies to detect undiagnosed type 2 diabetes and impaired glucose regulation within a multi-ethnic population.

INTRODUCTION: We compared test performance and cost per case for strategies detecting diabetes on the oral glucose tolerance test (OGTT) using either (a) glycated haemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) or (b) two HbA1c thresholds where the first cut-point 'rules out' and the second 'rules in' diabetes. HbA1c values in between the thresholds require confirmatory glucose testing for diagnosis. MATERIALS AND METHODS: We conducted an analysis of adults aged 40-75 years from the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort (Leicester, UK), from 2002 to 2008, who underwent oral glucose tolerance testing (OGTT) and HbA1c testing. RESULTS: From 8696 individuals (mean age 57.3 years, 73% white Europeans (WE) and 27% South Asians (SA)), HbA1c ≥ 6.5% produced sensitivity of 62.1% for detecting diabetes in WE and 78.9% in SA. Using two selected thresholds, HbA1c ≤ 5.8% (rule-in, 40 mmol/mol) and HbA1c ≥ 6.8% (rule-out, 51 mmol/mol) produced high sensitivity/specificity (> 91.0%) for detecting diabetes, however, 28.8% of the cohort with HbA1c 5.9%-6.7% required a subsequent glucose test. The two cut-point threshold produced a lower cost per case of diabetes detected in WE, compared to HbA1c ≥ 6.5% of £38.53 (1.89 to 86.81) per case, but was more expensive in SA by £84.50 (69.72 to 100.92) per case. Using a risk score to determine HbA1c testing, the same costs per case became £63.33 (23.33 to 113.26) in WE and £69.21 (55.60 to 82.41) in SA. CONCLUSION: Using a two-threshold strategy may have some benefits over a single cut-point; however, 28.8% of individuals required two blood tests.

Variability and reproducibility of circulating vitamin D in a nationwide U.S. population.

CONTEXT: Most studies examining associations between circulating vitamin D and disease are based on a single measure of vitamin D, which may not reflect levels over time, particularly because vitamin D concentrations vary by season. Few studies evaluated how well multiple 25-hydroxyvitamin D [25(OH)D] measures track within the same individual over time. OBJECTIVE: This study examined variability and reproducibility of vitamin D by evaluating repeat measurements of plasma 25(OH)D concentrations while accounting for determinants of circulating concentrations including dietary supplement use and latitude of residence from a population of U.S. radiologic technologists. DESIGN AND PARTICIPANTS: We analyzed circulating 25(OH)D in blood samples taken from 538 men and women from a prospective, nationwide study at two time points within a 1-yr period, most measured in different seasons. Inter- and intra-individual variability, reliability coefficients, and measurement error were examined. RESULTS: The spearman rank correlation between two measurements of 25(OH)D concentrations was moderate (r = 0.75, P < 0.001) and did not vary significantly by participant characteristics including age, race, or latitude. The intraclass correlation coefficient was 0.72 (95% confidence interval = 0.68-0.76). The deattenuation factor of plasma 25(OH)D levels was 1.39, suggesting that a single measure of vitamin D on a continuous scale in regression analyses may result in attenuated relationships of about 40%. CONCLUSION: Our results suggest that a single blood sample obtained in spring or fall provides a reasonable average for 25(OH)D over a 1-yr period, but additional studies are needed to estimate variability and agreement in plasma 25(OH)D measurements over longer intervals and younger populations.

Validating metabolic syndrome through principal component analysis in a medically diverse, realistic cohort.

BACKGROUND: The concept of metabolic syndrome has been subject to etiological and clinical controversies in recent years. Associations among the five risk factors (obesity, hypertension, hyperglycemia, high triglyceride levels, and low high-density lipoprotein cholesterol) may help establish the validity of the concept, especially in a cohort representative of an actual population. METHODS: We used principal component analysis (PCA) to analyze the structure of the physiological components of metabolic syndrome in 7213 patients contained in an administrative database for the Centre Hospitalier Universitaire de Sherbrooke in Sherbrooke, Quebec, a realistic cohort with diverse medical histories. We validated the results by repeating the analysis on stratified and random subgroups of patients, and on different combinations of risk factors. The first axis of the PCA was used to predict coronary heart disease (CHD) and diabetes. RESULTS: The two first axes explained 53% of the variance. The first axis (33%) was associated in the expected direction with all five predictor variables, consistent with its interpretation as metabolic syndrome. The first axis was more predictive of subsequent CHD and diabetes than the formal definition of metabolic syndrome. CONCLUSIONS: These results suggest that the concept of metabolic syndrome accurately captures an existing underlying physiological process. A continuous indicator could be constructed to identify metabolic syndrome more accurately, thus improving risk assessment for CHD and diabetes mellitus. Metabolic syndrome can be measured well even without all five predictors. However, discrepancies with other studies suggest that our results may not be generalizable, perhaps because our cohort tends to be sicker.