Fitness, fatness, and cardiovascular risk factors in type 2 diabetes: look ahead study

PURPOSE: Most studies comparing the effects of fitness and fatness on cardiovascular (CVD) risk have been done with young, healthy participants with low rates of obesity and high levels of fitness. The present study examined the association of cardiorespiratory fitness and obesity with CVD risk factors in an ethnically diverse sample of overweight/obese individuals with type 2 diabetes. METHOD: Baseline data from Look AHEAD, a study of 5145 overweight or obese individuals with type 2 diabetes, were used to examine the association of BMI categories (overweight, class I, II, or III obesity) and cardiorespiratory fitness (assessed with a maximal graded exercise test and categorized by age- and gender-specific quintiles) on cardiovascular risk factors and on the odds of having hypertension, hyperlipidemia, or HbA1c > or = 7%. RESULTS: BMI categories and fitness quintiles were highly associated with each other (P < 0.0001), with the heaviest participants being the least fit. Only 2-3% of participants had class III obesity and were in the two fittest quintiles or, conversely, were overweight and in the two least-fit quintiles. When fitness and BMI were included in the same model (adjusting for age, smoking, diabetes duration, and race), HbA1c, ankle/brachial index (ABI), and Framingham risk score were most strongly associated with fitness. Systolic blood pressure was most strongly associated with BMI category. Similar results occurred when waist circumference and fitness were considered together. CONCLUSION: In this large, ethnically diverse sample of overweight/obese individuals with type 2 diabetes, fitness and fatness were highly related to each other but seemed to have different impact on specific CVD risk factors.     

Reliability and validity of Axis I of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) with proposed revisions*

Summary The research diagnostic criteria for temporomandibular disorders (RDC/TMD) have been employed internationally since 1992 for the study of temporomandibular muscle and joint disorders (TMD). This diagnostic protocol incorporates a dual system for assessment of TMD for Axis I physical diagnoses as well as Axis II psychological status and pain‐related disability. Because the reliability and criterion validity of RDC/TMD had not yet been comprehensively characterised, the National Institute of Dental and Craniofacial Research funded in 2001 the most definitive research to date on the RDC/TMD as a U01 project entitled, ‘Research Diagnostic Criteria: Reliability and Validity’. The results of this multi‐site collaboration involving the University of Minnesota, the University of Washington, and the University at Buffalo were first reported at a pre‐session workshop of the Toronto general session of the International Association of Dental Research on 2 July 2008. Summaries of five reports from this meeting are presented in this paper including: (i) reliability of RDC/TMD Axis I diagnoses based on clinical signs and symptoms; (ii) reliability of radiographic interpretations used for RDC/TMD Axis I diagnoses; (iii) reliability of self‐report data used for RDC/TMD Axis I diagnoses; (iv) validity of RDC/TMD Axis I diagnoses based on clinical signs and symptoms; and (v) proposed revisions of the RDC/TMD Axis I diagnostic algorithms.     

FAILURE OF POSITIVE FEEDBACK IN NORMAL MEN AND SUBJECTS WITH TESTICULAR FEMINIZATION

The abdity of the hypothalamic-pituitary unit to release luteinizing hormone (LH) in response to oestrogen Cpositive feedback) was studied in normal men and women and in subjects with testicular feminization or XY gonadal dysgenesis. Ethinyloestra-diol (200 μg a day for 3 days) given orally to six regularly menstruating women during the early to mid follicular phase of the cycle evoked an LH surge which started between 48 and 72 h after the initiation of treatment. A similar positive feedback effect on the secretion of follicle-stimulating hormone (FSH) could not be demonstrated. In eight normal men there was no evidence for a stimulatory effect of ethinyl-oestradiol (in doses of 200 μg or 500 μg a day for 3 days) on gonadotrophin release even though the levels of plasma ethyloestradiol in men on the higher dosage regime were greater than those found in women. Changes of peripheral LH, but not FSH, in men were inversely related to plasma ethinyloestradiol concentrations. A patient with XY pure gonadal dysgenesis exhibited a female type of LH release in response to ethinyloestradiol administration (200 μg a day for 3 days), but two patients with the syndrome of testicular feminization failed to release LH. The results suggest that normal adults of the two sexes differ in their ability to respond to ethinyloestradiol administration with LH release. The female response in XY gonadal dysgenesis emphasizes the importance of testicular secretions for the suppression of positive feedback whereas the male type of response in cases of testicular feminization indicates that testosterone does not represent the central mediator of this testicular function. The reported observations are compatible with the concept that the organizing action of the testes on positive feedback is mediated through 17β-oestradiol.     

EFFECTS OF ETHINYLOESTRADIOL ON PLASMA LEVELS OF PITUITARY GONADOTROPHINS, TESTICULAR STERIODS AND SEX HORMONE BINDING GLOBULIN IN NORMAL MEN

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17β-oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE₂) in a dose of 30 μg/day for 5 days following a 5-day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17β-oestradiol during EE₂ administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE₂ in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE₂ doses in such studies may be less ‘physiologic’ than is often assumed.     

HYPOTHALAMIC-PITUITARY-OVARIAN FUNCTION IN PERIMENOPAUSAL WOMEN

In a group of nine perimenopausal women, aged 37–52 years, with dynsfunctional uterine bleeding (DUB), serial measurements were made of urinary total oestrogen and pregnanediol excretion and of plasma gonadotrophin and steroid levels under basal conditions and during dynamic tests (oestrogen provocation and LHRH-tests). Results were compared to those obtained in a control group of regularly menstruating women, 23–45 years of age. Four different patterns of hypothalamic-pituitary-ovarian (H.P.O.) activity were identified in the perimenopausal subjects with DUB. In two patients with a history of persistent anovulation and cystic glandular hyperplasia of the endometrium, basal plasma gonadotrophin levels were normal but there was a failure to release an adequate amount of LH in response to endogenous and exogenous oestrogen stimulation. One subject had regular ovulatory cycles but the follicular phase was shorter and circulating levels of FSH, but not of LH, were higher than in controls. A similar monotropic increase in FSH was also present in a further patient whose cycles were irregular and included an ovulatory cycle with short follicular phase, an ovulatory cycle of normal length and an anovulatory cycle. In the remaining five women follicular development was infrequent and anovulation the rule. FSH and LH levels in these women were elevated despite the presence of circulating 17β-oestradiol levels in the early-mid follicular phase range. At the time of menopausal transition in one of these subjects, the decline of plasma 17β-oestradiol to undetectable levels was associated with a further rise of both gonadotrophins. Conversely, following a prolonged period of follicular development with elevated urinary total oestrogen excretion in another subject, the raised gonadotrophin concentrations were suppressed and the pituitary response to LHRH was within the normal range. LHRH responses in the other four women were augmented. Oestrogen administration failed to induce a normal LH surge in three out of the five subjects. The results indicate that marked changes in the pattern of pituitary gonadotrophin secretion can be found in perimenopausal women with DUB. The observed increase in peripheral levels of FSH (with or without concomitant increase in LH) may be due to a change in hypothalamic-pituitary sensitivity to the feedback effects of oestrogen. Alternatively, it is possible that these changes result from a decrease in the ovarian secretion of a hypothetical ‘inhibin-like' substance produced by the growing follicle and for which the name ‘FSH-release inhibiting substance’ (‘FRIS’) is proposed.     

The utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer

The objective of this study was to evaluate the ability of a preoperative serum CA125 to predict whether optimal debulking (OD) could be achieved for patients with stage III and IV epithelial ovarian cancer (EOC). The records of consecutive patients who underwent primary surgery for EOC at Indiana University Hospital between January 1997 and January 2003 were reviewed. Eligibility criteria included FIGO stage III/IV disease, surgery by gynecologic oncology faculty, preoperative CA125, and an operative note clearly defining volume of residual disease. The Medcalc software statistical package was used to generate a receiver-operating characteristic (ROC) curve. Two hundred and eighty-nine cases of stage III/IV EOC were identified, of which 164 met the eligibility criteria. Serum CA125 /=75% of the time. Conversely, OD was achieved in /=4500. The area under the ROC curve for CA125 was .670. The OD rate for those with and without ascites was 49% and 79%, respectively (P < 0.001). In a multivariate analysis using CA125, age, and ascites, the area under the curve was 0.686. We conclude that preoperative serum CA125 did not reliably predict OD in patients with stage III-IV EOC.