Physical Activity Compliance to American Cancer Society Recommendations Amongst Hematopoietic Stem Cell Transplant Survivors.

BACKGROUND AND OBJECTIVES: The aims of this study were to determine the extent to which hematopoietic cell transplantation (HCT) survivors adhere to the American Cancer Society recommendations for weekly physical activity and identify potential demographic and transplant characteristics associated with the lack of compliance. METHODS: This cross-sectional study included adults who had undergone HCT and were at least 1 year post transplantation. Physical activity was assessed using the screening tool of the Block 2014. The type of activity, frequency, and intensity were converted into the metabolic equivalent of task (MET) scores (0-499.0 MET min/week, inadequate activity; 500-1000 MET min/week, adequate activity; >1000 MET min/week, highly vigorous activity). RESULTS: Participants (n = 81) reported a median MET score of 153 min/week, and 83% failed to reach the physical activity guideline of >500 MET min/week. Only 17.3% met the ACS recommendations, with three reporting above 1000 MET min/week. Median daily moderate and vigorous physical activity minute totals were 18.0 and 5.9 min/d, with 85.2% and 60.5% of participants involved, respectively. The median total physical activity energy expenditure was 744 kcal/d. Only race was associated with MET score, with Whites reporting higher MET scores. CONCLUSION: Most HCT survivors assessed in this study did not meet the ACS physical activity recommendations. These findings reinforce the need to incorporate screening for physical activity into HCT survivorship care, offer counseling to those who do not meet the recommended levels, and encourage a physically active lifestyle among HCT survivors.

The prevalence of medical reasons for non-participation in the Scottish breast and bowel cancer screening programmes.

OBJECTIVE: Increasing uptake of cancer screening is a priority for health systems internationally, however, some patients may not attend because they are undergoing active treatment for the cancer of interest or have other medical reasons that mean participation would be inappropriate. This study aims to quantify the proportion of non-participants who have a medical reason for not attending cancer screening. METHODS: Medical reasons for not participating in breast and bowel screening were defined a priori on the basis of a literature review and expert opinion. The notes of 700 patients at two GP practices in Scotland were reviewed, to ascertain the prevalence of medical reasons amongst non-participants. Simple proportions and confidence intervals were calculated. RESULTS: 17.4% of breast and 2.3% of bowel screening non-participants had a medical reason to not participate. The two most common reasons were previous breast cancer follow up (8.86%) and recent mammogram (6.57%). CONCLUSION: These patients may not benefit from screening while also being distressed by receiving an invitation. This issue also makes accurate monitoring and target-setting for improving uptake difficult. Further work is needed to estimate robustly the extent to which medical reasons account for screening non-participation in a larger population.

Biology undergraduates' misconceptions about genetic drift.

This study explores biology undergraduates' misconceptions about genetic drift. We use qualitative and quantitative methods to describe students' definitions, identify common misconceptions, and examine differences before and after instruction on genetic drift. We identify and describe five overarching categories that include 16 distinct misconceptions about genetic drift. The accuracy of students' conceptions ranges considerably, from responses indicating only superficial, if any, knowledge of any aspect of evolution to responses indicating knowledge of genetic drift but confusion about the nuances of genetic drift. After instruction, a significantly greater number of responses indicate some knowledge of genetic drift (p = 0.005), but 74.6% of responses still contain at least one misconception. We conclude by presenting a framework that organizes how students' conceptions of genetic drift change with instruction. We also articulate three hypotheses regarding undergraduates' conceptions of evolution in general and genetic drift in particular. We propose that: 1) students begin with undeveloped conceptions of evolution that do not recognize different mechanisms of change; 2) students develop more complex, but still inaccurate, conceptual frameworks that reflect experience with vocabulary but still lack deep understanding; and 3) some new misconceptions about genetic drift emerge as students comprehend more about evolution.

Alphacoronaviruses in New World bats: prevalence, persistence, phylogeny, and potential for interaction with humans.

Bats are reservoirs for many different coronaviruses (CoVs) as well as many other important zoonotic viruses. We sampled feces and/or anal swabs of 1,044 insectivorous bats of 2 families and 17 species from 21 different locations within Colorado from 2007 to 2009. We detected alphacoronavirus RNA in bats of 4 species: big brown bats (Eptesicus fuscus), 10% prevalence; long-legged bats (Myotis volans), 8% prevalence; little brown bats (Myotis lucifugus), 3% prevalence; and western long-eared bats (Myotis evotis), 2% prevalence. Overall, juvenile bats were twice as likely to be positive for CoV RNA as adult bats. At two of the rural sampling sites, CoV RNAs were detected in big brown and long-legged bats during the three sequential summers of this study. CoV RNA was detected in big brown bats in all five of the urban maternity roosts sampled throughout each of the periods tested. Individually tagged big brown bats that were positive for CoV RNA and later sampled again all became CoV RNA negative. Nucleotide sequences in the RdRp gene fell into 3 main clusters, all distinct from those of Old World bats. Similar nucleotide sequences were found in amplicons from gene 1b and the spike gene in both a big-brown and a long-legged bat, indicating that a CoV may be capable of infecting bats of different genera. These data suggest that ongoing evolution of CoVs in bats creates the possibility of a continued threat for emergence into hosts of other species. Alphacoronavirus RNA was detected at a high prevalence in big brown bats in roosts in close proximity to human habitations (10%) and known to have direct contact with people (19%), suggesting that significant potential opportunities exist for cross-species transmission of these viruses. Further CoV surveillance studies in bats throughout the Americas are warranted.

Endothelial colony-forming cells and mesenchymal stem cells from ECMO circuits of term infants.

OBJECTIVE: Endothelial progenitor cells (EPCs) have been examined in numerous adult diseases and have been suggested as a cellular-based therapy. However, there are no reports describing EPCs being isolated from newborn peripheral blood. STUDY DESIGN: Endothelial colony-forming cells (ECFCs), a subtype of EPCs, were isolated from blood collected from 12 neonatal extracorporeal membrane oxygenation (ECMO) circuits. RESULT: ECFCs were isolated in all samples. We unexpectedly isolated a distinctly different colony of mesenchymal stem cells (MSCs) in seven samples. Both cell types expressed the expected endothelial or mesenchymal cell surface antigens. CONCLUSION: To our knowledge, this is the first report of ECFCs and MSCs isolated from peripheral blood of critically ill term newborns. Both cells types may be mobilized in response to critical illness or to the ECMO circuit. Further studies evaluating the role of stem cells in various newborn conditions are warranted.

The role of SMAD4 in early-onset colorectal cancer.

OBJECTIVE: Chromosomal loss within the region of 18q and loss of SMAD4 expression have been reported to be frequent somatic events during colorectal cancer tumour progression; however, their associations with age at onset have not been widely studied. METHOD: We analysed 109 tumours from a population-based case-family study based on colorectal cancers diagnosed before the age of 45 years. These patients with early-onset colorectal cancer had been previously screened for germ-line mismatch repair gene mutations, microsatellite instability (that included the mononucleotide repeat in TGFbetaRII) and somatic k-ras mutations. We measured SMAD4 protein expression using immunohistochemistry and SMAD4 copy number using quantitative real-time PCR. RESULTS: Loss of SMAD4 protein expression was observed in 27/109 (25%) of cancers tested and was more commonly observed in rectal tumours (15/41, 36%) when compared with tumours arising in the colon (11/66, 17%) (P = 0.04). There was no association between SMAD4 protein expression and TGFbetaR11 mutation status, SMAD4 copy number, family history, MSI status, tumour stage or grade. CONCLUSION: Loss of SMAD4 expression is a common feature of early-onset colorectal tumours as it is in colorectal cancers diagnosed in other age-groups. Taken together, the molecular pathways (genetic and epigenetic) now known to be involved in early-onset colorectal cancer only explain a small proportion of the disease and require further exploration.

Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior.

One of the requirements for tumor growth is the ability to recruit a blood supply, a process known as angiogenesis. Angiogenesis begins early in the progression of cervical disease from mild to severe dysplasia and on to invasive cancer. We have previously reported that expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7) proteins in primary foreskin keratinocytes (HFKs) decreases expression of two inhibitors and increases expression of two angiogenic inducers [Toussaint-Smith, E., Donner, D.B., Roman, A., 2004. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene 23, 2988-2995]. Here we report that HPV-induced early changes in the keratinocyte phenotype are sufficient to alter endothelial cell behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7 expressing HFKs as well as from human cervical keratinocytes containing the intact HPV16 were able to stimulate proliferation and migration of human microvascular endothelial cells. In addition, introduction of the conditioned media into immunocompetent mice using a Matrigel plug model resulted in a clear angiogenic response. These novel data support the hypothesis that HPV proteins contribute not only to the uncontrolled keratinocyte growth seen following HPV infection but also to the angiogenic response needed for tumor formation.

Bacteria and cell cytocompatibility studies on coated medical grade titanium surfaces.

Acute and chronic osteomyelitis caused by staphylococci can be difficult to treat by conventional means and often has marked consequences for the patient. Current methods of treatment involve the use of systemic antibiotics, the local implantation of nondegradable drug carriers, and surgical debridement. A possible solution that could prevent initial bacterial adhesion could be to modify the implant surface with an antimicrobial coating while maintaining biocompatibility to host cells. This study describes the cytocompatibility evaluation of different coatings (poly(D,L-lactide) (PDLLA), politerefate (PTF), calcium phosphate/anodic plasma-chemical treatment (CaP/APC), polyurethane (PU), and polyvinylpyrollidone (PVP) on titanium surfaces with and without chlorhexidine diacetate (CHA) to Staphylococcus aureus, Staphylococcus epidermidis, and hTERT human fibroblasts. Surface characterization of the coatings showed no significant variation in the roughness or hydrophobicity of the coated surfaces, except the CaP/APC surface that was porous yet the smoothest, and PVP, PVP+CHA, and CaP/APC+CHA that were more hydrophilic in nature than the others. On the surfaces without CHA, both staphylococcal strains and spread fibroblasts were observed, but on the CHA impregnated surfaces few bacteria and no intact fibroblasts were seen. Flow cytometry found fewer bacteria in the media and on the surfaces containing CHA in comparison to the surfaces without CHA. The release kinetics varied from slow (over 200 h) to burst release: PDLLA>PTF>PU>CaP/APC=PVP. This study showed that PDLLA and PTF have the best potential as coatings on implants for drug delivery, as they were cytocompatible to hTERT fibroblasts, eluted CHA effectively, and passed mechanical testing. The actual release kinetics of PDLLA and PTF are important, as the amount of CHA present should remain above the minimal inhibitory concentration value for a limited time before disappearing completely.

Serologic survey for canine infectious diseases among sympatric swift foxes (Vulpes velox) and coyotes (Canis latrans) in southeastern Colorado.

Swift foxes (Vulpes velox) and coyotes (Canis latrans) are sympatric canids distributed throughout many regions of the Great Plains of North America. The prevalence of canid diseases among these two species where they occur sympatrically is presently unknown. From January 1997 to January 2001, we collected blood samples from 89 swift foxes and 122 coyotes on the US Army Piñon Canyon Maneuver Site, Las Animas County, SE Colorado (USA). Seroprevalence of antibodies against canine parvovirus (CPV) was 71% for adult (> 9 mo old) and 38% for juvenile (< or = 9 mo old) swift foxes. Adult (<1 yr old) and juvenile (<1 yr old) coyotes had a seroprevalence for CPV of 96% and 78%, respectively. Presence of antibodies against canine distemper virus (CDV) was 5% for adult foxes and 0% for juvenile foxes. Seroprevalence of CDV was 46% for adult coyotes and 18% for juvenile coyotes. No swift foxes had canine adenovirus (CAV) antibodies, whereas 81% and 63% of adult and juvenile coyotes, respectively, had antibodies for CAV. Seroprevalence of antibodies against Yersinia pestis was 68% among adult foxes and 34% among juvenile swift foxes. Seroprevalence of Y. pestis antibodies was 90% and 70% for adult and juvenile coyotes, respectively. No swift foxes had antibodies against Francisella tularensis, whereas seroprevalence was 4% among both adult and juvenile coyotes. Antibodies against CPV and plague were common in both species, whereas antibodies against CDV and CAV were more prevalent in coyotes compared to swift foxes.

Molecular pathologic analysis enhances the diagnosis and management of Muir-Torre syndrome and gives insight into its underlying molecular pathogenesis.

The Muir-Torre syndrome (MTS) is an autosomal dominantly inherited disorder, characterized by visceral malignancies and sebaceous skin lesions. In a subset of MTS families the disease is due to an underlying DNA mismatch-repair defect. We have identified a MTS family whose spectrum of reported neoplasia included adenocarcinomas of numerous gastrointestinal sites, carcinomas of the endometrium, ovary and breast, papillary transitional cell carcinoma of the ureter, a range of cutaneous tumors, as well as keratoacanthomas. All tumors were tested for microsatellite instability and immunohistochemically stained for expression of MLH1 and MSH2 proteins. All tumors were found to be microsatellite unstable and lacking in MSH2 protein expression. The subsequent mutation detection focused on hMSH2, and a germline mutation was identified (CAA-->TAA, Gln-->STOP, codon 337). This mutation was subsequently found in a family member with a single skin lesion only. We propose that the combination of immunohistologic and microsatellite instability analysis can be exploited to screen individuals with characteristic skin lesions even before development of visceral tumors and to direct the subsequent germline mutation search. The profile of microsatellite instability and the genes rendered dysfunctional differed between tumor samples, suggesting that the molecular pathogenesis varied between lesions, despite a common germline mutation.

Functional role of matrix metalloproteinases (MMPs) in mammary epithelial cell development.

The extracellular matrix (ECM) is an important regulator of mammary epithelial cell (MEC) function and is remodeled by matrix metalloproteinases (MMPs). To investigate the significance and regulation of MMP activity in normal MEC, we utilized a primary culture model in which rat MEC were grown three dimensionally within a reconstituted basement membrane (RBM) in defined serum-free medium. Zymograms of culture medium demonstrated that five major gelatinases of 97, 80, 74, 69, and 65 kDa were secreted by MEC and were distinct from gelatinases of RBM origin. Based on molecular weight, p-aminophenylmercuric acid activation, immunoblotting with MMP-specific antibodies, inhibition by EDTA, a peptide containing the prodomain sequence of MMP (TMRKPRCGNPDVAN) and two synthetic MMP inhibitors (BB-94 and CGS 27023A), these were classified as inactive and active forms of MMP-9 and MMP-2. The maximal MMP activities occurred when MEC were in a rapid proliferation and branching phase and declined after they underwent functional differentiation. Known regulators of MEC growth and differentiation were evaluated for their ability to modulate gelatinase activity in primary culture. Secretion of one or both MMPs was inhibited by EGF, TGFalpha, prolactin, and hydrocortisone and stimulated by progesterone. Furthermore, the functional significance of MMPs was demonstrated since three MMP inhibitors blocked branching morphogenesis elicited by the absence of hydrocortisone. Additionally, two synthetic MMP inhibitors not only inhibited epithelial cell growth but also inhibited normal alveolar development of the MEC. Finally, these drugs were found to enhance MMP secretion from MEC, although the activity of the secreted MMPs was inhibited as long as the drug was present.

Genetic structure of the blue ridge dusky salamander (Desmognathus orestes): inferences from allozymes, mitochondrial dna, and behavior.

The plethodontid salamander Desmognathus orestes, a member of the D. ochrophaeus species complex, is distributed in southwestern Virginia, eastern Tennessee, and western North Carolina. Previous allozyme analyses indicate that D. orestes consists of two distinct groups of populations (D. orestes 'B' and D. orestes 'C') with extensive intergradation and probable gene flow between these two groups. Spatially varying allele frequencies can reflect historical associations, current gene flow, or a combination of population-level processes. To differentiate among these processes, we use multiple markers to further characterize divergence among populations of D. orestes and assess the degree of intergradation between D. orestes 'B' and D. orestes 'C', specifically investigating variation in allozymes, mitochondrial DNA (mtDNA), and reproductive behavior among populations. On a broad scale, the mtDNA genealogies reconstruct haplotype clades that correspond to the species identified from previous allozyme analyses. However, at a finer geographic scale, the distributions of the allozyme and mtDNA markers for D. orestes 'B' and D. orestes 'C' are discordant. MtDNA haplotypes corresponding to D. orestes 'B' are more broadly distributed across western North Carolina than predicted by allozyme data, and the region of intergradation with D. orestes 'C' indicates asymmetric gene flow of these markers. Asymmetric mating may contribute to observed discordance in nuclear versus cytoplasmic markers. Results support describing D. orestes as a single species and emphasize the importance of using multiple markers to examine fine-scale patterns and elucidate evolutionary processes affecting gene flow when making species-level taxonomic decisions.

Physician, heal Thyself? Regular source of care and use of preventive health services among physicians.

BACKGROUND: Little is known about the regular source of care (RSOC) among physicians, a group whose self-care may reflect the attitudes and recommendations they convey to their patients. METHODS: We performed a cohort study of physicians who graduated from the Johns Hopkins School of Medicine from 1948 through 1964 to identify predictors of not having an RSOC, and to determine whether not having an RSOC was associated with subsequent receipt of preventive services. The RSOC was assessed in a 1991 survey; use of cancer screening tests and the influenza vaccine was assessed in 1997. RESULTS: The response rate in 1991 was 77% (915 respondents); 35% (312) had no RSOC. Internists (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.58-6.74), surgeons (OR, 2.42; 95% CI, 1.17-5.02), and pathologists (OR, 5.46; 95% CI, 2.09-14.29) were significantly more likely to not have an RSOC than pediatricians. Not having an RSOC was inversely related to the belief that health is determined by health professionals (OR, 0.45; 95% CI, 0.29-0.68) and directly related to the belief that chance (OR, 1.90; 95% CI, 1.28-2.82) determines health. Not having an RSOC in 1991 predicted not being screened for breast, colon, and prostate cancer, as well as not receiving an influenza vaccine at 6 years of follow-up. CONCLUSIONS: A large percentage of physicians in our sample had no RSOC, and this was associated with both medical specialty and beliefs about control of health outcomes. Not having an RSOC was significantly associated with failure to use preventive services several years later. Arch Intern Med. 2000;160:3209-3214.

Joint injury in young adults and risk for subsequent knee and hip osteoarthritis.

BACKGROUND: Knee and hip injuries have been linked with osteoarthritis in cross-sectional and case-control studies, but few prospective studies have examined the relation between injuries in young adults and risk for later osteoarthritis. OBJECTIVE: To prospectively examine the relation between joint injury and incident knee and hip osteoarthritis. DESIGN: Prospective cohort study. SETTING: Johns Hopkins Precursors Study. PARTICIPANTS: 1321 former medical students. MEASUREMENTS: Injury status at cohort entry was recorded when the mean age of participants was 22 years. Injury during follow-up and incident osteoarthritis were determined by using self-administered questionnaires. Osteoarthritis was confirmed by symptoms and radiographic findings. RESULTS: Over a median follow-up of 36 years, 141 participants reported joint injuries (knee alone [n = 111], hip alone [n = 16], or knee and hip [n = 14]) and 96 developed osteoarthritis (knee alone [n = 64], hip alone [n = 27], or knee and hip [n = 5]). The cumulative incidence of knee osteoarthritis by 65 years of age was 13.9% in participants who had a knee injury during adolescence and young adulthood and 6.0% in those who did not (P = 0.0045) (relative risk, 2.95 [95% CI, 1.35 to 6.45]). Joint injury at cohort entry or during follow-up substantially increased the risk for subsequent osteoarthritis at that site (relative risk, 5.17 [CI, 3.07 to 8.71] and 3.50 [CI, 0.84 to 14.69] for knee and hip, respectively). Results were similar for persons with osteoarthritis confirmed by radiographs and symptoms. CONCLUSIONS: Young adults with knee injuries are at considerably increased risk for osteoarthritis later in life and should be targeted in the primary prevention of osteoarthritis.

Feasibility of using recipients of health promotional newsletters for post-marketing surveillance.

Achieving an adequate sample size is one of the major difficulties in performing post-marketing observational studies of health outcomes in persons taking specific drug preparations. We assessed the feasibility of recruiting participants for such a study of Cardizem CD from approximately 400,000 U.S. recipients of a health promotion newsletter. A three-page questionnaire was sent to a 2.5% random sample (n = 10,000) of recipients, stratified by geographic region. After two mailings, 2779 (28%) returned the questionnaire. Of the 2779 respondents, 2132 (77%) reported having high blood pressure. Eighty-seven percent indicated a willingness to participate in a long-term prospective study. In a multivariate model, calcium channel blocker (CCB) use was associated with a history of coronary heart disease, duration of hypertension medication use greater than 1 year, a rating of good or excellent hypertension care, higher systolic blood pressure, higher education level, family history of cardiovascular disease, and history of smoking. These results indicate that self-reported CCB users may be at greater risk of cardiovascular heart disease and that it is feasible to use health promotion newsletters as a source of participants in prospective studies of cardiovascular disease.

Neural systems underlying the recognition of familiar and newly learned faces.

Memory for famous faces can be used to examine the neural systems underlying retrieval from long-term memory. To date, there have been a limited number of functional neuroimaging investigations examining famous face recognition. In this study, we compared recognition of famous faces to recognition of newly learned faces. Whole-brain, event-related functional magnetic resonance imaging was used to image regional changes in neural activity in 11 subjects during the encoding of unfamiliar faces and during familiarity judgments for: (1) newly learned faces, (2) unfamiliar face distractors, and (3) famous faces. Image analyses were restricted to correct recognition trials. Recognition accuracy and response time to famous and recently learned faces were equivalent. Recognition of famous faces was associated with a widespread network of bilateral brain activations involving the prefrontal, lateral temporal, and mesial temporal (hippocampal and parahippocampal regions) regions compared to recognition of recently encoded faces or unfamiliar faces seen for the first time. Findings are discussed in relation to current proposals concerning the neural regions thought to participate in long-term memory retrieval and, more specifically, in relation to retrieval of information from the person identity semantic system.

Mammary fibroblasts stimulate growth, alveolar morphogenesis, and functional differentiation of normal rat mammary epithelial cells.

Stromal-epithelial interactions play a profound role in regulating normal and tumor development in the mammary gland. The molecular details of these events, however, are incompletely understood. A novel serum-free transwell coculture system was developed to study the natural paracrine interactions between mammary epithelial cells (MEC) and mammary fibroblasts (MFC) isolated from normal rats during puberty. The MEC were cultured within a reconstituted basement membrane (RBM) in transwell inserts with or without MFC in the lower well. The presence of MFC stimulated epithelial cell growth, induced alveolar morphogenesis, and enhanced casein accumulation, a marker of the functional differentiation of MEC, but did not induce ductal morphogenesis. Potent mitogenic, morphogenic, and lactogenic effects were observed when the MFC were cultured either on plastic or within a layer of RBM. Although most MFC maintained on plastic died after 1 wk in serum-free medium, fibroblast survival was enhanced significantly when the MFC were cultured within the RBM. Taken together, this in vitro model effectively reconstitutes a physiologically relevant three-dimensional microenvironment for MEC and MFC, and seems ideal for studying the locally derived factors that regulate the developmental fate of the epithelial and fibroblast compartments of the mammary gland.

Body weight patterns from 20 to 49 years of age and subsequent risk for diabetes mellitus: the Johns Hopkins Precursors Study.

BACKGROUND: Obesity in middle age is a well-known risk factor for the development of type 2 diabetes mellitus. However, the importance of weight and weight gain at younger ages is less certain. OBJECTIVE: To determine the relationship of body weight patterns from 20 to 49 years of age with the subsequent risk for type 2 diabetes mellitus. SETTING: An ongoing longitudinal study of former medical students. PARTICIPANTS: Nine hundred sixteen white men without diabetes at 50 years of age. MEASUREMENTS: Weight and height measured in medical school, then assessed by mailed questionnaire to 49 years of age. MAIN OUTCOME: Incident type 2 diabetes mellitus based on physician self-report. RESULTS: During 14 255 person-years of follow-up, there were 35 incident cases of type 2 diabetes mellitus (2.5 per 1000 person-years). After simultaneous adjustment for age, physical activity, lifetime maternal history of diabetes, and smoking, body mass indexes (BMIs; calculated as weight in kilograms divided by the square of height in meters) at 25, 35, and 45 years of age were all strongly associated with diabetes risk (relative risks for overweight [BMI> or =25.0] vs. not overweight, >3.0; all Ps<.05), as were maximum and average BMI to 49 years of age. The relationship of BMI at 25 years of age to diabetes risk was substantially attenuated by adjustment for BMI at 45 years of age and average BMI, but was independent of weight change, weight variability, or maximum BMI. CONCLUSION: In men, overweight at 25 years of age strongly predicts diabetes risk in middle age, largely through its association with overweight at 45 years of age and high average BMI to 49 years of age.