Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxyvitamin D of 41 ng/ml than in NHANES cohort with median of 22 ng/ml.

Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with lower risk of type 2 diabetes. This study compared incidence rates of type 2 diabetes among participants aged ≥20 years in two U.S. cohorts with markedly different median 25(OH)D concentrations. The median 25(OH)D concentration in the GrassrootsHealth (GRH) cohort was 41 ng/ml (N=4933) while in the 2005-6 National Health and Nutrition Examination Survey (NHANES) it was 22 ng/ml (N=4078) (P<0.0001). The adjusted annual incidence rate of type 2 diabetes was 3.7 per 1000 population (95% confidence interval=1.9, 6.6) in the GRH cohort, compared to 9.3 per 1000 population (95% confidence interval=6.7, 12.6) in NHANES. In the NHANES cohort, the lowest 25(OH)D tertiles (<17, 17-24 ng/ml) had higher odds of developing diabetes than the highest tertile (OR: 4.9, P=0.02 and 4.8, P=0.01 respectively), adjusting for covariates. Differences in demographics and methods may have limited comparability. Raising serum 25(OH)D may be a useful tool for reducing risk of diabetes in the population.

Lower prediagnostic serum 25-hydroxyvitamin D concentration is associated with higher risk of insulin-requiring diabetes: a nested case-control study.

AIMS/HYPOTHESIS: Low serum 25-hydroxyvitamin D [25(OH)D] concentration may increase risk of insulin-requiring diabetes. METHODS: A nested case-control study was performed using serum collected during 2002-2008 from military service members. One thousand subjects subsequently developed insulin-requiring diabetes. A healthy control was individually matched to each case on blood-draw date (±2 days), age (±3 months), length of service (±30 days) and sex. The median elapsed time between serum collection and first diagnosis of diabetes was 1 year (range 1 month to 10 years). Statistical analysis used matched pairs and conditional logistic regression. RESULTS: ORs for insulin-requiring diabetes by quintile of serum 25(OH)D, from lowest to highest, were 3.5 (95% CI 2.0, 6.0), 2.5 (1.5, 4.2), 0.8 (0.4, 1.4), 1.1 (0.6, 2.8) and 1.0 (reference) (p (trend) <0.001). The quintiles (based on fifths using serum 25(OH)D concentration in the controls) of serum 25(OH)D in nmol/l, were <43 (median 28), 43-59 (median 52), 60-77 (median 70), 78-99 (median 88) and ≥100 (median 128). CONCLUSIONS/INTERPRETATION: Individuals with lower serum 25(OH)D concentrations had higher risk of insulin-requiring diabetes than those with higher concentrations. A 3.5-fold lower risk was associated with a serum 25(OH)D concentration ≥60 nmol/l.

Incidence of insulin-requiring diabetes in the US military.

AIMS/HYPOTHESIS: The aim of the study was to determine age- and race-related, and overall incidence rates of insulin-requiring diabetes in adults in the US military. METHODS: Electronic records for admissions to US military and Tricare hospitals during 1990-2005 and visits to military clinics during 2000-2005 were identified using the Career History Archival Medical and Personnel System at the Naval Health Research Center, San Diego, CA, USA. Population data were obtained from the Defense Manpower Data Center and Defense Medical Epidemiology Database. RESULTS: In men there were 2,918 new cases of insulin-requiring diabetes in 20,427,038 person-years at ages 18-44 years (median age 28 years) for a total age-adjusted incidence rate of 17.5 per 100,000 person-years (95% CI 16.4-18.6). Incidence rates were twice as high in black men as in white men (31.5 vs 14.5 per 100,000, p < 0.001). In women there were 414 new cases in 3,285,000 person-years at ages 18-44 years (median age 27 years), for a total age-adjusted incidence rate of 13.6 per 100,000 (95% CI 12.4-14.9). Incidence rates were twice as high in black women as in white women (21.8 vs 9.7 per 100,000, p < 0.001). In a regression model, incidence of insulin-requiring diabetes peaked annually in the winter-spring season (OR 1.46, p < 0.01). Race and seasonal differences persisted in the multivariate analysis. CONCLUSIONS/INTERPRETATION: Differences in incidence rates by race and season suggest a need for further research into possible reasons, including the possibility of a contribution from vitamin D deficiency. Cohort studies using prediagnostic serum 25-hydroxyvitamin D should be conducted to further evaluate this relationship.

The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide.

AIMS/HYPOTHESIS: This study is an analysis of the relationship between ultraviolet B (UVB) irradiance, the primary source of circulating vitamin D in humans, and age-standardised incidence rates of type 1 diabetes mellitus in children, according to region of the world. METHODS: The association of UVB irradiance adjusted for cloud cover to incidence rates of type 1 diabetes in children aged <14 years during 1990--1994 in 51 regions worldwide was assessed using multiple regression. Incidence data were obtained from the Diabetes Mondial Project Group. RESULTS: Incidence rates were generally higher at higher latitudes (R2 = 0.25, p < 0.001). According to multiple regression, UVB irradiance adjusted for cloud cover was inversely associated with incidence rates (p < 0.05), while per capita health expenditure (p < 0.004) was positively associated (overall R2 = 0.42, p < 0.0001). CONCLUSIONS/INTERPRETATION: An association was found between low UVB irradiance and high incidence rates of type 1 childhood diabetes after controlling for per capita health expenditure. Incidence rates of type 1 diabetes approached zero in regions worldwide with high UVB irradiance, adding new support to the concept of a role of vitamin D in reducing the risk of the disease.

Could ultraviolet B irradiance and vitamin D be associated with lower incidence rates of lung cancer?

BACKGROUND: This study examines whether insufficient ultraviolet B (UVB) irradiance, a marker of vitamin D inadequacy, might contribute to lung cancer incidence. METHODS: The association of latitude and UVB irradiance with age-adjusted incidence rates of lung cancer in 111 countries was investigated. Independent associations with UVB irradiance, cloud cover, anthropogenic aerosols, and cigarette smoking, were assessed using multiple regression. RESULTS: Latitude was positively related to incidence rates in men (R(2) = 0.55, p<0.01) and women (R(2) = 0.36, p<0.01). In men, cigarette consumption (p<0.001) was positively related to risk, whereas UVB irradiance was inversely associated (p = 0.003). There were positive associations with UVB absorbers, in particular cloud cover (p = 0.05) and aerosol optical depth (p = 0.005). The R(2) for the model was 0.78 (p<0.001). UVB irradiance was also inversely associated with incidence rates in women (p = 0.0002), whereas cigarette consumption (p<0.001), total cloud cover (p = 0.02) and aerosol optical depth (p = 0.005) were positively associated. The R(2) for the model was 0.77 (p<0.001). CONCLUSIONS: Lower levels of UVB irradiance were independently associated with higher incidence rates of lung cancer in 111 countries.

A model of the expected occurrence of adverse pregnancy outcomes aboard U.S. Navy ships.

The goal of this study was to model the incidence of ectopic pregnancy and spontaneous abortion if pregnant women in the first 20 weeks of gestation were to remain aboard ship while at sea during deployments. Ectopic pregnancies and other pregnancy complications at sea can be life-threatening events. Data sources included shipboard medical departments, an Enlisted Personnel Survey, and the Naval Health Research Center Hospitalized Pregnancy and Women Aboard Ship studies. The overall pregnancy rate was 19 per 100 woman-years (95% confidence interval, 18-20), based on the complement of women assigned to participating ships. If pregnant women routinely were to remain aboard ships at sea during deployments through their first 20 weeks of pregnancy, it is expected that approximately 9 ectopic pregnancies and 40 spontaneous abortions would occur aboard ships at sea.

Calcium and vitamin D. Their potential roles in colon and breast cancer prevention.

The geographic distribution of colon cancer is similar to the historical geographic distribution of rickets. The highest death rates from colon cancer occur in areas that had high prevalence rates of rickets--regions with winter ultraviolet radiation deficiency, generally due to a combination of high or moderately high latitude, high-sulfur content air pollution (acid haze), higher than average stratospheric ozone thickness, and persistently thick winter cloud cover. The geographic distribution of colon cancer mortality rates reveals significantly low death rates at low latitudes in the United States and significantly high rates in the industrialized Northeast. The Northeast has a combination of latitude, climate, and air pollution that prevents any synthesis of vitamin D during a five-month vitamin D winter. Breast cancer death rates in white women also rise with distance from the equator and are highest in areas with long vitamin D winters. Colon cancer incidence rates also have been shown to be inversely proportional to intake of calcium. These findings, which are consistent with laboratory results, indicate that most cases of colon cancer may be prevented with regular intake of calcium in the range of 1,800 mg per day, in a dietary context that includes 800 IU per day (20 micrograms) of vitamin D3. (In women, an intake of approximately 1,000 mg of calcium per 1,000 kcal of energy with 800 IU of vitamin D would be sufficient.) In observational studies, the source of approximately 90% of the calcium intake was vitamin D-fortified milk. Vitamin D may also be obtained from fatty fish. In addition to reduction of incidence and mortality rates from colon cancer, epidemiological data suggest that intake of 800 IU/day of vitamin D may be associated with enhanced survival rates among breast cancer cases.

Expression and genetic variation of the Aplysia egg-laying hormone gene family in the atrial gland.

We have screened an Aplysia atrial gland cDNA library using an egg-laying hormone (ELH) precursor probe and have isolated and characterized five different clones, four of which are full-length and approximately 0.8 kb in size. The characterization of these cDNA clones firmly established the genetic variation of the ELH-related precursors expressed in the atrial gland and provided a rational basis for their revised nomenclature proposed herein. The five precursor ELH-related cDNA sequences obtained predicted the following genetically distinct polypeptide precursors designated as: A, [Asp143]A, [Glu94,Gln139]A, [Pro25]B, and [Phe96,Asp107]BT. The [Phe96,Asp107]Br cDNA sequence predicted a truncated form of a B-type precursor. Northern blot analysis of atrial gland RNA identified two transcripts of about equal intensity of 0.9 kb and 1.1 kb. Polymerase chain reaction of genomic DNA, together with DNA sequence analysis, resolved previously reported discrepancies between genomic and cDNA sequences of the ELH-related precursors. Taken together the results obtained identified the expression of five ELH-related precursor genes in the atrial gland of Aplysia from at least two genetic loci per haploid genome.

Carpal tunnel syndrome and occupation in U.S. Navy enlisted personnel.

The objectives of this study were to (a) describe demographic factors associated with high rates of carpal tunnel syndrome (CTS), cubital tunnel syndrome, and other neuritis of the arm and hand, and (2) identify the high-risk occupations associated with these disorders in the Navy. Computerized records of first hospitalizations of all active-duty Navy-enlisted personnel were searched for all cases of CTS, cubital tunnel syndrome, and other neuritis of the arm and hand (ICD-9 CM codes 354.0-354.9) during 1980-1988. There were 1039 first hospitalizations (including 493 cases of CTS) for all neuritis of the arm and hand in 4095708 person-years in men and 186 first hospitalizations (including 90 cases of CTS) in 365668 person-years in women. Incidence rates of hospitalized cases with CTS rose with age for both sexes. Rates in white women were approximately three times those in white men (p < .0001), but rates in black women were not significantly different from those in black men. Rates of cubital tunnel syndrome also increased with age in both sexes and were higher in white women than white men (p < .05). Occupations with significantly high standardized incidence ratios (p < .05) for CTS in men included aviation-support equipment technician, engineman, hull-maintenance technician, boatswain's mate, and machinist's mate. In women, occupations with significantly high standardized incidence ratios included boatswain's mate, engineman, hospital corpsman, ocean-systems technician, and personnelman. Several occupations for each sex had significantly high standardized incidence ratios for cubital tunnel syndrome, with high rates in hospital corpsmen of both sexes (p < .05). Gender and race differences according to occupation did not account for the occupations at highest risk. Further research is needed to determine the extent to which CTS and related disorders could be prevented by modifying the motions currently performed in occupations with the highest standardized incidence ratios.

Western blot banding patterns of HIV rapid progressors in the U.S. Navy Seropositive Cohort: implications for vaccine development. Navy Retroviral Working Group.

Although human immunodeficiency virus (HIV) infection is progressive, the rate of decline in CD4+ lymphocyte counts varies. The role of immune system components in limiting HIV infection has yet to be defined, but a previous report on the U.S. Navy HIV Seropositive Cohort reported that strong reactivity in the anti-p55 (core precursor), p24 (core) and p53 (reverse transcriptase) Western blot bands was associated with higher CD4+ lymphocyte counts at the first clinical evaluation for HIV. The previous report examined the cross-sectional association between Western blot banding patterns and initial CD4+ lymphocyte counts. This report examines the association between these banding patterns in individuals who progressed rapidly as compared with patterns of patients who did not, based on their trends in repeated CD4+ lymphocyte counts as a marker of progression. Rapid and slower progressors were identified from a cohort of 3414 Navy and Marine Corps personnel who had a first positive HIV Western blot during 1986-1991. For purposes of this study, rapid progressors were defined as individuals whose CD4+ lymphocyte counts declined to < 500 cells/mm3 within 1 year of seroconversion. A total of 325 individuals met these criteria. A comparison group of 63 slower progressors also was identified; this group consisted of those whose CD4+ lymphocyte counts remained at > or = 500 cells/mm3 for a minimum of 5 years of follow-up after their first positive Western blot. Rapid progressors were slightly younger than slower progressors and were more likely to be never married but did not differ significantly from slower progressors in race or sex. Rapid progressors had weaker reactivity in the anti-p55 core precursor (P < 0.0001), p15 core (P < 0.01), gp41 transmembrane (P < 0.01) and p31 endonuclease (P < 0.05) bands on the Western blot. The odds ratio for rapid progressor status associated with weak or absent reactivity was 7.8 in the anti-p55 band and ranged from 2.0 to 3.2 in the anti-p31, p15, and gp41 bands. These associations remained significant after adjustment for age, race, and sex. The p55 association persisted in repeated Western blots during routine clinical evaluation during a period of 5 years after the first positive Western blot. It was concluded that several possible explanations may account for the weaker reactivity of rapid progressors: (i) weak anti-p55 reactivity might have been a marker of early immune system damage; (ii) high concentrations of p55 or related proteins in the serum may have bound the available anti-p55 antibodies in rapid progressors, making them difficult to identify on the Western blot; or (iii) lack of anti-p55, p15, gp41, or p31 reactivity might have allowed more rapid progression.

Molecular cloning of prohormone convertase 1 from the atrial gland of Aplysia.

We have screened an Aplysia atrial gland cDNA library using a prohormone convertase (PC)1 probe prepared by polymerase chain reaction (PCR) and have isolated an Aplysia PC1-related full-length 3.6-kb cDNA clone. The cDNA sequence (3,565 bp) encoded a putative preproendoprotease (APC1) of 703 amino acid residues that showed considerable sequence identity with other eukaryotic PC1s, and indicated a high degree of sequence identity with an Aplysia nervous system PC sequence (aPC1B). Northern blot analysis of atrial gland RNA identified two APC1 transcripts of 3.9 kb and 5.0 kb. APC1 is a candidate PC that may play an important role in the processing of egg-laying hormone (ELH)-related precursors in atrial gland secretory cells and represents one of the first examples of PC1 expression in an exocrine tissue.

Molecular cloning and cellular localization of a furin-like prohormone convertase from the atrial gland of Aplysia.

Prohormone convertases (PCs) are Ca(2+)-dependent subtilisin-related endoproteases that have been implicated in the post-translational processing of prohormones and other proproteins. Furin is an ubiquitously expressed PC that has been shown to hydrolyze a wide variety of precursor proteins in secretory pathways. We have screened an Aplysia atrial gland cDNA library using a furin probe prepared by polymerase chain reaction (PCR) and have isolated an Aplysia furin-related 6.7-kb cDNA partial clone that was truncated on the 5' end. The remaining 5' atrial gland furin nucleotide sequence was obtained by two stages of reverse transcription PCR. The final composite nucleotide sequence of the atrial gland furin cDNA was 7,837 bp in length. This sequence encoded a putative preproendoprotease (Afurin2) of 824 amino acid residues that was related to other eukaryotic furins, and showed a high sequence identity with a recently reported Aplysia nervous system furin-like sequence. In situ hybridization demonstrated extensive expression of Afurin2 in atrial gland secretory cells. The cDNA clone contained a relatively long 3' untranslated region of 5,230 nucleotides that included a microsatellite repeat region (TG)n. The characterized Aplysia Afurin2 is a candidate PC that may play an important role in the processing of egg-laying hormone (ELH)-related precursors in the secretory cells of the atrial gland. In addition, comparative structural studies of Afurin2, together with previously reported localization studies, argue for the occurrence of a furin-like convertase within secretory granules.

Molecular cloning, cDNA sequence, and localization of a prohormone convertase (PC2) from the Aplysia atrial gland.

Neuropeptides and peptide hormones are synthesized as part of larger precursor proteins that are processed post-translationally by subtilisin-related calcium-dependent prohormone convertases (PCs), frequently at multiple basic sites, to generate biologically active peptides. The atrial gland of Aplysia californica produces large quantities of egg-laying hormone (ELH)-related peptides, providing a unique opportunity to study prohormone processing. We have screened an Aplysia atrial gland cDNA library using a Lymnaea stagnalis PC2 probe and have isolated an Aplysia PC2-related 4.6-kb cDNA partial clone that was truncated on the 5' end. The remaining 5' atrial gland PC2 nucleotide sequence was obtained by reverse transcription/polymerase chain reaction (RT-PCR). The composite cDNA structure (5.6 kb) was deduced from sequence analysis of the RT-PCR product combined with the sequence obtained from the cDNA clone. The deduced cDNA of Aplysia atrial gland PC2 encoded a putative preproendoprotease of 653 amino acids that was evolutionarily related to other eukaryotic PC2s, and showed the strongest sequence identity with recently reported Aplysia nervous tissue PC2 sequences. In situ hybridization demonstrated extensive expression of PC2 in atrial gland secretory cells. The cDNA clone contained a relatively long 3'untranslated region (3'-UTR) of 3,632 nucleotides. Strikingly, the 3'-UTR also contained several major nucleotide repeat sequences including the microsatellite repeats, (CA)n and (TG)n, and a TA-rich region comprised largely of the triplet repeat (TTA)n. The characterized Aplysia PC2 is a candidate endoprotease that may play an important role in the processing of ELH-related precursors in the atrial gland and represents the first example of PC2 expression in exocrine tissue.

Specific western blot bands are associated with initial CD4+ lymphocyte counts in human immunodeficiency virus seroconverters. The Navy HIV Working Group.

The Western blot is the most widely used confirmatory test for determining human immunodeficiency virus (HIV) seropositivity. Specific bands in the Western blot indicate antibody responses to various portions of HIV or its precursors, and each is assigned a score from 0 to 3+. While the precise role of humoral antibody responses has not been fully established, specific antibody responses might influence the course of HIV infection. This study investigated the association between antibody reactivity to nine principal Western blot bands and initial CD4+ counts among 877 Navy and Marine Corps personnel during 1988 to 1991. Multiple regression was used to evaluate the strength and significance of the associations and to adjust for age and estimated duration of infection. Strong antibody responses to the p24 core (P < 0.05), p53 reverse transcriptase (P < 0.005), and p55 core precursor (P < 0.0001) antigens were associated with higher initial CD4+ counts, with 33 to 48 additional cells/mm3 associated with each unit increase in the Western blot score, according to a multiple regression analysis which controlled for age and duration of infection (maximum 24 months). By contrast, antibodies to the gp41 transmembrane antigen (P < 0.0001) were associated with lower initial CD4+ counts. Each unit increase in the gp41 band was associated with 76 fewer CD4+ cells/mm3. A negative association was also observed for the gp160 envelope precursor antigen, with each unit increase in reactivity associated with 51 fewer CD4+ cells, although this association was not statistically significant (P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of insulin-dependent diabetes mellitus in young adults: experience of 1,587,630 US Navy enlisted personnel.

First hospitalizations (n = 1,293) for diabetes mellitus between 1974 and 1988 were used as a surrogate for insulin-dependent diabetes mellitus incidence among 17-34-year-old US Navy enlisted personnel followed for 6,077,856 person-years. In the 15-year period, the overall incidence of insulin-dependent diabetes mellitus was 21.3 per 100,000 person-years. Incidence did not differ significantly by sex, but was higher for blacks than whites (28.4 vs. 20.2 per 100,000 person-years, respectively; p < 0.05). Incidence increased with age threefold for white men and fivefold for black men (p < 0.05) between the ages of 17-19 and 30-34 years.

Lack of association of human immunodeficiency virus seroconversion with visits to foreign ports in US Navy personnel.

BACKGROUND: The US Navy visits ports on all continents and many islands of the world, many of which are reported to have a high endemicity of human immunodeficiency virus (HIV) infection. The objective of this study was to determine whether visits to foreign ports by active-duty navy personnel were associated with increased risk of HIV infection. METHODS: The Naval Health Research Center in San Diego, Calif, maintains records of all HIV enzyme-linked immunosorbent assay and Western blot tests given in the navy. This information, along with career histories and ship movement data, was used in a nested case-control design to examine the relationship between visits to the 100 foreign ports most frequently visited by the navy and risk of HIV seroconversion. All visits to a port and total time in each port during the study period were examined. A total of 813 seroconverters were matched to 6993 seronegative active-duty controls by age, race, sex, occupational group, home port, and year of test. RESULTS: Estimated relative risks of seroconversion associated with visits to foreign ports showed no statistically significant excess risk of HIV infection for navy personnel after visits to any foreign port. CONCLUSIONS: These results do not imply that an individual's risk of acquisition of HIV would be less in a foreign port if the individual engaged in high-risk activity there. Rather, they imply that despite the mobility of the US Navy and the large variation in HIV seroprevalence rates throughout the world, navy personnel generally do not appear to be acquiring HIV infections abroad.

Geographic variation in human immunodeficiency virus seroconversion rates in the U.S. Navy.

The Navy population is centered around 19 U.S. home ports and several inland duty stations. This is a study of variation in human immunodeficiency virus (HIV) seroconversions in Navy enlisted men by location in the United States, based on 949,570 enzyme-linked immunosorbent assays and 812 seroconversions during 1987-90. Seroconversion rates were higher in personnel in San Francisco (p = 0.0004), Washington, D.C. (p = 0.001), and Orlando, FL (p = 0.04) than in other areas. They were lower in Charleston, SC, New London, CT, Seattle; and Brunswick, ME (p < 0.05). Black men had triple the seroconversion rate of all other men (p < 0.0001). After adjustment for race, age, marital status, and occupation, risk of seroconversion remained high in San Francisco (p = 0.02) and Orlando (p = 0.03). The risk of seroconversion in San Francisco was twice that of other areas in a cohort that did not change location (p = 0.01). In contrast to declining trends overall in the Navy, rates did not decrease in Washington, D.C., a result consistent with previous calculations indicating a delayed second wave of HIV infection in the region.