Prediabetes and Diabetes Screening in Dental Care Settings: NHANES 2013 to 2016.

Introduction: Early recognition of prediabetes may prevent progression to diabetes, yet not all adults are aware of their prediabetes risk. To reach all adults unaware of their risk, additional risk assessment strategies are warranted. Objectives: The objective of this study was to evaluate the potential scope of benefit from prediabetes risk assessment in the dental care setting and to identify characteristics of dental patients likely to unknowingly have prediabetes or diabetes. Methods: Data from 10,472 adults in the National Health and Nutrition Examination Survey from 2013 to 2014 and 2015 to 2016 were analyzed for associations among prediabetes/diabetes risk factors, health care use, and hemoglobin A1C levels according to chi-square tests and multivariate logistic regression. Results: A total of 7.73% of US adults had seen a dentist but not a medical provider in the past 12 mo. The composition of this subpopulation was significantly different from that who saw a medical provider, in ways that might affect their diabetes risk. In addition, 31.27% of this subpopulation would be identified as being at high risk for prediabetes according to the CDC Prediabetes Screening Test (Centers for Disease Control and Prevention), and 15.83% had hemoglobin A1C levels indicative of undiagnosed prediabetes or diabetes. Screening in a dental setting would have the highest odds of identifying someone unaware of his or her diabetes risk among those who were non-White, obese, or ≥45 y old. Conclusion: Extrapolation from this analysis indicates that screening for prediabetes at dental visits has the potential to alert an estimated 22.36 million adults of their risk for prediabetes or diabetes. Incorporating prediabetes or diabetes risk assessment into routine dental visits may enable 1) those with prediabetes to take action to decrease their risk of developing diabetes and 2) those with diabetes to engage in treatment to decrease their risk of diabetes-related complications. Knowledge Transfer Statement: Screening for prediabetes and diabetes during dental visits has the potential to raise patients' awareness of diabetes risk and prevent prediabetes from progressing to diabetes. For some patients, the dental visit may be the only point of contact with the health care system, which heightens the importance of including diabetes risk assessment for patient well-being.

Clinician Perceptions of 4 Hearing Protection Devices.

Common equipment in the dental operatory generate cumulative noise at sufficient decibel levels that can damage hearing. Although noise exposure in the dental office is typically intermittent, dentists and other dental care providers have been shown to be at risk of hearing loss. This article provides dentist-generated insight to use when incorporating hearing protection devices during dental practice. Four hearing protection devices (HPDs) were provided to 15 dentists in randomized sequence for evaluation. Perceptions were gathered via questionnaires and analyzed to determine mean ratings and product preferences. Battery requirements of electronic HPDs were also examined. Qualitative assessments of the HPDs evaluated are presented, including dentist preferences and recommendations. There were statistically significant differences ( P ≤ 0.0031) among the HPDs in terms of ease of insertion, aesthetics, ability to hear while using a handpiece, and the openness of the ear. Battery life was not found to differ between the 2 electronic HPDs evaluated. Dentists most highly valued ease of hearing, ability to communicate, and comfort while wearing HPDs. The DI-15 High-Fidelity Electronic Earplugs HPD was ranked the highest, followed by Music PRO Electronic Earplugs. Battery longevity for these electronic HPDs was similar under all tested conditions studied. Knowledge Transfer Statement: Dentists should understand the potential ramifications of hearing loss and be aware that there are commercially available hearing protection products that preserve the ability to communicate with patients and coworkers.

Strain- and Diet-Related Lesion Variability in Aging DBA/2, C57BL/6, and DBA/2xC57BL/6 F1 Mice.

Genetic and environmental factors both play a role in the occurrence of age-related disease. To examine the genetic contribution to the development of spontaneous lesions in aging animals, a complete range of tissues was comprehensively analyzed by histopathology from 180 individually housed ad libitum-fed or 40% calorically restricted 24-month-old male and female mice of 2 parental strains-DBA/2NNia (D2) and C57BL/6NNia (B6)-and the F1 cross B6D2F1/NNia. Several strain- and diet-dependent patterns of lesions were identified. Many lesions were genotype dependent and exhibited recessive phenotypic expression, defined as being common in 1 parental strain but infrequently observed in the F1 cross (eg, glomerulonephritis in B6 mice), while others were maintained from 1 parental strain to the F1 with similar frequencies (eg, reproductive tract leiomyoma in D2 mice). Other lesions were common regardless of genotype (osteoarthritis, periodontitis). Only rare lesions were more common in the F1 but underrepresented in the 2 parental strains. Furthermore, F1 mice had a lower number of overall total lesions and a lower number of tumors than either parental strain. Caloric restriction reduced the total number of lesions and neoplasms regardless of genotype but differentially affected genotype-dependent lesions in B6 and D2 mice, with B6 mice more sensitive to the effects of caloric restriction than D2 mice. In summary, genetics and environmental factors (eg, dietary restriction) both substantially contribute to the pattern of lesions that develop as animals age.

Diet restriction and age alters skeletal muscle capillarity in B6C3F1 mice.

The effects of 40% diet restriction on skeletal muscle fiber area, capillary density (CD) and capillary to fiber ratio (C/F) were compared in 12, 24 and 30-month-old female B6C3F1 female hybrid mice. We hypothesized that diet restriction (DR) would retard the aging effects observed in skeletal muscle, in particular DR would pose opposite effects on skeletal muscle capillarity and fiber area. Samples were prepared for light microscopic examination by standard methods and for morphometric analysis using NIH-image software. There was a significant effect of age on muscle fiber area (p<0.05). The age-associated decrease in fiber area between 12 and 30 months of age was greater (p<0.05) in the ad libitum (AL) (37.7%) animals as compared to the diet restricted (DR) mice (29.2%). Diet had a significant effect on CD (p<0.05) and C/F (p<0.05). This finding suggests that the lower capillarity in the older DR mice may have been due to their larger muscle fibers. The results of this study support the contention that diet restriction delays the progression of age-associated muscle atrophy.

Childhood energy intake and cancer mortality in adulthood.

A retrospective mortality follow-up of a British survey of family diet and health (1937-1939) identified significant associations between childhood energy intake and mortality from cancer, particularly those cancers not thought to be associated with smoking. This is the first large-scale epidemiologic study to suggest that the observed reduction in tumor incidence in energy-restricted rodents has relevance for humans.

Lesion biomarkers of aging in B6C3F1 hybrid mice.

This study of B6C3F1 hybrid mice was designed to determine the effects of caloric restriction (CR) on age-related pathologic changes. These changes accompany and may, in part, account for the apparent effect of CR in slowing the rate of aging. The study also explored whether lesions observed in groups of animals killed at 6 month intervals can serve as biomarkers of aging. Approximately 30 mice of each sex and each of two diet groups--CR and ad libitum fed (AL)--and each of six age groups--6, 12, 18, 24, 30, and 36 months of age--from the Biomarkers of Aging Program of the National Institute on Aging were killed and all tissues from each were examined for the histological presence or absence of lesions. A total of 209 distinct lesions were observed, of which 51 occurred in at least 10% of the AL or CR mice. The average number of lesions per mouse increased linearly with age in all diet-sex groups except in male CR mice. This increase was significantly smaller in CR than in AL mice of both sexes. The number of distinct lesions also increased with age in both diet groups but much less rapidly in CR mice. Nearly all lesions, including neoplastic, and nonneoplastic proliferative and degenerative ones, occurred significantly less often in CR than in AL mice at all ages. Foci of leukocytes in the liver, however, occurred more frequently in CR mice. Lung adenomas in old female mice occurred with equal frequency in both diet groups. A parsimonious classification tree analysis showed that diet groups could have been distinguished at each age by an evaluation of relatively few lesions and tissues. Altogether, this study suggests strongly that the prevalence of many individual lesions, the total lesion burden, and the total types of lesions are good biomarkers of aging because they increase with age and reflect the effect of CR in slowing the aging process. The study also shows that lesions occur stochastically, randomly, and independently in genetically homogeneous mice raised in a nonvariable environment.

Effects of genotype and diet on age-related lesions in ad libitum fed and calorie-restricted F344, BN, and BNF3F1 rats.

The effects of calorie restriction (CR) on age-related lesions in Brown Norway, Fischer 344, and BNF3F1 hybrid rats are presented. A logistic regression analysis of data from histologic samples from rats of each genotype, sex, and diet at 12, 18, 24, 30, and 36 months of age demonstrated the effects of age, diet, and sex on lesion prevalence in all three genotypes. CR reduced the prevalence of neoplastic, nonneoplastic proliferative, and degenerative lesions. All genotype-sex-age cohorts demonstrated a reduced average lesion burden with CR. Importantly, some lesions common to Brown Norway rats seldom occurred in Fischer 344 rats and vice versa. Some lesions that occurred in only one parental strain also occurred in BNF3F1 rats. Many traits occurred in all three genotypes but at significantly different prevalence rates. We suggest that the diseases and lesions that rats develop as they age are controlled by genes and environmental factors such as CR.

Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program.

The collaborative Interagency Agreement between the National Center for Toxicological Research (NCTR) and the National Institute on Aging (NIA) was aimed at identifying and validating a panel of biomarkers of aging in rodents in order to rapidly test the efficacy and safety of interventions designed to slow aging. Another aim was to provide a basis for developing biomarkers of aging in humans, using the assumption that biomarkers that were useful across different genotypes and species were sensitive to fundamental processes that would extrapolate to humans. Caloric restriction (CR), the only intervention that consistently extends both mean and maximal life span in a variety of species, was used to provide a model with extended life span. C57BI/6NNia, DBA/2JNia, B6D2F1, and B6C3F1 mice and Brown Norway (BN/RijNia), Fischer (F344/NNia) and Fischer x Brown Norway hybrid (F344 x BN F1) rats were bred and maintained on study. NCTR generated data from over 60,000 individually housed animals of the seven different genotypes and both sexes, approximately half ad libitum (AL) fed, the remainder CR. Approximately half the animals were shipped to offsite NIA investigators internationally, with the majority of the remainder maintained at NCTR until they died. The collaboration supplied a choice of healthy, long-lived rodent models to investigators, while allowing for the development of some of the most definitive information on life span, food consumption, and growth characteristics in these genotypes under diverse feeding paradigms.

Disease incidence and longevity are unaltered by dietary antioxidant supplementation initiated during middle age in C57BL/6 mice.

The ability of augmented antioxidant consumption to alter disease incidence, lesion burden and/or longevity was studied in adult male C57BL/6 mice. Mice were fed modified AIN76 diet or modified AIN76 supplemented with vitamin E, glutathione (GSH), vitamin E and GSH, melatonin or strawberry extract starting at 18 months of age. All the mice in this study were heavier than reference populations of male C57BL/6 mice fed NIH-07 or NIH-31, which were maintained without a mid-life change in diet. Fatty liver, focal kidney atrophy and proteinacious casts in the renal tubules were observed more frequently in this study population than in the reference populations. Lesion burden and incidence of specific lesions observed amongst the various groups in this study did not differ. There were no differences observed for longevity of any of the study groups. The longevity observed in this study was similar to that previously reported for male C57BL/6 mice. Thus, diet supplementation with antioxidants initiated during middle age did not appear to affect age-associated lesions patterns, lesion burden or longevity for ad libitum fed male C57BL/6 mice.

Effects of caloric restriction or augmentation in adult rats: longevity and lesion biomarkers of aging.

Caloric restriction (CR) initiated in young rodents has been thoroughly documented to enhance longevity, but its efficacy when introduced at older ages has not been well investigated. Cohorts of 18- and 26-month-old male F344 x BN F1 hybrid rats were fed either: 1) NIH-31 meal (C); 2) vitamin and mineral fortified NIH-31 meal (R); or 3) vitamin and mineral fortified NIH-31 meal supplemented with corn oil and sweetened condensed milk (S). The C control rats were fed ad libitum, R rats were restricted to 32% of the caloric intake of the controls, and S rats were allowed to consume not more than 8% more calories than C rats. After 6 weeks, the average weights were significantly different between all diet and age groups. Although calorie manipulation altered body weight, no significant effect of the dietary intervention on longevity was found. The average lesion burden, including tumor burden and prevalence of nearly all commonly occurring lesions, were comparable between the groups. Thus, the manipulation of weight at ages beyond middle age has a much less profound impact than similar interventions during growth and maturation in rats.

The effect of long-term dietary supplementation with antioxidants.

The impact of diet and specific food groups on aging and age-associated degenerative diseases has been widely recognized in recent years. The modern concept of the free radical theory of aging takes as its basis a shift in the antioxidant/prooxidant balance that leads to increased oxidative stress, dysregulation of cellular function, and aging. In the context of this theory, antioxidants can influence the primary "intrinsic" aging process as well as several secondary age-associated pathological processes. For the latter, several epidemiological and clinical studies have revealed potential roles for dietary antioxidants in the age-associated decline of immune function and the reduction of risk of morbidity and mortality from cancer and heart disease. We reported that long-term supplementation with vitamin E enhances immune function in aged animals and elderly subjects. We have also found that the beneficial effect of vitamin E in the reduction of risk of atherosclerosis is, in part, associated with molecular modulation of the interaction of immune and endothelial cells. Even though the effects of dietary antioxidants on aging have been mostly observed in relation to age-associated diseases, the effects cannot be totally separated from those related to the intrinsic aging process. For modulation of the aging process by antioxidants, earlier reports have indicated that antioxidant feeding increased the median life span of mice to some extent. To further delineate the effect of dietary antioxidants on aging and longevity, middle-aged (18 mo) C57BL/6NIA male mice were fed ad libitum semisynthetic AIN-76 diets supplemented with different antioxidants (vitamin E, glutathione, melatonin, and strawberry extract). We found that dietary antioxidants had no effect on the pathological outcome or on mean and maximum life span of the mice, which was observed despite the reduced level of lipid peroxidation products, 4-hydroxynonenol, in the liver of animals supplemented with vitamin E and strawberry extract (1.34 +/- 0.4 and 1.6 +/- 0.5 nmol/g, respectively) compared to animals fed the control diet (2.35 +/- 1.4 nmol/g). However, vitamin E-supplemented mice had significantly lower lung viral levels following influenza infection, a viral challenge associated with oxidative stress. These and other observations indicate that, at present, the effects of dietary antioxidants are mainly demonstrated in connection with age-associated diseases in which oxidative stress appears to be intimately involved. Further studies are needed to determine the effect of antioxidant supplementation on longevity in the context of moderate caloric restriction.

Pathobiology of aging rodents: inbred and hybrid models.

The definition of inbred strains of animals is provided, underscoring the homogeneity of the individuals in a strain, as well as the lack of allelic variation within each individual. Inbred animals present long-term reproducibility and relative stability, which facilitates experimentation over a long period of time. The derivations of several specific groups of inbred animals including coisogenic, congenic, and recombinant inbred lines are detailed. Applications for inbred strains to the study of aging including analysis of longevity characteristics, genes involved in the control of age-related parameters and gene interactions with other genes or the environment are presented. The concept of aging as a consequence of genes and the ramifications of competitive pleiotropy are discussed. The distinction between aging and age-related diseases or lesions is explored. Cumulative lesion incidence is suggested as a biomarker of aging.

Evidence that lysosomal storage of proteolipids is a cell autonomous process in the motor neuron degeneration (mnd) mouse, a model of neuronal ceroid lipofuscinosis.

The motor neuron degeneration (mnd) mouse has been documented to accumulate proteolipid and thus is a model of neuronal ceroid lipofuscinosis [Dunn, W.A., Raizada, M.K., Vogt, E.S. and Brown, E.A., Int. J. Dev. Neurosci., 12 (1994) 185-196; Faust, J.R., Rodman, J.S., Daniel, P.F., Dice, J.F. and Bronson, R.T., J. Biol. Chem., 269 (1994) 10150-10155]. While accumulation of proteolipid in the hippocampus of chimeric mice composed of mnd and +/+ cells was found to be proportional to the contribution of mnd in the brain, accumulation within individual cells was the same for cells from chimeric and age-matched mnd mice. Bone marrow transplantation was used to altering the milieu of circulating factors to determine whether this might modify the disease phenotype in mnd mice. Transplantation of bone marrow in neonatal or young mice did not reduce the age-associated accumulation of proteolipid within hippocampal neurons. The results of these experiments indicate that mnd results in a cell autonomous defect.

Pathologic characterization of brown Norway, brown Norway x Fischer 344, and Fischer 344 x brown Norway rats with relation to age.

The rat is a common laboratory animal utilized in a variety of investigations including experimental gerontology. Gerontologic investigations can be compromised when the differences observed when comparing young and old animals are actually differences between normal and disease states. It is of critical interest to know the pathology of the animals being studied and to understand the impact of these disease processes on the parameters being measured. The incidence and average age of occurrence for lesions have been characterized and are reported here for one inbred (Brown Norway) and two hybrid strains (Brown Norway x Fischer 344 and Fischer 344 x Brown Norway) of rat. Total lesion incidence functions as a biomaker of aging for all of the strains examined (p < or = .00001). These three genotypes have significantly lower incidence of several major pathologic processes (including glomerulonephritis, retinal atrophy, and leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized strains. Additionally, the BN and F344 x BN F1 hybrid attain 50% mortality at 130 and 146 weeks of age, respectively, which is significantly greater than the 103 weeks for the F344 rat. It is hoped that access to basic information on these three rat genotypes will increase their utilization by the community of gerontologic scientists.

Weight gain by middle-aged mice: dietary modification does not result in loss.

Dietary induced obesity susceptibility and persistence was examined in middle aged female retired C57BL/6J breeder mice. One year old mice were fed control chow (C), chow with added corn oil (O), or chow with added sweetened condensed milk (SCM) for 18 weeks, during which time food consumption and weight change were monitored. Mice in both the O and SCM groups gained significantly more weight than the C group. Weight increase correlated with caloric intake for the O and SCM groups. All mice were then fed standard laboratory chow for 22 weeks. The increased weight of both supplemented groups was maintained during this time suggesting that caloric intake is not the sole variable controlling weight maintenance in adult female mice. We encourage the use of older mice as a model to explore means of manipulating adult weight in humans.

Dietary restriction delays cataract and reduces ascorbate levels in Emory mice.

Dietary restriction can effectively extend lifespan and retard many age-related debilities. One hypothesis to explain the beneficial effects of dietary restriction is that it prolongs maintenance of cellular homeostasis by limiting endogenous oxidative stress and preserves oxidative defense mechanisms during aging. Ascorbate, a primary antioxidant, may play a major role in preventing oxidative damage. Ascorbate levels were determined in dietary restricted (R) and control (C) Emory mice, a strain which develops age-related cataract due in part to oxidative damage to lens proteins. Mice which consumed a diet restricted by 40% in calories had lower ascorbate concentrations in plasma, liver and kidney. Nevertheless, R animals showed significantly delayed progression of cataract which extended over the entire second half of life. The R diet did not result in different ascorbate levels in this lens. Aging was associated with a decrease in ascorbate in all the examined tissues except lens of both the R and C groups. It is not clear from these data that ascorbate is a prominent factor in the delay of cataract formation or other debilities in R Emory mice. However, it also appears unlikely that lens ascorbate is cataractogenic.

Is late-life caloric restriction beneficial?

Caloric restriction initiated in young mice and rats results in increases in mean and median life span. When caloric restriction is implemented in older animals, an increase in life span is still observed; however, the magnitude of the increase is not as great as that observed in animals calorie restricted since they were young. Here we report the results of a pilot study in which caloric restriction was initiated in mature, older rats. Survival rates and terminal pathology were characterized and compared between a cohort of 17 continually ad libitum fed Long Evans rats and a cohort of 18 Long Evans rats, which were gradually introduced to 33% restriction in diet consumption at 18 months of age. No difference in the median life span was observed between the two groups. The data suggest there may be a level of maturity, or a stage in the aging process, after which caloric restriction no longer increases longevity.

Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer.

The Emory mouse is the best model for age-related cataract. In this work we compare the effects of feeding a control diet (C) with a diet restricted (R) by 40% relative to C animals. In the R animals, median lifespan was extended by 40%. The proportion of R mice with advanced cataract was lower than C mice as early as 5 months of age. The mean grade of cataract was lower in R animals, beginning at 11 months and continuing until the end of the study. Ascorbate levels in R plasma and liver were 41-56% of C animals. There was no difference between diet groups with respect to lens ascorbate. Aging was associated with a decrease in ascorbate in lenses and kidneys in C and R mice. By 22 months, R animals had 48% higher liver glutathione levels than C mice. Liver glutathione levels were maximal at 12 months. Plasma glucose levels were > 27% lower in R animals at 6.5 and 22 months, and there was a 14% increase in glucose levels upon aging for both diet groups. In R mice, glycohemoglobin levels were 51% lower and tail collagen breaktime was decreased by 40%, even in younger animals. Collagen breaktime increased > 360% upon aging for both diet groups. Rates of production of urinary oxo8dG and oxo8G were higher in R animals compared with C animals, and increased upon aging. C animals exhibited more cancer and dermatological lesions, but less tail tip necrosis and inflamed genitals than R mice. These data allow evaluation of several theories of aging.

Husbandry factors and the prevalence of age-related amyloidosis in mice.

A retrospective study of the prevalence of amyloidosis in mice from several facilities was done. Amyloid deposition is an age-related lesion. The influence of common laboratory factors on the occurrence of this lesion was analyzed. This study documented genotypic difference in susceptibility to amyloidosis and showed that caging and pathogen status both impact on the number of cases of amyloidosis seen in a population. The lowest percentage of affected mice was seen when the animals were individually caged in a specific pathogen-free facility where conditions of stress were minimized.

FRAR course on laboratory approaches to aging. The role of pathology in rodent experimental gerontology.

The distinction between aging and age-related disease is a blurred one at best. Pathologic lesions and diseases, while having obvious importance for the well-being of an individual, are not more indicative of aging than are silent or benign aging changes. All lesions are useful as biomarkers of aging. They are definable, and can be characterized in terms of their prevalence and severity in different species, genotypes, genders, and age groups. Some data from previous studies are presented as examples. Many lesions of aging are quite restricted, in terms of prevalence or severity, to specific genotypes, species or genders. Recognition of the very great diversity of lesion biomarkers between genotypes, genders and species should prevent investigators from extrapolating findings in one genotype-gender to any other.