Widely Used Benzalkonium Chloride Disinfectants Can Promote Antibiotic Resistance.

While the misuse of antibiotics has clearly contributed to the emergence and proliferation of resistant bacterial pathogens, with major health consequences, it remains less clear if the widespread use of disinfectants, such as benzalkonium chlorides (BAC), a different class of biocides than antibiotics, has contributed to this problem. Here, we provide evidence that exposure to BAC coselects for antibiotic-resistant bacteria and describe the underlying genetic mechanisms. After inoculation with river sediment, BAC-fed bioreactors selected for several bacterial taxa, including the opportunistic pathogen Pseudomonas aeruginosa, that were more resistant to several antibiotics than their counterparts in a control (no BAC) bioreactor. A metagenomic analysis of the bioreactor microbial communities, confirmed by gene cloning experiments with the derived isolates, suggested that integrative and conjugative elements encoding a BAC efflux pump together with antibiotic resistance genes were responsible for these results. Furthermore, the exposure of the P. aeruginosa isolates to increasing concentrations of BAC selected for mutations in pmrB (polymyxin resistance) and physiological adaptations that contributed to a higher tolerance to polymyxin B and other antibiotics. The physiological adaptations included the overexpression of mexCD-oprJ multidrug efflux pump genes when BAC was added in the growth medium at subinhibitory concentrations. Collectively, our results demonstrated that disinfectants promote antibiotic resistance via several mechanisms and highlight the need to remediate (degrade) disinfectants in nontarget environments to further restrain the spread of antibiotic-resistant bacteria.IMPORTANCE Benzalkonium chlorides (BAC) are biocides broadly used in disinfectant solutions. Disinfectants are widely used in food processing lines, domestic households, and pharmaceutical products and are typically designed to have a different mode of action than antibiotics to avoid interfering with the use of the latter. Whether exposure to BAC makes bacteria more resistant to antibiotics remains an unresolved issue of obvious practical consequences for public health. Using an integrated approach that combines metagenomics of natural microbial communities with gene cloning experiments with isolates and experimental evolution assays, we show that the widely used benzalkonium chloride disinfectants promote clinically relevant antibiotic resistance. Therefore, more attention should be given to the usage of these disinfectants, and their fate in nontarget environments should be monitored more tightly.

Genomic and Transcriptomic Insights into How Bacteria Withstand High Concentrations of Benzalkonium Chloride Biocides.

Benzalkonium chlorides (BAC) are commonly used biocides in broad-spectrum disinfectant solutions. How microorganisms cope with BAC exposure remains poorly understood, despite its importance for disinfection and disinfectant-induced antibiotic resistance. To provide insights into these issues, we exposed two isolates of an opportunistic pathogen, Pseudomonas aeruginosa, to increasing concentrations of BAC. One isolate was preadapted to BAC, as it originated from a bioreactor fed with subinhibitory concentrations of BAC for 3 years, while the other originated from a bioreactor that received no BAC. Replicated populations of both isolates were able to survive high concentrations of BAC, up to 1,200 and 1,600 mg/liter for the non- and preadapted strains, respectively, exceeding typical application doses. Transcriptome sequencing (RNA-seq) analysis revealed upregulation of efflux pump genes and decreased expression of porins related to BAC transport as well as reduced growth rate. Increased expression of spermidine (a polycation) synthase genes and mutations in the pmrB (polymyxin resistance) gene, which cause a reduction in membrane negative charge, suggested that a major adaptation to exposure to the cationic surfactant BAC was to actively stabilize cell surface charge. Collectively, these results revealed that P. aeruginosa adapts to BAC exposure by a combination of mechanisms and provided genetic markers to monitor BAC-resistant organisms that may have applications in the practice of disinfection.IMPORTANCE BAC are widely used as biocides in disinfectant solutions, food-processing lines, domestic households, and health care facilities. Due to their wide use and mode of action, there has been rising concern that BAC may promote antibiotic resistance. Consistent with this idea, at least 40 outbreaks have been attributed to infection by disinfectant- and antibiotic-resistant pathogens such as P. aeruginosa However, the underlying molecular mechanisms that bacteria use to deal with BAC exposure remain poorly elucidated. Elucidating these mechanisms may be important for monitoring and limiting the spread of disinfectant-resistant pathogens. Using an integrated approach that combined genomics and transcriptomics with physiological characterization of BAC-adapted isolates, this study provided a comprehensive understanding of the BAC resistance mechanisms in P. aeruginosa Our findings also revealed potential genetic markers to detect and monitor the abundance of BAC-resistant pathogens across clinical or environmental settings. This work contributes new knowledge about high concentrations of benzalkonium chlorides disinfectants-resistance mechanisms at the whole-cell genomic and transcriptomic level.

Quantifying the Importance of the Rare Biosphere for Microbial Community Response to Organic Pollutants in a Freshwater Ecosystem.

A single liter of water contains hundreds, if not thousands, of bacterial and archaeal species, each of which typically makes up a very small fraction of the total microbial community (<0.1%), the so-called "rare biosphere." How often, and via what mechanisms, e.g., clonal amplification versus horizontal gene transfer, the rare taxa and genes contribute to microbial community response to environmental perturbations represent important unanswered questions toward better understanding the value and modeling of microbial diversity. We tested whether rare species frequently responded to changing environmental conditions by establishing 20-liter planktonic mesocosms with water from Lake Lanier (Georgia, USA) and perturbing them with organic compounds that are rarely detected in the lake, including 2,4-dichlorophenoxyacetic acid (2,4-D), 4-nitrophenol (4-NP), and caffeine. The populations of the degraders of these compounds were initially below the detection limit of quantitative PCR (qPCR) or metagenomic sequencing methods, but they increased substantially in abundance after perturbation. Sequencing of several degraders (isolates) and time-series metagenomic data sets revealed distinct cooccurring alleles of degradation genes, frequently carried on transmissible plasmids, especially for the 2,4-D mesocosms, and distinct species dominating the post-enrichment microbial communities from each replicated mesocosm. This diversity of species and genes also underlies distinct degradation profiles among replicated mesocosms. Collectively, these results supported the hypothesis that the rare biosphere can serve as a genetic reservoir, which can be frequently missed by metagenomics but enables community response to changing environmental conditions caused by organic pollutants, and they provided insights into the size of the pool of rare genes and species.IMPORTANCE A single liter of water or gram of soil contains hundreds of low-abundance bacterial and archaeal species, the so called rare biosphere. The value of this astonishing biodiversity for ecosystem functioning remains poorly understood, primarily due to the fact that microbial community analysis frequently focuses on abundant organisms. Using a combination of culture-dependent and culture-independent (metagenomics) techniques, we showed that rare taxa and genes commonly contribute to the microbial community response to organic pollutants. Our findings should have implications for future studies that aim to study the role of rare species in environmental processes, including environmental bioremediation efforts of oil spills or other contaminants.

Reviving a Smile: A Multidisciplinary Approach to Dentin Dysplasia.

Dentin dysplasia Type 1 (DD1) is an uncommon inherited condition marked by structural irregularities in dentin, leading to notable dental abnormalities. Clinically, patients typically present with generalized slight yellowish discoloration and tooth mobility, while radiographic examination often reveals a reduced pulp chamber with the absence of pulp stones, a hallmark feature of DD1. Treatment involves a multidisciplinary approach including extraction of affected teeth, direct sinus lift procedure bilaterally, implant placement, and subsequent fixed prosthesis placement. In a recent case, after six months, a patient demonstrated improved oral health-related quality of life with stabilized implant-supported prostheses providing functional and esthetic benefits. This emphasizes the importance of early diagnosis and intervention in managing DD1, underscoring the effectiveness of a multidisciplinary approach in enhancing oral function and esthetics. Further research is warranted to deepen our understanding of the genetic basis of this condition and develop targeted therapies.

Mechanical Properties and Potential Clinical Implications of Improved Superelastic Orthodontic Archwires: An Observational Study.

BACKGROUND: Superelastic materials have gained popularity due to their ability to maintain a constant force over a prolonged period during orthodontic treatment. However, high hysteresis and frictional properties had limited the use of superelastics as archwire material that demanded the need for improved superelastic orthodontic archwires with enhanced mechanical properties. AIM: The present study aimed to investigate the differences in mechanical properties and frictional resistance of improved superelastic orthodontic archwires against conventional archwires and to evaluate their potential implications in clinical orthodontic practice. MATERIALS AND METHODS: A total of 45 samples with 15 in each category respectively from low hysteresis superelastic archwire (L&H Titan; Tomy Inc., Tokyo, Japan), nickel-titanium (NiTi) archwires (Ormco, Brea, CA, USA) and NiTi with copper (CuNiTi) archwires (Ormco) of equal diameter (0.016 x .022 inches) and length (10 cm) were randomly assigned in combination among metal and ceramic orthodontic brackets group. The frictional properties of the archwires were measured using a universal testing machine (Instron, Norwood, MA, USA) equipped with a custom-made jig. The load-displacement data were recorded, and other mechanical properties that included tensile strength, compressive strength and deflective force at 4mm were also evaluated. The data were analysed using independent Student t-tests to compare the mean frictional resistance of the three archwires followed by analysis of variance (ANOVA) to evaluate differences between the means with p-value of less than 0.05 considered as statistically significant. RESULTS: The improved superelastic wires had the least frictional resistance among the three archwires tested. Further intergroup comparison to evaluate differences between the frictional resistance means among the three archwire categories with two orthodontic brackets groups revealed a significant difference at p<.05. Pairwise comparison also showed significant differences with higher frictional resistance between metal brackets and low hysteresis superelastic archwire category than ceramic brackets and NiTi with copper archwires (.0003) and ceramic brackets with NiTi archwires category (.003) respectively. The lowest deflective force at 4mm with better tensile and compressive strength was seen with the improved superelastic wires. CONCLUSION: The results of this study suggest that low hysteresis superelastic archwires have lower frictional forces when combined with metal orthodontic brackets compared with ceramic orthodontic brackets. Better tensile strength with least compressive strength and deflective forces at 4mm of testing among low hysteresis L&H Titan superelastic archwire than CuNiTi and NiTi archwires was observed making them potentially advantageous for orthodontic applications.

Bacillary Angiomatosis Mimicking Pyogenic Granuloma.

Bacillary angiomatosis (BA) is an angioproliferative disease caused by Bartonella species. It manifests as nodules or papules in immunocompromised patients. Oral lesions are very rare, unlike cutaneous lesions, and histopathology plays a vital role in distinguishing these lesions from other similar ones. Treatment mainly comprises macrolides erythromycin, clarithromycin, or doxycycline.

Influence of Injection Barrier on Vertical Organic Field Effect Transistors.

Organic field-effect transistors (OFETs) have shown great potential for applications that require low temperature deposition on large and flexible substrates. To increase their performance, in particular a high transconductance and transit frequency, the transistor channel length has to be scaled into the submicrometer regime, which can be easily achieved in vertical organic field effect transistors (VOFETs). However, despite high performance observed in VOFETs, these transistors usually suffer from short channel effects like weak saturation of the drain current and direct source-drain leakage resulting in large off currents. Here, we study the influence of the injection barrier at the source electrode on the OFF currents, on/off ratio, and transconductance of vertical OFETs. We use two semiconducting materials, 2,6-diphenyl anthracene (DPA), and C60 to vary the injection barrier at the source electrode and are able to show that increasing the Schottky barrier at the source electrode can decrease the direct source/drain leakage by 3 orders of magnitude. However, the increased injection barrier at the source electrode comes at the expense of an increased contact resistance, which in turn will decrease its transconductance and transit frequency. With the help of a 2D drift-diffusion simulation we show that the trade-off between low off currents and high transconductance is inherent to the current VOFET device setup and that new approaches have to be found to design VOFETs that combine good switching properties with high performance.

Analytic Device Model of Organic Field-Effect Transistors with Doped Channels.

Doping has been shown to not only provide additional degrees of freedom in the design of organic field-effect transistors (OFETs) but to increase their performance and stability as well. An analytical model based on the assumption of a square doping profile inside the channel is presented here that describes the effect of doping on the transfer characteristic of OFETs. The model is validated experimentally by a series of OFETs with varying doping conditions. The precise doping profile in the transistor channel is determined by fitting the capacitance/voltage response of doped metal-insulator-semiconductor (MIS) junctions using an AC small-signal drift-diffusion simulation. It is shown that the real doping profile deviates from the simplifying assumptions of the analytical model, i.e., it is found that the effective doping concentration at the dielectric/semiconductor interface is reduced. However, it is shown that the analytical model is not sensitive to this deviation as only the total density charges per unit area determine the changes in the transistor behavior. Overall, the presented theory provides new design rules that can be used to guide the development of doped OFETs with high performance.

Finding the equilibrium of organic electrochemical transistors.

Organic Electrochemical Transistors are versatile sensors that became essential for the field of organic bioelectronics. However, despite their importance, an incomplete understanding of their working mechanism is currently precluding a targeted design of Organic Electrochemical Transistors and it is still challenging to formulate precise design rules guiding materials development in this field. Here, it is argued that current capacitive device models neglect lateral ion currents in the transistor channel and therefore fail to describe the equilibrium state of Organic Electrochemical Transistors. An improved model is presented, which shows that lateral ion currents lead to an accumulation of ions at the drain contact, which significantly alters the transistor behavior. Overall, these results show that a better understanding of the interface between the organic semiconductor and the drain electrode is needed to reach a full understanding of Organic Electrochemical Transistors.

Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults.

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.

A high glycemic meal suppresses the postprandial leptin response in normal healthy adults.

BACKGROUND/AIMS: To evaluate the metabolic effects of meals with varying glycemic index (GI). METHODS: We measured the glucose, insulin and leptin responses to two contrasting breakfast cereals in a group of 10 young healthy volunteers. Meals were provided on two separate occasions in random order after a 12-hour overnight fast, and consisted of 50 g of available carbohydrate from either Corn Flakes (Kellogg's), or Fiber One (General Mills). Blood samples were obtained at rest, and 30, 60, 90 and 120 min after eating. The GI was calculated from the glucose response to the test meal normalized against a 50 g oral glucose load. RESULTS: The GI for Corn Flakes was 125 +/- 17 units and 49 +/- 8 units for Fiber One(R). These meals were classified as high GI and low GI, respectively, and were significantly different from each other (p < 0.0003). The area under the insulin response curve (AUC) following the low glycemic meal was significantly attenuated compared to the high glycemic meal (14,064 +/- 2,694 vs. 6,828 +/- 1,182 pmol/l.min, p < 0.02). The leptin AUC revealed that circulating leptin was suppressed by the high glycemic meal compared to the low (3.1 +/- 1.5 vs. 9.6 +/- 3.6 ng/ml.min, p < 0.04). CONCLUSIONS: Lower insulin and higher leptin suggests that low glycemic meals promote a postprandial metabolic milieu that is favorable for reduced food consumption; this may be advantageous in the control of obesity and related disorders including insulin resistance and type 2 diabetes.

Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat.

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 +/- 1 yr, body mass index = 33.2 +/- 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 +/- 0.8 vs. 24.3 +/- 1.0 ml.kg(-1).min(-1), P < 0.0001), decreased body weight (P < 0.0001) and fat mass (P < 0.001), while fat-free mass was not altered (P > 0.05). VF (176 +/- 20 vs. 136 +/- 17 cm2, P < 0.0001), subcutaneous fat (351 +/- 34 vs. 305 +/- 28 cm2, P < 0.03), and total abdominal fat (525 +/- 40 vs. 443 +/- 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower (P < 0.003) after training, but total adiponectin and tumor necrosis factor-alpha remained unchanged. Insulin resistance was reversed by exercise (40.1 +/- 7.7 vs. 27.6 +/- 5.6 units, P < 0.01) and correlated with changes in VF (r = 0.66, P < 0.01) and maximal oxygen consumption (r = -0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.

Impaired substrate oxidation in healthy elderly men after eccentric exercise.

The metabolic response to eccentric exercise in healthy older adults is unknown. Therefore, substrate metabolism was examined in the basal state and after sustained hyperglycemia (180 min, 10 mM) in eight healthy, sedentary older [66 +/- 2 yr; body mass index (BMI) of 25.5 +/- 1.2 kg/m] and nine younger (23 +/- 1 yr; BMI of 23.6 +/- 1.7 kg/m) men, under control conditions and 48 h after eccentric exercise. Indirect calorimetry was performed to evaluate carbohydrate and lipid oxidation (C(ox) and L(ox), respectively). Eccentric exercise caused muscle soreness and increased plasma creatine kinase in both groups of men (P < 0.02). Although a similar level of hyperglycemia was maintained in the two groups, glucose infusion rates were lower (P < 0.001) in the older men. Compared with basal levels, hyperglycemia stimulated an increase in C(ox) and a decrease in L(ox) during the control and exercise trials in the younger group (P < 0.03), but only during the control trial in the older subjects (P < 0.007). C(ox) was unchanged after eccentric exercise in the younger men [4.00 +/- 0.30 vs. 3.54 +/- 0.44 mg x kg fat-free mass (FFM)(-1) x min(-1); exercise vs. control] but was suppressed by 20% in the older group (3.37 +/- 0.37 vs. 4.21 +/- 0.23 mg x kg FFM(-1) x min(-1); P < 0.04). Moreover, L(ox) was reduced by 38% in the younger subjects (0.47 +/- 0.09 vs. 0.76 +/- 0.10 mg x kg FFM(-1) x min(-1); P< 0.03) but was augmented by 89% in the older group (0.68 +/- 0.11 vs. 0.36 +/- 0.08 mg x kg FFM(-1) x min(-1); P < 0.04). In addition, hyperglycemia-stimulated C(ox), L(ox), and respiratory exchange ratio responses to eccentric exercise were related to abdominal adiposity (r = -0.57, P < 0.04, r = 0.68, P < 0.02 and r = -0.60, P < 0.02, respectively). Despite normal glucose tolerance and the absence of obesity per se, older men experience a reduction in carbohydrate oxidation in response to hyperglycemia after eccentric exercise.

Acute altitude-induced hypoxia suppresses plasma glucose and leptin in healthy humans.

To examine the effects of acute altitude-induced hypoxia on the hormonal and metabolic response to ingested glucose, 8 young, healthy subjects (5 men and 3 women; age, 26 +/- 2 years; body mass index, 23.1 +/- 1.0 kg/m(2)) performed 2 randomized trials in a hypobaric chamber where a 75-g glucose solution was ingested under simulated altitude (ALT, 4300 m) or ambient (AMB, 362 m) conditions. Plasma glucose, insulin, C-peptide, epinephrine, leptin, and lactate concentrations were measured at baseline and 30, 60, 90, and 120 minutes after glucose ingestion during both trials. Compared with AMB, the plasma glucose response to glucose ingestion was reduced during the ALT trial (P = .04). There were no differences in the insulin and C-peptide responses between trials or in insulin sensitivity based on the homeostasis model assessment of insulin resistance. Epinephrine and lactate were both elevated during the ALT trial (P < .05), whereas the plasma leptin response was reduced compared with AMB (P < .05). The data suggest that the plasma glucose response is suppressed at ALT, but this is not due to insulin per se because insulin and C-peptide levels were similar for both trials. Elevated plasma epinephrine and lactate during ALT are indicative of increased glycogenolysis, which may have masked the magnitude of the reduced glucose response. We conclude that, during acute altitude exposure, there is a rapid metabolic response that is accompanied by a shift in the hormonal milieu that appears to favor increased glucose utilization.

Effects of exercise and caloric restriction on insulin resistance and cardiometabolic risk factors in older obese adults--a randomized clinical trial.

BACKGROUND: The prevalence of insulin resistance, metabolic syndrome, and cardiovascular disease is greatest in older obese patients, and effective evidence-based treatment strategies are lacking. METHODS: A prospective controlled study was conducted on 24 older (65.5 +/- 5.0 years) obese (body mass index, 34.3 +/- 5.2 kg/m(2)) adults with clinically diagnosed metabolic syndrome. We examined the effect of exercise alone (EX) or exercise combined with moderate caloric restriction (-500 kcal, EX + CR) on metabolic and cardiovascular risk factors. Measures of insulin sensitivity assessed by euglycemic hyperinsulinemic clamp and by oral glucose tolerance test, lipid profiles, blood pressure, body composition, abdominal fat, and aerobic capacity were all obtained before and after the interventions. RESULTS: Both groups experienced significant weight loss, but the reduction was greater in the EX + CR group than in the EX group (-6.8 +/- 2.7 kg vs -3.7 +/- 3.4 kg, respectively, p = .02). Both interventions improved insulin sensitivity (2.4 +/- 2.4 mg/kg FFM/min and 1.4 +/- 1.7 mg/kgFFM/min, respectively, p < .001) and indices of metabolic syndrome (systolic/diastolic blood pressure, waist circumference, glucose, and triglycerides; p < .05). High-density lipoprotein levels remained unchanged. Total abdominal, subcutaneous, and visceral fat; aerobic capacity; and total and low-density lipoprotein cholesterol were also improved. With the exception of weight loss and subcutaneous fat, there was no difference in the magnitude of improvement between the interventions. CONCLUSION: These data suggest that exercise alone is an effective nonpharmacological treatment strategy for insulin resistance, metabolic syndrome, and cardiovascular disease risk factors in older obese adults.

Effects of aging on basal fat oxidation in obese humans.

Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44.6 +/- 7.1 vs 38.3 +/- 6.0 mL/kg fat-free mass per minute, P = .03); but insulin sensitivity, lipemia, and leptinemia were not different between groups (P > .05). Fat oxidation was most related to age (r = -0.61, P = .003) and VO(2)max (r = 0.52, P = .01). These data suggest that aging per se is responsible for reduced basal fat oxidation and maximal oxidative capacity in older obese individuals, independent of changes in insulin resistance, body mass, and abdominal fat. This indicates that age, in addition to obesity, is an independent risk factor for weight gain and for the metabolic complications of elevated body fat.

Glucose clearance is delayed after hyperglycemia in healthy elderly men.

Delayed glucose clearance after hyperglycemia may contribute to insulin resistance. Rates of glucose and insulin decay were measured after 3 h of sustained hyperglycemia (10 mmol/L) in 8 healthy older men (66 +/- 2 y) and were compared with those of 8 younger men (22 +/- 1 y). Fractional glucose clearance rates were calculated by regression analysis. Insulin decay was estimated from insulin levels through 30 min postinfusion. Abdominal adiposity was estimated from waist-to-hip ratios. Body weight and basal plasma glucose, insulin and C-peptide concentrations did not differ between groups. Fat mass, abdominal adiposity, fasting serum triglycerides and total cholesterol, although normal, were higher (P < 0.05) in the older group. The elderly group experienced lower glucose clearance rates (1.9 +/- 0.2 vs. 2.9 +/- 0.1%/min, P < 0.002) and higher plasma insulin after hyperglycemia (P < 0.03). Glucose and insulin decay correlated with glucose infusion rates (r = 0.88, P < 0.0002 and r = 0.51, P < 0.05). Delayed glucose clearance was associated with greater abdominal adiposity (r = -0.56, P < 0.03), higher serum triglycerides (r = -0.73, P < 0.003) and elevated serum cholesterol (r = -0.56, P < 0.04). In conclusion, modest increases in abdominal adiposity and circulating lipids are associated with abnormal glucose clearance in clinically healthy older men; this may be a precursor to the development of insulin resistance and related complications that arise from prolonged postprandial hyperglycemia.