Genetic mechanisms of knee osteoarthritis: a population-based longitudinal study

To describe the differences in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain, physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9% versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain, suggesting that these factors might have a role in their initiation.     

Genetic mechanisms of knee osteoarthritis: a population-based longitudinal study

To describe the differences in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain, physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9% versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain, suggesting that these factors might have a role in their initiation.     

Lifecourse socioeconomic position and weight change among blacks: The Pitt County study

Objective: The elevated prevalence of obesity among U.S. blacks has been attributed to low socioeconomic position (SEP), despite inconsistent empirical findings. It is unclear whether low SEP at various lifecourse stages differentially influences adulthood BMI and BMI change. Research Methods and Procedures: Among 1167 black adults in the Pitt County Study, we examined independent cross‐sectional and longitudinal associations between SEP, measured in childhood and adulthood, and BMI and 13‐year BMI change. Low vs. high childhood SEP was measured by parental occupation and childhood household deprivation; low vs. high adulthood SEP was assessed by employment status, education, and occupation. Using childhood and adulthood SEP, four lifecourse SEP categories were created: low‐low, low‐high, high‐low, high‐high. Results: We found no consistent associations between SEP and BMI or BMI change among men. Among women, we observed the expected inverse association between SEP and BMI at baseline. In multivariable‐adjusted analyses, socioeconomically advantaged women demonstrated larger 13‐year increases in BMI: skilled vs. unskilled parental occupation (6.1 vs. 4.8 kg/m², p = 0.04); college‐educated vs. < high school (6.2 vs. 4.5 kg/m², p = 0.04); white‐collar vs. blue‐collar job (5.8 vs. 4.8 kg/m², p = 0.05); and high‐high vs. low‐low lifecourse SEP (6.5 vs. 4.6 kg/m², p = 0.02). Discussion: For women in this black cohort, lower SEP predicted earlier onset of obesity; however, low SEP was less predictive of BMI increases over time. Our findings demonstrate complex patterns of association between SEP and BMI change among black women.     

BMI Independently Predicts Younger Age at Hip and Knee Replacement

Obesity has been identified as a risk factor for the development of hip and knee osteoarthritis (OA) and may play a role in exacerbating existing disease. Therefore, we hypothesized that obese patients would present for hip and knee replacement surgery at a younger age than nonobese patients. From our registry, we performed a cross‐sectional study of 841 hip and 804 knee replacement patients. Patients were categorized by BMI ≤25 kg/m², 25.1–29.9 kg/m², 30–34.9 kg/m², and ≥35 kg/m². Linear regression modeling was used to examine the relationship between BMI and age at surgery. Hip and knee replacement patients' mean age at surgery was 7.1 and 7.9 years younger, respectively, if their BMI was ≥35 kg/m² when compared to patients with a BMI ≤25 kg/m² (P = 0.002). BMI was a significant independent (of gender, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, surgeon, and comorbidity) predictor of age at knee replacement (P < 0.05). WOMAC scores were significantly worse preoperatively in patients with a BMI ≥35 kg/m² compared to those with a BMI ≤25 kg/m² (P < 0.05). Our study indicates that obese patients, especially those with a BMI ≥35 kg/m², presented for and underwent joint replacement surgery at a younger age as compared to nonobese patients.     

Lipoprotein Oxidation and Plasma Vitamin E in Nondiabetic Normotensive Obese Patients

Objective: To correlate the susceptibility of low‐(LDL) and very‐low‐density lipoprotein to oxidation in vitro and the concentrations of serum antibodies against malondialdehyde‐modified LDL and plasma vitamin E with the anthropometric and laboratory characteristics of obesity. Research Methods and Procedures: A total of 75 nondiabetic, normotensive obese patients were assigned to one of four groups according to their body mass index (BMI): moderately obese (30 ≤ BMI ≤ 34.9 kg/m², n = 11), severely obese (35 ≤ BMI ≤ 39.9 kg/m², n = 20), morbidly obese (40 ≤ BMI ≤ 50 kg/m², n = 29), and very severely obese (BMI > 50 kg/m², n = 15). Results: The oxidation lag time for LDL from patients with a BMI ≥35 kg/m² was shorter than that for LDL from non‐obese controls (n = 13), whereas very‐low‐density lipoprotein oxidation lag times were not significantly different. The serum antibodies against modified LDL were similar in all groups, whereas the plasma vitamin E concentrations of obese patients were decreased (p ≤ 0.01). There was a negative correlation between LDL oxidation lag time and BMI (r = ?0.35, p = 0.0008), and between plasma vitamin E and BMI (r = ?0.53, p < 0.0001) and waist‐to‐hip ratio (r = ?0.40, p = 0.0003). Discussion: The LDL of nondiabetic, normotensive obese patients is more readily oxidized, and plasma vitamin E concentrations are low. These are both risk factors for coronary heart disease.     

Adapted Changes in Left Ventricular Structure and Function in Severe Uncomplicated Obesity

Objective: A massive amount of fat tissue, as that observed in obese subjects with BMI over 50 kg/m², could affect cardiac morphology and performance, but few data on this issue are available. We sought to evaluate cardiac structure and function in uncomplicated severely obese subjects. Research Methods and Procedures: We studied 55 uncomplicated severely obese patients, 40 women, 15 men, mean age 35.5 ± 10.2 years, BMI 51.2 ± 8.8 kg/m², range 43 to 81 kg/m², with a history of fat excess of at least 10 years, and 55 age‐matched normal‐weight subjects (40 women, 15 men, mean BMI 23.8 ± 1.2 kg/m²) as a control group. Each subject underwent an echocardiogram to evaluate left ventricular (LV) mass and geometry and systolic and diastolic function. Results: Severely obese subjects showed greater LV mass and indexed LV mass than normal‐weight subjects (p < 0.01 for all parameters). Nevertheless, LV mass was appropriate for sex, height^2.7, and stroke work in most (77%) uncomplicated severely obese subjects. In addition, no significant difference in LV mass indices and LV mass appropriateness between obese subjects with BMI ≥ 50 kg/m² and those with BMI ≤ 50 kg/m² was found. Obese subjects also showed higher ejection fraction and midwall shortening than normal‐weight subjects (p = 0.05 and p < 0.01, respectively), suggesting a hyperdynamic systolic function. No significant difference in systolic performance between obese subjects with BMI ≥ 50 kg/m² and those with BMI ≤ 50 kg/m² was seen. Discussion: Our data show that uncomplicated severe obesity, despite the massive fat tissue amount, is associated largely with adapted and appropriate changes in cardiac structure and function.     

Prevalence of Uncomplicated Obesity in an Italian Obese Population

Objective: The existence of healthy obese subjects has been suggested but not clearly reported. We sought to address the prevalence of uncomplicated obesity and adverse risk factors in a large Italian obese population. Research Methods and Procedures: This was a cross‐sectional study of a population of consecutive Italian obese subjects. We studied 681 obese subjects (514 women and 167 men), with a mean age of 41.1 ± 13.9 years (range, 16 to 77 years), mean BMI of 40.2 ± 7.6 kg/m² (range, 30 to 89.8 kg/m²), and a history of obesity for 20.5 ± 7 years (range, 10.5 to 30 years). Anthropometric, metabolic, cardiac, and obesity‐related risk factors were evaluated. Results: The prevalence of uncomplicated subjects was 27.5%, independent of BMI and duration of obesity. The youngest group of obese subjects showed a higher, but not statistically significantly higher, prevalence of uncomplicated obesity. No statistical difference for the prevalence of impaired fasting glucose, glucose intolerance, high triglycerides, high total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol among BMI categories (from mild to extremely severe obesity degree) was found. Obese subjects with BMI >50 kg/m² showed a higher prevalence of high blood pressure only when they were compared with the group with a BMI of 30 to 35 kg/m² (p < 0.01). Obese subjects with BMI >40 kg/m² showed a higher prevalence of hyperinsulinemia than subjects with BMI 30 to 35 kg/m² (p < 0.01). Discussion: This study shows that a substantial part of an Italian obese population has uncomplicated obesity, and the prevalence of adverse risk factors in this sample is unexpectedly low and partially independent of obesity degree. Uncomplicated obesity could represent a well‐defined clinical entity.     

Role of Ghrelin Polymorphisms in Obesity Based on Three Different Studies

Objective: Associations between preproghrelin DNA variants and obesity‐related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. Research Methods and Procedures: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. Results: Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin‐like growth factor‐1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p < 0.05) in SOS subjects whose BMI was ≤25 kg/m² than in those with BMI >25 kg/m² (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%). Discussion: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.     

Sugar‐Added Beverages and Adolescent Weight Change

Objectives : The increase in consumption of sugar‐added beverages over recent decades may be partly responsible for the obesity epidemic among U.S. adolescents. Our aim was to evaluate the relationship between BMI changes and intakes of sugar‐added beverages, milk, fruit juices, and diet soda. Research Methods and Procedures : Our prospective cohort study included >10, 000 boys and girls participating in the U.S. Growing Up Today Study. The participants were 9 to 14 years old in 1996 and completed questionnaires in 1996, 1997, and 1998. We analyzed change in BMI (kilograms per meter squared) over two 1‐year periods among children who completed annual food frequency questionnaires assessing typical past year intakes. We studied beverage intakes during the year corresponding to each BMI change, and in separate models, we studied 1‐year changes in beverage intakes, adjusting for prior year intakes. Models included all beverages simultaneously; further models adjusted for total energy intake. Results : Consumption of sugar‐added beverages was associated with small BMI gains during the corresponding year (boys: +0.03 kg/m² per daily serving, p = 0.04; girls: +0.02 kg/m², p = 0.096). In models not assuming a linear dose‐response trend, girls who drank 1 serving/d of sugar‐added beverages gained more weight (+0.068, p = 0.02) than girls drinking none, as did girls drinking 2 servings/d (+0.09, p = 0.06) or 3+ servings/d (+0.08, p = 0.06). Analyses of year‐to‐year change in beverage intakes provided generally similar findings; boys who increased consumption of sugar‐added beverages from the prior year experienced weight gain (+0.04 kg/m² per additional daily serving, p = 0.01). Children who increased intakes by 2 or more servings/d from the prior year gained weight (boys: +0.14, p = 0.01; girls +0.10, p = 0.046). Further adjusting our models for total energy intake substantially reduced the estimated effects, which were no longer significant. Discussion : Consumption of sugar‐added beverages may contribute to weight gain among adolescents, probably due to their contribution to total energy intake, because adjustment for calories greatly attenuated the estimated associations.     

Ethnic Differences in Visceral Adipose Tissue and Type 2 Diabetes: Filipino,African‐American,and White Women

Objective: To compare ethnic differences in visceral adipose tissue (VAT), assessed by computed tomography, and type 2 diabetes risk among 55‐ to 80‐year‐old Filipino, African‐American, and white women without known cardiovascular disease. Research Methods and Procedures: Subjects were participants in the Rancho Bernardo Study (n = 196), the Filipino Women's Health Study (n = 181), and the Health Assessment Study of African‐American Women (n = 193). Glucose and anthropometric measurements were assessed between 1995 and 2002. Results: African‐American women had significantly higher age‐adjusted BMI (29.7 kg/m²) and waist girth (88.1 cm) compared with Filipino (BMI, 25.5 kg/m²; waist girth, 81.9 cm) or white (BMI: 26.0 kg/m²; waist girth: 80.7 cm) women. However, VAT was significantly higher among Filipino (69.1 cm³) compared with white (62.3 cm³; p = 0.037) or African‐American (57.5 cm³, p < 0.001) women. VAT correlated better with BMI (r = 0.69) and waist (r = 0.77) in whites, compared with Filipino (r = 0.42; r = 0.59) or African‐American (r = 0.50; r = 0.56) women. Age‐adjusted type 2 diabetes prevalence was significantly higher in Filipinas (32.1%) than in white (5.8%) or African‐American (12.1%) women. Filipinas had higher type 2 diabetes risk compared with African Americans [adjusted odds ratio, 2.30; 95% confidence interval (CI), 1.09 to 4.86] or whites (adjusted odds ratio, 7.51; 95% CI, 2.51 to 22.5) after adjusting for age, VAT, exercise, education, and alcohol intake. Discussion: VAT was highest among Filipinas despite similar BMI and waist circumference as whites. BMI and waist circumference were weaker estimates of VAT in Filipino and African‐American women than in whites. Type 2 diabetes prevalence was highest among Filipino women at every level of VAT, but VAT did not explain their elevated type 2 diabetes risk.     

Hypocretin Deficiency in Narcoleptic Humans Is Associated with Abdominal Obesity

Objective: To determine the prevalence of obesity among patients with narcolepsy, to estimate associated long‐term health risks on the basis of waist circumference, and to distinguish the impact of hypocretin deficiency from that of increased daytime sleepiness (i.e., reduced physical activity) on these anthropometric measures. Research Methods and Procedures: A cross‐sectional, case‐control study was conducted. Patients with narcolepsy (n = 138) or idiopathic hypersomnia (IH) (n = 33) were included. Age‐matched, healthy members of the Dutch population (Monitoring Project on Risk Factors for Chronic Diseases and Doetinchem Project; n = 10, 526) were used as controls. BMI and waist circumference were determined. Results: Obesity (BMI ≥ 30 kg/m²) and overweight (BMI 25 to 30 kg/m²) occurred more often among narcolepsy patients [prevalence: 33% (narcoleptics) vs. 12.5% (controls) and 43% (narcoleptics) vs. 36% (controls), respectively; both p < 0.05]. Narcoleptics had a larger waist circumference (mean difference 5 ± 1.4 cm, p < 0.001). The BMI of patients with IH was significantly lower than that of narcolepsy patients (25.6 ± 3.6 vs. 28.5 ± 5.4 kg/m²; p = 0.004). Discussion: Overweight and obesity occur frequently in patients with narcolepsy. Moreover, these patients have an increased waist circumference, indicating excess fat storage in abdominal depots. The fact that patients with IH had a lower BMI than narcoleptics supports the notion that excessive daytime sleepiness (i.e., inactivity) cannot account for excess body fat in narcoleptic patients.     

Effects of joint unloading and reloading on human cartilage morphology and function, muscle cross-sectional areas, and bone density - a quantitative case report

Recent studies have shown that thinning of human cartilage occurs with unloading, but no data are available on the effect of remobilization (after immobilization) on knee joint cartilage status in humans. We examined a 36-year-old patient after 6 weeks of unilateral immobilization. Knee joint cartilage morphology (patella and tibia), patellar cartilage deformation, and thigh muscle cross-sectional areas were assessed with quantitative MR imaging and bone density with peripheral quantitative computed tomography (pQCT) during 24 months of remobilization. The immobilized limb displayed lower muscle cross-sectional areas (MCSA) of the knee extensors (-36%), lower bone density of the femur and tibia (-12/-6%), lower patellar cartilage thickness (-14%), but no side differences of tibial cartilage thickness. During remobilization, side differences decreased to -4% for knee extensor MCSAs, to -6%/-3% for femoral and tibial BMD, and to -8% for patellar cartilage thickness. No change was observed in tibial cartilage. Patellar deformation decreased from 9% to 4% after 15 months. In conclusion, we observed substantial changes of thigh MCSAs, but little (patella) to no (tibia) change in cartilage thickness during remobilization. These preliminary results indicate that human cartilage macro-morphology may be less adaptive to variations of the mechanical loading than muscle and bone.     

Elevated extracellular matrix production and degradation upon bone morphogenetic protein-2 (BMP-2) stimulation point toward a role for BMP-2 in cartilage repair and remodeling

Bone morphogenetic protein-2 (BMP-2) has been proposed as a tool for cartilage repair and as a stimulant of chondrogenesis. In healthy cartilage, BMP-2 is hardly present, whereas it is highly expressed during osteoarthritis. To assess its function in cartilage, BMP-2 was overexpressed in healthy murine knee joints and the effects on proteoglycan (PG) synthesis and degradation were evaluated. Moreover, the contribution of BMP in repairing damage induced by interleukin-1 (IL-1) was investigated. Ad-BMP-2 was injected intra-articularly into murine knee joints, which were isolated 3, 7, and 21 days after injection for histology, immunohistochemistry, and autoradiography. In addition, patellar and tibial cartilage was isolated for RNA isolation or measurement of PG synthesis by means of ³⁵SO₄ ^2- incorporation. To investigate the role for BMP-2 in cartilage repair, cartilage damage was induced by intra-articular injection of IL-1. After 2 days, Ad-BMP-2, Ad-BMP-2 + Ad-gremlin, Ad-gremlin, or a control virus was injected. Whole knee joints were isolated for histology at day 4 or patellae were isolated to measure ³⁵SO₄ ^2- incorporation. BMP-2 stimulated PG synthesis in patellar cartilage on all days and in tibial cartilage on day 21. Aggrecan mRNA expression had increased on all days in patellar cartilage, with the highest increase on day 7. Collagen type II expression showed a similar expression pattern. In tibial cartilage, collagen type II and aggrecan mRNA expression had increased on days 7 and 21. BMP-2 overexpression also induced increased aggrecan degradation in cartilage. VDIPEN staining (indicating matrix metalloproteinase activity) was elevated on day 3 in tibial cartilage and on days 3 and 7 in patellar cartilage, but no longer was by day 21. Increased NITEGE staining (indicating aggrecanase activity) was found on days 7 and 21. In IL-1-damaged patellar cartilage, BMP-2 boosted PG synthesis. Blocking of BMP activity resulted in a decreased PG synthesis compared with IL-1 alone. This decreased PG synthesis was associated with PG depletion in the cartilage. These data show that BMP-2 boosts matrix turnover in intact and IL-damaged cartilage. Moreover, BMP contributes to the intrinsic repair capacity of damaged cartilage. Increased matrix turnover might be functional in replacing matrix molecules in the repair of a damaged cartilage matrix.     

Modeling the Impact of Adjustable Gastric Banding on Survival in Patients with Morbid Obesity

Objective: Morbid obesity is associated with premature death. Adjustable gastric banding may lead to substantial weight loss in patients with morbid obesity. Little is known about the impact of weight loss on survival after adjustable gastric banding. We therefore developed a mathematical model to estimate life expectancy in patients with a body mass index (BMI) ≥40 kg/m² undergoing bariatric surgery. Research Methods and Procedures: We developed a nonhomogeneous Markov chain consisting of five states: the absorbing state (“dead”) and the four recurrent states BMI ≥40 kg/m², BMI 36 to 39 kg/m², BMI 32 to 35 kg/m², and BMI 25 to 31 kg/m². Scenarios of weight loss and age‐ and sex‐dependent risk of death, as well as BMI‐dependent excess mortality were extracted from life tables and published literature. All patients entered the model through the state of BMI ≥40 kg/m². Results: In men aged either 18 or 65 years at the time of surgery, who moved from the state BMI ≥40 kg/m² to the next lower state of BMI 36 to 39 kg/m², life expectancy increased by 3 and 0.7 years, respectively. In women aged either 18 or 65 years at the time of surgery, who moved from the state BMI ≥40 kg/m² to the next lower state BMI 36 to 39 kg/m², life expectancy increased by 4.5 and 2.6 years, respectively. Weight loss to lower BMI strata resulted in further gains of life expectancy in both men and women. Discussion: Within the limitations of the modeling study, adjustable gastric banding in patients with morbid obesity may substantially increase life expectancy.     

Prevalence of Pre‐obesity and Obesity in Urban Adult Mexicans in Comparison with Other Large Surveys

Objective: 1. To estimate the prevalence of pre‐obesity and obesity in a 1992 to 1993 national survey of the Mexican urban adult population. 2. To compare our findings with other national surveys and with data for Mexican Americans. Research Methods and Procedures: The national representative sample of the Mexican urban adult population included 8462 women and 5929 men aged 20 to 69 years from 417 towns of >2500 people. Body mass index (BMI), calculated from measured weight and height, was classified using the World Health Organization categories of underweight (BMI < 18.5 kg/m²), normal weight (BMI 18.5 to 24.9 kg/m²), pre‐obesity (PreOB = BMI 25 to 29.9 kg/m²) and obesity (OB = BMI 30+ kg/m²). Estimates for Mexican Americans were calculated from U.S. survey data. Results: Overall, 38% of the Mexican urban adult population were classified as pre‐obese and 21% as obese. Men had a higher prevalence of pre‐obesity than women did at all ages, but women had higher values of obesity. Both pre‐obesity and obesity increased with age up to the age range brackets of 40 to 49 or 50 to 59 years for both men and women. Both pre‐obesity and obesity prevalence estimates were remarkably similar to data for Mexican Americans from 1982 through 1984. Comparison with other large surveys showed that countries differed more in the prevalence of obesity than of pre‐obesity, leading to differences in the PreOB/OB ratio, and that countries also differed in the gender ratio (female/male) for both pre‐obesity and obesity. Discussion: Pre‐obesity and obesity were high in our population and increased with age. Our approach of characterizing large surveys by PreOB/OB and gender ratios appeared promising.     

Obesity and Quality of Life: Mediating Effects of Pain and Comorbidities

Objective: To estimate the association between body mass index (BMI) and health‐related quality of life (HRQL) and examine whether joint pain and obesity‐related comorbidities mediate the BMI‐HRQL association. Research Methods and Procedures: Population‐based survey data from the 1999 Behavioral Risk Factor Surveillance Survey. Adults (N = 155, 989) were classified according to BMI as underweight (<18.5 kg/m²), desirable weight (18.5 to 24.9 kg/m²), overweight (25 to 29.9 kg/m²), obese class I (30 to 34.9 kg/m²), obese class II (35 to 39.9 kg/m²), and obese class III (≥40 kg/m²). Data including general health status, unhealthy days in the past 30 caused by physical problems and mental problems, and total unhealthy days in the past 30 were collected. Results: After adjusting for age, sex, race, smoking, education, and income, we observed J‐shaped associations between BMI and HRQL. Compared with desirable weight adults, underweight, overweight, and obesity classes I, II, and III adults [odds ratio (OR) = 1.57, 1.19, 1.95, 2.72, and 4.36, respectively] were significantly (p < 0.001) more likely to report fair/poor general health status. For unhealthy days caused by physical problems, the corresponding ORs were 1.51, 1.15, 1.66, 2.27, and 3.61 (p < 0.001). For unhealthy days caused by mental problems, the ORs were 1.35, 1.14 1.43, 1.57, and 2.25 (p < 0.001). For total unhealthy days, the corresponding ORs were 1.27, 1.09, 1.37, 1.73, and 2.46 (p < 0.01). Adding joint pain and obesity‐related comorbidities into models attenuated BMI‐HRQL associations. Discussion: Associations between BMI and HRQL indices were J‐shaped. Joint pain and comorbidities may mediate BMI‐HRQL associations.     

Work‐Related Physical Activity Is Not Associated with Body Mass Index and Obesity

Objective: To analyze the association of work‐related physical activity (WRPA) and leisure‐time physical activity (LTPA) with body mass index (BMI) and obesity in the Spanish adult population aged 20 to 60 years. Research Methods and Procedures: The data were taken from the 1993 Spanish National Health Survey. We analyzed a sample of 12,044 men and women representative of the Spanish population aged 20 to 60 years. BMI and frequency of obesity (BMI ≥ 30 kg/m²) were obtained from self‐reported weight and height. Multiple linear regression and logistic regression models were constructed, adjusting for the main confounding factors. WRPA and LTPA were measured by two questions to classify subjects into four categories of physical activity. Results: Neither mean BMI nor percentage of obesity varied significantly (p > 0.05) by WRPA. Mean BMI was significantly higher (p < 0.01) in those who were inactive in their leisure time (25.90 kg/m² in men and 24.43 kg/m² in women) than in those who reported vigorous activity (24.42 kg/m² and 22.97 kg/m² in men and women, respectively). The odds ration (OR) for obesity decreased with increasing level of LTPA in both men (OR of 0.64 for vigorous activity) and women (OR = 0.68), showing a statistically significant dose‐response relation in both men (for linear trend, p = 0.0021) and women (p = 0.0245). Discussion: These results raise questions about the association between WRPA and obesity and suggest the need to reexamine models of the obesity epidemic that point to automation of the workplace as one of the major explanatory factors.     

Relationship of Insulin Sensitivity and Left Ventricular Mass in Uncomplicated Obesity

Objective: We studied uncomplicated obesity as a model to evaluate the influence of insulin sensitivity per se on left ventricular mass (LVM) and geometry. Research Methods and Procedures: We selected 50 obese subjects (BMI > 30 kg/m²; 38 women and 12 men; mean age, 38.4 ± 10 years; BMI, 36.4 ± 10.5 kg/m²) with normal blood pressure, glucose tolerance, and plasmatic lipid levels. Thirty lean subjects formed the control group. Each subject underwent euglycemic insulin clamp (7 pmol/min per kg) to evaluate whole body glucose use (M index) and echocardiogram to calculate LVM and indexed LVM. Results: Insulin‐resistant obese subjects had higher LVM, LVM/h^2.7, LVM/body surface area, and LVM/fat‐free mass_kg (p = 0.001; p = <0.001 p = 0.001, and p = 0.04, respectively) than obese subjects with normal insulin sensitivity. Multivariate regression analysis showed that M index was the strongest independent correlate of LVM (r² = 0.34; p = 0.03). Discussion: Our findings showed that insulin resistance, in uncomplicated obesity, is associated with an increased LVM and precocious changes of left ventricular geometry, whereas preserved insulin sensitivity is not associated with increased LVM.     

Obesity Increases the Risk of Spontaneous Abortion during Infertility Treatment

Objective: This study examines the relationship between body mass and the risk of spontaneous abortion in a large cohort of patients who received infertility treatment. Research Methods and Procedures: This is a retrospective study using data on pregnancies (n = 2349) achieved after treatment in a tertiary medical center from 1987 to 1999. One pregnancy per subject was included, and the subjects were stratified into five body mass groups based on body mass index (BMI): underweight, <18.5 kg/m²; normal, 18.5 to 24.9 kg/m²; overweight, 25 to 29.9 kg/m²; obese, 30 to 34.9 kg/m²; and very obese, ≥35 kg/m². Logistical regression analysis was used. Results: The overall incidence of spontaneous abortion was 20% (476 of 2349). The effect of BMI on the risk of spontaneous abortion was significant after adjusting for several independent risk factors. Compared with the reference group (BMI 18.5 to 24.9 kg/m²), underweight women had a similar risk of spontaneous abortion, whereas there was progressive increase of risk in overweight, obese, and very obese groups (p < 0.05, p < 0.01, and p < 0.001, respectively). Discussion: Of all known risk factors for spontaneous abortion, the control of obesity has great significance because it is noninvasive, potentially modifiable, possibly amenable to low cost, and self‐manageable by patients. This study established a positive relationship between BMI and the risk of spontaneous abortion in women who became pregnant after assisted reproductive technology treatment.     

Abnormal Signal‐Averaged Electrocardiogram (SAECG) in Obesity

Objective: The occurrence of small high‐frequency electrocardiogram (ECG) potentials (1 to 20 μV) seen at the end of the QRS complex and into the ST segment have been correlated with increased risk for ventricular arrhythmias and sudden cardiac death. Computer‐assisted analysis of these “late potentials” by signal‐averaged electrocardiography (SAECG) has been studied and utilized to predict the likelihood of ventricular arrhythmias in various clinical states. Obesity is associated with significant cardiovascular morbidity and sudden death. Ventricular arrhythmias are postulated causes. We studied the occurrence of late potentials in a randomly selected group of obese patients and healthy volunteers. Research Methods and Procedures: We performed SAECG on 105 subjects. Of these, 62 were obese ambulatory patients with body mass index (BMI) of >30 kg/m², whereas 43 were healthy asymptomatic volunteers with a BMI of <30 kg/m². Patients with a history of clinical heart disease and pulmonary disease, electrolyte abnormalities, recent hospitalizations, or abnormal screening ECG or taking medications known to alter the QRS interval were excluded. At least 250 beats were analyzed with a noise level of <0.50 μV. Criteria of a late potential include QRS duration >114 ms, high‐frequency low amplitude >38 ms, and root‐mean‐square voltage <20 μV. Patients were divided into four subgroups based on BMI values. The prevalence of SAECG abnormalities in each BMI subgroup was studied. We utilized multiple logistic regression analysis to study the effect of obesity, hypertension, and diabetes mellitus on abnormal SAECG results. Results: Compared to age‐ and sex‐matched healthy volunteers with BMI of <30 kg/m², obese patients with BMI of >30 kg/m² had significantly more abnormalities on SAECG (4.6% vs. 55%). In the obese group, the prevalence and number of abnormalities increased with increase in BMI (35% in the BMI 31 to 40 kg/m² subgroup, 86% in the BMI 41 to 50 kg/m² subgroup, and 100% in patients with BMI of >50 kg/m²). Multiple logistic regression analysis shows that BMI is an independent predictor variable of abnormal SAECG results in obese patients (n = 62) with BMI of >30kg/m² as well as in all study subjects (n = 105). BMI also predicts abnormality of each abnormal SAECG criterion in both obese and all subjects. Hypertension was found to influence the QRS duration alone in obese and all subjects. Discussion: Obesity is associated with increased occurrence of abnormal SAECG results. These abnormalities are found both in obese patients with and without hypertension and/or diabetes. Obesity is an independent predictor variable of abnormal SAECG results. A history of hypertension predicts abnormality of QRS duration only.