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Background: A proportion of obese subjects appear metabolically healthy (MHO) but little is known about the natural history of MHO and factors predicting its future conversion to metabolically unhealthy obese (MUO)., Objectives: The aim was to determine prospectively the frequency of conversion of MHO to MUO and the clinical variables that independently predicted this conversion, with a particular focus on the role of body composition., Methods: We identified 85 Japanese Americans with MHO (56 men, 29 women), aged 34-73 years (mean age 49.8 years) who were followed at 2.5, 5 and 10 years after enrollment with measurements of metabolic characteristics, lifestyle and abdominal and thigh fat areas measured by computed tomography. Obesity was defined using the Asian body mass index criterion of ⩾25 kg m(-2). Metabolically healthy was defined as the presence of ⩽2 of 5 metabolic syndrome components proposed by the National Cholesterol Education Program Adult Treatment Panel III, while metabolically unhealthy was defined as ⩾3 components., Results: Over 10 years of follow-up, 55 MHO individuals (64.7%) converted to MUO. Statistically significant univariate predictors of conversion included dyslipidemia, greater insulin resistance and greater visceral abdominal (VAT) and subcutaneous abdominal fat area (SAT). In multivariate analysis, VAT (odds ratio per 1-s.d. increment (95% confidence interval) 2.04 (1.11-3.72), P=0.021), high-density lipoprotein (HDL) cholesterol (0.24 (0.11-0.53), P<0.001), fasting plasma insulin (2.45 (1.07-5.62), P=0.034) and female sex (5.37 (1.14-25.27), P=0.033) were significantly associated with future conversion to MUO. However, SAT was not an independent predictor for future conversion to MUO., Conclusions: In this population, MHO was a transient state, with nearly two-thirds developing MUO over 10 years, with higher conversion to MUO independently associated with VAT, female sex, higher fasting insulin level and lower baseline HDL cholesterol level.

Background: Obesity is thought to be highly prevalent in persons with lower extremity amputations (LEAs) and can impair physical and social functioning., Objective: The aim of this study was to determine the prevalence of weight loss intention, weight loss strategies, dietary patterns, and barriers to making dietary changes, and their associations with body mass index (BMI, kg/m(2)), amputation characteristics, health status, and socioeconomic factors., Methods: We conducted a cross-sectional study (n = 150) using data from a self-administered questionnaire., Results: 43% of participants were obese and 48% were trying to lose weight; 83% of those trying to lose weight reported trying to "eat differently", but only 7% were following a comprehensive weight loss program involving dietary changes, physical activity, and behavioral counseling. 21% of participants reported ≥ 6 barriers to changing their eating habits (e.g., habit, too little money, stress/depression). Obesity was associated with younger age, lower physical health scores, hypertension, arthritis, and diabetes. Compared to those not trying to lose weight, a greater proportion of those trying to lose weight had a BMI ≥ 35 kg/m(2), age <55 years, higher physical and mental health scores, and more frequent consumption of vegetables, beans, chicken, and fish., Conclusions: Though over half of overweight and obese individuals with LEA were trying to lose weight, few reported following a comprehensive program to lose weight, which may indicate an unmet need for services for this group. To be effective, these programs will need to address the complex physical and mental health challenges that many of these individuals face., (Published by Elsevier Inc.)

Background: Although overweight and obesity are less prevalent among active-duty military personnel compared with similar persons not serving in the military, no such differences have been observed between veterans and non-veterans., Objectives: To assess the magnitude of weight changes before, concurrent with and following discharge from the military, relative to weight during service, and to determine the demographic, service-related and psychological characteristics associated with clinically important weight gain among those who were discharged from military service during follow-up., Methods: Eligible Millennium Cohort Study participants (n=38 686) completed the questionnaires approximately every 3 years (2001, 2004 and 2007) that were used to estimate annual weight changes, as well as the percentage experiencing clinically important weight gain, defined as 10%. Analyses were stratified by sex., Results: Weight gain was greatest around the time of discharge from service and in the 3 years before discharge (1.0-1.3 kg per year), while it was nearly half as much during service (0.6-0.7 kg per year) and 3 years after service ended (0.7 kg per year). Consequently, 6-year weight gain was over 2 kg greater in those who were discharged compared with those who remained in the military during follow-up (5.7 vs 3.5 kg in men; 6.3 vs 4.0 kg in women). In those who were discharged, younger age, less education, being overweight at baseline, being in the active-duty component (vs Reserve/National Guard) and having experienced deployment with combat exposures (vs non-deployment) were associated with increased risks of clinically important weight gain., Conclusions: This study provides the first prospectively collected evidence for an increased rate of weight gain around the time of military discharge that may explain previously reported higher rates of obesity in veterans, and identifies characteristics of higher-risk groups. Discharge from military service presents a window of risk and opportunity to prevent unhealthy weight gain in military personnel and veterans.

Aims/hypothesis: Hyperglycaemia is a risk factor for cardiovascular disease (CVD) and all-cause mortality in individuals without diabetes. We investigated: (1) whether the risk of all-cause and CVD mortality extended continuously throughout the range of fasting plasma glucose (FPG), 2 h plasma glucose (2hPG) and HbA(1c) values; and (2) the ability of these measures to improve risk prediction for mortality., Methods: Data on 10,026 people aged >or=25 years without diagnosed diabetes were obtained from the population-based Australian Diabetes, Obesity and Lifestyle study. Between 1999 and 2000, FPG, 2hPG and HbA(1c) were assessed and all-cause (332 deaths) and CVD (88 deaths) mortality were obtained after 7 years., Results: Both 2hPG and HbA(1c) exhibited linear relationships with all-cause and CVD mortality, whereas FPG showed J-shaped relationships. The adjusted HR (95% CI) for all-cause mortality per SD increase was 1.2 (1.1-1.3) for 2hPG and 1.1 (1.0-1.2) for HbA(1c). The HR for FPG <5.1 mmol/l (per SD decrease) was 2.0 (1.3-3.0); for FPG >or=5.1 mmol/l (per SD increase) the HR was 1.1 (1.0-1.2). Corresponding HRs for CVD mortality were 1.2 (1.0-1.4), 1.2 (1.0-1.3), 4.0 (2.1-7.6) and 1.3 (1.1-1.4). The discriminative ability of each measure was similar; no measure substantially improved individual risk identification over traditional risk factors., Conclusions/interpretation: In individuals without diagnosed diabetes, 2hPG and FPG, but not HbA(1c) were significant predictors of all-cause mortality, whereas all measures were significant predictors of CVD mortality. However, these glucose measures did not substantially improve individual risk identification.

Objective: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the beta-3 adrenergic receptor, tumor necrosis factor-alpha, leptin, and leptin receptor (Lepr) in a cohort of Australian women., Research Methods and Procedures: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double-energy X-ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2-year follow-up. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of all polymorphisms., Results: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2-year period were not associated with genetic variation in the beta-3 adrenergic receptor (Trp64Arg), tumor necrosis factor-alpha promoter, or leptin genes in non-obese or obese women., Discussion: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.

Background: Despite having lower average body mass indexes (BMIs) than do whites, Asians are at high risk of type 2 diabetes, possibly because of their greater central adiposity. The criteria for identifying individuals at risk of obesity-related conditions are usually not population specific., Objective: Our goal was to determine whether the National Heart, Lung, and Blood Institute (NHLBI) overweight and obesity guidelines are useful for identifying diabetes risk in Japanese Americans., Design: This was a prospective, cohort study of 466 nondiabetic Japanese Americans [age: 52.2 +/- 0.6 y; BMI (in kg/m(2)): 24.1 +/- 0.2; +/- SEM]. Diabetes status at a 5-y follow-up visit was assessed with an oral-glucose-tolerance test., Results: Among 240 subjects aged < or = 55 y, incident diabetes was strongly associated with overweight (BMI > or = 25) at baseline [relative risk (RR): 22.4; 95% CI: 2.7, 183; adjusted for age, sex, smoking, and family history] and weight gain of > 10 kg since the age of 20 y (adjusted RR: 4.5; 95% CI: 1.4, 14.5). NHLBI definitions of central obesity (waist circumference > or = 88 cm for women and > or = 102 cm for men) were unsuitable for this population because only 15 of 240 subjects met these criteria. A waist circumference greater than or equal to the third tertile was associated with diabetes (adjusted RR: 5.4; 95% CI: 1.7, 17.0). Among 226 subjects aged >55 y, incident diabetes was not associated with BMI, weight gain, or waist circumference., Conclusions: NHLBI definitions are useful for identifying overweight Japanese Americans aged < 55 y who are at high risk of diabetes. Although central adiposity is an important risk factor, the guidelines for waist circumference are insensitive predictors of diabetes risk in this population.

Objective: To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men., Design: Prospective observational study., Subjects: Second-generation Japanese-American males enrolled in a community-based population study., Measurements: At baseline, 110 men received a 75g oral glucose tolerance test (OGTT), and an assessment of body mass index (BMI); visceral adiposity measured as intra-abdominal fat area (IAF) using computed tomography (CT); fasting insulin and C-peptide levels; and total testosterone levels. IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen, thorax and thigh. The total fat (TF) was calculated as the sum of IAF and total subcutaneous fat areas (SCF)., Results: After 7.5y, IAF increased by a mean of 8.0 cm2 (95% CI: 0.8, 15.3). Baseline total testosterone was significantly correlated with change in IAF (r= -0.26, P= 0.006), but not to any appreciable degree with change in BMI, TF, or SCF. In a linear regression model with change in IAF as the dependent variable, baseline testosterone was significantly related to this outcome while adjusting for baseline IAF, SCF, BMI, age, diabetes mellitus status (OGTT by the WHO diagnostic criteria) and fasting C-peptide (regression coefficient for baseline testosterone [nmol/l] = -107.13, P = 0.003)., Conclusions: In this Japanese-American male cohort, lower baseline total testosterone independently predicts an increase in IAF. This would suggest that by predisposing to an increase in visceral adiposity, low levels of testosterone may increase the risk of type 2 diabetes mellitus.

Obesity and Type 2 diabetes are now major public health issues in developed nations and have reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican-Americans, African-Americans, and Australian Aborigines. These groups all show hyperinsulinemia and insulin resistance, which have been demonstrated to be future predictors of Type 2 diabetes and have also been suggested as key factors in the etiology of the Metabolic Syndrome. It is now increasingly recognized that Type 2 diabetes is part of a cluster of cardiovascular disease (CVD) risk factors comprising the Metabolic Syndrome. This group is at very high risk of atherosclerosis because each of the risk factors in the Metabolic Syndrome cluster in its own right is an important CVD risk factor. They also contribute cumulatively to atherosclerosis. A key strategy in reducing macrovascular disease lies in the better understanding of the Metabolic Syndrome--glucose intolerance, hypertension, hyperlipidemia, and central obesity. Although it has been suggested that hyperinsulinemia/insulin resistance is the central etiological factor for the Metabolic Syndrome, epidemiological data do not support the idea that this can account for all of the cluster abnormalities. We have animal and human data suggesting that hyperleptinemia rather than, or synergistically with, hyperinsulinemia may play a central role in the genesis of the CVD risk factor cluster that constitutes the syndrome. Studies in Psammomys obesus (the Israeli sand rat) suggest hyperinsulinemia/insulin resistance is an early metabolic lesion in the development of obesity and Type 2 diabetes. This animal also develops other features of the Metabolic Syndrome, making it an excellent model to investigate etiology. Psammomys, when placed on an ad libitum laboratory diet, develops hyperinsulinemia, insulin resistance, impaired glucose tolerance, diabetes, and dyslipidemia. It also develops hyperleptinemia and leptin insensitivity, and hyperleptinemia is correlated with insulin resistance independent of changes in body weight. It is likely that a similar sequence occurs in the transition from the prediabetic state to Type 2 diabetes in humans. More recently, other potential players in the etiology of the Metabolic Syndrome have been suggested including endothelial dysfunction and acetylation-stimulating protein (ASP). It has been suggested that endothelial dysfunction may be an antecedent for both Type 2 diabetes and the Metabolic Syndrome. In addition, ASP is a serious new candidate for an important role in insulin resistance. The ASP pathway plays a critical role in fatty acid metabolism and storage, and it has been suggested that ineffective storage of fatty acids by adipocytes due to a defect in the ASP pathway may lead to insulin resistance and Type 2 diabetes.

Objective: Determine the prevalence of hypertension in Alaska Natives and evaluate risk factors., Design: Population-based univariate and multivariate analysis of blood pressure in 1124 Alaska Natives over 20 years of age., Results: The sample had mean: age 45 years, body mass index 27, systolic pressure 123 mmHg and diastolic pressure 73 mmHg. The age-adjusted rate of hypertension > or = 160/95 mmHg was 9.1% and 6.8% among Athabascan Indians and Yup'ik Eskimos, respectively. After controlling for age and sex there was significantly more hypertension among Athabascan Indians (OR = 1.53, CI = 1.07-2.2, p = 0.019) compared to Yup'ik Eskimos. Race was significantly associated with blood pressure > or = 140/90 when controlled for age and overweight (p = 0.01, OR = 0.78, CI = 0.69-0.95). The presence of hypertension was significantly associated with the following: intake of non-indigenous food (p = 0.01); mechanized activities (p = 0.01); and glucose intolerance in both women (p = 0.043) and men (p = 0.001). Multiple regression analysis revealed age (OR = 1.06, CI = 1.05-1.08) and overweight in both men (OR = 3.02, CI = 1.85-4.93) and women (OR = 2.76, CI = 1.81-4.19) to be significantly associated with BP > or = 140/90., Conclusion: Hypertension is no longer rare in Alaska Natives and is associated with overweight, non-indigenous diet, mechanized activities, and glucose intolerance.

Objective: Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM., Research Design and Methods: We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (Si) was also determined in a subset of nondiabetic subjects (n = 38)., Results: Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to Si (r = -0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and Si was not. Conversely, the relationship between plasma leptin and BMI was independent of Si, whereas that between insulin and BMI was dependent on Si. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observed in nondiabetic subjects., Conclusions: We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM does not influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to be different.

Insulin resistance and hyperinsulinemia occur more frequently in subjects with greater visceral adiposity, but it is not known whether these metabolic abnormalities precede or follow visceral fat accumulation. We prospectively studied the development of visceral adiposity in relation to fasting and stimulated insulin and C-peptide levels. We followed 137 nondiabetic, second-generation Japanese-American men for changes in visceral adiposity over 5 years. Intra-abdominal fat (IAF) area (square centimeters) was measured at the umbilicus by computed tomography at baseline and after 5 years. Plasma insulin and C-peptide levels were measured after an overnight fast and during an oral glucose tolerance test. Beta-cell function was measured by the insulin secretion ratio (30-0 min plasma insulin difference)/(30-0 min plasma glucose difference). After adjustment for baseline IAF in multiple linear regression models, baseline fasting insulin (coefficient = 0.241, P = 0.048) and C-peptide (coefficient = 38.538, P < 0.001) levels were positively correlated, while the baseline insulin secretion ratio was negatively correlated with IAF change (coefficient = -0.099, P = 0.027). With IAF difference coded as a dichotomous variable (> 0 cm2 vs. < or = 0 cm2), the highest versus lowest tertile of baseline fasting insulin (odds ratio [OR] = 3.0, 95% CI 1.0-9.7) and fasting C-peptide (OR = 8.1, 95% CI 2.4-26.8) levels and the lowest versus highest tertile of the insulin secretion ratio (OR = 3.3, 95% CI 1.0-10.0) were associated with higher odds of IAF gain. Greater insulin resistance and reduced insulin secretion precede visceral fat accumulation in nondiabetic Japanese-American men.

The adipocyte hormone, leptin (OB protein), is proposed to be an "adiposity signal" that acts in the brain to lower food intake and adiposity. As plasma leptin levels are elevated in most overweight individuals, obesity may be associated with leptin resistance. To investigate the mechanisms underlying brain leptin uptake and to determine whether reduced uptake may contribute to leptin resistance, we measured immunoreactive leptin levels in plasma and cerebrospinal fluid (CSF) of 53 human subjects. Leptin concentrations in CSF were strongly correlated to the plasma level in a nonlinear manner (r = 0.92; p = 0.0001). Like levels in plasma, CSF leptin levels were correlated to body mass index (r = 0.43; p = 0.001), demonstrating that plasma leptin enters human cerebrospinal fluid in proportion to body adiposity. However, the efficiency of this uptake (measured as the CSF:plasma leptin ratio) was lower among those in the highest as compared with the lowest plasma leptin quintile (5.4-fold difference). We hypothesize that a saturable mechanism mediates CSF leptin transport, and that reduced efficiency of brain leptin delivery among obese individuals with high plasma leptin levels results in apparent leptin resistance.

There is good evidence that central (visceral) adiposity is important in the development of the insulin resistance or metabolic syndrome (obesity, hyperinsulinemia, dyslipidemia, glucose intolerance, hypertension, and coronary heart disease). It is proposed that some non-Caucasian populations are especially susceptible to development of this syndrome, and that lifestyle changes may play important etiologic roles. We postulate that this is due to the presence in these populations of a genetic predisposition to weight gain, perhaps related to a "thrifty" genotype, leading to the concentration of weight gain in visceral fat depots, when there is exposure to conditions associated with westernization.

Objective: To investigate frequency of food intake, body weight, and glucose intolerance in Alaska Natives., Design: Height, weight, and random blood glucose levels were measured and a frequency-of-food-intake questionnaire was obtained. This questionnaire classified persons as consumers of indigenous foods or nonindigenous foods within three food groups. Those with a random blood glucose measurement > or = 6.72 mmol/L received an oral glucose tolerance test., Setting: Community screening in 15 villages in Alaska., Subjects: Nutrition screenings were done for 1,124 Alaska Native residents aged 20 years or older. An oral glucose tolerance test was done for 202 subjects., Outcomes Measured: Subjects were classified as consumers of indigenous or nonindigenous foods within three food groups. A diagnosis of non-insulin-dependent diabetes mellitus (NIDDM) was made on the basis of World Health Organization criteria. A determination of overweight was made on the basis of National Center for Health Statistics criteria., Statistical Analysis: A chi 2 test with Yates correction, t test, and linear regression, with two-sided P values., Results: Athabascan Indians had twice the rate of NIDDM as Yup'ik Eskimos with significantly higher frequency of nonindigenous food intake, plus lower frequency of indigenous carbohydrate and fat intake. Subjects < or = 30 years old consumed significantly more nonindigenous protein and fat and low-nutrient-density carbohydrates than those > or = 60 years old. Persons who had glucose intolerance reported significantly greater consumption of nonindigenous protein and less seal oil. Incidence of overweight was significantly higher than was found 25 years ago. Participants with glucose intolerance were significantly more overweight than others., Conclusion: A pattern of increased frequency of nonindigenous protein, low-nutrient-density carbohydrate, and fat intake with less indigenous carbohydrate and fat consumption was found in subjects < or = 30 years old and in association with the higher rate of NIDDM found in the Athabascan Indians. Persons with glucose intolerance were significantly more overweight than others., Applications: Although the nutritional value of indigenous foods for reducing disease risk should be promoted, nutrition education, especially among young adults, should also include building skills to select and prepare nonindigenous foods to attain a healthful diet. Although snacking is a concern, dietary fat was the most significant factor in obesity and NIDDM.

Obesity is associated with noninsulin-dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD), and these interactions have usually been related to changes in immunoreactive insulin (IRI) levels. A role of proinsulin (PI) in this association has been suggested. We, therefore, examined IRI, PI, and true insulin levels and the PI/IRI ratio by glucose tolerance or CHD status in a cross-sectional study of 170 Japanese-American men (45-74 yr old) in whom 2 measures of adiposity (body mass index and intraabdominal fat) were made to assess potential associations in this population with a high prevalence of both NIDDM and CHD. Subjects were classified as having normal glucose tolerance (n = 58), impaired glucose tolerance (IGT; n = 55), or NIDDM (n = 57) or were classified by CHD status (without CHD, n = 127; with CHD, n = 43). A positive linear relationship existed between obesity, determined either as the body mass index or intraabdominal fat, and IRI, PI, and true insulin, but not the PI/IRI ratio. In the NIDDM subjects, PI levels were disproportionately greater than those in subjects with normal glucose tolerance or IGT, so the PI/IRI ratio was significantly greater in the NIDDM group [mean (95% confidence interval): normal glucose tolerance, 11.8% (range, 10.4-13.5); IGT, 12.8% (range, 10.8-15.1); NIDDM, 19.2% (range, 15.4-24.0); P = 0.0002] even when adjusted for obesity (P = 0.0004). In subjects with CHD compared to subjects without CHD, IRI (P = 0.0026) and true insulin levels (P = 0.0043) were increased, but PI levels were not. However, these differences were not present after adjustment for obesity. In contrast, when intraabdominal fat was adjusted for IRI or true insulin, a significant effect of intraabdominal fat on CHD risk was maintained (P = 0.045 and P = 0.029, respectively), suggesting that another factor(s) associated with central obesity may be involved in CHD risk. Thus, in Japanese-American men, elevated PI and PI/IRI ratio are markers of B-cell dysfunction, and these are not the result of obesity. An elevated true insulin level is present in those with CHD, but this appears to be the result of obesity. In contrast, central adiposity confers an additional risk for CHD independent of insulin.

Obesity is a major health problem in the United States and a growing concern among members of the military. Posttraumatic stress disorder (PTSD) has been associated with overweight and obesity and may increase the risk of those conditions among military service members. Disordered eating behaviors have also been associated with PTSD and weight gain. However, eating disorders remain understudied in military samples. We investigated longitudinal associations among PTSD, disordered eating, and weight gain in the Millennium Cohort Study, which includes a nationally representative sample of male (n = 27,741) and female (n = 6,196) service members. PTSD at baseline (time 1; 2001-2003) was associated with disordered eating behaviors at time 2 (2004-2006), as well as weight change from time 2 to time 3 (2007-2008). Structural equation modeling results revealed that the association between PTSD and weight change from time 2 to time 3 was mediated by disordered eating symptoms. The association between PTSD and weight gain resulting from compensatory behaviors (vomiting, laxative use, fasting, overexercise) was significant for white participants only and for men but not women. PTSD was both directly and indirectly (through disordered eating) associated with weight change. These results highlight potentially important demographic differences in these associations and emphasize the need for further investigation of eating disorders in military service members. [ABSTRACT FROM AUTHOR]

Objective: We conducted a prospective study among Japanese Americans of diabetes incidence in relation to visceral and regional adiposity, fasting insulin and C-peptide, and a measure of insulin secretion, because little prospective data exist on these associations.Research Design and Methods: Baseline variables included plasma glucose, C-peptide, and insulin measured after an overnight fast and 30 and 120 min after a 75-g oral glucose tolerance test; abdominal, thoracic, and thigh fat areas by computed tomography (CT); BMI (kg/m2); and insulin secretion (incremental insulin response [IIR]).Results: Study subjects included 290 second-generation (nisei) and 230 third-generation (sansei) Japanese Americans without diabetes, of whom 65 and 13, respectively, developed diabetes. Among nisei, significant predictors of diabetes risk for a 1 SD increase in continuous variables included intra-abdominal fat area (IAFA) (odds ratio, 95% CI) (1.6, 1.1-2.3), fasting plasma C-peptide (1.4, 1.1-1.8), and the IIR (0.5, 0.3-0.9) after adjusting for age, sex, impaired glucose tolerance, family diabetes history, and CT-measured fat areas other than intra-abdominal. Intra-abdominal fat area remained a significant predictor of diabetes incidence even after adjustment for BMI, total body fat area, and subcutaneous fat area, although no measure of regional or total adiposity was related to development of diabetes. Among sansei, all adiposity measures were related to diabetes incidence, but, in adjusted models, only IAFA remained significantly associated with higher risk (2.7, 1.4-5.4, BMI-adjusted).Conclusions: Greater visceral adiposity precedes the development of type 2 diabetes in Japanese Americans and demonstrates an effect independent of fasting insulin, insulin secretion, glycemia, total and regional adiposity, and family history of diabetes. [ABSTRACT FROM AUTHOR]

Although the hormone leptin seems to play a role in ensuring the maintenance of adequate energy stores and thereby protects against starvation, its role in the regulation of body weight and adiposity under normal circumstances is unclear. Overweight individuals have markedly elevated circulating leptin levels, suggesting that leptin's effect on food intake and thermogenesis is diminished or absent in obesity. Recent evidence, though, indicates that weight gain in Pima Indians is associated with relatively decreased levels of the hormone. Because it is important to understand whether a deficiency in circulating leptin contributes to the development of obesity, we sought to determine whether there is a relationship between leptin levels and subsequent changes in adiposity in a more typical population. We compared baseline plasma leptin concentrations to changes over 5 years in body weight, BMI, and computed tomography-determined total fat in 492 second- and third-generation Japanese Americans. Subjects were of 100% Japanese ancestry; male subjects had a mean BMI at baseline of 25.4 kg/m2 and a mean age of 54 years; female subjects had a mean BMI of 23.1 kg/m2 and a mean age of 53 years. Changes in weight (men: r = 0.17, P < 0.05; women: r = 0.20, P < 0.05), BMI (men: r = 0.17, P < 0.05; women: r = 0.18, P < 0.05), and total fat (men: r = 0.19, P < 0.05; women: r = 0.20, P < 0.01) were positively correlated with baseline leptin levels adjusted for baseline adiposity, fasting insulin, and age. In Japanese Americans, then, relatively increased leptin levels are associated with greater subsequent gains in weight and adiposity. We concluded that in this population, fat accumulation is associated not with leptin deficiency but possibly with leptin resistance and is preceded by increased leptin levels. [ABSTRACT FROM AUTHOR]