Infrapatellar branch of the saphenous nerve lesion following tibial nailing: it is possible to avoid it?

BACKGROUND: Iatrogenic injury to the infrapatellar branches of saphenous nerve is a common complication following tibial nailing. This lesion seems to be directly related to the surgical approach adopted for nail insertion. The aim of the present study was to systematically review the current literature in order to assess the eventual superiority of one surgical approach for tibial nailing over the others in limiting the neurological impairment related to infrapatellar branch injury. MATERIALS AND METHODS: The available literature was systematically screened searching papers dealing with iatrogenic injury to the infrapatellar branch of saphenous nerve after intramedullary tibial nailing. The terms "Saphenous" and "Infrapatellar branch" were used in combination with "intramedullary nailing" and "tibial fractures", supplying no limits regarding the publication year. Only publications in English were considered. Case reports, technical notes, instructional course, literature reviews, biomechanical and/ or in vitro studies were all excluded. Coleman methodological score was performed in all the retained articles. RESULTS: Four articles matched the inclusion criteria. There were one original article and three retrospective study. Hypoesthesia and a larger extension of the area of sensory-loss were more frequently observed after vertical incision approach in three out of four articles. A trend towards a lower rate of iatrogenic nerve damage using a transverse incision was found in the remaining one, without any statistical significance. CONCLUSIONS: In order to avoid infrapatellar nerve lesion, horizontal or oblique incisions or percutaneous approaches should be favored, although in some cases a longitudinal incision is required. Limited-extension incisions could minimize the risk and the incidence of this complication.

Visceral abdominal fat accumulation predicts the conversion of metabolically healthy obese subjects to an unhealthy phenotype.

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.

Antibodies against the second extracellular loop of ß1-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat.

Autoantibodies against ß1-adrenoceptors (ß1-ARs) have been detected in the serum of patients with various cardiac diseases; however, the pathological impact of these autoantibodies (ß1-AABs) has only been evaluated in cardiac tissue. The purpose of the present study was to evaluate whether ß1-AABs have deleterious effects on vascular reactivity in rats. An enzyme-linked immunosorbent assay was used to detect ß1-AABs in sera from immunized rats over a period of 1-3 months using the peptidic sequence of the second extracellular loop of human ß1-AR. Functional studies were performed in thoracic aortic (TA) and small mesenteric artery (SMA) rings from immunized rats. Following pre-contraction with phenylephrine (0.3 µM and 3 µM for the TA and SMA respectively), cumulative concentration-response curves (CCRCs) to various ß-AR agonists (isoproterenol, dobutamine, salbutamol, SR 58611A), acetylcholine, A23187, and sodium nitroprusside (SNP) were then plotted. The relaxations induced by dobutamine, SR 58611A, and acetylcholine were significantly impaired, but salbutamol-induced relaxations were not affected, in both vessels from immunized rats. A significant impairment of isoproterenol-induced relaxation was only observed in SMA. CCRCs to SNP were not modified in either of the vessels. A23187-induced relaxation was impaired in immunized rats. Following pretreatment with L-arginine, vasorelaxation to acetylcholine and SR 58611A was restored in immunized rats. This study demonstrates that immunization against the second extracellular loop of ß1-ARs has a deleterious impact on vasorelaxations in the TA and SMA of rats, involving alterations in endothelium-dependent NO signaling pathways.

Results in treatment of distal femur fractures using polyaxial locking plate.

Indications and techniques of locked plate fixation for the treatment of challenging fractures continue to evolve. As design variant of classic locked plates, the polyaxial locked plate has the ability to alter the screw angle and thereby, enhance fracture fixation. The aim of this observational study was to evaluate clinical and radiographic results in 89 patients with 90 fractures of the distal femur treated, between June 2006 and November 2011, with such a polyaxial locked plating system (Polyax™ Locked Plating System, DePuy, Warsaw, IN, USA). Seventy-seven fractures formed the report of this study. These cases were followed up until complete fracture healing or for a mean time of 77 weeks. At the time of last follow-up, 58 of 77 fractures (75.3 %) progressed to union without complication and radiographic healing occurred at a mean time of 16.3 weeks. Complications occurred in ten fractures that did not affect the healing and in nine fractures that showed delayed or non-union. The mean American Knee Society Score at the time of final follow-up was 83 for the Knee Score and 71.1 for the Functional Score. In conclusion, there is a high union rate for complex distal femoral fractures associated with a good clinical outcome in this series.

Single level cervical fusion by an anterior approach using autologous bone graft influences the adjacent levels degenerative changes: clinical and radiographic results at 10-year minimum follow-up.

INTRODUCTION: Cervical degenerative pathology can produce pain and disability and, in case of failure of conservative treatment surgery is indicated. MATERIALS AND METHODS: 107 patients affected by single level cervical degenerative pathology were surgically treated by Cloward procedure. On radiographs, the sagittal segmental alignment (SSA) of the affected level and sagittal alignment of the cervical spine were measured. RESULTS: Preoperatively, mean SSA was 0.6° and at the last follow-up 1.8°. In particular, adjacent-level degeneration occurred more frequently in Group A than in Group B. CONCLUSION: Lordotic SSA angle can be considered a protective factor against adjacent-level degeneration.

Arm length is associated with type 2 diabetes mellitus in Japanese-Americans.

AIMS/HYPOTHESIS: The aim of the study was to examine the association of type 2 diabetes mellitus with arm length as a marker for early life environment and development. METHODS: This was a cross-sectional analysis of 658 second- and third-generation Japanese-Americans (349 men and 309 women). Different arm length (total, upper and forearm length) and leg length (total and lower leg length) measurements were performed. Type 2 diabetes was defined by the use of hypoglycaemic medication, fasting plasma glucose (FPG) ≥ 7 mmol/l or glucose at 2 h ≥ 11.1 mmol/l during an OGTT. Persons meeting the criteria for impaired glucose tolerance were excluded from these analyses (FPG <7 mmol/l and 2 h glucose during an OGGT <11.1 but ≥ 7.8 mmol/l). Multivariable logistic regression was used to estimate associations between prevalence of diabetes and limb length while adjusting for possible confounders. RESULTS: A total of 145 individuals had diabetes. On univariate analysis, arm and leg length were not associated with diabetes. After adjustment for age, sex, computed tomography-measured intra-abdominal fat area, height, weight, smoking status and family history of diabetes, total arm length and upper arm length were inversely related to diabetes (OR for a 1 SD increase 0.49, 95% CI 0.29, 0.84 for total arm length, and OR 0.56, 95% CI 0.36, 0.87 for upper arm length). Forearm length, height and leg length were not associated with diabetes after adjustment for confounding variables. CONCLUSIONS/INTERPRETATION: Our findings of associations between arm lengths and prevalence of type 2 diabetes supports a role for factors that determine bone growth or their correlates in the development of this condition.

Subcutaneous thigh fat area is unrelated to risk of type 2 diabetes in a prospective study of Japanese Americans.

AIMS/HYPOTHESIS: Cross-sectional research has reported a negative association between subcutaneous thigh fat (STF) and type 2 diabetes prevalence but no prospective research on this association exists using direct measurements of STF obtained from imaging studies while adjusting for other fat depots. We studied the independent associations of intra-abdominal fat (IAF), subcutaneous abdominal fat (SAF) and STF with future risk of diabetes. METHODS: We prospectively followed 489 non-diabetic Japanese Americans (BMI 25.0-29.9 kg/m(2) 32.7%, ≥30.0 kg/m(2) 5.4%) over 10 years for the development of diabetes defined by use of hypoglycaemic medication or a fasting plasma glucose ≥7.0 mmol/l or 2 h ≥11.1 mmol/l during an OGTT. STF, SAF and IAF area were measured by computed tomography scan and mid-thigh circumference (TC) by tape measure at baseline. RESULTS: Over 10 years, 103 people developed diabetes. STF area was not independently associated with the odds of developing diabetes in a univariate or multiple logistic regression model (OR for a 1 SD increase 0.8 [95% CI 0.5, 1.2]) adjusted for age, sex, BMI, IAF and SAF. The only fat depot associated with diabetes odds in this model was IAF. TC was borderline significantly associated with a lower odds of developing diabetes (0.7 [95% CI 0.5, 1.0], p = 0.052). CONCLUSIONS/INTERPRETATION: Similar to other research, TC was negatively associated with diabetes risk, whereas STF was not, arguing that the negative association between TC and diabetes observed in other research is not due to STF mass. IAF area emerged as the only measured fat depot that was independently associated with type 2 diabetes risk.

Greater hand-grip strength predicts a lower risk of developing type 2 diabetes over 10 years in leaner Japanese Americans.

AIMS: Much is known about body composition and type 2 diabetes risk but less about body function such as strength. We assessed whether hand-grip strength predicted incident diabetes. METHODS: We followed 394 nondiabetic Japanese-American subjects (mean age 51.9) for the development of diabetes. We fit a logistic regression model to examine the association between hand-grip strength at baseline and type 2 diabetes risk over 10 years, adjusted for age, sex, and family history. RESULTS: A statistically significant (p = 0.008) and negative (coefficient -0.208) association was observed between hand-grip strength and diabetes risk that diminished at higher BMI levels. Adjusted ORs for a 10-pound hand-grip strength increase with BMI set at the 25th, 50th or 75th percentiles were 0.68, 0.79, and 0.98, respectively. CONCLUSIONS: Among leaner individuals, greater hand-grip strength was associated with lower risk of type 2 diabetes, suggesting it may be a useful marker of risk in this population.

Intra-abdominal fat accumulation predicts the development of the metabolic syndrome in non-diabetic Japanese-Americans.

AIMS/HYPOTHESIS: Intra-abdominal fat (IAF) is an important risk factor for CHD and type 2 diabetes, and in cross-sectional studies is associated with the metabolic syndrome (MetS). Our aim was to determine whether IAF accumulation predicts the future development of MetS in non-diabetic Japanese-Americans. SUBJECTS AND METHODS: We conducted a prospective study of 457 Japanese-American men and women (mean+/-SD: age 51.5 +/- 12.0 years, BMI 23.9 +/- 3.1 kg/m(2)) without diabetes or MetS at baseline. Of these, 408 completed a 5-year follow-up and 366 completed a 10-year follow-up. BMI, waist circumference, IAF and subcutaneous fat (SCF) areas by computed tomography, blood pressure, fasting plasma glucose, insulin, triacylglycerol and HDL-cholesterol were measured at baseline and at 5- and 10-year follow-up. MetS was defined using National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Incidence of MetS was 15.3% at 5 years and 17.8% at 10 years. A change of 1 SD in IAF area was associated with a 2.1-fold increase in the odds of MetS at 10 years (odds ratio = 2.08, 95% CI 1.41-3.07) after adjusting for age, sex, baseline IAF and the presence of each individual MetS criteria at baseline. This association was independent of changes in fasting insulin and SCF areas. CONCLUSIONS/INTERPRETATION: We conclude that IAF accumulation over time independently predicts the development of MetS and thus may play an important role in the development of MetS in Japanese-Americans.

Heritability of C-reactive protein and association with apolipoprotein E genotypes in Japanese Americans.

Numerous studies have demonstrated that increased C-reactive protein (CRP) levels predict coronary heart disease, stroke, peripheral vascular disease, and diabetes, and are associated with features of the metabolic syndrome. Only three previous studies have investigated the heritability of CRP levels, primarily in samples of Caucasian families. The purpose of the present study was to estimate the magnitude of genetic influences on CRP levels, and to examine potential associations between variation in the APOE gene and CRP levels, using a sample of 562 individual Japanese Americans from 68 extended kindreds. In general, correlation coefficients between first-degree relatives for CRP were approximately 0.2, and spouse correlations did not differ from zero, consistent with genetic influences. Heritability estimates were approximately 0.3 (p < 0.01), even with adjustment for factors known to influence CRP levels. A significant relationship was seen between unadjusted CRP levels and APOE genotypes (p = 0.02), with the highest mean CRP level among epsilon2 carriers (1.20 mg/L), and nearly the same mean levels among epsilon3/epsilon3 subjects and epsilon4 carriers (0.72 and 0.74 mg/L, respectively). However, this relationship was diminished with adjustment for covariates (p = 0.07). These results demonstrate the presence of both genetic and environmental effects on CRP levels among Asian Americans, and additional studies are needed to determine if the APOE gene contributes to these genetic influences.

Standard definitions of overweight and central adiposity for determining diabetes risk in Japanese Americans.

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.

Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose.

OBJECTIVE: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.

Type 2 diabetes and the metabolic syndrome in Japanese Americans.

Japanese Americans have experienced a higher prevalence of type 2 diabetes than in Japan. Research conducted in Seattle suggests that lifestyle factors associated with 'westernization' play a role in bringing out this susceptibility to diabetes. These lifestyle factors include consumption of a diet higher in saturated fat and reduced physical activity. A consequence of this is the development of central (visceral) adiposity, insulin resistance, and other features associated with this insulin resistance metabolic syndrome, such as dyslipidemia (high triglycerides, low HDL-cholesterol, and small and dense LDL particles), hypertension, and coronary heart disease. We have postulated that the superimposition of insulin resistance upon a genetic background of reduced beta-cell reserve results in hyperglycemia and diabetes among Japanese Americans. This article reviews evidence that support this view.

Analysis of birth intervals in a non-contracepting Indian population: an evolutionary ecological approach.

Reproductive strategies are related to ecological constraints. This paper examines data on early birth spacing in a scheduled caste, Bengali-speaking, non-contracepting population of the Karimganj district of southern Assam, India, taking an evolutionary ecological perspective. It is found that on average birth intervals closed by boy-boy are longer than those closed by girl-girl. Birth spacing tends to be longer among upper-income and Craftsman sub-caste mothers. The presence of a 'grandmother' in the household shortens spacing. These findings are compatible with an evolutionary-based reproductive decision-making process.

Visceral adiposity and risk of type 2 diabetes: a prospective study among Japanese Americans.

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.

Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men.

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.

Preventing diabetes--applying pathophysiological and epidemiological evidence.

This is a review of research carried out in Japanese Americans that points towards possible approaches to prevention of type 2 diabetes mellitus. The natural history of type 2 diabetes usually includes both insulin resistance and beta-cell dysfunction. Insulin secretion may compensate for insulin resistance. Alternatively, enhanced insulin sensitivity may mask an insulin secretory defect. Epidemiological data support the view that in the vast majority of cases of type 2 diabetes, insulin resistance is essential to the pathogenesis of hyperglycemia. Increased diabetes prevalence as ethnic groups migrate to more urban or westernized regions has been attributed to increased occurrence of insulin resistance. Research among Japanese Americans in Seattle, Washington, showed a higher prevalence of type 2 diabetes than in Japan, which suggested that factors associated with 'westernization' might be playing a role in bringing out underlying susceptibility to diabetes. Our research has shown that these impressions were correct and that the abnormalities that characterize the metabolic syndrome play a significant role. Due to increased intra-abdominal fat deposition, Japanese Americans were likely to be 'metabolically obese' despite relatively normal BMI. A diet higher in animal fat and lower levels of physical activity were risk factors leading to increased intra-abdominal fat deposition, insulin resistance, and diabetes. Information from epidemiological studies such as these may be used to determine whether diabetes may be prevented through changes in lifestyle or application of specific therapies targeted towards identified metabolic abnormalities.

Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study.

OBJECTIVE: To identify risk factors for incident coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: A total of 175 Japanese-American men without CHD were followed for up to 10 years. Baseline variables were blood pressure, weight, BMI, fat areas by computed tomography, skinfold thicknesses, abdominal circumference, plasma insulin, C-peptide, cholesterol, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, and HDL3 cholesterol, triglycerides, apoproteins A1 and B, and diagnosis of diabetes and hypertension. CHD was diagnosed by electrocardiogram and clinical events. Logistic regression was used to estimate odds ratio. RESULTS: There were 50 incident cases of CHD. Using univariate logistic regression analysis, significant risk factors were intra-abdominal fat (P = 0.0090), fasting glucose (P = 0.0002), 2-h glucose (P = 0.0008), fasting HDL cholesterol (P = 0.0086), fasting HDL2 cholesterol (P = 0.030), fasting HDL3 cholesterol (P = 0.018), fasting triglycerides (P = 0.013), systolic (P = 0.0007) and diastolic blood pressure (P = 0.0002), and presence of diabetes (P = 0.0023). Multiple logistic regression models adjusted for BMI and age showed that intra-abdominal fat accounted for the effects of HDL cholesterol or triglycerides. In a multiple logistic regression model that included intra-abdominal fat, all systolic blood pressure and fasting glucose were significant. Substituting diastolic blood pressure for systolic blood pressure and 2-h glucose or diabetes status for fasting glucose produced similar results. CONCLUSIONS: Visceral adiposity, blood pressure, and plasma glucose are important independent risk factors for incident CHD in this population of diabetic and nondiabetic Japanese-American men.

Reduced amylin release is a characteristic of impaired glucose tolerance and type 2 diabetes in Japanese Americans.

Islet amyloid is a characteristic feature of type 2 diabetes. Its major component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disproportionate release of amylin may explain the propensity for amyloid deposition in type 2 diabetes, we measured plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucose tolerance (NGT; n=56), impaired glucose tolerance (IGT; n=10), and type 2 diabetes (n=28) as defined by World Health Organization criteria. The incremental increase in ALI, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUC) during the 2 h of the oral glucose tolerance test. As expected, plasma glucose concentrations at both fasting (NGT, 5.0+/-0.4; IGT, 5.5+/-0.1; type 2 diabetes, 6.2+/-0.3 mmol/l; P < 0.0001) and 2 h (NGT, 6.7+/-0.1; IGT, 9.4+/-0.3; type 2 diabetes, 13.2 +/-0.5 mmol/l; P < 0.0001) were elevated in individuals with IGT and type 2 diabetes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with reduced glucose tolerance, as reflected in the deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4 pmol/l; P < 0.0001) and deltaALI/deltaG (NGT, 2.6+/-0.2; IGT, 1.8+/-0.3; type 2 diabetes, 1.2+/-0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min incremental ALI and IRI responses were proportionate such that the molar ratio of ALI to IRI was not different among the three groups (NGT, 2.6+/-0.2; IGT, 2.9 +/-0.3; type 2 diabetes, 2.9+/-0.3%; NS). Further, the relationship between beta-cell function, measured as either deltaIRI/deltaG or deltaALI/deltaG, and glucose metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2 values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. We conclude that the reduced beta-cell function of IGT and type 2 diabetes includes proportionate reductions in both IRI and ALI release. Thus, it is unlikely that the development of islet amyloid in type 2 diabetes is the result of increased release of ALI.

Effect of regional fat distribution and Prader-Willi syndrome on plasma leptin levels.

Variability in the relationship of plasma leptin level to body mass index (BMI) could be caused by imperfect estimation of adipose mass by the BMI, heterogeneity in the pathogenesis of obesity in mixed subject groups, or variation in adipose tissue distribution. To investigate these possibilities, we examined the correlation of plasma leptin and BMI in an ethnically mixed population, a group of subjects with the Prader-Willi syndrome, and a group of Japanese-American subjects who underwent computerized tomographic measurement of adipose tissue cross-sectional areas. Highly significant and indistinguishable linear relationships between plasma leptin levels and BMI were found in the three study groups. Intersubject variability was also similar in the three groups and was reduced only when more accurate techniques for assessing adipose tissue mass were substituted for the BMI. The plasma leptin level of Japanese-American subjects in the highest quartile of intraabdominal fat area (mean area = 154.5 +/- 38.4 cm2) was 12.5 +/- 8.7 ng/mL as compared to 12.3 +/- 9.6 ng/mL (P = 0.91) for subjects in the lowest quartile of intraabdominal fat area (mean area = 51.2 +/- 20.1 cm2, P < 0.001 for difference in fat areas). We conclude that the circulating leptin level reflects total adipose tissue mass rather than a combination of adipose tissue mass and distribution, and that the Prader-Willi syndrome does not alter the relationship between these two variables.