Impacts of dance on non-motor symptoms, participation, and quality of life in Parkinson disease and healthy older adults.

Evidence indicates exercise is beneficial for motor and non-motor function in older adults and people with chronic diseases including Parkinson disease (PD). Dance may be a relevant form of exercise in PD and older adults due to social factors and accessibility. People with PD experience motor and non-motor symptoms, but treatments, interventions, and assessments often focus more on motor symptoms. Similar non-motor symptoms also occur in older adults. While it is well-known that dance may improve motor outcomes, it is less clear how dance affects non-motor symptoms. This review aims to describe the effects of dance interventions on non-motor symptoms in older adults and PD, highlights limitations of the literature, and identifies opportunities for future research. Overall, intervention parameters, study designs, and outcome measures differ widely, limiting comparisons across studies. Results are mixed in both populations, but evidence supports the potential for dance to improve mood, cognition, and quality of life in PD and healthy older adults. Participation and non-motor symptoms like sleep disturbances, pain, and fatigue have not been measured in older adults. Additional well-designed studies comparing dance and exercise interventions are needed to clarify the effects of dance on non-motor function and establish recommendations for these populations.

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.

A comparison of dance interventions in people with Parkinson disease and older adults.

It is important for our aging population to remain active, particularly those with chronic diseases, like Parkinson disease (PD), which limit mobility. Recent studies in older adults and people with PD suggest dance interventions provide various motor benefits. The literature for dance in PD is growing, but many knowledge gaps remain, relative to what is known in older adults. The purpose of this review is to: (1) detail results of dance intervention studies in older adults and in PD, (2) describe limitations of dance research in these populations, and (3) identify directions for future study. Generally, a wide variety of dance styles have been investigated in older adults, while a more limited subset has been evaluated in PD. Measures vary widely across studies and a lack of standardized outcomes measures hinders cross-studies comparisons. Compared to the dance literature in older adults, there is a notable absence of evidence in the PD literature in outcome domains related to cardiovascular health, muscle strength, body composition, flexibility, and proprioception. As a whole, the dance literature supports substantial and wide-ranging benefits in both populations, but additional effort should be dedicated to well-designed comparative studies using standardized outcome measures to identify optimal treatment programs.

Cerebral blood flow responses to dorsal and ventral STN DBS correlate with gait and balance responses in Parkinson's disease.

OBJECTIVES: The effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on gait and balance vary and the underlying mechanisms remain unclear. DBS location may alter motor benefit due to anatomical heterogeneity in STN. The purposes of this study were to (1) compare the effects of DBS of dorsal (D-STN) versus ventral (V-STN) regions on gait, balance and regional cerebral blood flow (rCBF) and (2) examine the relationships between changes in rCBF and changes in gait and balance induced by D-STN or V-STN DBS. METHODS: We used a validated atlas registration to locate and stimulate through electrode contacts in D-STN and V-STN regions of 37 people with Parkinson's disease. In a within-subjects, double-blind and counterbalanced design controlled for DBS settings, we measured PET rCBF responses in a priori regions of interest and quantified gait and balance during DBS Off, unilateral D-STN DBS and unilateral V-STN DBS. RESULTS: DBS of either site increased stride length without producing significant group-level changes in gait velocity, cadence or balance. Both sites increased rCBF in subcortical regions and produced variable changes in cortical and cerebellar regions. DBS-induced changes in gait velocity are related to premotor cortex rCBF changes during V-STN DBS (r=-0.40, p=0.03) and to rCBF changes in the cerebellum anterior lobe during D-STN DBS (r=-0.43, p=0.02). CONCLUSIONS: DBS-induced changes in gait corresponded to rCBF responses in selected cortical and cerebellar regions. These relationships differed during D-STN versus V-STN DBS, suggesting DBS acts through distinct neuronal pathways dependent on DBS location.

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.

Effects of deep brain stimulation of dorsal versus ventral subthalamic nucleus regions on gait and balance in Parkinson's disease.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function, including gait and stability, in people with Parkinson's disease (PD) but differences in DBS contact locations within the STN may contribute to variability in the degree of improvement. Based on anatomical connectivity, dorsal STN may be preferentially involved in motor function and ventral STN in cognitive function. METHODS: To determine whether dorsal DBS affects gait and balance more than ventral DBS, a double blind evaluation of 23 PD patients with bilateral STN DBS was conducted. Each participant underwent gait analysis and balance testing off Parkinson's medication under three DBS conditions (unilateral DBS in the dorsal STN region, unilateral DBS in the ventral STN region and both stimulators off) on 1 day. RESULTS: Improvements were seen in Unified Parkinson's Disease Rating Scale (UPDRS)-III scores and velocity in walking trials as fast as possible (Fast gait) and preferred pace (Pref gait), as well as stride length for Fast and Pref gait, with dorsal and ventral stimulation compared with the off condition (post hoc tests, p<0.05). However, there were no differences with dorsal compared to ventral stimulation. Balance, assessed using the multi-item mini-Balance Evaluation Systems Test (mini-BESTest), was similar across conditions. CONCLUSIONS: Absence of differences in gait and balance between the dorsal and ventral conditions suggests motor connections involved in gait and balance may be more diffusely distributed in STN than previously thought, as opposed to neural connections involved in cognitive processes, such as response inhibition, which are more affected by ventral stimulation.

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.

Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial.

OBJECTIVE: We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk. DESIGN: This study was a two-centre, two-armed, randomized controlled trial. The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week, with at least three of the sessions being facility based. The control group was asked not to change their activity and both groups were asked not to change their diet. SUBJECTS: A total of 320 postmenopausal, sedentary, normal weight-to-obese women aged 50-74 years who were cancer-free, nondiabetic and nonhormone replacement therapy users were included in this study. MEASUREMENTS: Anthropometric measurements of height, weight and waist and hip circumferences; dual energy X-ray absorptiometry measurements of total body fat; and computerized tomography measurements of abdominal adiposity were carried out. RESULTS: Women in the exercise group exercised a mean of 3.6 days (s.d.=1.3) per week and 178.5 min (s.d.=76.1) per week. Changes in all measures of adiposity favored exercisers relative to controls (P<0.001). The mean difference between groups was: -1.8 kg for body weight; -2.0 kg for total body fat; -14.9 cm(2) for intra-abdominal fat area; and -24.1 cm(2) for subcutaneous abdominal fat area. A linear trend of greater body fat loss with increasing volume of exercise was also observed. CONCLUSION: A 1-year aerobic exercise program consistent with current public health guidelines resulted in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer.

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.

Lipoprotein and apolipoprotein abnormalities in familial combined hyperlipidemia: a 20-year prospective study.

In order to characterize the lipoprotein abnormalities in familial combined hyperlipidemia (FCHL) and to describe factors associated with the stability of the FCHL phenotype during 20-year follow-up, 287 individuals from 48 families with FCHL originally identified in the early 1970s (baseline) were studied. Hyperlipidemia was defined as lipid-lowering medication use, or > or =age- and sex-specific 90th percentile for triglycerides or cholesterol. Triglyceride, cholesterol and medical history data were obtained at baseline and 20-year follow-up. Additional follow-up measures included HDL-C, LDL-C, LDL particle size, lipoprotein(a), apolipoprotein (apo) A-I, apoB, and apoE polymorphism. Longitudinally, two-thirds of relatives were consistently normolipidemic or hyperlipidemic, and one third were discordant for hyperlipidemic status at baseline and 20-year follow-up. Individuals with hyperlipidemia at baseline and/or follow-up had higher apoB levels than those with consistently normal lipids (P<0.05), whereas small LDL size was associated with concurrent hyperlipidemia. Among individuals who were normolipidemic at baseline, the following variables were independently associated with development of hyperlipidemia over 20 years: older age at baseline, male sex, greater increase in BMI during follow-up, and apoE alleles epsilon 2 or epsilon 4. In conclusion, apoB is associated with hyperlipidemia and apoE polymorphism is associated with later onset of hyperlipidemia in FCHL.

Lipoprotein(a) as a risk factor for maternal cardiovascular disease mortality in kindreds with familial combined hyperlipidemia or familial hypertriglyceridemia.

Most but not all epidemiologic studies have shown that lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD). Lp(a) levels are also strongly genetically influenced. The purpose of this study was to evaluate the association between Lp(a) levels in adult offspring and parental CVD mortality in 61 kindreds with familial forms of hyperlipidemia. The study sample consisted of offspring-parent pairs in which offspring had fasting Lp(a) measurements and parents had 20-year vital status data and standardized cause-of-death classification if deceased. Linear regression analyses, using a robust variance estimator, were performed separately for 241 offspring with known maternal history (114 mothers) and 194 offspring with known paternal history (93 fathers). Maternal history of CVD mortality was significantly (p=0.004) associated with 2.4-fold higher median Lp(a) levels in offspring compared with those with no maternal history, independent of diabetes, lipid-lowering medications and hormone use. No association was observed between paternal CVD mortality and offspring Lp(a) levels (p=0.505). Adjusting for apolipoprotein(a) kringle 4 number did not alter these parent-specific associations. In conclusion, Lp(a) levels in offspring may be associated with maternal but not paternal history of CVD mortality. This parent-specific finding needs to be confirmed in other samples of high-risk families.

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.

Low-density lipoprotein particle size, triglycerides, and high-density lipoprotein cholesterol as risk factors for coronary heart disease in older Japanese-American men.

Decreased low-density lipoprotein (LDL) particle size is associated with coronary heart disease (CHD) risk among middle-aged Caucasian populations, and has been consistently correlated with increased plasma levels of triglyceride and decreased levels of high-density lipoprotein (HDL) cholesterol. This study examines whether these risk factors predict CHD among older Japanese-American men. With use of the Honolulu Heart Program Lipoprotein Exam 3 (1980 to 1982) as baseline, and 12-year follow-up for CHD events, a nested, case-control study was designed. One hundred forty-five incident CHD cases were identified and matched to 2 controls each. LDL particle diameter (size) was determined by gradient gel electrophoresis. A 10-angstrom (A) decrease in LDL size at baseline was associated with increased risk of incident CHD (relative risk 1.28, 95% confidence interval 1.01 to 1.63). After adjustment for baseline risk factors, the LDL size association was no longer statistically significant (relative risk 1.13, 95% confidence interval 0.86 to 1.49). When principal components analysis was used to define a composite variable for LDL size, triglycerides, and HDL cholesterol, this component predicted CHD independent of smoking, alcohol consumption, physical activity, body mass index, hypertension, diabetes, and beta-blocker use (p <0.01). Therefore, this prospective analysis of data from older, Japanese-American men demonstrated that decreased LDL size is a univariate predictor of incident CHD, and that a composite risk factor of LDL size, triglyceride, and HDL cholesterol was a risk factor for CHD independent of other risk factors.

Cardiovascular disease mortality in familial forms of hypertriglyceridemia: A 20-year prospective study.

BACKGROUND: Familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG) are 2 of the most common familial forms of hyperlipidemia. There is a paucity of prospective data concerning the risk of cardiovascular disease (CVD) in such families. The purposes of this study were to estimate 20-year total and CVD mortality risk among relatives in these families and to evaluate plasma triglyceride as a predictor of death. METHODS AND RESULTS: The study was based on lipid and medical history data from 101 families ascertained in 2 studies conducted in the early 1970s. Vital status and cause of death was determined during 1993 to 1997 for 685 family members, including first-degree relatives of the probands and spouse control subjects. Compared with spouse control subjects, 20-year CVD mortality risk was increased among siblings and offspring in FCHL (relative risk 1.7, P=0.02) after adjustment for baseline covariates. In FHTG families, the relative risk was also 1.7 but was not statistically significant (P=0.39). Baseline triglyceride was associated with increased CVD mortality risk independent of total cholesterol among relatives in FHTG families (relative risk 2.7, P=0.02) but not in FCHL families (relative risk 1.5, P=0.16) after adjustment for baseline covariates. CONCLUSIONS: This prospective study establishes that relatives in FCHL families are at increased risk for CVD mortality and illustrates the need for effective prevention strategies in this group. Baseline triglyceride level predicted subsequent CVD mortality among relatives in FHTG families, adding to the growing evidence for the importance of hypertriglyceridemia as a risk factor for CVD.

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.