Association of apolipoprotein E phenotype with hypertension in Japanese-Americans: data from the Hawaii-Los Angeles-Hiroshima Study.

We evaluated the association between the phenotypes or alleles of apolipoprotein E and hypertension in Japanese-Americans living in Hawaii or Los Angeles. The study consisted of 932 nondiabetic participants aged 40-79 years. Of these participants, 315 were hypertensive, while the remainder were normotensive. The prevalence of hypertension was higher in subjects with the e2 allele than in those without. Using a multivariable prediction model that included age, serum glucose, insulin, lipids, and body mass index, we found the epsilon2 allele to be associated with hypertension in men (odds ratio (OR), 1.53; 95% confidence interval (CI), 1.05-2.24) and for both sexes combined (OR, 1.35; 95% CI, 1.05-1.73). In a follow-up study, 37 of the 352 (11%) normotensive subjects had developed hypertension 4 years after the baseline examination. The frequencies of the apolipoprotein E phenotype E3/2 and the epsilon2 allele were higher in the subjects who became hypertensive than in those who remained normotensive. The E3/2 phenotype was associated with incidence of hypertension after adjustment for age, sex, baseline body mass index, and systolic blood pressure (OR, 1.75; 95% CI, 1.01-2.90). When serum lipids, glucose, and insulin were included in this analysis, the E3/2 phenotype tended to be associated with the incidence of hypertension. In conclusion, the epsilon2 allele of apolipoprotein E was associated with hypertension in Japanese-Americans. This association may be mediated via high levels of serum triglycerides that in turn are mediated in part by the epsilon2 allele. Nonlipid mechanisms may also be responsible for the effect of the epsilon2 allele on hypertension.

Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study.

The present study was to assess the association of metabolic factors including hyperinsulinemia, with the development of hypertension in Japanese-Americans. One hundred forty normotensive (<140/90 mmHg) subjects aged 40 to 69 years old from the Hawaii-Los Angeles-Hiroshima study were followed for 15 years. Patients with cardiovascular disease were excluded. Body mass index (BMI), blood pressure (BP), serum total cholesterol (TC), triglycerides (TG), uric acid (UA), and glucose and insulin responses at baseline, 1 h, and 2 h after a glucose load were analyzed. Seventeen subjects became hypertensive (systolic BP > or = 160 mmHg, diastolic BP > or = 95 mmHg, or received drug treatment) during follow-up. Age- and sex-adjusted BMI, BP, serum UA, TG, insulin, and changes in fasting glucose during follow-up were higher in subjects who later became hypertensive than in those who did not. There was no difference in the change in BMI. Age- and sex-adjusted relative risks for the development of hypertension by quartiles of BMI, serum UA, TG, and the sum of insulin values (sigmainsulin) during a glucose load were highest in highest quartile of the distribution. When age, sex, systolic BP, BMI, serum UA, TC, TG, fasting glucose, sigmainsulin, and the change in BMI were used in a proportional hazard analysis, hyperinsulinemia, hyperuricemia, and systolic BP were found to be significant risk factors for hypertension. In conclusion, hyperinsulinemia, as well as obesity, hyperuricemia, and hypertriglyceridemia were associated with hypertension in Japanese-Americans. Hyperinsulinemia and hyperuricemia were independent predictors of the development of hypertension.

Beta(3)-adrenergic receptor gene variant is associated with upper body obesity only in obese Japanese-American men but not in women.

We investigated gender differences in the relationships between the Trp64Arg variant of the beta(3)-adrenergic receptor (AR) gene in obesity and insulin resistance in nondiabetic subjects. In 476 nondiabetic Japanese-Americans (M/F=204/272), the Trp64Arg variant of the beta(3)-AR gene was examined. The presence or absence of the Trp64Arg mutation was examined in DNA separated from leukocytes in peripheral blood using the PCR-RFLP method. The frequency of abnormal allele of the beta(3)-AR gene was 0.18 for males and 0.17 for females, almost the same as the reported values in Japanese. There was no difference in the frequency of the beta(3)-AR gene variant between obese and non obese subjects for each gender. However, among obese males (body mass index > or =24.2 kg/m(2)), with the beta(3)-AR gene mutation, the waist-to-hip ratio, fasting insulin, 2-h insulin, total insulin, and HOMA, an index of insulin resistance, were all significantly higher than obese males without the mutation. In females, the index of obesity, insulin resistance, or lipid metabolism did not differ significantly between the subjects with or without the beta(3)-AR gene variant either in the obese and non-obese group. We suggest that the beta(3)-AR gene variant is not important as an obesity-inducing factor in Japanese. However, in males, when obesity becomes obvious, the beta(3)-AR gene variant is considered to influence the enhancement of insulin resistance, in association with visceral obesity.

Insulin resistance precedes the appearance of albuminuria in non-diabetic subjects: 6 years follow up study.

Microalbuminuria is a marker of increased risk of cardiovascular mortality in type 1 and type 2 diabetes, and in non-diabetic subjects. Little is known about the association between prospective changes of microalbuminuria and the risk factors of atherosclerosis, or gene polymorphism in non-diabetic subjects. We conducted a 6-year prospective study of risk factors for progression of albuminuria in non-diabetic subjects. The participants were 116 non-diabetic subjects who consecutively underwent medical examinations for Japanese-Americans living in Hawaii. In the baseline examination in 1992, normoalbuminuria was found in all subjects. After 6 years, 101 subjects remained normoalbuminuria (non-progressors), 15 subjects changing from normoalbuminuria to microalbuminuria or proteinuria and were defined as progressors. In progressors, compared with non-progressors, the fasting insulin level and HOMA-R were significantly higher at 3 years follow-up, and the systolic and diastolic pressure and Sigma insulin level were significantly higher at 6 years follow-up. Insulin resistance appeared earlier than the appearance of hypertension and albuminuria. In progressors, there was no significant correlation with angiotensin-converting enzyme (ACE) genotype or angiotensinogen (AGT) genotype compared with non-progressors. Therefore, the appearance of insulin resistance should be regarded as a remarkable mediator of albuminuria.

Gln27Glu variant of the beta2-adrenergic receptor gene is not associated with obesity and diabetes in Japanese-Americans.

The beta(3)-adrenergic receptor (AR) gene variant (Trp64Arg) has been reported to be associated with obesity and insulin resistance in humans. However, this association remains controversial. We investigated the relationships between the beta(2)-AR gene variant (Gln27Glu) and obesity, insulin resistance, and serum lipids in Japanese-Americans. The frequency of an abnormal Gln27Glu allele in the beta(2)-AR gene in 652 subjects was 0.092 in males, 0.077 in females, and 0.084 overall, markedly lower than the previously reported value of 0.4 in Caucasian men and women. In both males and females, there were no differences in the indices of obesity, insulin resistance, and serum lipid levels between the subjects with and without the beta(2)-AR gene (Gln27Glu) variant in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes (DM). The frequency of the beta(2)-AR gene (Gln27Glu) variant tended to increase with worsening of glucose tolerance, but the differences were not statistically significant. Furthermore, there were no differences in the frequency of the beta(2)-AR gene variant in either males or females with obesity (body mass index [BMI], > or = 25.2). Even in Japanese-Americans, who have a more westernized life style than Japanese, the association of the beta(2)-AR gene (Gln27Glu) variant with the parameters of obesity, insulin resistance, and serum lipid level has yet to be clarified. We conclude that the beta(2)-AR gene (Gln27Glu) variant might not be an important factor for obesity or IGT in Japanese subjects.

DiGeorge syndrome with Graves' disease: A case report.

DiGeorge syndrome (DGS) is characterized by aplasia or hypoplasia of the thymus and parathyroid glands, cardiac defects and anomaly face. This syndrome is usually associated with hypocalcemia resulting from hypoparathyroidism. In most cases the initial symptom is tetany caused by hypocalcemia within 24-48 hours after birth, with symptoms by immune abnormality appearing later. We report a woman who passed with no symptoms before age 18 and was diagnosed DiGeorge syndrome by tetany with developing auto-immune thyroid disease (Graves' disease). She had surgery for intraventricular septal defect at age 3, hypoparathyroidism, decrease of T cells in peripheral blood and the deletion of the 22nd chromosome long arm (22q11.2). It is supposed that abnormalities of immune function of this case are not complete as indicated by complicating of Graves' disease, and contributing to her long-term survival.

Association of sex hormone-binding globulin and insulin resistance among Japanese-American subjects.

An association between sex hormone-binding globulin (SHBG) and insulin resistance expressed by the homeostasis model (HOMA-R), and the significance of both variables as risk factors for the development of type 2 diabetes were investigated in 483 Japanese-American subjects. The serum SHBG level was significantly higher in women (68.7 nmol/l) than in men (45.1 nmol/l). This difference was also significant independently of age, body mass index (BMI), waist to hip ratio (WHR), and HOMA-R. When multiple regression analysis was performed after adjustment for age and BMI, SHBG was not correlated with HOMA-R in men. In women, SHBG was not significantly correlated with HOMA-R after adjustment for age, BMI, and WHR. In a 3-year prospective analysis, HOMA-R was significantly higher in converters to type 2 diabetes than non-converters in both men and women which was independent of age, BMI and WHR. However, after adjusting these variables, SHBG was not a significant risk factor either in men or women. These results indicate that SHBG might be related to insulin resistance secondarily via BMI and/or WHR in both men and women among Japanese-Americans. HOMA-R is a useful index for both men and women as a risk factor of type 2 diabetes when only fasting blood samples can be obtained.

Association of beta3-adrenergic receptor gene polymorphism with insulin resistance in Japanese-American men.

The Trp64Arg variant of the beta3-adrenergic receptor (beta3-AR) gene is relatively common in Japanese people. We hypothesized that this variant may be associated with obesity and insulin resistance when combined with a westernized lifestyle. To test this hypothesis, we investigated the relationships between the beta3-AR gene variant and obesity and insulin resistance in Japanese-American men, who are known to have a higher prevalence of type 2 diabetes mellitus (DM). The subjects were 152 Japanese-American men living in Hawaii, 83 with normal glucose tolerance (NGT), 40 with impaired glucose tolerance (IGT), and 29 with DM. The frequency of the Trp64Arg allele of the beta3-AR gene was 0.18, almost identical to that of the mainland Japanese. The prevalence of the Trp64Arg allele was 30.1% in NGT, 35.0% in IGT, and 41.4% in DM subjects (nonsignificant). The Trp64Arg variant of the beta3-AR gene showed no significant relationship with obesity or insulin resistance in NGT subjects. However, fasting and 2-hour insulin levels and insulin resistance as determined by homeostasis model assessment (HOMA) were significantly higher in IGT subjects with the Trp64Arg variant. Although indices of obesity were the same in IGT subjects with and without the Trp64Arg variant, differences in the body mass index (BMI) and percent body fat between NGT and IGT subjects were greater for individuals with the Trp64Arg variant. Thus, there is an association between the Trp64Arg variant of the beta3-AR gene and insulin resistance in Japanese-Americans with IGT.

Reduced prevalence of diabetes according to 1997 American Diabetes Association criteria.

AIMS/HYPOTHESIS: We examined the prevalence of diabetes and investigated the characteristics of subjects diagnosed by the American Diabetes Association and the World Health Organization criteria. METHODS: A total of 1235 Japanese-Americans living in Hawaii and Los Angeles was studied. Of the subjects 114 were classified as previously diagnosed as having diabetes. A 75-g glucose tolerance test was given to the rest of the subjects. RESULTS: When abnormal glucose tolerance was diagnosed by the American Diabetes Association criteria, it was possible to identify only 40 % of diabetic subjects who had not been previously diagnosed compared with the current World Health Organization criteria based on a glucose tolerance test. In addition, the subjects identified by the American Diabetes Association criteria had higher glucose concentrations and had less insulin secretory capacity and they were in need of intensive treatment for diabetes. On the other hand, the subjects not diagnosed by the American Diabetes Association criteria alone were those whose glucose tolerance would be more likely to improve with lifestyle modification. CONCLUSION/INTERPRETATION: It might be better to use the fasting plasma glucose criterion advocated by the American Diabetes Association in combination with a glucose tolerance test after taking a detailed medical history. To reduce the number of subjects requiring the glucose tolerance test, priority should be given to subjects with impaired fasting glucose (6.1

[Mechanisms of anti-atherogenic action of probucol].

Probucol has been recognized to have antioxidant properties as well as lipid-lowering effects, and contribute to prevention of atherosclerosis. Pharmacologically, this agent has shown several unique actions, and a lot of investigations have been reported regarding the mechanisms. Recently, it has been reported that probucol increases selective uptake of high density lipoprotein cholesterol esters by the medium of the class B, type I scavenger receptor (SR-BI), and that antioxidant potent may inhibit the restenosis of post coronary angioplasty. This review attempts to focus on the mechanism of antioxidant and HDL-lowering effects of probucol.

Dissociation of microangiopathy and macroangiopathy in patients with type 2 diabetes.

OBJECTIVE: Although persistent hyperglycemia contributes greatly to the progression of diabetic micro- and macroangiopathy, microangiopathy progresses more rapidly than macroangiopathy in some type 2 diabetic patients, with the opposite being true in others. This study was conducted to identify factors responsible for such dissociation. RESEARCH DESIGN AND METHODS: Patients with proliferative diabetic retinopathy and a carotid intima-media thickness (IMT) level < or =1.0 mm were classified as the microangiopathy group (MIG); those with an IMT level >1.1 mm and without retinopathy or with background retinopathy were assigned to the macroangiopathy group (MAG). Only middle-aged patients, 50-69 years old, were included in this study. There were 54 patients in the MIG and 68 patients in the MAG. RESULTS: Patients in the MIG were significantly younger at the onset of diabetes, and those in the MAG had a significantly higher mean ratio of apoprotein (apo) B to apoAI. The percentage of patients with a family history of diabetes was significantly higher in the MIG. Maternal inheritance was common among these patients. Those with obesity, a family history of diabetes, and younger onset of hypertension were more common in the MAG. In the multiple logistic regression analyses, maternal inheritance and early onset of diabetes were independent risk factors for the acceleration of microangiopathy. A personal history of obesity and a family history of hypertension were independently related to the development of macroangiopathy. CONCLUSIONS: Our results suggest that patients with early onset and maternal inheritance of diabetes may have a high risk for the progression of diabetic microangiopathy, while patients with hyperlipidemia, a history of obesity, and a family history of hypertension seem prone to the development of atherosclerosis.

Association of intraabdominal fat and carotid atherosclerosis in non-obese middle-aged men with normal glucose tolerance.

OBJECTIVE: To investigate the association of visceral fat accumulation and carotid atherosclerosis in non-obese men with normal glucose tolerance. SUBJECTS: Ninety eight middle-aged men with normal glucose tolerance who had a body mass index (BMI) < 25 kg/m2 (mean age: 52.6 y, mean BMI: 22.5 kg/m2). METHOD: Using ultrasonography, we simultaneously measured the abdominal fat distribution and intima-media thickness (IMT) of the carotid artery wall. RESULTS: Pmax, an index of the absolute amount of visceral fat, was found to be significantly correlated with IMT and fasting Insulin concentration (r = 0.37, P < 0.005 and r = 0.54, P < 0.0001). Abdominal wall fat index (AFI), the ratio of maximum thickness of the preperitioneal fat and the minimum thickness of the subcutaneous fat, was not correlated with IMT. CONCLUSION: Visceral fat accumulation may play a role in the progression of atherosclerosis even in non-obese middle-aged men.

Carotid atherosclerosis and serum lipoprotein(a) concentrations in patients with NIDDM.

OBJECTIVE: To investigate the association of carotid atherosclerosis and serum lipoprotein(a) [Lp(a)] concentrations in subjects with NIDDM. RESEARCH DESIGN AND METHODS: We measured carotid intima-media thickness (IMT) and Lp(a) concentrations in 117 NIDDM subjects. Subjects were divided into tertiles according to IMT values and number of plaques. RESULTS: Serum Lp(a), but not lipid and apoprotein levels, increased significantly with increasing IMT (20.0 +/- 2.3, 24.7 +/- 3.3, and 39.8 +/- 4.3 mg/dl [mean +/- SE], respectively, P < 0.001). Serum Lp(a) increased with increasing number of plaques (18.4 +/- 2.5 mg/dl in 59 subjects with no plaques, 25.8 +/- 2.5 mg/dl in 24 subjects with 1 plaque, and 38.7 +/- 5.1 mg/dl in 34 subjects with more than 1 plaque; P < 0.05). Furthermore, the mean IMT and Lp(a) levels in the subjects with cerebrovascular disease (CD) were significantly higher than in those without CD (1.25 +/- 0.04 mm and 41.2 +/- 4.7 mg/dl vs. 1.08 +/- 0.03 mm and 22.2 +/- 1.9 mg/dl; P < 0.005). The mean IMT and Lp(a) levels were higher in subjects with ischemic heart disease (IHD) than in those without IHD, although statistical significance was not observed (1.21 +/- 0.06 mm and 31.7 +/- 4.7 mg/dl vs. 1.10 +/- 0.03 mm and 27.0 +/- 2.4 mg/dl, respectively). CONCLUSIONS: Elevated serum Lp(a) concentrations are associated with carotid atherosclerosis in NIDDM subjects.

Incidence of non-insulin-dependent diabetes mellitus and its risk factors in Japanese-Americans living in Hawaii and Los Angeles.

UNLABELLED: The incidence of non-insulin-dependent diabetes mellitus (NIDDM) and its risk factors were analysed from data of a follow-up study conducted on Japanese-Americans living in Hawaii and Los Angeles areas known to have a high prevalence of NIDDM. There were 1144 Japanese-Americans aged 40 years or more (mean (+/- SD) age: 60.7 +/- 10.1) available for follow-up, and who were non-diabetic based on glucose tolerance test (GTT) results conducted at the time of the initial examination. During the study period (6.3 +/- 3.2 yr), 124 cases of NIDDM occurred with an incidence rate as high as 10.8% or 17.2 persons per 1000 person-years. The incidence of NIDDM was 1.25 times higher in males than in females, and the rate increased with age. The incidence in obese people (body mass index: BMI > or = 25) was approximately twice that in the non-obese, the rate increasing with the level of obesity. Using Cox's proportional hazards model, the risk factors for NIDDM were analysed after adjusting for sex and age. Significant risk factors were the serum glucose (SG) level (fasting, 1-h, 2-h), the serum immuno-reactive insulin (IRI) level (1-h, 2-h) during GTT, BMI, serum triglycerides, high density lipoprotein (HDL)-cholesterol, serum uric acid, diastolic blood pressure, systolic blood pressure, serum total protein, and delta IRI/delta SG (0-30 min) level. In particular the hyperinsulinaemia was a significant risk factor even after adjusting for sex, age, and obesity. The incidence of NIDDM in the sub-group whose delta IRI/delta SG (0-30 min) level was under 0.3 was higher than that of the over 0.8 sub-group by a factor of approximately 12. Likewise, after dividing the subjects into five sub-groups according to the fasting or 2 h IRI level, the incidence of NIDDM was higher in the highest quintile than in the lowest quintile sub-group by a factor of approximately 3 and 7, respectively. The results of the GTT of the subjects who developed NIDDM during the follow-up period were analysed longitudinally and compared with the results obtained 8 years before occurrence of NIDDM. An increase in the 2-h serum IRI was observed initially, followed by an increase in the 2-h serum glucose level, preceding the appearance of NIDDM. IN CONCLUSION: 1. A high incidence of NIDDM is clearly observed in the population of Japanese-Americans, who are genetically indistinguishable from native Japanese; causes of this increase, from the survey results, are suspected to include westernization of lifestyle, particularly the reduction in the level of physical activity, conversion to a diet containing markedly more animal fat, simple carbohydrates, and less complex carbohydrates. 2. In the Japanese-Americans, diminished early insulin release to an oral glucose challenge and increased insulin resistance characterized by hyperinsulinaemia are suspected to be some of the important risk factors for NIDDM. Consequently, this study strongly suggested the possibility that the development of NIDDM in Japanese persons may be influenced by environmental factors.

Urinary excretion of type IV collagen and laminin in the evaluation of nephropathy in NIDDM: comparison with urinary albumin and markers of tubular dysfunction and/or damage.

To clarify the diagnostic relevance of urinary type IV collagen (IV-C) and laminin in diabetic nephropathy, the excretion of these basement membrane proteins were determined by enzyme immunoassay in 172 non-insulin-dependent diabetic patients with different grades of nephropathy and 64 non-diabetic control subjects, and were evaluated in comparison with those of urinary albumin, N-acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin (alpha 1MG). These excretions were also compared between a group of non-diabetic renal disease (NDRD) patients (n = 24) and a subgroup of the diabetic patients studied (n = 76), whose urinary albumin excretion (UAE) varied within the ranges of micro- and macroalbuminuria. Of the diabetic patients studied, 49.7%, 53.4% and 32.4% had raised urinary albumin, NAG and alpha 1 MG excretion, respectively. In these patients, 54% and 53% exceeded the upper limit of normal for urinary IV-C and laminin. The level of IV-C and laminin excretion and the prevalence of their abnormal excretion showed a trend to increase with increasing grade of nephropathy, as assessed by UAE. In the normoalbuminuric [UAE < 20 mg/g creatinine (Cr)] stage, 28.3% and 26.3% patients had raised urinary IV-C and laminin excretion, respectively. In this stage, the excretion values for IV-C and laminin also rose significantly even when the UAE was < or = 10 mg/g Cr (P < 0.05 and P < 0.005, respectively). There was a close linear relationship between IV-C and laminin excretion (r = 0.73, P < 0.0001), together with their significant relationships with albumin, NAG and alpha 1MG excretion. The relationship of urinary IV-C and laminin with urinary NAG and alpha 1MG excretion remained significant even in normoalbuminuric patients. The normoalbuminuric patients with raised NAG and/or alpha 1MG excretion also had a higher prevalence of raised IV-C and laminin excretion than those with normal NAG and alpha 1MG excretion. The excretion values for IV-C and laminin, and the excretion ratios for IV-C/albumin and laminin/albumin were significantly higher in diabetic patients with evidence of incipient and clinical nephropathy than in NDRD patients, though the two patient groups had a comparable level of serum Cr and UAE. We conclude that the measurement of urinary IV-C and laminin may have potential for the evaluation of diabetic nephropathy. Furthermore, their determination might be helpful for distinguishing diabetic versus non-diabetic etiologies of altered renal function in diabetic patients.

Serum and urinary type IV collagen concentrations in the assessment of diabetic microangiopathy.

We investigated the role of measurement of serum and urinary type IV collagen (IV-C) levels in monitoring diabetic microangiopathy. Furthermore, we compared these levels in diabetic nephropathy and non-diabetic renal disease (NDRD). A one-step sandwich enzyme immunoassay was used to measure IV-C levels in 82 diabetic patients, 33 NDRD patients and 20 healthy non-diabetic control subjects. The diabetic patients were classified into four groups according to urinary albumin/creatinine index (ACI) (mg/g) and serum creatinine (s-Cr) (mg/dl): normoalbuminuria (ACI < 30), microalbuminuria (ACI 30-300), albuminuria (ACI > 300, s-Cr < 1.99 mg/dl) and renal insufficiency (s-Cr > 1.99 mg/dl). Serum and urinary IV-C levels were significantly elevated even in diabetic patients without clinical evidence of microangiopathy compared with control subjects (p < 0.05 and p < 0.01, respectively). Both levels were significantly higher in normoalbuminuric patients than in the control subjects, and in patients with microalbuminuria, albuminuria or renal insufficiency than in normoalbuminuric patients, with significant differences between these groups (serum and urinary IV-C, both p < 0.0001 by ANOVA). Urinary IV-C and albumin levels were significantly correlated, even in normo- and microalbuminuric patients (r = 0.55, p < 0.0001). Serum IV-C in normoalbuminuric patients rose significantly as the degree of retinopathy progressed from background to proliferative stages (p < 0.05). Neither serum nor urinary IV-C levels were influenced by glycemic control. Albuminuric diabetic patients (with and without renal insufficiency) had significantly higher levels of serum IV-C compared with those in proteinuric NDRD patients (p < 0.005), though there was no significant difference in the urinary IV-C level. However, the urinary IV-C/albumin ratio was significantly higher in albuminuric diabetic patients than in proteinuric NDRD patients, even after adjusting for s-Cr and creatinine clearance (p < 0.0001). In conclusion, we suggest that measured serum and urinary IV-C concentrations may serve as new markers for monitoring the development and progression of diabetic microangiopathy, particularly nephropathy. Furthermore, the measurement of serum IV-C concentrations and urinary IV-C/albumin ratios in diabetic patients may allow diabetic nephropathy and non-diabetic renal disease to be differentiated.

The high prevalence of diabetes mellitus and hyperinsulinemia among the Japanese-Americans living in Hawaii and Los Angeles.

A comparative epidemiologic investigations was conducted among Japanese immigrants and their offspring living in Hawaii and the Los Angeles area, and among Japanese living in Hiroshima. All subjects received an oral glucose tolerance test and the diagnosis of diabetes was made on the basis of WHO criteria. In the subjects aged 40 years or older, the age, sex, and obesity-specific prevalence of diabetes was 2-3 times higher among Japanese living in America than those in Hiroshima. The fasting and post-glucose load serum immunoreactive insulin concentrations were higher in the Japanese-Americans compared to the Hiroshima inhabitants with the same degree of obesity and glucose tolerance. We suggest that a westernized lifestyle induces peripheral insulin resistance and promotes the development of diabetes among Japanese.