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D L Leonetti

Publications and source records attributed to D L Leonetti.

At least 37 records · Page 2Linked to original sources

Relationship of proinsulin and insulin with noninsulin-dependent diabetes mellitus and coronary heart disease in Japanese-American men: impact of obesity--clinical research center study.

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

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Proinsulin as a marker for the development of NIDDM in Japanese-American men.

Disproportionate hyperproinsulinemia is one manifestation of the B-cell dysfunction observed in non-insulin-dependent diabetes mellitus (NIDDM), but it is unclear when this abnormality develops and whether it predicts the development of NIDDM. At baseline, measurements of proinsulin (PI) and immunoreactive insulin (IRI) levels were made in 87 second-generation Japanese-American men, a population at high risk for the subsequent development of NIDDM, and, by using World Health Organization criteria, subjects were categorized as having normal glucose tolerance (NGT; n = 49) or impaired glucose tolerance (IGT; n = 38). After a 5-year follow-up period, they were recategorized as NGT, IGT, or NIDDM using the same criteria. After 5 years, 16 subjects had developed NIDDM, while 71 had NGT or IGT. Individuals who developed NIDDM were more obese at baseline, measured as intra-abdominal fat (IAF) area on computed tomography (P = 0.046) but did not differ in age from those who continued to have NGT or IGT. At baseline, subjects who subsequently developed NIDDM had higher fasting glucose (P = 0.0042), 2-h glucose (P = 0.0002), fasting C-peptide (P = 0.0011), and fasting PI levels (P = 0.0033) and disproportionate hyperproinsulinemia (P = 0.056) than those who continued to have NGT or IGT after 5 years of follow-up. NIDDM incidence was positively correlated with the absolute fasting PI level (relative odds = 2.35; P = 0.0025), even after adjustment for fasting IRI, IAF, and body mass index (relative odds = 2.17; P = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)

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Visceral adiposity, fasting plasma insulin, and blood pressure in Japanese-Americans.

OBJECTIVE: To examine the associations among blood pressure, body mass index (BMI), intra-abdominal fat, and fasting plasma insulin levels among nondiabetic subjects. RESEARCH DESIGN AND METHODS: Second- (Nisei, n = 290) and third- (Sansei, n = 230) generation Japanese-American subjects without non-insulin-dependent diabetes mellitus (NIDDM) were selected from a community-based study of NIDDM incidence and complications. A cross-sectional comparison of measures obtained at the baseline visit was performed. Intra-abdominal fat (IAF) area was assessed using computed tomography. Associations among blood pressure, fasting insulin, and adiposity measures were assessed by comparison of mean values and multiple linear regression analysis. RESULTS: Hypertensive men and women had significantly higher mean IAF areas. Fasting insulin levels were somewhat higher in hypertensive subjects, with the only significant difference occurring among Sansei men. Both systolic and diastolic blood pressure correlated more strongly with IAF than BMI or skinfold thicknesses among Nisei, whereas among Sansei, IAF and BMI correlated equally well with either blood pressure. Significant positive correlations were found between fasting insulin level and blood pressure among Sansei only, even after adjustment for IAF and BMI (diastolic blood pressure-insulin coefficient = 0.24, P = 0.0043; systolic blood pressure-insulin coefficient = 0.36, P = 0.0025). CONCLUSIONS: IAF correlated more strongly with blood pressure than BMI or skinfold thicknesses among older, second-generation Japanese-Americans and was positively correlated with blood pressure among Sansei independent of fasting insulin level. Fasting insulin was significantly correlated with blood pressure independent of visceral and overall adiposity among third-generation Japanese-Americans.

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Earlier appearance of impaired insulin secretion than of visceral adiposity in the pathogenesis of NIDDM. 5-Year follow-up of initially nondiabetic Japanese-American men.

OBJECTIVE--To identify risk factors for development of non-insulin-dependent diabetes mellitus (NIDDM) during a 5-year longitudinal follow-up of second-generation Japanese-American (Nisei) men. RESEARCH DESIGN AND METHODS--For 5 years, 137 initially nondiabetic Nisei men were followed with 75-g oral glucose tolerance tests at the initial visit and at 2.5- and 5-year follow-up visits. Body fat distribution was assessed by computed tomography (CT) and body mass index (BMI) calculated at each visit. Fasting insulin and C-peptide, the increment of insulin and C-peptide at 30 min after the oral glucose load, intra-abdominal and total subcutaneous fat by CT, and BMI were compared between those who remained nondiabetic (non-DM) and those who had developed NIDDM at 2.5 years (DM-A) and 5 years (DM-B). RESULTS--At baseline, the DM-A group had significantly increased intra-abdominal fat, elevated fasting plasma C-peptide, and lower C-peptide response at 30 min after oral glucose. At the 2.5-year follow-up, this group had markedly increased fasting plasma insulin and decreased 30-min insulin and C-peptide response to oral glucose. The DM-B group also had significantly lower insulin response at 30 min after oral glucose at baseline but no significant difference in intra-abdominal fat or fasting plasma insulin and C-peptide levels. When this group developed NIDDM by 5-year follow-up, however, an increase of intra-abdominal fat was found superimposed on the pre-existing lower insulin response. Fasting plasma insulin and C-peptide remained low. CONCLUSION--In DM-A, lower 30-min insulin response to oral glucose (an indicator of beta-cell lesion) and increased intra-abdominal fat and fasting C-peptide (indicators of insulin resistance) were the risk factors related to the development of NIDDM. DM-B subjects had a lower 30-min insulin response to oral glucose at baseline and increased intra-abdominal fat at 5-years, when they were found to have NIDDM. Thus, both insulin resistance and impaired beta-cell function contribute to the development of NIDDM in Japanese-Americans, and impaired beta-cell function may be present earlier than visceral adiposity in some who subsequently develop NIDDM.

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Metabolic and adipose risk factors for NIDDM and coronary disease in third-generation Japanese-American men and women with impaired glucose tolerance.

Since second-generation (Nisei) Japanese Americans are prone to develop the insulin resistance syndrome, younger third-generation (Sansei) Japanese Americans from a cross-sectional 10% volunteer sample of Sansei men (n = 115) and women (n = 115) 34 years or older in King County, Washington with normal glucose tolerance or IGT were examined for metabolic and adipose risk factors associated with this syndrome. After an overnight 10-h fast, blood samples were taken for measurement of glucose, insulin, C-peptide, lipids, and lipoproteins, followed by a 3-h 75-g oral glucose tolerance test with blood samples taken for glucose, insulin, and C-peptide measurement. BMI (kg/m2), skinfolds, and body fat areas (by computed tomography) were measured. IGT was diagnosed in 19% of the men and 31% of the women. Men with IGT had more adiposity, both overall and in thoracic and visceral sites, had higher fasting plasma insulin and C-peptide, and tended to have higher fasting triglyceride and lower HDL cholesterol than men with normal glucose tolerance. Women with IGT had more thoracic subcutaneous fat and intra-abdominal fat and lower fasting HDL cholesterol than women with normal glucose tolerance, and tended to have higher fasting triglyceride and LDL cholesterol. Women with IGT also had higher fasting plasma insulin than women with normal glucose tolerance but tended to be less hyperinsulinaemic than men. Differences in fasting insulin, C-peptide, and lipids were best predicted by intra-abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)

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Diabetes and diabetes risk factors in second- and third-generation Japanese Americans in Seattle, Washington.

In Seattle, Washington, the prevalence of diabetes was 20% in second-generation (Nisei) Japanese-American men and 16% in Nisei women 45-74 years old, while the prevalence of impaired glucose tolerance (IGT) was 36% in Nisei men and 40% in Nisei women. Hyperglycemia was less and duration of diabetes shorter in women. Related to diabetes and IGT in Nisei were higher fasting plasma insulin levels and central (visceral) adiposity. Prevalence of diabetes was low among the younger (34-53 years old) third-generation (Sansei) men and women. Among self-reported non-diabetic Sansei, however, prevalence of IGT was 19% in men and 29% in women, and IGT was associated with both increased fasting plasma insulin levels and more visceral fat, suggesting that many Sansei are at risk of future diabetes. An important lifestyle factor in the development of NIDD in Japanese Americans appeared to be dietary saturated (animal) fat. Another factor may be physical inactivity. In Japanese-American women, menopause also appeared to be an important risk factor. These risk factors may be related to fostering the accumulation of visceral fat and the development of insulin resistance. Five-year follow-up examinations performed in non-diabetic Nisei men and women have yielded additional information concerning the prognosis of IGT. Of those women who were IGT at baseline, 34% were diabetic at follow-up while 17% returned to normal. In men who had been IGT at baseline, 18% were diabetic at follow-up while 36% returned to normal. Over the 5-yr follow-up interval, proportionally more women progressed from normal to IGT (54%) then went from IGT to normal (17%). For men, roughly equal proportions went from normal to IGT (37%) as from IGT to normal (36%). It would therefore appear that greater proportions of Nisei women are progressing to IGT and to NIDD than are Nisei men. This observation may be related to the increased risk of developing central obesity and insulin resistance following menopause. Prevalence of cardiovascular disease (hypertension, peripheral vascular disease, and/or coronary heart disease) was increased in Japanese Americans with IGT and NIDD. Neuropathy and retinopathy were associated only with NIDD.

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Height is an independent risk factor for neuropathy in diabetic men.

Height may increase the risk of diabetic polyneuropathy, but previous studies are inconclusive. Our purposes were to further examine the hypothesis that height (HT) is an independent risk factor for diabetic polyneuropathy and to determine which electrophysiologic measures are influenced by HT in diabetic subjects. We studied 170 Japanese American men (ages 43-73 years, mean 61) including: 69 diabetic men (mean HT 166 cm), 54 normal men (mean HT 167 cm), and 47 men with impaired glucose tolerance (IGT) (mean HT 164 cm), measuring 28 nerve conduction study (NCS) parameters. We used data from normal men in developing regression models to adjust NCS parameters for HT, age, and temperature. Factor analysis was employed to reduce the 28 NCS parameters to five physiologically meaningful factors, one of which, a factor representing median and peroneal sensory amplitudes, was significantly correlated with HT (r = -0.38, P = 0.0011) in diabetic men; taller subjects having smaller sensory nerve amplitudes. No significant correlation was found between this factor and body mass index. This factor had no correlation with HT in normal or IGT men. Our data do not confirm previous reports of associations between HT and slowed motor conduction velocities in diabetic subjects. This study does, however, support the hypothesis that HT is an independent risk factor for sensory polyneuropathy in diabetic subjects.

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Educational attainment and the risk of non-insulin-dependent diabetes or coronary heart disease in Japanese-American men.

Japanese-American men have higher rates of non-insulin-dependent diabetes mellitus and coronary heart disease than same-aged men in Japan. Associations of educational attainment with either non-insulin-dependent diabetes mellitus or coronary heart disease were examined in a sample of 229 second-generation Japanese-American men (aged 45 to 74 years) living in King County, Washington (1984 through 1985). Men with a terminal school education showed higher frequencies of both disease compared to men with any college education and to men with high school educations. Occupation, income, diet, physical activity, weight, insulin, lipids, and lipoproteins were examined to determine whether they could account for the observed associations of educational attainment with disease. Logistic regression analysis indicates that the association of educational attainment with risk of coronary heart disease is explained, in part, by the larger average body mass index, higher total and VLDL triglyceride, and lower HDL and HDL-2 cholesterol observed in men with technical school educations compared to the other men. The association of educational attainment with risk of non-insulin-dependent diabetes is not explained by any of the factors examined. The findings suggest that attainment of a college education ameliorates some of the negative effects of westernization on the health of Japanese-American men.

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Ophthalmoscopy versus fundus photographs for detecting and grading diabetic retinopathy.

Reported here is the agreement between three examination methods chosen to detect and grade diabetic retinopathy in 124 subjects with type II (noninsulin-dependent) diabetes mellitus. These three examination methods include ophthalmoscopy (indirect and direct) by a retina specialist, seven standard field fundus photographs read by the same retina specialist, and the same photographs read by a trained photographic grader at the Fundus Photograph Reading Center. For the 59 subjects examined with all three methods, these results indicated fair to good (kappas, 0.69-0.84) agreement between the retina specialist's and trained grader's reading of photographs, fair to good (kappas, 0.58-0.79) agreement between the retina specialist's ophthalmoscopic findings and the specialist's reading of photographs, and fair (kappas, 0.49-0.62) agreement between the retina specialist's ophthalmoscopic findings and the trained grader's reading of fundus photographs. Analysis of the disagreements confirmed earlier reports that ophthalmoscopy misses approximately 50% of eyes with microaneurysms only. Other disagreements resulted from the trained grader's overreading photographs of eyes with lesions simulating diabetic retinopathy. Of the 393 total subjects (diabetic and nondiabetic) in this study, such lesions were seen with ophthalmoscopy in six eyes of six subjects (2.4% of diabetic patients and 1.1% of nondiabetic subjects). The authors believe at least one definite retinal microaneurysm should be present in one eye before establishing the diagnosis of diabetic retinopathy in diabetic patients.

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Glucose intolerance and diabetic complications among Japanese-American women.

The prevalence of glucose intolerance and diabetic complications was determined in second-generation Japanese-American (Nisei) women and compared to previously obtained results in Nisei men. A volunteer study sample of 191 Nisei women 45-74 years old was enrolled from a study population of 1489 Nisei women born 1913-1942, raised and educated in the U.S., and residing in King County, Washington. The enrolled sample included 72 with normal glucose tolerance, 67 with impaired glucose tolerance (IGT), and 52 with non-insulin-dependent diabetes. A random sample was also drawn from the study population to form a reference sample of 157 women. Based upon observations in the reference and enrolled samples, an estimated 16% of Nisei women in the study population have diabetes and 40% IGT. These rates compare to 20% diabetes and 36% IGT previously estimated for Nisei men 45-74 years old. The prevalence of cardiovascular disease (hypertension, peripheral vascular disease, and/or coronary heart disease) was highest among diabetic women, lowest in those with normal glucose tolerance, and intermediate in women with IGT. In comparison to diabetic men, there was a significantly lower frequency of neuropathy, peripheral vascular disease, and coronary heart disease in diabetic women. However, hypertension occurred equally often in both. Thus Japanese-American men and women 45-74 yr old have a similar prevalence of glucose intolerance, although less severe in women, and complications, except for hypertension, are reduced in women.

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Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.

The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus, intra-abdominal fat showed a unique set of relationships to metabolic parameters which could be further related to certain environmental variables.

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Relationship of absence or presence of a family history of diabetes to body weight and body fat distribution in type 2 diabetes.

In a study sample of second generation Japanese American men (age range 45-74 years), family history of diabetes in a sibling or parent was present in 69 men (24 of 79 normal men and 45 of 78 type 2 diabetic men, P less than 0.001). Both general adiposity and body fat distribution have been associated with type 2 diabetes. Our hypothesis was that the association of both overall adiposity and of larger specific regional fat deposits with type 2 diabetes would differ depending upon family history. The relationships between diabetes and differences in general adiposity (whether current or maximum lifetime body mass index or BMI, sum of skinfolds, or sum of computed tomography or CT fat areas) and between diabetes and body fat distribution (measured as abdominal and thigh circumferences, cross-sectional body fat areas by CT of thorax, abdomen, and thigh, and skinfold thicknesses of triceps, biceps, forearm, chest, subscapula, abdomen, and thigh) were more apparent in those men without a family history of diabetes than in those with a family history. In men without a family history, diabetic men had significantly higher values for several variables which assessed overall adiposity: current BMI (P less than 0.001), maximum lifetime BMI (P less than 0.001), sum of skinfolds (P less than 0.006), and sum of CT fat areas (P less than 0.015). In addition several measurements of upper truncal adiposity were significantly increased in diabetic men: abdominal circumference (P less than 0.004), thoracic (P less than 0.015) and abdominal (P less than 0.03) subcutaneous CT fat areas, intra-abdominal CT fat areas (P less than 0.001), and chest (P less than 0.03) and subscapular (P less than 0.0002) skinfold thicknesses. The results pertaining to those without a family history appear to be due to increased adiposity and associated larger specific regional fat depots leading to diabetes and lesser adiposity and smaller amounts of fat in the same regional depots protecting against diabetes.

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Association of plasma triglyceride and C-peptide with coronary heart disease in Japanese-American men with a high prevalence of glucose intolerance.

In a community-based study of second-generation Japanese-American men known to have a high prevalence of both Type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance, there was a highly significant association of coronary heart disease with glucose intolerance in a study sample of 219 men. Intra-abdominal cross sectional fat area determined by computed tomography was significantly elevated in men with coronary heart disease even after adjustment for glucose intolerance and body mass index (p = 0.026). Other differences that were significantly related to coronary heart disease after adjustment for glucose intolerance were lower high density lipoprotein cholesterol levels (p = 0.001), elevated total triglyceride and very low density lipoprotein triglyceride (p less than 0.001), and elevated fasting insulin and C-peptide levels p = 0.001. When these variables were tested in a stepwise multiple logistic regression model, significant independent associations with coronary heart disease were found only for total triglyceride and fasting C-peptide after adjustment for glucose tolerance status. Variables identified to be associated with coronary heart disease were interpreted as representing or manifesting an insulin resistant state. Thus, insulin resistance may be the underlying risk factor aetiologically linking glucose intolerance with coronary heart disease.

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Cigarette smoking, adiposity, non-insulin-dependent diabetes, and coronary heart disease in Japanese-American men.

PURPOSE: Coronary heart disease has been described to be increased with both glucose intolerance and cigarette smoking. All three of these have also been reported to be associated with central adiposity (disproportionate deposition of fat on the trunk compared to the extremities). The purpose of this analysis was to determine the relationship of cigarette smoking to glucose intolerance and coronary heart disease, the relationship of cigarette smoking to risk factors such as adiposity, body fat distribution, and plasma lipoprotein and insulin levels, the relationship of cigarette smoking to these risk factors independent of disease status, and whether these risk factors could account for any of the relationship between cigarette smoking and disease status. PATIENTS AND METHODS: The study design was cross-sectional. The study sample contained 219 middle-aged and elderly Japanese-American men: 77 with normal and 74 with impaired glucose tolerance and 68 with type II diabetes. There were 54 men with coronary heart disease. A detailed smoking history was obtained. Glucose tolerance status was established by medical history and a 75-g oral glucose tolerance test. Coronary heart disease was determined by medical history and a resting electrocardiogram. Adiposity and fat distribution measurements were body mass index (kg/m2), skinfold thicknesses, body circumferences, and cross-sectional fat areas by computed tomography. Levels of insulin, C-peptide, cholesterol (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], HDL2, HDL3, very-low-density lipoprotein [VLDL]), and triglyceride (total, VLDL) were measured in fasting blood specimens. RESULTS: A central pattern of body fat was associated with both non-insulin-dependent diabetes mellitus and coronary heart disease. Smoking history was related to both adiposity and body fat distribution, and was strongly related to coronary heart disease but not to diabetes. Past smokers who had smoked up to a month ago were the heaviest while present smokers who were currently smoking or had smoked within the past month were the leanest. However, although present smokers had reduced amounts of fat, this was attributable to those present smokers without heart disease. Present smokers with heart disease were not as lean and had increased amounts of intra-abdominal fat. Past smokers had the greatest amount of central fat and this was attributable to those with heart disease. By two-way (smoking history and coronary heart disease status) analysis of covariance, smoking history was significantly related only to subcutaneous fat disposition on the chest and abdomen independent of coronary heart disease, while coronary heart disease status was strongly related to plasma levels of insulin C-peptide, VLDL, HDL, HDL2, and HDL3 cholesterol, and total and VLDL triglyceride, independent of smoking history. Further analysis showed that none of the body fat variables could account for the risk of coronary heart disease associated with smoking history. Higher fasting plasma C-peptide levels in past smokers accounted statistically for part of the risk of coronary heart disease associated with cigarette smoking. However, this effect was not mediated by any of the body fat measurements. CONCLUSIONS: Disproportionately increased intra-abdominal fat is related to coronary heart disease but not to smoking history. Smoking history is related to coronary heart disease but not to diabetes. Weight gain is associated with smoking cessation and appears to be concentrated in the central subcutaneous regions, especially for those who have coronary heart disease. Weight gain associated with cessation of smoking appears to be unrelated to atherogenic changes in lipids, lipoproteins, or insulin. Other pathogenic processes must be considered in the association between smoking and coronary heart disease.

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Diet of second-generation Japanese-American men with and without non-insulin-dependent diabetes.

Second-generation Japanese-American (Nisei) men have rates of non-insulin-dependent diabetes mellitus four times higher than men in Japan, suggesting a role for environmental factors in the etiology of this disease. Dietary intake was assessed for 229 Nisei men with diabetes (DM, n = 78), impaired glucose tolerance (IGT, n = 72), and normal glucose tolerance (NGT, n = 79). The diet of Nisei men with DM compared with men with IGT or NGT was similar in kilocalories but higher in fat and protein. Absence of diabetes was self-reported by 153 men (N-entry) of which 76 were confirmed to have NGT and 17 were discovered to have DM. Animal-protein and -fat intakes were significantly higher in N-entry DM men than in N-entry NGT men. Overall the Nisei diet, particularly that of Nisei men with DM, resembled more the diet of US men than men in Japan.

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Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance.

Two hundred and nineteen second generation Japanese-American men were classified with a 75-g oral glucose tolerance test: 77 with normal glucose tolerance, 74 with impaired glucose tolerance (IGT), and 68 with noninsulin-dependent diabetes mellitus (NIDDM). The peak insulin response to the oral glucose load was progressively delayed with each of the 3 glucose tolerance categories. A similar finding was observed with the peak C-peptide response to oral glucose, except for the absence of distinction between IGT and NIDDM. Variables measuring the initial rate of insulin or C-peptide secretion (0-30 min) after oral glucose also demonstrated a progressive diminution with increasing glucose intolerance. The relative incremental insulin response at 30 min and the relative incremental C-peptide response at 30 min were highly correlated with the fasting glucose levels (r = -0.61 and r = -0.62; P less than 0.0001, respectively). Variables measuring the 0-30 min secretory response had high variances, whereas the variance for fasting glucose was low. Twelve men who were initially classified as IGT subsequently developed NIDDM. These 12 men had significantly higher fasting glucose levels at baseline than the remaining men who did not develop diabetes, but the 30 min secretory parameters after oral glucose, although lower in those who subsequently developed diabetes, were not significantly different at baseline. However, if fasting glucose is used as a surrogate measure of secretory response, these 12 men appear to have had an impairment of oral glucose-stimulated insulin secretion antedating the development of NIDDM. The inability of the secretory parameters to detect the abnormality may be due to a type II statistical error, which may be resolved by a larger sample size.

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Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese-American men.

The Japanese-American population of King County, Washington, is known to have a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). As part of a community-based study, we reexamined 146 second-generation Japanese-American men who had been initially classified as nondiabetic. At a mean follow-up period of 30 mo, 15 men had developed NIDDM, and 131 remained nondiabetic. The variables measured at the initial visit that distinguished the 15 diabetic men from the 131 nondiabetic men were older age, higher serum glucose level at 2 h after 75 g oral glucose, higher fasting plasma C-peptide level, and increased cross-sectional intra-abdominal fat area as determined by computed tomography. Both older age and higher 2-h glucose levels are variables that have been associated with the development of NIDDM, but the association of higher fasting C-peptide level and greater intra-abdominal fat area with subsequent development of NIDDM were new observations. The elevated fasting C-peptide level persisted after adjustment for fasting serum glucose. The elevated C-peptide level represents hypersecretion of insulin and was interpreted to reflect a compensatory response to an underlying insulin-resistant state that antedates the development of NIDDM. The fasting C-peptide level was correlated with the intra-abdominal fat area, suggesting that the intra-abdominal fat area may be associated with insulin resistance. Thus, in individuals who develop NIDDM, insulin resistance, increased insulin secretion, and increased intra-abdominal fat are present before diabetic glucose tolerance can be demonstrated.

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Early-life background and the development of non-insulin-dependent diabetes mellitus.

The relationship of early-life background factors to type 2, or non-insulin-dependent, diabetes mellitus (NIDDM) was examined with reference to family history of diabetes in two groups of Nisei (U.S. born/raised Japanese American) men from King County, Washington with identical mean (+/- S.E.M.) ages: 78 with NIDDM, 61.6 (+/- 0.7) years of age; and 79 with normal glucose tolerance (NGT), 61.6 (+/- 0.6) years of age. The early-life variables were birthplace, parents' education, father's occupation and mother's employment status during subject's childhood, sibship size, son birth order, physical activity and weight assessed for ages 15-20 years, and educational achievement. Multivariate logistic regression models were used to test for the effect of each variable on the risk for diabetes in the presence of other variables. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Significantly higher risk for NIDDM was found with urban birthplace (vs. rural, OR = 2.09, 95% CI = 1.37-3.19), parents' education above primary level (vs. primary level or less, OR = 1.64, 95% CI = 1.08-2.50), mother being employed (vs. housewife, OR = 2.17, 95% CI = 1.43-3.45), subject being less active-lean as a youth (vs. more active-lean, OR = 1.69, 95% CI = 1.11-2.63), and subject's not attaining a college degree (vs. college degree, OR = 2.17, 95% CI = 1.41-3.33). In separate analyses of the early-life variables by family history of diabetes, the interplay of environmental influences with familial predisposition to NIDDM is evident. The developmental background of NIDDM is discussed with reference to the concept of phenotype amplification within the context of the effects of westernization.

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