Myelosuppressive changes from single or repeated doses of radioantibody therapy: effect of bone marrow transplantation, cytokines, and hematopoietic suppression

Apolipoprotein E phenotype (APOE phenotype) has been demonstrated to be a genetic determinant of cardiovascular disease. This atherogenicity may be a reflection of the association of APOE phenotype and plasma lipoprotein concentrations. The Coronary Artery Risk Development in Young Adults (CARDIA) Study affords the opportunity to assess the frequency of apolipoprotein E alleles in population-based samples of African Americans and whites in the United States and to compare the associations of APOE phenotype with lipoprotein and apoprotein concentrations. Data from 3,485 African-American and white men and women between the ages of 25 and 37 years who attended the fourth CARDIA Study examination in 1992-1993 were used in this analysis. African-American men and women had significantly higher frequencies of E2 and E4 phenotype and thus higher frequencies of *epsilon2 and *epsilon4 alleles (p < 0.005). Men and women of both races with APOE4 phenotype generally had higher low density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) concentrations and lower high density lipoprotein cholesterol concentration, and individuals with APOE3 phenotype had the lowest triglyceride concentration. Major differences between African Americans and whites were observed in the distribution of APOE phenotypes and *epsilon alleles, but APOE phenotype was associated with similar differences in lipoprotein and apoprotein concentrations in both races. The data suggest that APOE phenotype may be a risk factor for cardiovascular disease in both African Americans and whites because it is associated similarly with an adverse lipoprotein profile.     

Rabies postexposure prophylaxis survey--Kentucky, 1994

Prompted by the recent findings that a tryptophan to arginine (Trp64Arg) mutation in the beta3-adrenergic receptor gene was associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians, with abdominal obesity and insulin resistance in Finns, and with an increased capacity to gain weight in French whites, we studied the prevalence of this mutation in 231 diabetic and 95 nondiabetic Japanese subjects and assessed its contribution to the development of obesity and NIDDM. The allelic frequencies of the mutation were 0.18 in diabetic and 0.23 in nondiabetic subjects, showing no significant difference between the two groups (P = .067). In nondiabetic subjects, body mass index (BMI) did not differ between those with and without the mutation (22.2 +/- 3.5 v 21.4 +/- 3.2 kg/m2, P = .252). In NIDDM subjects, BMI at the time of study and maximal BMI before the start of treatment did not differ between those with and without the mutation (22.8 +/- 2.6 v 23.2 +/- 3.7 kg/m2, P = .678, and 24.7 +/- 2.6 v 24.9 +/- 3.1 kg/m2, P = .277). Homozygotes for the mutation did not have trends to have increased BMI in either diabetic or nondiabetic subjects. The age at diagnosis of NIDDM also did not differ between the two groups (48.8 +/- 9.9 v 47.8 +/- 12.5 years, P = .796). Fasting serum cholesterol and triglyceride levels and systolic and diastolic blood pressure before the start of treatment did not differ between NIDDM subjects with and without the mutation. In conclusion, although the Trp64Arg mutation is not uncommon in Japanese, it does not appear to be associated with obesity, NIDDM, age at diagnosis of NIDDM, or dyslipidemia. Our results suggest that the mutation has minor effects, if any, on the development of obesity and NIDDM in Japanese.     

Retinopathy in African Americans and whites with insulin-dependent diabetes mellitus

BACKGROUND: The development and progression of diabetic retinopathy in African Americans with insulin-dependent diabetes mellitus is not known. METHODS: Two hundred subjects with insulin-dependent diabetes mellitus with duration of diabetes 16 years or less at first visit were studied; 58 were African Americans and 142 were whites. All had gradable stereoscopic color fundus photographs (seven standard fields) from at least two visits (mean time between first and second visit was 4.1 years). Subjects with hemoglobinopathy or proliferative retinopathy or subjects who had evidence of treatment for proliferative retinopathy at first visit were excluded. Masked grading of photographs was conducted using the modified Airlie House classification scheme. RESULTS: African Americans were older, heavier, had higher systolic blood pressure (all P < .05), and marginally higher hemoglobin A1 (HbA1) values (P = .06) than the whites at first visit. African Americans had a lower rate of two steps or more progression from preexistent retinopathy (19%) than whites (43%). Progression to proliferative retinopathy or treatment was similar by race. Multivariate analysis predicting development oe progression of retinopathy, while controlling for length of follow-up, found higher HbA1 (odds ratio [OR] = 2.15), longer duration of insulin-dependent diabetes mellitus (OR = 1.69), higher serum creatinine concentration (OR = 1.59), and white race (OR = 2.62) to be independent risk factors. CONCLUSIONS: These data suggest a previously unsuspected reduction in the adjusted risk for development and progression of retinopathy in African Americans. The reason for this apparently reduced risk are not known.     

Mortality mapping in Hong Kong, 1979-83 and 1984-88: the patterns of major non-malignant diseases

In this study, human platelets were used as a cellular model for exploring cytosolic free Ca (Cai) regulation in non-insulin-dependent diabetes mellitus (NIDDM). Cai levels were monitored in resting and thrombin-stimulated platelets from obese females with NIDDM; obese, nondiabetic women, and nonobese, nondiabetic women. All subjects were black. Significant and marked elevation of basal Cai levels was observed in platelets from the diabetic subjects when no aspirin was used during platelet isolation. However, no significant differences were observed in Cai between aspirin-treated platelets from women with NIDDM and platelets from nondiabetic women. The rate of the Cai return to basal level after thrombin stimulation was significantly lower in platelets from the diabetic subjects, suggesting an abnormality in platelet Ca extrusion or sequestration in NIDDM. Platelet Cai levels positively correlated with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL/HDL) and fasting blood glucose. These findings suggest abnormalities in platelet Cai homeostasis in NIDDM that are influenced by the serum lipid profile and perhaps glucose.     

NIDDM incidence in a tri-ethnic population of diagnosed hypertensives

OBJECTIVE: Significant racial/ethnic differences exist in the prevalence of hypertension (HTN) and non-insulin dependent diabetes mellitus (NIDDM). The purpose of this study was to determine if ethnicity (African-American, Hispanic and non-Hispanic white) was related to NIDDM incidence over a maximum follow-up period of 10 years. DESIGN: Retrospective cohort study. SETTING: A large, urban public health care system serving over 200,000 predominantly minority persons. The system includes nine primary care health centers. PATIENTS: African-American, Hispanic and non-Hispanic white patients with diagnosed hypertension who received primary care in the study setting. METHODS: Medical records of 2,941 hypertensives free of NIDDM at their baseline visit were reviewed to document incident NIDDM during follow-up. Sociodemographic characteristics and physiologic covariates consistently available in the medical record (blood pressure, height, weight, and blood glucose) were also abstracted. RESULTS: The mean age of patients at the baseline visit was 56 years; 67% were female, 63% were African-American. 17% Hispanic, and 20% non-Hispanic white. Two hundred thirty-six incident cases of NIDDM were identified in the cohort. In Cox proportional hazards analysis, the risk of developing NIDDM was not related to ethnicity either in univariate analysis or after adjusting for age, baseline blood glucose, and body mass index (adjusted RR for African Americans compared with whites = .82, 95% CI = .57-1.18; adjusted RR for Hispanics compared with whites = .84, 95% CI = .51-1.38). CONCLUSION: The lack of association between ethnicity and NIDDM risk among hypertensives is unexpected, and may indicate differences in the pathogenetic mechanisms that underlie the development of hypertension and NIDDM in these three ethnic groups.     

Lipoprotein(a) in android obesity and NIDDM

OBJECTIVE: To assess the level of serum lipoprotein(a) [Lp(a)] in nonobese and obese NIDDM subjects with android body distribution. RESEARCH DESIGN AND METHODS: Serum Lp(a) levels were measured in 30 long-standing NIDDM patients (duration of diabetes 12.5 +/- 3 years, mean +/- SD), with 15 of the patients being obese of android distribution (BMI > 30 kg/m2 and waist-to-hip ratio > 0.8). In addition, there were 15 android obese nondiabetic subjects and 10 healthy subjects serving as the control group. RESULTS: All groups of patients in this study (diabetic, obese, and obese diabetic) showed significantly higher levels of Lp(a) than the healthy control group. Lp(a) concentrations were significantly higher in NIDDM patients with android type of obesity than in nondiabetic androids (24.1 +/- 5.6 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Significantly greater levels of Lp(a) were found in nonobese subjects with diabetes when compared with obese subjects without diabetes (22.3 +/- 4.1 vs. 14.8 +/- 2.4 mg/dl, P < 0.001). Furthermore, Lp(a) serum concentrations were not dependent on the degree of glycemic control (controlled NIDDM 23.6 +/- 5.0 vs. uncontrolled NIDDM 21.4 +/- 2.7 mg/dl, NS), but were much greater in subjects with diabetes complicated by vascular disease (complicated 26.3 +/- 5.0 vs. uncomplicated 20.5 +/- 2.7 mg/dl, P < 0.001). No correlation was found between Lp(a) and other lipid parameters in this study. CONCLUSIONS: Lp(a) levels are significantly elevated in both android-obese and nonobese NIDDM patients regardless of the degree of glycemic control. Lp(a) is an independent risk factor showing greater elevations in those subjects complicated with diabetic vascular diseases.     

Lack of relations of hostility, negative affect, and high-risk behavior with low plasma lipid levels in the Coronary Artery Risk Development in Young Adults Study

BACKGROUND: Previous studies have suggested that low plasma cholesterol levels or cholesterol lowering may increase the risk of suicide and violent death. Increased aggression, risk-taking behavior, or depression has been associated with low cholesterol levels in some studies. METHODS: A total of 4240 subjects of the Coronary Artery Risk Development in Young Adults study, aged 23 to 35 years, were included in the study. Analyses were stratified by race (black or white) and sex. Persons in the lowest 10% of plasma total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were compared with the other participants in each race/sex group, using standardized measures of hostility, anger suppression, depressive symptoms, and anxiety. The relations between 5-year change in hostility and 5-year change in lipid levels also were examined. The relations between lipid levels and high-risk behavior (e.g., violent arguments or having a gun at home) were examined in a subset of subjects. All analyses were adjusted for relevant covariates. RESULTS: In cross-sectional analyses, low total cholesterol levels were not related to any of the psychological measures in any race/sex group. Among black women only, low low-density lipoprotein cholesterol was related to greater anxiety, and low triglycerides were related to lower anger suppression (P < or = .002). Among white men only, increases in hostility during the 5-year follow-up were related to increases in triglycerides (P < .01), but changes in hostility were unrelated to changes in cholesterol levels. Among a subset of 371 subjects with initially elevated total cholesterol (> or = 5.17 mmol/L [> or = 200 mg/dL]) and a non-medicated decrease of 0.52 mmol/L (> or = 20 mg/dL) or more during 5 years, hostility decreased in a univariate analysis (P < .001). High-risk behaviors also were not associated with low lipid levels. CONCLUSION: The results do not support a consistent relation between hostility, negative affect, or high-risk behaviors with low lipid levels or lipid-lowering among young adults.     

Gastric emptying in Mexican Americans compared to non-Hispanic whites

Mexican Americans, a group at high risk for type II diabetes mellitus, have higher postprandial insulin and glucose levels when compared to non-Hispanic whites. A rapid rate of gastric emptying contributes to an increased rate of nutrient absorption and subsequent greater elevation of postprandial glucose and insulin levels. A more rapid rate of gastric emptying and hyperinsulinemia have been observed in patients with recently diagnosed type II diabetes mellitus. In this study, we examined whether Mexican Americans have a more rapid rate of gastric emptying than non-Hispanic whites. Gastric emptying studies were performed on 32 nondiabetic Mexican Americans and on 31 nondiabetic non-Hispanic whites. The rate of gastric emptying following a liquid glucose meal was measured. Serum insulin, plasma glucose, and GIP levels were measured in fasting and postprandial blood samples collected at 15-min intervals for 2 hr. Adjusting for age, body mass index, and gender, the gastric half-emptying time of a glucose meal was significantly (P < 0.05) more rapid for the Mexican American subjects (56.5 +/- 3.4 min) compared to the non-Hispanic white subjects (66.4 +/- 3.5 min). Nondiabetic Mexican Americans empty a liquid glucose meal more rapidly from their stomachs than nondiabetic non-Hispanic whites. Rapid gastric emptying is associated with hyperinsulinemia as a normal physiologic response to increased nutrient availability. The rapid gastric emptying observed in nondiabetic Mexican Americans is associated with hyperinsulinemia and could be a contributing factor for the increased risk of obesity and type II diabetes in this population.     

Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992

BACKGROUND: Little is known about the cause of inflammatory breast carcinoma (IBC), the most aggressive form of breast cancer. To the authors' knowledge, no studies have investigated whether IBC risk factors are different from those for breast carcinoma overall, and there has been only one report of IBC incidence and survival patterns. METHODS: The authors used data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for the period 1975-1992 to calculate age-adjusted incidence and survival rates for 913 white and 121 African American women with IBC involving dermal invasion of lymphatic ducts and 166,375 white and 13,674 African American women with other types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992, IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000 person-years and among African Americans from 0.6 to 1.1 cases. However, rates for African Americans varied due to the small numbers of IBC cases. The twofold increase in IBC incidence was higher than that observed for non-IBC during the same period (27% for African Americans and 25% for whites). IBC patients were significantly younger at diagnosis than non-IBC patients; and among both IBC and non-IBC patients, African Americans were younger than whites. Overall survival was significantly worse for IBC patients than for non-IBC patients and for African Americans than for whites. Among whites, 3-year survival improved more for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992, increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence trends and age at diagnosis, particularly according to race, highlight the need for further investigation of the differences between IBC and non-IBC incidence.     

Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinemic women

OBJECTIVE: To assess the effect on various aspects of carbohydrate and lipid metabolism of administering a quick-release formulation of bromocriptine (Ergoset) to obese, nondiabetic, hyperinsulinemic women. RESEARCH DESIGN AND METHODS: Hourly concentrations of prolactin, glucose, insulin, free fatty acid (FFA), and triglyceride were measured for 24 h before and after approximately 8 weeks of treatment with Ergoset. In addition, fasting lipid and lipoprotein concentrations and the steady-state plasma glucose (SSPG) concentration in response to a continuous infusion of somatostatin, insulin, and glucose were determined before and after Ergoset administration. RESULTS: Circulating prolactin concentrations were dramatically decreased (P < 0.001) following treatment, associated with a significant fall (P < 0.05) in 24-h-long plasma glucose, FFA, and triglyceride concentrations. Neither circulating plasma insulin concentrations nor the ability of insulin to mediate glucose disposal changed with treatment. Finally, fasting total cholesterol fell (P < 0.05) and the ratio of total to HDL cholesterol decreased (P = 0.06) in association with Ergoset treatment. CONCLUSIONS: The fact that significant metabolic improvement was seen in the obese nondiabetic hyperinsulinemic women studied suggests that Ergoset could be of therapeutic benefit in clinical conditions of hyperglycemia and/or dyslipidemia.     

A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM

OBJECTIVE: To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks. RESULTS: The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure. CONCLUSIONS: In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control.     

Racial differences in survival from gynecologic cancer

OBJECTIVE: To determine whether survival from gynecologic cancer is different between African-American and white patients at an inner-city hospital with both a large clinic and a private service. METHODS: We studied 538 patients (89 African American, 449 white) diagnosed with cervical, uterine, or ovarian cancer at a single institution from January 1, 1989 through December 31, 1993. Information was obtained on age, stage, site of disease, histology, and type of health insurance (public or commercial). Insurance coverage was used as a proxy for socioeconomic status. Overall survival was estimated by the method of Kaplan and Meier and compared by the log-rank test. Cox proportional hazard modeling was used to evaluate the effects of multiple factors on survival. RESULTS: African-American patients were significantly older and were more likely to have cervical cancer and public insurance than white patients. Overall survival was worse for African-American patients than for white patients (P < .05). However, stage for stage, there was no significant difference in survival between the groups. There was also no difference when patients were grouped by insurance status. African Americans had a significantly worse survival for cervical cancer than whites, and African-American patients older than 65 years had a worse survival than whites of similar age. On multivariate analysis, only stage and insurance coverage were significant predictors of survival. CONCLUSIONS: African-American patients with gynecologic cancer at our institution have worse overall survival than white patients. The survival difference seems to be due predominantly to differences in socioeconomic status and stage at diagnosis.     

Predictable value of fasting blood glucose level for the incidence of non-insulin-dependent diabetes mellitus]

In order to investigate the predictable value of fasting blood glucose (FBG) level for the incidence of non-insulin-dependent diabetes mellitus (NIDDM), 638 nondiabetic subjects who were investigated in 1986 (including 341 subjects with normal glucose tolerance and 297 subjects with impaired glucose tolerance) were reexamined in 1992. The results showed that the 6-year-incidence of NIDDM was significantly increased with rising of baseline FBG level. After adjusting for age, sex and body mass index (BMI), proportional hazard regression analysis showed that FBG level in impaired glucose tolerance group was positively associated with the development of NIDDM (P = 0.0001). Subjects with mean FBG level of 5.19 mmol/L had a higher risk of developing NIDDM than subjects with mean FBG level of 4.61 mmol/L (RR 2.1, 95% CI 1.19-3.74, P = 0.01). The risk ratio of NIDDM was further increased in the group with mean FBG level of 6.l5 mmol/L (RR = 2.9, 95% CI 1.79-4.59, P = 0.0001). The result indicates that FBG level is an independent risk factor for the development of NIDDM.     

Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors

Measurements of carotid artery wall thickness are often used as a surrogate for atherosclerosis. However, few studies have performed these measurements in populations of Mexican origin. Since Mexicans in Mexico City consume high-carbohydrate diets and have carbohydrate-induced dyslipidemia (high triglyceride and low HDL cholesterol levels) compared with Mexican Americans living in San Antonio, Tex, we questioned whether they also had more atherosclerosis than San Antonio Mexican Americans. Mean maximum intimal-medial thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries were measured in 867 subjects aged 35 to 64 years (40% men) in two Mexican-origin populations, one from San Antonio (n = 202) and the other from Mexico City (n = 665). IMT's in the two cities were compared, and their associations with cardiovascular risk factors were analyzed. Older age, male sex, high levels of total cholesterol, low levels of HDL cholesterol, and high systolic blood pressure were positively associated with both CCA IMT and ICA IMT. Cigarette smoking was significantly associated with ICA IMT. CCA and ICA IMTs in diabetic subjects were thicker than in nondiabetic subjects in both men and women (all P < = .05). CCA IMT was thicker in the San Antonio than the Mexico City subjects after adjustment for cardiovascular risk factors (0.81 versus 0.76 mm in men and 0.77 versus 0.71 mm in women; P < .001 for city difference). San Antonio men also had thicker ICA IMT than their counterparts in Mexico City (0.88 versus 0.83 mm), but the reverse was true for women (0.73 versus 0.77 mm; interaction between sex and city, P < .05). Our results indicate that men had higher carotid IMTs than women. CCA IMT was thicker in San Antonio Mexican Americans than in Mexico City residents. The differences in ICA IMTs between San Antonio and Mexico City were inconsistent. Thus, since Mexico City residents consume high-carbohydrate diets, the data do not support an atherogenic effect of such diets. The interaction between sex and city on ICA IMT deserves further study.     

Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus

OBJECTIVE: To study effects of variation in carbohydrate content of diet on glycemia and plasma lipoproteins in patients with non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: A four-center randomized crossover trial. SETTING: Outpatient and inpatient evaluation in metabolic units. PATIENTS: Forty-two NIDDM patients receiving glipizide therapy. INTERVENTIONS: A high-carbohydrate diet containing 55% of the total energy as carbohydrates and 30% as fats was compared with a high-monounsaturated-fat diet containing 40% carbohydrates and 45% fats. The amounts of saturated fats, polyunsaturated fats, cholesterol, sucrose, and protein were similar. The study diets, prepared in metabolic kitchens, were provided as the sole nutrients to subjects for 6 weeks each. To assess longer-term effects, a subgroup of 21 patients continued the diet they received second for an additional 8 weeks. MAIN OUTCOME MEASURES: Fasting plasma glucose, insulin, lipoproteins, and glycosylated hemoglobin concentrations. Twenty-four-hour profiles of glucose, insulin, and triglyceride levels. RESULTS: The site of study as well as the diet order did not affect the results. Compared with the high-monounsaturated-fat diet, the high-carbohydrate diet increased fasting plasma triglyceride levels and very low-density lipoprotein cholesterol levels by 24% (P < .0001) and 23% (P = .0001), respectively, and increased daylong plasma triglyceride, glucose, and insulin values by 10% (P = .03), 12% (P < .0001), and 9% (P = .02), respectively. Plasma total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels remained unchanged. The effects of both diets on plasma glucose, insulin, and triglyceride levels persisted for 14 weeks. CONCLUSIONS: In NIDDM patients, high-carbohydrate diets compared with high-monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable.     

Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms

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

Accuracy of calculated serum low-density lipoprotein cholesterol for the assessment of coronary heart disease risk in NIDDM patients

OBJECTIVE: To evaluate the accuracy of LDL cholesterol calculated with Friedewald's equation in the assessment of cardiovascular risk in NIDDM patients. RESEARCH DESIGN AND METHODS: The calculation of LDL cholesterol according to Friedewald's formula was compared with the measurement of LDL cholesterol separated by ultracentrifugation in 151 NIDDM patients with fairly good metabolic control (HbA1c < or =10%) and in 405 nondiabetic subjects. RESULTS: Measured and calculated LDL cholesterol was found to be well correlated in both diabetic (r = 0.95) and nondiabetic (r = 0.97) subjects. Compared with measured LDL cholesterol, the calculated LDL cholesterol differed by > or =10% in 34% of samples from diabetic patients and in 26% of samples from nondiabetic subjects (chi(2) = 3.885, P < 0.05). The percentage of error increased when the serum triglyceride (TG) level was > or =200 mg/dl (2.26 mmol/l) and when the ratio of VLDL cholesterol to TG was <0.20 or >0.29 in both groups of subjects. Although the percentage of error from calculated LDL cholesterol was greater in diabetic than in nondiabetic subjects because of the greater prevalence of hypertriglyceridemia in the former group, the misclassification of coronary heart disease risk, according to the cutoff points of the National Cholesterol Education Program (NCEP), was similar in the two groups (25% in diabetic and 22% in nondiabetic subjects). In both groups of patients, the misclassification of coronary heart disease risk was higher when calculation of LDL cholesterol produced values near the cutoff points. CONCLUSIONS: Although accuracy in the estimation of LDL cholesterol is less than ideal, Friedewald's equation seems to be of value in the correct assignment of coronary heart disease risk classes in the great majority of diabetic as well as nondiabetic subjects. Caution must be exercised for subjects in whom calculated LDL cholesterol is close to the cutoff points of the NCEP guidelines.     

Apolipoprotein(a) concentrations in type 2 (non-insulin dependent) diabetic patients from Romania

Several studies suggested that lipoprotein (a)-Lp(a) is an independent atherogenic risk factor. Since non-insulin-dependent diabetes mellitus (NIDDM) is characterized by an increased risk of coronary heart disease (CHD) as related to the general population, the main purpose of our study was to compare the plasma levels of apolipoprotein (a)-(apo) (a) in 30 NIDDM patients hospitalized in our department, and in 20 non-diabetic controls from Timi?oara. Apo (a) values were similar in the two groups (medians, 95% confidence intervals 57 (50-107) in NIDDM versus 58 (51-106) U/l in controls; p = 0.9097). We found weak correlations between apo (a) and hemoglobin A1 (HbA1) (r = 0.42). A significant association was noticed between apo (a) and apo B, both in NIDDM (r = 0.71) and in control subjects (r = 0.81) p < < 0.001. The diabetic patients were screened for microalbuminaria with the MICRAL-test and we compared apo (a) levels in those having albumin excretion values above and under the cut-off point (20 mg/l). Apo (a) concentrations were similar in both samples. We found no association between apo (a) and plasma lipid values. NIDDM patients on fair glycemic control have similar apo (a) concentrations to non-diabetic subjects and they do not seem to be influenced by diabetes duration, HbA1, microalbuminuria and plasma lipid values Apo (a) and apo B are significantly correlated, both in diabetic and non-diabetic subjects.     

Effects of heparin treatment on hemostatic abnormalities in obese non-insulin-dependent diabetic patients

This study was conducted to identify the mechanisms responsible for coagulative and fibrinolytic alterations and to study the effects of a short-term treatment with low-dose heparin on hemostatic abnormalities in obese non-insulin-dependent diabetes mellitus (NIDDM) patients. Four groups of age- and sex-matched patients were studied: (1) lean nondiabetic subjects (n = 30) with a body mass index (BMI) less than 25 kg/m2 (lean control subjects), (2) obese nondiabetic subjects (n = 30) with a BMI greater than 30 kg/m2 (obese control subjects), (3) lean NIDDM patients (n = 30), and (4) obese NIDDM patients (n = 30). All subjects were tested on the following parameters: fibrinogen, factor VII, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), tissue plasminogen activator (t-PA) antigen (Ag) before and after venous occlusion (VO), and plasminogen activator inhibitor type-1 (PAI-1) activity pre- and post-VO. In addition, all these parameters were evaluated in obese NIDDM patients after 10 days of treatment with a single dose of 12,500-U/d subcutaneous calcium heparin and after a 10-day washout period. At baseline, obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients displayed significantly (P < .01) higher levels of fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO and significantly (P < .01) lower levels of t-PA(Ag) post-VO. In obese NIDDM patients treated with heparin fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO levels significantly (P < .01) decreased and t-PA(Ag) post-VO levels significantly (P < .01) increased at the end of treatment. Our findings demonstrate in obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients the hemostatic abnormalities contributing to an enhanced risk of thrombotic complications. We conclude that in obese NIDDM patients, short-term treatment with heparin may reduce this thrombophilic state and have a potential benefit in the progression of diabetic microvascular and macrovascular disease and needs further investigation.     

Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns

BACKGROUND: Because visceral obesity predicts insulin resistance, we studied whether alterations in the gene encoding for the beta 3-adrenergic receptor in visceral fat are associated with insulin resistance. METHODS: We studied the frequency of a cytosine-to-thymidine mutation that results in the replacement of tryptophan by arginine at position 64 (Trp64Arg) of the beta 3-adrenergic receptor by restriction-enzyme digestion with BstOl in 335 subjects from western Finland, 207 of whom were nondiabetic and 128 of whom had non-insulin-dependent diabetes mellitus (NIDDM). We also determined the frequency of the mutation in 156 subjects from southern Finland. Sensitivity to insulin was measured by the hyperinsulinemic-euglycemic clamp technique in 66 randomly selected nondiabetic subjects. RESULTS: In the subjects from western Finland, the frequency of the mutated allele was similar in the nondiabetic subjects and the subjects with NIDDM (12 vs. 11 percent). The mean age of the subjects at the onset of diabetes was lower among those with the mutation than those without it (56 vs. 61 years, P = 0.04). Among the nondiabetic subjects, those with the mutation had a higher ratio of waist to hip circumference (P = 0.02), a greater increase in the serum insulin response after the oral administration of glucose (P = 0.05), a higher diastolic blood pressure (82 vs. 78 mm Hg, P = 0.01), and a lower rate of glucose disposal during the clamp study (5.3 vs. 6.5 mg [29 vs. 36 mumol] per kilogram of body weight per minute; P = 0.04) than the subjects without the mutated allele. In an analysis of sibling pairs, the siblings with the mutation generally had higher waist:hip ratios (P = 0.05) and higher responses of blood glucose and serum insulin after the oral administration of glucose than their siblings without the mutation (P = 0.02 and P = 0.005, respectively). CONCLUSIONS: The Trp64Arg allele of the beta 3-adrenergic receptor is associated with abdominal obesity and resistance to insulin and may contribute to the early onset of NIDDM: