A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2.

Obesity is a major predisposing factor for the development of several chronic diseases including non-insulin dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD). Leptin is a serum protein which is secreted by adipocytes and thought to play a role in the regulation of body fat. Leptin levels in humans have been found to be highly correlated with an individual's total adiposity. We performed a genome-wide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. A microsatellite polymorphism, D2S1788, mapped to chromosome 2p21 (approximately 74 cM from the tip of the short arm) and showed strong evidence of linkage with serum leptin levels with a lod score of 4.95 (P = 9 x 10(-7)). This locus accounted for 47% of the variation in serum leptin levels, with a residual additive genetic component contributing an additional 24%. This region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR) and pro-opiomelanocortin (POMC). Our results show strong evidence of linkage of this region of chromosome 2 with serum leptin levels and indicate that this region could contain an important human obesity gene.

Role of insulin in endogenous hypertriglyceridemia.

Dietary carbohydrate accentuation of endogenous triglyceride production has been studied in 33 patients. A broad and relatively continuous spectrum of steady-state plasma triglyceride concentrations was produced in 31 of the 33 subjects during 3 wk of a high carbohydrate (fat-free) liquid formula diet. Two patients developed plasma triglyceride concentrations in excess of 2000 mg/100 ml, and these were the only patients we have studied in which carbohydrate induction of hypertriglyceridemia seemed to be associated with a defect in endogenous plasma triglyceride removal mechanisms. In the remaining 31 patients the degree of hypertriglyceridemia was highly correlated with the insulin response elicited by the ingestion of the high carbohydrate formula (P < 0.005). No significant correlation existed between fasting plasma triglyceride concentration and either plasma glucose or free fatty acid concentrations after the high carbohydrate diet, nor was the degree of hypertriglyceridemia related to degree of obesity. It is suggested that hypertriglyceridemia in most subjects results from an increase in hepatic triglyceride secretion rate secondary to exaggerated postprandial increases in plasma insulin concentration.

Insulin delivery rate into plasma in normal and diabetic subjects.

Removal of insulin-(131)I from plasma was studied in normal and diabetic subjects with both single injection and continuous infusion of isotope techniques. Patients were studied either in the fasting state or during steady-state hyperglycemia produced by a continuous intravenous glucose infusion. Steady-state plasma insulin concentration during these studies ranged from 10 to 264 muU/ml. Labeled insulin specific activity time curves consisted of more than one exponential, indicating that a multicompartmental system for insulin metabolism exists. A mathematical technique which is applicable to non-first order processes was used to calculate the rate at which insulin was lost irreversibly from the plasma insulin pool. A direct, linear relationship was found between insulin irreversible loss rate and plasma insulin concentration over the range of concentrations studied. This linearity implies lack of saturability of the insulin removal mechanism. Since the plasma insulin pool was in a steady state during these studies, insulin irreversible loss rate was equal to the rate at which newly secreted insulin was being delivered to the general circulation. Therefore, these results indicate that changes in plasma insulin concentration result from parallel changes in the rate of insulin delivery and not from changes in the opposite direction of the rate of insulin removal. A wide range of insulin delivery rates was found among patients with similar plasma glucose concentrations, suggesting that there exists considerable variability in responsiveness to endogenous insulin among these patients.

A paired sibling analysis of the beta-3 adrenergic receptor and obesity in Mexican Americans.

The beta3 adrenergic receptor, located on chromosome 8, is a regulator of energy expenditure and lipolysis. A missense mutation in this gene, characterized by the replacement of tryptophan by arginine at codon 64 (Trp64Arg), is associated with obesity in some studies. We examined the effect of this variant on obesity in Mexican Americans, using a paired sibling design to minimize variability due to genetic background and a previously identified major susceptibility locus for obesity. We identified 45 sib-pairs that were concordant (identical by descent) for a locus on chromosome 2 which we have shown previously to be tightly linked to obesity in this population. The Trp64Arg variant, detected by PCR-restriction fragment length polymorphism analysis, was present in one sibling within each of the 45 sib-pairs. Presence of the variant was associated with significantly higher values in body mass index (P = 0.04), fat mass (P = 0.04), and waist circumference (P = 0.05). We conclude that the Trp64Arg variant is associated with obesity in this Mexican American population. The paired sibling design probably enhanced our ability to detect the effects of this variant by allowing us to account for variation attributable to another obesity susceptibility locus and to background genes.

Evaluation of tight junction protein 1 encoding zona occludens 1 as a candidate gene for albuminuria in a Mexican American population.

Albuminuria, a hallmark of diabetic nephropathy, has been shown to be significantly heritable in multiple studies. Therefore, the identification of genes that affect susceptibility to albuminuria may lead to novel avenues of intervention. Current evidence suggests that the podocyte and slit diaphragm play a key role in controlling the selective sieve of the glomerular filtration barrier, and podocyte-specific genes have been identified that are necessary for maintaining its integrity. We therefore investigated the role of gene variants of tight junction protein (TJP1) which encodes another slit diaphragm-associated protein zona occludens 1 as risk factors for albuminuria in the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), which consists of extended Mexican-American families with a high prevalence of type 2 diabetes. Albuminuria, defined as an albumin (mg/dl) to creatinine (mg/dl) ratio (ACR) of 0.03, which is approximately equivalent to a urinary albumin excretion (UAE) >30 mg/day, was present in a total of 14.9% of participants, and 31% had type 2 diabetes. The TJP1 exons, flanking intronic sequence, and putative proximal promoter regions were investigated in this population. Twentynine polymorphisms, including 7 nonsynonymous SNPs, were identified and genotyped in all subjects of this study for association analysis. Three sets of correlated SNPs, which include 3 exonic SNPs, were nominally associated with ACR (p value range 0.007-0.049); however, the association with the discrete trait albuminuria was not significant (p value range 0.094-0.338). We conclude that these variants in TJP1 do not appear to be major determinants for albuminuria in the SAFDGS; however, they may play a minor role in its severity in this Mexican-American population. Further examination of the TJP1 gene region in this and other cohorts will be useful to determine whether ZO-1 plays a significant role in glomerular permselectivity.

Breast cancer mortality and diet in the United States.

Internationally, breast cancer mortality is correlated with intestinal lactase sufficiency and dairy product consumption beyond childhood. Within the United States, age-adjusted breast cancer mortality is positively associated with consumption of milk, butter, and total milk fat in regional analyses, and it is associated with milk demand in state-based analyses. Breast cancer mortality is also positively associated with demand for total calories, protein, fat, beef, and table fats (butter and margarine), and it is negatively associated with egg demand. Only the associations with milk and egg demand, however, survive when the Southern states are eliminated from the analyses or when either age of first marriage or income is controlled. The associations with milk and egg demand persist despite multiple controls for other dietary and demographic variables, although the association with milk demand loses statistical significance in some second- and third-order partial correlations. The inverse correlation with egg demand is strong but in the opposite direction from what might have been expected from previous studies. The correlation between milk demand and breast cancer mortality, although weaker, is consistent with results from previous studies, and it suggests a possible special role for dairy products in the etiology of breast cancer.

Low fasting plasma glucose level as a predictor of cardiovascular disease and all-cause mortality.

BACKGROUND: Although medical textbooks usually classify fasting plasma glucose <70 or 80 mg/dL (<3.89 or 4.44 mmol/L) as abnormal, the prognosis for patients with low fasting plasma glucose is unclear. METHODS AND RESULTS: We conducted prospective cohort studies among 40 069 men and women to investigate the association between fasting plasma glucose levels and cardiovascular disease and all-cause mortality. We documented a U-shaped relation between fasting plasma glucose and mortality. In addition to diabetes and impaired fasting glucose levels, low fasting plasma glucose levels were also associated with high mortality. After multivariate adjustment for age, sex, study population, ethnicity, current smoking status, high blood pressure, total cholesterol, body mass index, triglycerides, history of cardiovascular disease and cancer, and a family history of cardiovascular disease, patients with fasting plasma glucose <70 mg/dL (<3.89 mmol/L) had a 3.3-fold increased risk of cardiovascular disease mortality, and patients with fasting plasma glucose 70 to 79 mg/dL (3.89 to 4.43 mmol/L) had a 2.4-fold increased risk compared with the risk in patients with fasting plasma glucose 80 to 109 mg/dL (4.44 to 6.05 mmol/L) (tests for trend P<0.0001). Participants with low fasting plasma glucose levels also had increased risk of all-cause mortality (test for trend P<0.0001). CONCLUSIONS: Participants with low fasting plasma glucose levels had a high risk of cardiovascular disease and all-cause mortality.

Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state.

BACKGROUND: Subjects who convert to type 2 diabetes mellitus have increased cardiovascular risk factors relative to nonconverters. However, it is not known whether these atherogenic changes in the prediabetic state are predominantly due to insulin resistance, decreased insulin secretion, or both. METHODS AND RESULTS: We examined this issue in the 7-year follow-up of the San Antonio Heart Study, in which 195 of 1734 subjects converted to type 2 diabetes. At baseline, converters had significantly higher body mass index, waist circumference, triglyceride concentration, and blood pressure and lower HDL cholesterol than nonconverters. Atherogenic changes in converters were markedly attenuated (and no longer significant) after adjustment for the homeostasis model assessment of insulin resistance (HOMA IR, a surrogate for insulin resistance); in contrast, the differences in risk factors between converters and nonconverters increased after adjustment for the ratio of early insulin increment to early glucose increment (DeltaI(30-0)/DeltaG(30-0)) during an oral glucose tolerance test (a surrogate for insulin secretion). We also compared converters who had a predominant insulin resistance (high HOMA IR and high DeltaI(30-0)/DeltaG(30-0)) (n=56) and converters who had a predominant decrease in insulin secretion (low HOMA IR and low DeltaI(30-0)/DeltaG(30-0)) (n=31) with nonconverters (n=1539). Only the converters who were insulin resistant had higher blood pressure and triglyceride levels and lower HDL cholesterol levels than nonconverters. CONCLUSIONS: Our data suggest that atherogenic changes in the prediabetic state are mainly seen in insulin-resistant subjects and that strategies to prevent type 2 diabetes might focus on insulin-sensitizing interventions rather than interventions that increase insulin secretion because of potential effects on cardiovascular risk.

Diabetes and cardiovascular disease. The "common soil" hypothesis.

Unlike classical microvascular complications, large-vessel atherosclerosis can precede the development of diabetes, suggesting that rather than atherosclerosis being a complication of diabetes, both conditions have common genetic and environmental antecedents, i.e., they spring from a "common soil." It is now known that adverse environmental conditions, perhaps related to less-than-optimal nutrition, in fetal and early life are associated with an enhanced risk of both diabetes and cardiovascular disease many decades later. These same adverse environmental conditions are also associated with the development in adult life of abdominal obesity and the insulin-resistance syndrome (IRS). The IRS consists of glucose intolerance, hyperinsulinemia, dyslipidemia (high triglyceride and low high-density lipoprotein [HDL] cholesterol levels), and hypertension. Although the mechanism underlying this cluster is controversial, the statistical association is well established. All of the elements of the IRS have been documented as risk factors for type II diabetes. Some, but not all, of these elements are also cardiovascular disease risk factors, in particular, hypertension and low HDL cholesterol. Other factors associated with the IRS that may enhance cardiovascular disease risk are plasminogen activator inhibitor 1 and small, dense low-density lipoprotein particles. Whether insulin itself is a risk factor remains controversial, but recent epidemiological evidence has been mostly negative. This question has marked clinical relevance because if the IRS enhances cardiovascular disease risk by virtue of its concomitant factors and not the hyperinsulinemia per se, this would tend to alleviate concerns that intensive insulin management of type II diabetic subjects could enhance the risk of large-vessel atherosclerosis. Clinical trials are urgently needed to settle this point.

Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans.

The relative importance of insulin resistance and abnormal insulin secretion as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM) is still controversial. Few data are available on insulin secretion as a risk factor for the development of NIDDM, especially in subjects with normal glucose tolerance. We examined the relation of fasting insulin (as a marker of insulin resistance) and the ratio of change in insulin to change in glucose during the first 30 min after glucose ingestion (delta I30/delta G30) (as a marker of insulin secretion) as predictors of the 7-year development of NIDDM in 714 initially nondiabetic Mexican-Americans. NIDDM developed in 99 subjects. The relative risk of NIDDM increased with higher quartiles of fasting insulin (quartile 1 [low], 1.0; quartile 2, 1.5; quartile 3, 2.0; and quartile 4 [high], 3.7; P < 0.0001) and lower delta I30/delta G30 (quartile 1 [low], 6.9; quartile 2, 1.9; quartile 3, 1.1; quartile 4 [high], 1.0; P < 0.001). Subjects with both increased fasting insulin and decreased delta I30/delta G30 had independent increases in NIDDM incidence (P < 0.001). Further, when we stratified subjects by baseline glucose tolerance, both increased fasting insulin and decreased delta I30/delta G30 significantly predicted NIDDM in subjects with both impaired and normal glucose tolerance at baseline. We conclude that both decreased insulin secretion (as assessed by low delta I30/delta G30) and increased insulin resistance (as assessed by fasting insulin) predict the development of NIDDM in Mexican-Americans, a group previously characterized as having hyperinsulinemia and insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Lp(a) concentrations in NIDDM.

NIDDM patients have a two- to fourfold increased risk of CHD relative to nondiabetic subjects. This excess risk is explained only partially by increased levels of standard risk factors. We compared the plasma concentrations of Lp(a) in NIDDM patients (n = 260) and nondiabetic subjects (n = 336) who participated in a population-based study (San Antonio Heart Study). Lp(a) was measured using a monoclonal anti-Lp(a) antibody. NIDDM patients and nondiabetic subjects had similar Lp(a) concentrations for both men (13.6 +/- 1.5 vs. 16.1 +/- 1.4 mg/dl) and women (12.6 +/- 0.8 vs. 15.9 +/- 1.3 mg/dl) (P = 0.361). Duration of diabetes and level of fasting glycemia were not significantly related to Lp(a) concentrations. Lp(a) levels were significantly higher in patients who had higher total and LDL cholesterol levels. We conclude that in a large population-based study, Lp(a) levels are not increased in NIDDM patients.

Effects of NIDDM on lipoprotein(a) concentration and apolipoprotein(a) size.

We investigated the effects of non-insulin-dependent diabetes mellitus (NIDDM) on lipoprotein(a) (Lp[a]) and apolipoprotein(a) (apo[a]) in a population of Mexican-Americans. In plasma samples from 536 subjects, we measured Lp(a) concentrations, and we estimated apo(a) isoform sizes following immunostaining of plasma proteins resolved using sodium dodecyl sulfate electrophoresis. We identified 81 diabetic subjects who had 108 distinct apo(a) isoform bands. We then identified 81 nondiabetic subjects from the remainder who were closely matched for apo(a) phenotype (i.e., number and size of apo(a) isoform bands). As expected, the diabetic group had higher levels of glucose and insulin (both fasted and 2 h after glucose challenge) and triglycerides, and lower levels of high-density lipoprotein (HDL) cholesterol when compared with the matching nondiabetic group. Moreover, the diabetic group also had significantly lower Lp(a) concentrations than the nondiabetic subjects (10.6 vs. 13.6 mg/dl, P = 0.045) using a paired Student's t test. To detect the effects of diabetes on apo(a) size, we identified by pedigree analysis the nondiabetic family members who possessed alleles identical to those in the diabetic group. When we compared the average sizes for each allele, we found that apo(a) isoforms averaged 4.1 kDa larger in diabetic subjects than the genetically identical apo(a) measured in nondiabetic subjects (P = 0.044, n = 36 alleles). In summary, we have detected significant effects of NIDDM both on Lp(a) concentrations and on apo(a) size.

Association between NIDDM, RH blood group, and haptoglobin phenotype. Results from the San Antonio Heart Study.

We examined seven red cell antigen and 10 polymorphic protein phenotypes in 1237 Mexican Americans randomly selected from three San Antonio neighborhoods. Statistically significant associations were found between non-insulin-dependent diabetes mellitus (NIDDM) and RH blood type (X2 = 32.87, df = 10, P = 0.0003) and haptoglobin phenotype (X2 = 9.15, df = 2, P = 0.010). The haptoglobin association showed a dose effect with a single dose of the haptoglobin-1 allele associated with an approximately 50% increase and a double dose of the haptoglobin-1 allele associated with an approximately 100% increase in NIDDM prevalence. Multivariate analysis indicated statistically significant associations between NIDDM and age, sex, adiposity, and neighborhood of residence. However, even after taking these potential confounding variables into account, there was still a significant, independent association between NIDDM and haptoglobin phenotype. The results suggest that the haptoglobin gene may be in linkage disequilibrium with a major susceptibility gene for NIDDM.

Relationship of proinsulin and insulin to cardiovascular risk factors in nondiabetic subjects.

Recent data suggest that proinsulin is strongly associated with cardiovascular risk factors in diabetic subjects. However, this relationship has not been examined in nondiabetic subjects. Therefore, we examined the relation of proinsulin to lipids, obesity (body mass index), and waist-to-hip ratio in 260 nondiabetic individuals from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Proinsulin was measured by radioimmunoassay, and insulin was measured by a Linco radioimmunoassay that does not cross-react with proinsulin. Fasting insulin was significantly associated with body mass index (0.42), waist-to-hip ratio (r = 0.30), triglyceride (r = 0.29), high-density lipoprotein cholesterol (r = -0.20), and systolic blood pressure (r = 0.16) but not significantly related to diastolic blood pressure (r = 0.11). Fasting proinsulin was significantly associated with body mass index (r = 0.19), waist-to-hip ratio (r = 0.25), triglyceride (r = 0.41), systolic blood pressure (r = 0.19), and diastolic blood pressure (r = 0.15). Proinsulin was more strongly related to increased triglyceride than insulin despite its weaker relationship to obesity. In multivariate analyses, proinsulin continued to be significantly related to triglyceride concentrations (explaining 23.1% of the variance) and to systolic blood pressure (explaining 4.0% of the variance), even after adjusting for insulin. These observations suggest that proinsulin should be measured in addition to insulin in epidemiological studies. Proinsulin may be a marker for metabolic decompensation in prediabetic subjects.

Higher proinsulin and specific insulin are both associated with a parental history of diabetes in nondiabetic Mexican-American subjects.

Both insulin resistance and decreased insulin secretion have been hypothesized to be precursors of non-insulin-dependent diabetes. An elevated proinsulin concentration reflects abnormal proinsulin processing and could indicate abnormal insulin secretion. We examined fasting insulin (measured by a radioimmunoassay that does not cross-react with proinsulin), as a marker of insulin resistance, and proinsulin and the fasting proinsulin-to-insulin ratio, as markers of impaired proinsulin processing, in 597 nondiabetic Mexican-Americans from the San Antonio Heart Study. Fasting insulin, proinsulin, and the fasting proinsulin-to-insulin ratio were higher in subjects with a parental history of diabetes than in subjects without such a history. These differences remained statistically significant after adjustment for obesity, body fat distribution, and glucose tolerance. A parental history of diabetes in nondiabetic Mexican-Americans is associated with an increase in fasting specific insulin and a disproportionate increase in proinsulin relative to insulin. These data suggest that both increased insulin resistance and abnormal processing of proinsulin are present in offspring of parents with diabetes.

Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution.

Few data exist on predictors of non-insulin-dependent (type II) diabetes mellitus. We examined body mass index (BMI), ratio of subscapular-to-triceps skin fold (centrality index), and fasting glucose and insulin concentrations as predictors of decompensation to type II diabetes in Mexican Americans, a population at high risk for this disorder. Twenty-eight of 474 initially nondiabetic Mexican Americans developed type II diabetes after 8 yr of follow-up. Converters to diabetes were older and had higher BMIs, centrality indices, and fasting glucose and insulin concentrations than nonconverters. Subjects in the highest quartile of the insulin distribution had 6.6 times the risk of developing type II diabetes as subjects in the remaining three quartiles combined (95% confidence interval [CI] = 3.14-13.7). In multivariate analysis, fasting glucose (odds ratio [OR] = 5.80, 95% CI = 2.57-13.1) and insulin (OR = 3.12, 95% CI = 1.36-7.14) remained significantly related to conversion to diabetes. However, BMI and centrality index, which were significantly related to conversion in the univariate analysis, were no longer significant in the multivariate analysis once glucose and insulin concentrations were taken into consideration, suggesting that the effect of these variables may be mediated by insulin resistance. Nearly half of the incident cases developed in a subset of the population who were simultaneously in the highest quartile of both fasting insulin and glucose concentrations (population-attributable risk 44.2%). Our results support the insulin resistance/pancreatic exhaustion theory of type II diabetes.

Leptin concentrations in diabetic and nondiabetic Mexican-Americans.

Leptin, the product of the OB gene, is increased in obese individuals, suggesting resistance to its effect. We questioned whether subjects with NIDDM have an altered regulation of serum leptin levels. We used a radioimmunoassay to measure serum leptin levels in three groups from the San Antonio Heart Study: 1) 50 Mexican-Americans with NIDDM; 2) 50 nondiabetic Mexican-Americans matched by age and sex to the diabetic Mexican-Americans; and 3) 50 nondiabetic Mexican-Americans matched by age, sex, and BMI to the diabetic Mexican-Americans. Leptin concentrations did not differ significantly by diabetic status. Leptin concentrations were significantly correlated with BMI in all groups (NIDDM women: r = 0.637; nondiabetic women: r = 0.772; NIDDM men: r = 0.849; and nondiabetic men: r = 0.686; all P < 0.001). Leptin levels were higher in women than in men regardless of diabetic status. We concluded that the leptin concentrations were not different in diabetic and nondiabetic subjects and that the association of leptin with obesity was similar in diabetic and nondiabetic subjects.

Do upper-body and centralized adiposity measure different aspects of regional body-fat distribution? Relationship to non-insulin-dependent diabetes mellitus, lipids, and lipoproteins.

Both central and upper-body adiposity are associated with high rates of type II non-insulin-dependent diabetes mellitus (NIDDM), high triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels. Previous data have also suggested that central and upper-body adiposity are relatively uncorrelated and hence may measure different aspects of regional body fat distribution. We assessed body mass index (BMI), the ratio of subscapular-to-triceps skinfold (STR), the ratio of waist-to-hip circumference (WHR), lipids, lipoproteins, and glucose tolerance in 738 Mexican Americans (ages 25-64 yr), who participated in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors. NIDDM was diagnosed according to National Diabetes Data Group criteria. In general, STR and WHR were associated with high NIDDM rates, low HDL cholesterol levels, and high triglyceride levels, although WHR was somewhat more predictive of these than STR. In females, BMI, WHR, and STR all made independent contributions to prediction of NIDDM and HDL cholesterol; in males, WHR and STR both made independent contributions to prediction of triglyceride levels. This suggests that both indices may measure different aspects of body-fat distribution. Investigators should consider measuring both of these indicators of body-fat distribution in studies of diabetes and other cardiovascular risk factors, although if only a single measure is feasible, WHR appears to be preferable.

Genetic and environmental determinants of type II diabetes in Mexico City and San Antonio.

To study genetic and environmental determinants of non-insulin-dependent (type II) diabetes, we compared a random sample of 35- to 64-yr-old Mexican-American men and women living in several low-income barrio neighborhoods of San Antonio to similarly aged Mexicans living in a low-income colonia of Mexico City (Colonia Liberales). A total of 1138 Mexican Americans, representing 64.3% of the original sample, and 646 Mexicans, representing 69.2% of the original sample, participated in the survey. Diabetes was diagnosed using World Health Organization criteria. Genetic susceptibility to type II diabetes was inferred from the percentage of Native American genetic admixture as estimated from skin reflectance measurements. The prevalence of diabetes was 36% higher among San Antonio Mexican Americans than among Mexicans in Mexico City; this difference was highly statistically significant (age- and sex-adjusted prevalence ratio 1.36, P = 0.006). This excess was observed despite the fact that genetic susceptibility, as inferred from the admixture estimates, was similar in the two cities. On the other hand, Mexicans were somewhat leaner as measured by body mass index and skin folds. Mexican women consumed fewer total calories than Mexican-American women, but there was no difference in the caloric intake of men. Mexico City residents ate less fat (18-19% of total calories vs. 31-32% in San Antonio, P less than 0.001), more carbohydrate (64-65 vs. 49%, P less than 0.001), and performed more physical activity than San Antonio Mexican Americans. Mexicans appeared to consume more refined sugar than Mexican Americans.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of NIDDM and impaired glucose tolerance in hypertensive subjects. The San Antonio Heart Study.

Hypertension often occurs in association with NIDDM and IGT. We examined the association of hypertension at baseline to the 8-yr incidence of NIDDM and IGT in 1471 subjects who participated in the San Antonio Heart Study. Subjects who were hypertensive at baseline had a higher incidence of NIDDM (8.9 vs. 4.9%, P = 0.041) and IGT (25.2 vs. 10.0%, P < 0.001) than subjects who were normotensive at baseline. After adjusting for age, sex, ethnicity, obesity, body fat distribution, fasting glucose, and insulin, this excess was eliminated for NIDDM, but not for IGT. Specifically, the adjusted OR for NIDDM in hypertensive versus normotensive patients was 0.73 (95% Cl 0.34-1.58), whereas the adjusted OR for IGT was 1.87 (95% Cl 1.08-3.22). The excess risk of NIDDM in hypertensive patients can be explained by their greater age, obesity, more unfavorable body fat distribution, and hyperinsulinemia, whereas the excess risk of IGT is independent of these factors.