[Show abstract][Hide abstract] ABSTRACT: Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it.
We studied 36 young Hispanic adults without diabetes (ages 18--40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups.
Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese.
Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.
[Show abstract][Hide abstract] ABSTRACT: We measured plasma markers of endothelial dysfunction, vascular inflammation, and pro-coagulation in obese Hispanic/Latino children and adolescents with normal glucose tolerance and determined their relationship to body composition and indexes of glucose and lipid metabolism.
A total of 38 lean or obese Hispanic children and adolescents (10-18 years of age) were selected. The overweight group (n = 21) had a BMI >85th percentile for their age and sex, and the lean group (n = 17) had a BMI between the 25th and 50th percentiles. Studies included an oral glucose tolerance test, measurements of plasma glucose and lipids, several markers of endothelial function and inflammation, and determination of body composition by dual X-ray absorptiometry.
The obese group had higher systolic blood pressure and plasma triglycerides and was more insulin resistant than the lean group. The obese group also had higher plasma soluble intercellular adhesion molecule (259.5 +/- 60.0 vs. 223.2 +/- 47.5 ng/ml, P = 0.047), tumor necrosis factor-alpha (2.57 +/- 1.1 vs. 1.74 +/- 0.6 pg/ml, P = 0.008), high-sensitivity C-reactive protein (2.0 vs. 0.13 mg/l, P < 0.0001), plasminogen-activated inhibitor-1 (47.0 +/- 35.7 vs. 12.0 +/- 5.2 ng/ml, P < 0.0001), tissue plasminogen activator (6.1 +/- 1.9 vs. 4.1 +/- 0.8 ng/ml, P = 0.001), and white blood cell count (6.9 vs. 5.3 x 10(3), P = 0.031) and lower levels of adiponectin (8.7 +/- 3.3 vs. 12.6 +/- 5.2 microg/ml, P = 0.022). No significant differences were observed for soluble vascular cell adhesion molecule or interleukin-6.
Overweight Hispanic children and adolescents with normal glucose tolerance exhibit increased plasma markers of endothelial dysfunction and subclinical inflammation in association with obesity and insulin resistance. These abnormalities may predispose them to the development of type 2 diabetes and cardiovascular disease.
Diabetes care 03/2008; 31(3):576-82. DOI:10.2337/dc07-1540 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify the fasting plasma glucose (FPG) value with the best performance for detecting an abnormal response on the oral glucose tolerance test (OGTT) in patients at risk for having type 2 diabetes.
All patients who underwent a 2-hour OGTT during an 18-month period were included in this study. Pretest and posttest odds, likelihood ratios, and receiver operating characteristic curves were used to identify the FPG value most strongly associated with an abnormal result on the OGTT (either diabetes or impaired glucose tolerance [IGT]).
Of the 1,371 patients who underwent an OGTT during the designated study period, 1,239 fulfilled the inclusion criteria. The prevalence of IGT was 25.34% (314 patients). Diabetes was diagnosed in 141 patients (11.38%). IGT was more commonly found in the FPG strata below 115 mg/dL; above this value, diabetes was more frequently diagnosed. In general, the percentage of cases of IGT increased progressively throughout the "normal" FPG range. The prevalence varied from 11.4% (in patients with FPG values <80 mg/dL) to 32% (in those with FPG levels from 95 to 99.9 mg/dL). FPG values between 95 and 99.9 mg/dL had a likelihood ratio of 2.1 for detecting an abnormal OGTT response, of 1.8 for detecting diabetes, and of 1.66 for detecting IGT. The odds ratio for detecting either IGT or diabetes was increased 2-fold by performing an OGTT. The FPG threshold with the best ability for detecting an abnormal response on the OGTT was 95 mg/dL (sensitivity of 0.72 and specificity of 0.65).
In patients at risk for type 2 diabetes, the FPG cut point (95 mg/dL) most useful for detecting an abnormal OGTT response is included in the normal range of the FPG.
Endocrine Practice 10/2007; 13(6):583-9. DOI:10.4158/EP.13.6.583 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are relatively common lipid disorders caused by mutations of the low-density lipoprotein receptor (LDLR) and apolipoprotein B (apoB) genes, respectively. A third locus on chromosome 1p34.1-p32 was recently linked to FH and the responsible gene has been identified [protein convertase subtilisin/kexin type 9 (PCSK9)].
We assessed the contribution of the LDLR, apoB, and PCSK9 genes as cause of FH in Mexico. Forty six unrelated probands, as well as 68 affected and 60 healthy relatives, were included.
All index cases were diagnosed as having heterozygous autosomal dominant FH. Seventeen of the 46 index cases had LDLR gene mutations, four of which were novel (Fs92ter108, C268R, Q718X, and Fs736ter743); and only one patient had an apoB mutation (R3500Q). We sequenced the PCSK9 gene in the remainder of the 28 probands with no identified LDLR or APOB gene defects; however, no PCSK9 mutations were found, including one large kindred with positive linkage to the 1p34.1-32 locus (multipoint LOD score of 3.3) and two small pedigrees. Linkage was excluded from these three loci in at least four kindreds suggesting that other yet uncharacterized genes are involved.
Our results underline substantial genetic heterogeneity for FH in the Mexican population.
Archives of Medical Research 02/2006; 37(1):102-8. DOI:10.1016/j.arcmed.2005.04.018 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this condition (1p35, 15q25-q26 and 13q). Recently, the responsible gene at the 1p35 locus, encoding an LDL receptor adaptor protein (ARH) has been identified. We studied a Mexican ARH family with two affected siblings. Sequence analysis of the ARH gene (1p35 locus) revealed that the affected siblings are homozygous for a novel mutation (IVS4+2T>G) affecting the donor splice site in intron 4, whereas both the parents and an unaffected sister are heterozygous for this mutation. The IVS4+2T>G mutation results in a major alternative transcript derived from a cryptic splice site, which carries an in-frame deletion of 78 nucleotides in the mature mRNA. The translation of this mRNA yields a mutant protein product (ARH-26) lacking 26 amino acids, resulting in the loss of beta-strands beta6 and beta7 from the PTB domain. This is the first case where a naturally occurring mutant with an altered PTB domain has been identified.
Human Genetics 01/2005; 116(1-2):114-20. DOI:10.1007/s00439-004-1192-9 · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Familial defective apolipoprotein B100 (FDB) is one of the known causes of familial hypercholesterolemia (FH). Its frequency among subjects with FH varies among ethnic groups; information on FH is insufficient for populations from Latin America. We proposed to describe prevalence of FDB in a cohort of Mexican FH probands (n = 30).
We searched for the known FDB mutations using polymerase chain reaction assays. In this set of patients, mean lipid values were representative of FH (cholesterol 351 mg/dL, LDL cholesterol 274 mg/dL, HDL cholesterol 51 mg/dL, and triglycerides 132 mg/dL).
One subject with Arg3500Gln mutation was found: a 44-year-old male with a history of coronary heart disease (CHD) among paternal relatives. His lipid profile was cholesterol 370 mg/dL, LDL-cholesterol 300 mg/dL, HDL-cholesterol 32 mg/dL, and triglycerides 189 mg/dL. Tendinous xanthomata were detected. Three of four siblings, one of three sons, and one of nine nieces and nephews carried the mutation. The mutation was confirmed by automated sequencing. Tendinous xanthomata were absent in affected subjects younger than age 20 years; additionally, the subjects had borderline cholesterol levels.
Our data suggest that FDB explains the small number of FH cases in Mexico. Inclusion of molecular biology assays to the clinical laboratory makes it possible to diagnose affected individuals with borderline cholesterol levels or without tendinous xanthomata.
Archives of Medical Research 01/2003; 34(1):70-5. DOI:10.1016/S0188-4409(02)00452-6 · 2.65 Impact Factor