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Biomedical subjects

Nicola Abate

Publications and source records attributed to Nicola Abate.

17 recordsLinked to original sources
PubMed2007

The Q121/Q121 genotype of ENPP1/PC-1 is associated with lower BMI in non-diabetic whites.

This study investigated the role of the ENPP1/PC-1 gene K121Q polymorphism in predicting BMI (kg/m2) in non-diabetic individuals. Three independent samples (n = 631, n = 304, and n = 505) of adult whites were analyzed. Selection criteria were fasting plasma glucose level <126 mg/dL, absence of severe obesity (BMI > or =40 kg/m2), and lack of treatment known to modulate BMI. In Sample 1, BMI values were different in individuals carrying the K121/K121 (KK), K121/Q121 (KQ), and Q121/Q121 (QQ) genotypes (25.5 +/- 4.3, 25.3 +/- 4.1, and 22.8 +/- 2.5 kg/m2, respectively (adjusted p = 0.022); BMI values in Samples 2 and 3 also tended to be different, although the differences, after adjustment for age and sex, did not reach statistical significance. When data were pooled, BMI values were 25.8 +/- 4.4, 25.6 +/- 4.4, and 23.6 +/- 3.3 kg/m2 in KK, KQ, and QQ individuals (adjusted p = 0.029). According to a recessive model, QQ individuals had lower BMI values than KK and KQ individuals combined (23.6 +/- 3.3 kg/m2 vs. 25.7 +/- 4.4 kg/m2; adjusted p = 0.008). These data suggest that the QQ genotype of the ENPP1/PC-1 gene is associated with lower BMI. If similar results are confirmed in prospective studies, the K121Q polymorphism may help identify people at risk for obesity.

Adult↗
PubMed2006

Other than potency, are all statins the same?

Statins have been shown to interact with metabolic pathways that potentially affect physiologic functions beyond cholesterol balance. We may broadly categorize non-lipid effects of statins as clinically favorable or clinically detrimental. Whether non-lipid effects of statins are of clinical significance and whether there are differences in non-lipid effects among statins remain points of major current controversy. This review evaluates the available information on potential differences among statins in non-lipid effects.

Clinical Trials as Topic↗
PubMed2006

Should all patients with metabolic syndrome be treated with statins?

The metabolic syndrome is a constellation of cardiovascular risk factors that include atherogenic dyslipidemia, elevated blood pressure, abdominal/truncal obesity, and glucose intolerance. Current National Cholesterol Education Program (NCEP) recommendations for specific treatment of the metabolic syndrome are centered on therapeutic lifestyle changes. A recent publication from the NCEP Adult Treatment Panel III suggests pharmacologic intervention for parameters of metabolic syndrome, including dyslipidemia, hypertension, and hyperglycemia, to prevent cardiovascular disease, based on risk category. This review looks at the clinical trial evidence to support the use of statins in metabolic syndrome.

Atherosclerosis↗
PubMed2006

Mechanisms of disease: Ectonucleotide pyrophosphatase phosphodiesterase 1 as a 'gatekeeper' of insulin receptors.

Insulin resistance is pathogenic for type 2 diabetes and cardiovascular disease. Several inhibitors of insulin signaling have a role in human insulin resistance. The transmembrane glycoprotein ectonucleotide pyrophosphatase phosphodiesterase 1 (E-NPP1; also known as plasma cell membrane glycoprotein PC-1) interacts with the insulin receptor and inhibits subsequent signaling by decreasing its beta-subunit autophosphorylation. E-NPP1 is overexpressed in skeletal muscle, adipose tissue and cultured skin fibroblasts of insulin-resistant individuals who are not yet obese or diabetic, which indicates that excessive E-NPP1 expression is an early, intrinsic defect in human insulin resistance. Genetic studies also support a primary role of E-NPP1 in insulin resistance. Among other variants, a missense polymorphism, Lys121Gln, has been described. The Gln121 variant is a stronger inhibitor than Lys121 of insulin receptor function, and is associated with insulin resistance, type 2 diabetes and both cardiovascular and nephrovascular complications in diabetic patients. E-NPP1 is measurable in human serum, where it might represent a valuable biomarker of insulin resistance, but its relationship to tissue and systemic insulin resistance remains to be thoroughly elucidated. Understanding the mechanisms that regulate E-NPP1 expression and/or function might render this protein a new target for strategies to treat and prevent type 2 diabetes and cardiovascular disease.

Animals↗
PubMed2006

Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity.

OBJECTIVE: To determine whether the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGN AND METHODS: South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-gamma Pro12Ala was determined using restriction fragment-length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS: The Caucasian diabetic subjects had significantly lower prevalence of PPAR-gamma 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P = 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR-gamma Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 +/- 68 and 54 +/- 33 microU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-gamma Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS: Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR-gamma Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

Absorptiometry, Photon↗
PubMed2005

Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus Atorvastatin (VYVA) study.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is the primary therapeutic target in the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines. This study tested the hypothesis that ezetimibe/simvastatin, a lipid-lowering agent that inhibits both intestinal cholesterol absorption and cholesterol synthesis, provides greater LDL-C reductions than atorvastatin across dose ranges. METHODS: This multicenter, double-blind, 6-week parallel-group study randomized 1902 patients with LDL-C above ATP III goal to atorvastatin (10, 20, 40, or 80 mg) or to ezetimibe/simvastatin (10/10, 10/20, 10/40, or 10/80 mg). Patients were stratified by prerandomization LDL-C level. RESULTS: At each milligram-equivalent statin dose comparison, and averaged across doses, ezetimibe/simvastatin provided greater LDL-C reductions (47%-59%) than atorvastatin (36%-53%). Ezetimibe/simvastatin 10/40 and 10/80 mg also provided significantly greater high-density lipoprotein cholesterol (HDL-C) increases than atorvastatin 40 and 80 mg. Triglyceride reductions were similar for all comparisons. More ezetimibe/simvastatin than atorvastatin patients with coronary heart disease (CHD) or CHD risk equivalents attained the ATP III LDL-C goal of <100 mg/dL and the optional LDL-C target of <70 mg/dL. C-reactive protein reductions were similar between treatment groups. Consecutive elevations in alanine aminotransferase and/or aspartate aminotransferase occurred in significantly more atorvastatin patients than ezetimibe/simvastatin patients. No myopathy or liver-related adverse events led to study discontinuation with either drug. CONCLUSIONS: Ezetimibe/simvastatin was more effective than atorvastatin in lowering LDL-C at each dose comparison and provided greater increases in HDL-C at the 40- and 80-mg statin dose. Ezetimibe/simvastatin is a highly efficacious, well-tolerated treatment option for hypercholesterolemic patients.

Adult↗
PubMed2005

ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes.

Genetic susceptibility modulates the impact of obesity on risk for type 2 diabetes. The present study evaluates the role of ENPP1 K121Q polymorphism in prediction of type 2 diabetes in three populations that differ in susceptibility to diabetes and environmental exposure. The three cohorts included 679 nonmigrant South Asians living in Chennai, India (223 with type 2 diabetes); 1,083 migrant South Asians living in Dallas, Texas (121 with type 2 diabetes); and 858 nonmigrant Caucasians living in Dallas, Texas (141 with type 2 diabetes). Patients with type 2 diabetes were included in these cohorts if they had diabetes onset before the age of 60 years. The prevalence of subjects carrying the polymorphic ENPP1 121Q allele was 25% in the nondiabetic group and 34% in the diabetic group of South Asians living in Chennai (P = 0.01). The prevalence in the nondiabetic and diabetic groups were 33 and 45% (P = 0.01) for the South Asians living in Dallas and 26 and 39% (P = 0.003) for the Caucasians. Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that ENPP1 121Q predicts genetic susceptibility to type 2 diabetes in both South Asians and Caucasians.

Adult↗
PubMed2004

The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance.

BACKGROUND: Uric acid nephrolithiasis primarily results from low urinary pH, which increases the concentration of the insoluble undissociated uric acid, causing formation of both uric acid and mixed uric acid/calcium oxalate stones. These patients have recently been described as exhibiting features of insulin resistance. This study was designed to evaluate if insulin resistance is associated with excessively low urinary pH in overtly healthy volunteers (non-stone formers) and if insulin resistance may explain the excessively low urinary pH in patients with uric acid nephrolithiasis. METHODS: Fifty-five healthy volunteers (non stone-formers) with a large range of body mass index and 13 patients with recurrent uric acid nephrolithiasis underwent hyperinsulinemic euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of adiposity. A subgroup of 35 non-stone formers had 2-hour timed urinary collection before and during the hyperinsulinemic phase of the clamp studies. RESULTS: For the non-stone former population, low insulin sensitivity measured as glucose disposal rate significantly correlated with low 24-hour urinary pH (r= 0. 35; P= 0.01). In addition to the previously described acidic urine pH and hypouricosuria, patients with recurrent uric acid nephrolithiasis were found to be severely insulin resistant (glucose disposal rate: uric acid stone-formers vs. normals; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg of lean body mass, P= 0.008). Acute hyperinsulinemia was associated with higher urinary pH (6.1 +/- 0.7 at baseline to 6.8 +/- 0.7 during hyperinsulinemia; P < 0.0001), urinary ammonia excretion (2.7 +/- 1.6 mEq/2 hr at baseline and 4.0 +/- 2.6 mEq/2 hr P= 0.002) and urinary citrate excretion (48 +/- 33 mg/2 hr at baseline and 113 +/- 68 mg/2 hr P < 0.0001). CONCLUSION: We conclude that one renal manifestation of insulin resistance may be low urinary ammonium and pH. This defect can result in increased risk of uric acid precipitation despite normouricosuria.

Acids↗
PubMed2004

Adipose tissue metabolites and insulin resistance in nondiabetic Asian Indian men.

Obesity-related insulin resistance is associated with changes in adipose tissue release of leptin, adiponectin, and nonesterified fatty acids (NEFAs). We have previously described that persons originating from the Indian subcontinent (Asian Indians) manifest excessive insulin resistance even in the absence of obesity. Therefore, in this study, we tested the hypothesis that nondiabetic, insulin-resistant Asian Indians differ from less insulin-resistant Caucasians of similar age and body composition in adipose tissue production of leptin and adiponectin, and in suppression of plasma NEFA concentrations during hyperinsulinemia. Seventy-nine Asian Indian men were compared with 61 Caucasian men. Higher plasma NEFAs and leptin in Asian Indians (P < 0.0001 and P = 0.003 for NEFAs and leptin, respectively) and lower plasma concentrations of adiponectin (P = 0.009) were not explained by body fat content and distribution. Oral glucose tolerance test studies revealed that Caucasian men had greater suppression of plasma NEFAs than Asian Indian men. We conclude that plasma concentrations of the adipose tissue metabolites leptin and NEFAs are higher and that of adiponectin is lower in insulin-resistant Asian Indians compared with more insulin-sensitive Caucasians. These differences may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease in nonobese Asian Indians.

Adiponectin↗
PubMed2003

Hyperhomocysteinemia in Asian Indians living in the United States.

Hyperhomocysteinemia has been reported in Asian Indians (people from Indian subcontinent) to be related to relatively low plasma levels of folate and vitamin B-12. However, a true ethnic-related characteristic has not been excluded. This study was done to determine whether Asian Indians have high plasma homocysteine compared with Caucasians in the United States in the era of folate fortification, and whether low vitamin B-12 or insulin resistance may account for possible interethnic differences in plasma homocysteine. A total of 227 Asian Indians (131 males and 96 females) and 155 Caucasians (66 males and 89 females) completed a questionnaire for medical, family, and personal history. They had height, weight, and blood pressure measured and fasting blood drawn for routine chemistry, TSH, plasma homocysteine, vitamin B-12, and folate. Oral glucose tolerance test and vitamin B-6 was measured in a subgroup of 66 Asian Indians (47 males and 19 females) and 63 Caucasians (33 males and 30 females). Asian Indians were found to have significantly higher plasma homocysteine than Caucasians (median of 12.6 and 8.0 micro mol/liter, P < 0.0001, respectively) and lower plasma concentrations of B-6 (median 49 vs. 70 nmol/liter; P = 0.05, respectively). Plasma folate was relatively high and similar in both ethnic groups. Plasma vitamin B-12 was significantly lower in Asian Indians than Caucasians (median of 204 vs. 320 pmol/liter, P < 0.0001, respectively). Vitamin B-12 correlated significantly with plasma homocysteine. When vitamin B-12 was between 150 and 379 pmol/liter, the regression curve between vitamin B-12 and homocysteine had significantly different slope in the two ethnic groups (P value < 0.05) and Asian Indians had significantly higher homocysteine for any level of vitamin B-12. Although insulin resistance, measured as insulin area under the curve by oral glucose tolerance test was higher in Asian Indians and correlated significantly with homocysteine, it did not explain inter-ethnic differences in plasma homocysteine in a multivariate analysis. We conclude that Asian Indians living in the United States have significant elevation of plasma homocysteine concentrations despite normal plasma folate. Lower plasma concentrations of vitamin B-12 and lower insulin sensitivity may contribute to this finding but only partially explained the ethnic-related hyperhomocysteinemia of the Asian Indians.

Adult↗
PubMed2003

Elevated plasma high-sensitivity C-reactive protein concentrations in Asian Indians living in the United States.

Proinflammatory state may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease observed in populations originating from the Indian subcontinent (Asian Indians). This study was conducted to evaluate whether nondiabetic Asian Indian men living in the United States manifest a proinflammatory state when compared with Caucasians of similar age and body fat content. We also compared the relationships between plasma high-sensitivity C-reactive protein (hs-CRP), a marker of low-grade inflammation, and various parameters of body composition and fat distribution and insulin sensitivity in Asian Indians and Caucasians. For this purpose, plasma hs-CRP, oral glucose tolerance test, and anthropometric measurements were conducted in 82 Asian Indian men and 55 Caucasian men of similar age. The two groups had similar body fat content and truncal skinfolds thickness. Asian Indians had higher insulin areas under the curve during oral glucose tolerance tests, indicating a greater insulin resistance. Asian Indians also manifested a significant elevation of plasma hs-CRP. We conclude that young, overtly healthy Asian Indian men have both greater insulin resistance and higher hs-CRP levels than do Caucasians. This difference cannot be explained by greater adiposity in Asian Indians and suggests that many Asian Indians have an underlying proinflammatory state that may contribute to their increased risk for both type 2 diabetes and cardiovascular disease.

Adipose Tissue↗
PubMed2003

Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance.

Genetic susceptibility may be responsible for high prevalence of insulin resistance in Asian Indians. This study was carried out in samples of local Asian Indians and Caucasians to determine whether plasma cell membrane glycoprotein (PC)-1 K121Q and insulin receptor substrate-1 (IRS-1) G972A polymorphisms contribute significantly to susceptibility to insulin resistance in Asian Indians. The frequency of carrying at least one copy of the PC-1 121Q variant in Asian Indians was significantly higher than that in Caucasians (P = 0.01), but the frequency was similar for IRS-1 972A (6% and 7%). A significantly higher insulin area under the curve during oral glucose tolerance testing (P < 0.0001) and lower insulin sensitivity during hyperinsulinemic-euglycemic clamps (P = 0.04) were found in Asian Indians with PC-1 121Q variant compared with Asian Indians with wild-type PC-1 and with Caucasians with or without the polymorphism. IRS-1 972A was not associated with any change in insulin sensitivity. We conclude that the PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. A relatively high frequency of this polymorphism thus may be one factor contributing to insulin resistance susceptibility in Asian Indians. This finding indicates the need for expanded studies on the association between PC-1 K121Q and insulin resistance in a representative sample of the Asian Indian population.

Adult↗
PubMed2002

Diet composition and the metabolic syndrome: what is the optimal fat intake?

Two cholesterol-raising fatty acids in the diet, saturated fatty acids and trans fatty acids, increase the serum low-density lipoprotein cholesterol concentration. This fact justifies the recommendation of a reduced intake of cholesterol-raising fatty acids. Emerging data suggest that diets higher in unsaturated fatty acids, particularly monounsaturated fatty acids, have several advantages over high-carbohydrate intakes. This advantage appears to hold, particularly for populations having a high prevalence of insulin resistance, such as the US population. If the US public were to modify its eating habits in the direction of better weight control and more exercise, higher intakes of carbohydrate might be better tolerated. At the same time, the experience with the Mediterranean population reveals that in healthier populations, diets relatively high in unsaturated fatty acids are well tolerated and are associated with a low prevalence of both coronary heart disease and type 2 diabetes.

Blood Glucose↗
PubMed2002

Pathophysiology of uric acid nephrolithiasis.

Humans although a predominantly ureotylic organism, has preserved the ability to excrete nitrogen as uric acid and ammonia. An imbalance between these two secondary modes of nitrogen excretion has resulted in uric acid precipitation in human urine. Uric acid nephrolithiasis can arise from diverse etiologies all with distinct underlying defects converging to one or more of three defects of hyperuricosuria, acidic urine pH, and low urinary volume, originating from secondary, genetic or heretofore undefined (idiopathic) causes. A subset of idiopathic uric acid nephrolithiasis (gouty diathesis) may be the "tip of the icebergp" of a broader systemic illness characterized by insulin resistance. A novel renal manifestation of insulin resistance is a mild defect in ammonium excretion, which is not severe enough to disturb acid-base homeostasis, but is sufficient to set up the chemical milieu for uric acid nephrolithiasis.

Humans↗
PubMed2002

Sex steroid hormones, upper body obesity, and insulin resistance.

Low plasma levels of SHBG and free testosterone have been associated with increased insulin resistance and risk for type 2 diabetes in males. As truncal obesity, a condition accompanied by increased insulin resistance, is also associated with low SHBG and testosterone levels, the independent association of low free testosterone and SHBG with excessive insulin resistance remains to be determined. In this study we evaluated whether in normogonadic men, plasma levels of SHBG and free testosterone are primarily related to insulin resistance or to generalized and regional adiposity. Hyperinsulinemic-euglycemic clamps and iv glucose tolerance tests were performed in 24 healthy volunteer and 33 patients with mild type 2 diabetes. The 2 groups were chosen to have similar body mass index and were found to have similar body composition and fat distribution, assessed by underwater weighing, skinfold thickness, and magnetic resonance imaging of the abdomen. In the 2 groups combined, plasma levels of SHBG correlated inversely with fat accumulation in both sc and intraabdominal areas. Plasma levels of free testosterone correlated inversely with both truncal and peripheral skinfold thickness only in the nondiabetic men. No associations between plasma levels of sex steroid hormones and insulin resistance, hepatic glucose output, or insulin secretion were found to be independent of adiposity. Furthermore, although patients with diabetes were more insulin resistant than those without diabetes, the 2 groups had similar plasma concentrations of free testosterone (55 +/- 14 and 67 +/- 27 pmol/liter, respectively), SHBG (19 +/- 13 and 19 +/- 13 nmol/liter), estradiol (83 +/- 5 and 81 +/- 21 pmol/liter), and dehydroepiandrosterone sulfate (3.6 +/- 2.2 and 2.8 +/- 1.7 nmol/liter). We conclude that in normogonadal nondiabetic males, the variability in plasma bioavailable testosterone concentrations is predictive of the variability in fat deposition in the sc adipose tissue compartments of both truncal and peripheral areas. Low plasma levels of bioavailable testosterone do not independently predict excessive insulin resistance, beta-cell dysfunction, or hepatic glucose output in normogonadal men.

Adipose Tissue↗
PubMedDate not supplied

The impact of ethnicity on type 2 diabetes.

The rapid increase of diabetes prevalence in the US population and across all westernized world has been associated with environmental changes that promote obesity. Although dietary factors, such as total caloric intake, relative excess of dietary saturated fats content and lack of fibers, together with reduced level of physical activity clearly determine the main features of the "obesogenic" environment typical of "western" societies, the impact of lifestyle factors on obesity and diabetes appears to differ in various ethnic groups. Although ethnic-related differences in lifestyle factors may account for some of the predisposition to obesity and diabetes of various ethnic groups, genetic factors may play a more determinant role. These observations pose important public health questions in regard to strategies for treatment and prevention of diabetes both within the multiethnic US population and in the population of origin of various ethnicities. The elucidation of the pathophysiologic mechanisms responsible for the heterogeneous relationship between obesity and type 2 diabetes in various ethnicities may give important contributions to better understand the complex mechanisms involved in the development of this disease. This review examines epidemiological and pathophysiological aspects of the interaction between environment and ethnic predisposition to type 2 diabetes.

Adipose Tissue↗