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Biomedical subjects

Frida Leonetti

Publications and source records attributed to Frida Leonetti.

At least 19 recordsLinked to original sources
PubMed2006

Aminotransferase activity in morbid and uncomplicated obesity: predictive role of fasting insulin.

BACKGROUND AND AIMS: An elevation in liver enzymes and, most notably, high serum alanine aminotransferase (ALT) activity, has been correlated with metabolic syndrome and obesity. However, whether obesity per se or obesity-related co-morbidities affect aminotransferase activity is still unclear. In this study we sought to evaluate serum aminotransferase activity in morbid and uncomplicated obese subjects METHODS: In this cross-sectional study, serum aminotransferase activity, anthropometric and metabolic parameters were assessed in 290 morbid and 105 uncomplicated consecutive obese subjects matched for body mass index (BMI) (40.1+/-6.8 vs. 39.9+/-8.3 kg/m(2), respectively), age (35.9+/-10 vs. 34.8+/-9.6 years, respectively), sex distribution and duration of obesity. RESULTS: Uncomplicated obese subjects showed significantly lower serum ALT activity (17.58+/-6.3 (range 10-39) vs. 23.43+/-16 (range 12-89) U/l, (p<0.001)), and lower aspartate aminotransferase (AST), AST/ALT ratios and gamma-glutamyltranspeptidase (gammaGT) (p<0.01 for all) than morbid obese subjects. Only 11% women and 19% men in the uncomplicated obese group showed high ALT levels, while ALT activity was high in 48% women and 51% men in the morbid obese group. Fasting insulin was the best correlate of ALT activity (R(2)=0.21, p=0.003). CONCLUSIONS: Our findings show that elevated ALT and AST activity are associated with increased fasting insulin and not with obesity per se, suggesting that the presence of insulin resistance, rather than BMI alone, plays a role in mediating the increased aminotransferase activity.

Adult↗
PubMed2006

Non-invasive evaluation of endothelial dysfunction in uncomplicated obesity: relationship with insulin resistance.

Obesity is associated with increased cardiovascular morbidity and amortality. Endothelial dysfunction, involved in the pathogenesis of cardiovascular events, has been demonstrated in obese patients with invasive techniques requiring artery catheterization. The aim of our investigation was to evaluate, with a non-invasive method readily employable on clinical grounds, impaired vasodilatation and its relationship with insulin resistance in uncomplicated obesity. 15 uncomplicated obese subjects (BMI = 36.6 +/- 3.2) and 10 lean controls (BMI = 22.9 +/- 1.25) were enrolled in this study. All subjects underwent measurement of endothelium-dependent (FBFr) vasodilatation by forearm venous occlusion pletysmography after increasing times of ischemia, and measurement of insulin sensitivity by the euglycemic hyperinsulinemic clamp technique (M index), by fasting glucose and insulin (HOMA-IR) and by oral glucose tolerance test (ISI index). Endothelium-independent (N-FBFr) vasodilatation was assessed as well. The FBFr was markedly blunted in obese patients versus lean controls (30 s: 2.12 +/- 0.34 vs. 3.63 +/- 0.22, P < 0.01; 60 s: 2.34 +/- 0.42 vs. 3.82 +/- 0.53, P < 0.01; 180 s: 3.20 +/- 0.45 vs. 7.15 +/- 0.35, P < 0.01; 300 s: 4.08 +/- 0.94 vs. 14.1 +/- 0.82, P < 0.001). The N-FBFr was not different in the two groups. High correlation was found between M index and FBFr at all ischemia times. HOMA-IR and ISI were not related with FBFr. The non-invasive evaluation of endothelial dysfunction by a simple and reliable method based on venous occlusive plethysmography shows high correlation between impaired endothelium-dependent vasodilatation and insulin resistance in uncomplicated obesity. This non-invasive test of endothelial function may be routinely performed in the assessment of cardiovascular risk in uncomplicated obesity.

Adult↗
PubMed2006

Left ventricular mass and +276 G/G single nucleotide polymorphism of the adiponectin gene in uncomplicated obesity.

The single nucleotide polymorphism at position 276 in the adiponectin gene (APM1/ACDC +276 G>T) and left ventricular mass (LVM) have been associated with increased cardiovascular risk. We sought to evaluate whether +276 G>T variants in the adiponectin gene are correlated with LVM in uncomplicated obese subjects. APM1/ACDC +276 G>T single nucleotide polymorphism, echocardiographic indexed LVM (LVM/body surface area and LVM/height(2.7)), insulin sensitivity by euglycemic clamp, and plasma adiponectin levels were analyzed in 62 obese subjects without complications (51 women and 11 men; mean age, 34.2 +/- 10.2 years; BMI, 38.6 +/- 9.1 kg/m2). Forty lean subjects formed the control group for LVM evaluation. We found 23 (37%) uncomplicated obese subjects with the APM1/ACDC +276 G/G genotype, 25 (40%) with the G/T genotype, and 14 (23%) with the T/T genotype. G/G uncomplicated obese subjects showed significant higher LVM/body surface area and LVM/height(2.7) (within the normal range in the majority of them) than uncomplicated obese subjects carrying the G/T and T/T genotypes (p < 0.01 and p < 0.05, respectively). This study showed that LVM is significantly higher in uncomplicated obese subjects carrying the G/G genotype at position 276 of the human adiponectin gene.

Adiponectin↗
PubMed2006

Association of beta2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels.

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The beta(2) adrenergic receptor (beta(2)-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between beta(2)-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the beta(2)-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5'LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the beta(2)-AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5'LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5'LC-Arg19 homozygous (P=0.03 and P=0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P=0.02 and P=0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P=0.01 and P=0.03, respectively). The 5'LC-Cys(19)Arg(16)Gln(27) haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5'LC-Arg(19)Gly(16)Glu(27) haplotype (P=0.05 and P=0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5'LC-Cys(19)Arg(16)Gln(27) haplotype.

Cholesterol, LDL↗
PubMed2006

Effectiveness of laparoscopic sleeve gastrectomy (first stage of biliopancreatic diversion with duodenal switch) on co-morbidities in super-obese high-risk patients.

BACKGROUND: We evaluated laparoscopic sleeve gastrectomy (LSG) on major co-morbidities (hypertension, type 2 diabetes / impaired glucose tolerance, obstructive sleep apnea syndrome (OSAS) and on American Society of Anesthesiologists (ASA) operative risk score in high-risk super-obese patients undergoing two-stage laparoscopic biliopancreatic diversion with duodenal switch (LBPD-DS). METHODS: 41 super-obese high-risk patients (mean BMI 57.3+/-6.5 kg/m(2), age 44.6+/-9.7 years) were entered into a prospective study (BMI > or = 60, or BMI > or = 50 with at least two severe co-morbidities, no Prader-Willi syndrome, no conversion, minimum follow-up 12 months). 9 patients had BMI > or = 60. 17 patients (41.4%) had OSAS on C-PAP therapy. In 10 patients, at least one intragastric balloon had been positioned and 4 had undergone laparoscopic adjustable gastric banding, all with unsatisfactory results. At surgery, 41.5% were classified ASA 4 and 58.5% as ASA 3 (mean ASA score 3.4+/-0.5). Patients underwent evaluation every 3 months postoperatively and were restaged at 12 months and/or before the second step. RESULTS: 60% of major co-morbidities were cured and 24% improved. Average BMI after 6 and 12 months was 44.5+/-8.1 and 40.8+/-8.5 respectively (mean follow-up 22.2+/-7.1 months). After 12 months, 57.8% of the patients were co-morbidity-free and 31.5% had only one major co-morbid condition. At restaging, 20% of patients were still classified as ASA score 4 (OSAS on C-PAP therapy). 3 patients showed BMI <30 and were co-morbidity-free 12 months after LSG. CONCLUSIONS: LSG represents a safe and effective procedure to achieve marked weight loss as well as significant reduction of major obesity-related co-morbidities. The procedure reduced the operative risk (ASA score) in super-obese patients undergoing two-stage LBPD-DS.

Adult↗
PubMed2005

Normal serum alanine aminotransferase activity in uncomplicated obesity.

AIM: To evaluate serum alanine aminotransferase (ALT) activity in a well-characterized group of uncomplicated obese subjects and its correlation with insulin resistance, plasma adiponectin, and leptin concentrations. METHODS: One hundred and five uncomplicated obese subjects (87 women, 18 men, age 34.3+/-9.6 years, BMI 39.9+/-8.3 kg/m(2)) were studied. Serum ALT activity was evaluated. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M index) and fasting insulin. Plasma leptin and adiponectin levels were also measured. RESULTS: Serum ALT concentration in the whole group of uncomplicated obese subjects was 17.73+/-6.33 U/L with none of the subjects presenting ALT levels greater than 43 U/L and only 9 (11%) women and 3 (19%) men showed ALT levels >19 and >30 U/L for women and men, respectively. No significant difference was detected in serum ALT levels between severe obese subjects (BMI >40 kg/m(2)) and those with BMI <40 kg/m(2) (18.63+/-6.25 vs 17.26+/-6.02 U/L). ALT was significantly correlated with fasting insulin (r = 0.485, P = 0.02) and triglycerides (r = 0.358, P = 0.03). CONCLUSION: Serum ALT activity is practically normal in uncomplicated obese subjects, independently of their obesity degree. These findings suggest the role of obesity-related comorbidities and not of BMI as main risk factors for elevated ALT levels in obese subjects.

Adiponectin↗
PubMed2005

Epicardial adipose tissue and insulin resistance in obese subjects.

CONTEXT: Epicardial adipose tissue has been recently recognized as a source of bioactive molecules as well as free fatty acids, adiponectin, and inflammatory cytokines. Epicardial fat reflects intraabdominal visceral fat, and the echocardiographic assessment of this tissue is an easy and reliable marker of visceral adiposity. OBJECTIVE: In this study we evaluated whether epicardial adipose tissue is related to insulin sensitivity and glucose metabolism in obese subjects. PATIENTS: Thirty obese subjects (20 women and 10 men; mean age, 40.8 +/- 11.5 yr; body mass index, 43 +/- 9.1 kg/m2) were included in this study. No subject was taking drugs or had a history or evidence of metabolic, cardiovascular, respiratory, or hepatic disease. MAIN OUTCOME MEASURES: Each subject underwent a transthoracic echocardiogram to evaluate epicardial adipose tissue thickness, a euglycemic hyperinsulinemic clamp to estimate insulin sensitivity, and an oral glucose tolerance test to evaluate glucose tolerance. RESULTS: The thickness of the epicardial adipose tissue on the right ventricle varied between 4 and 17.4 mm. Echocardiographic epicardial adipose tissue was significantly correlated with whole-body glucose uptake index from the clamp and with all indices of insulin resistance and glucose intolerance measured, except the 120-min plasma glucose level after an oral glucose tolerance test. CONCLUSIONS: Our study showed that the epicardial fat is significantly related to obesity-related insulin resistance. This finding could be of potential interest in clinical practice and research of obesity-related risk stratification.

Adipose Tissue↗
PubMed2005

Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease.

BACKGROUND: Intra-peritoneal adipose tissue is recognized as a predictor of metabolic syndrome and may contribute to the risk for cardiovascular disease by the production of adipocytokines, including adiponectin. Nevertheless, there is no knowledge on whether other visceral depots of adipose tissue, including the epicardial fat, have any metabolically active role, including production of adiponectin. AIM OF THE STUDY: We sought to evaluate adiponectin protein expression in epicardial adipose tissue in vivo both in patients with severe coronary artery disease (CAD) and in subjects without CAD. METHODS: Twenty-two patients were enrolled for the study. We selected 16 patients who underwent elective coronary artery bypass graft surgery for critical CAD, 5 who underwent surgery for valve replacement and 1 for correction of an interatrial defect. Epicardial adipose tissue biopsy samples were obtained before the initiation of cardiopulmonary bypass. Adiponectin protein level in epicardial adipose tissue was evaluated by Western blotting. RESULTS: Adiponectin protein value, expressed as adiponectin/actin ratio, in epicardial adipose tissue was significantly lower in patients with severe CAD than in those without CAD (1.42 +/- 0.77 vs 2.36 +/- 0.84 p = 0.02, 95% CI 0.64-1.74). CONCLUSIONS: This study showed for the first time that human epicardial adipose tissue expresses adiponectin. Adiponectin expression is significantly lower in epicardial fat isolated from patients with CAD.

Adiponectin↗
PubMed2005

Effect of acute hyperinsulinemia on ventricular repolarization in uncomplicated obesity.

BACKGROUND: Acute hyperinsulinemia has been shown to increase QTc interval in lean subjects, but data on obese subjects are still unclear. Aim of this study was to evaluate the effect of acute hyperinsulinemia on QTc interval and QTc dispersion in uncomplicated obesity. METHODS: We calculated QTc duration and QTc dispersion in 30 uncomplicated obese subjects (mean age 32.2 +/- 7, BMI 36.7 +/- 9.4 kg/m(2)) by measurements of 12-lead ECG recording during a euglycemic hyperinsulinemic clamp. RESULTS: Insulin infusion during the clamp did not significantly modify QTc interval and QTc dispersion in uncomplicated obese subjects (401.5 +/- 29.2 vs. 413.7 +/- 30.5; 35.4 +/- 10.5 vs. 38.7 +/- 14.5, respectively). CONCLUSIONS: Acute hyperinsulinemia seems to no significantly affect ventricular repolarization in uncomplicated obesity. Insulin resistance and the absence of diabetes and hypertension could explain, at least in part, this finding.

Acute Disease↗
PubMed2005

Prevalence of uncomplicated obesity in an Italian obese population.

OBJECTIVE: The existence of healthy obese subjects has been suggested but not clearly reported. We sought to address the prevalence of uncomplicated obesity and adverse risk factors in a large Italian obese population. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of a population of consecutive Italian obese subjects. We studied 681 obese subjects (514 women and 167 men), with a mean age of 41.1+/-13.9 years (range, 16 to 77 years), mean BMI of 40.2+/-7.6 kg/m2 (range, 30 to 89.8 kg/m2), and a history of obesity for 20.5+/-7 years (range, 10.5 to 30 years). Anthropometric, metabolic, cardiac, and obesity-related risk factors were evaluated. RESULTS: The prevalence of uncomplicated subjects was 27.5%, independent of BMI and duration of obesity. The youngest group of obese subjects showed a higher, but not statistically significantly higher, prevalence of uncomplicated obesity. No statistical difference for the prevalence of impaired fasting glucose, glucose intolerance, high triglycerides, high total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol among BMI categories (from mild to extremely severe obesity degree) was found. Obese subjects with BMI>50 kg/m2 showed a higher prevalence of high blood pressure only when they were compared with the group with a BMI of 30 to 35 kg/m2 (p<0.01). Obese subjects with BMI>40 kg/m2 showed a higher prevalence of hyperinsulinemia than subjects with BMI 30 to 35 kg/m2 (p<0.01). DISCUSSION: This study shows that a substantial part of an Italian obese population has uncomplicated obesity, and the prevalence of adverse risk factors in this sample is unexpectedly low and partially independent of obesity degree. Uncomplicated obesity could represent a well-defined clinical entity.

Adolescent↗
PubMed2005

Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women.

BACKGROUND: A possible relationship between thyroid hormones and adipose tissue metabolism in humans has been suggested. Aim of the study We sought to evaluate thyroid function and its possible relationship with body mass index (BMI), leptin, adiponectin and insulin sensitivity in euthyroid obese women. MATERIALS AND METHODS: Eighty-seven uncomplicated obese women (mean age 34.7 +/- 9 years, mean BMI 40.1 +/- 7 kg/m(2)) were studied. Levels of TSH, free thyroxine (FT4), free triiodothyronine (FT3), plasma adiponectin and leptin were evaluated. Insulin sensitivity was assessed by euglycaemic hyperinsulinaemic clamp (M index), fasting insulin and HOMA-IR. RESULTS: Uncomplicated obese women with BMI > 40 kg/m(2) showed higher serum TSH than obese subjects with BMI < 40 kg/m(2) (P < 0.01). TSH was correlated with BMI (r = 0.44, P = 0.01) leptin (r = 0.41, P = 0.01), leptin/BMI ratio (r = 0.33, P = 0.03), body surface area (r = 0.26, P = 0.05), HOMA-IR (r = 0.245, P = 0.05) and inversely with adiponectin (r = -0.25, P = 0.05) and M index (r = -0.223 P = 0.05). CONCLUSIONS: Our data show that, although thyroid function was normal in the studied obese population, TSH and BMI were positively related. TSH has been found to be correlated also with leptin adjusted for BMI. TSH could represent a marker of altered energy balance in severe, but uncomplicated obese women.

Adiponectin↗
PubMed2005

The Gly482Ser missense mutation of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) gene associates with reduced insulin sensitivity in normal and glucose-intolerant obese subjects.

Among the putative candidate genes for insulin resistance, the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator of PPARgamma and alpha, regulating a wide range of processes involved in energy production and utilization, such as thermogenesis, liver gluconeogenesis, glucose uptake in muscle. In population studies a Gly482Ser substitution in PGC-1alpha has been reported to be associated with increased risk of type diabetes 2 and insulin resistance. In the present study we have analysed the association between the Gly482Ser missense mutation of the PGC-1alpha gene and insulin sensitivity and glucose tolerance in a population of obese non-diabetic subjects. The Gly482Ser SNPs was detected by PCR-RFLP in a cohort of 358 Caucasian obese subjects (223 with normal glucose tolerance (NGT) and 125 with impaired glucose tolerance (IGT). We observed a significant association (p <0.007) between carriers of the Gly482Ser variant of the PGC-1alpha gene and insulin resistance measured by HOMAIR. Multivariate analysis confirmed that the Gly482Ser SNP was a significant (p < 0.02) determinant of decreased insulin sensitivity, independently from other well-known modulators of insulin action. In conclusion, we have found significant association between the Gly482Ser variant of the PGC-1alpha gene and reduced insulin sensitivity in obese subjects. This association resulted independent from all other known modulators of insulin resistance, and suggests a primary role for the PGC-1alpha gene on the genetic susceptibility to insulin resistance in obesity.

Adult↗
PubMed2004

Acute insulin infusion decreases plasma ghrelin levels in uncomplicated obesity.

BACKGROUND: Plasma ghrelin levels have been shown to decrease after insulin infusion in lean subjects. Nevertheless, the mechanism of the suggested inhibitory effect of insulin on ghrelin is still unclear and no data about the effect of acute insulin infusion on plasma ghrelin concentration in obese subjects are available. OBJECTIVE: We sight to evaluate plasma ghrelin concentration during an hyperinsulinemic euglycemic clamp in uncomplicated obese subjects. METHODS: 35 uncomplicated obese subjects, body mass index (BMI) 43.3+/-10.1 kg/m(2), 33 women and 2 men, mean age 34.9+/-10, with a history of excess fat of at least 10 years underwent euglycemic hyperinsulinemic clamp. Blood samples for ghrelin were performed at baseline and steady state of euglycemic insulin clamp. RESULTS: Ghrelin concentrations decreased over time to 10.6+/-15% (range 2-39%) of baseline, from a mean of 205.53+/-93.79 pg/ml to 179.03+/-70.43 pg/ml during the clamp (95% CI, 10.69 to 36.44, P<0.01). In a univariate linear regression analysis baseline plasma ghrelin levels were inversely correlated to BMI (r=-0.564, P=0.04). A linear positive trend between whole body glucose utilization (M(FFMkg) index) and ghrelin reduction during the clamp was found (chi(2) 3.05, p=0.05). CONCLUSIONS: Our data seem to suggest that hyperinsulinemia during a euglycemic clamp is able to suppress plasma ghrelin concentrations in uncomplicated obesity. This effect appears to be positively related to insulin sensitivity.

Adult↗
PubMed2004

Relation between epicardial adipose tissue and left ventricular mass.

Visceral adiposity is a cardiovascular risk factor of growing interest. This study sought to evaluate the hypothesis of a relation between epicardial adipose tissue, the visceral adipose tissue deposited around the heart, and left ventricular morphology in healthy subjects with a wide range of adiposity. We found for the first time that an increase in epicardial fat is significantly related to an increase in left ventricular mass.

Adipose Tissue↗
PubMed2004

Adapted changes in left ventricular structure and function in severe uncomplicated obesity.

OBJECTIVE: A massive amount of fat tissue, as that observed in obese subjects with BMI over 50 kg/m(2), could affect cardiac morphology and performance, but few data on this issue are available. We sought to evaluate cardiac structure and function in uncomplicated severely obese subjects. RESEARCH METHODS AND PROCEDURES: We studied 55 uncomplicated severely obese patients, 40 women, 15 men, mean age 35.5 +/- 10.2 years, BMI 51.2 +/- 8.8 kg/m(2), range 43 to 81 kg/m(2), with a history of fat excess of at least 10 years, and 55 age-matched normal-weight subjects (40 women, 15 men, mean BMI 23.8 +/- 1.2 kg/m(2)) as a control group. Each subject underwent an echocardiogram to evaluate left ventricular (LV) mass and geometry and systolic and diastolic function. RESULTS: Severely obese subjects showed greater LV mass and indexed LV mass than normal-weight subjects (p < 0.01 for all parameters). Nevertheless, LV mass was appropriate for sex, height(2.7), and stroke work in most (77%) uncomplicated severely obese subjects. In addition, no significant difference in LV mass indices and LV mass appropriateness between obese subjects with BMI > or = 50 kg/m(2) and those with BMI < or = 50 kg/m(2) was found. Obese subjects also showed higher ejection fraction and midwall shortening than normal-weight subjects (p = 0.05 and p < 0.01, respectively), suggesting a hyperdynamic systolic function. No significant difference in systolic performance between obese subjects with BMI > or = 50 kg/m(2) and those with BMI < or = 50 kg/m(2) was seen. DISCUSSION: Our data show that uncomplicated severe obesity, despite the massive fat tissue amount, is associated largely with adapted and appropriate changes in cardiac structure and function.

Adaptation, Physiological↗
PubMed2004

Association of the human adiponectin gene and insulin resistance.

Adiponectin is an adipocyte-secreted protein that modulates insulin sensitivity and whose low circulating concentration is associated with insulin resistance. In the present study, we analysed the association between two single-nucleotide polymorphisms (SNPs) in the adiponectin gene and insulin resistance in 253 nondiabetic subjects. In addition, we investigated whether this association is modulated by body mass index (BMI) levels. The SNPs +45T>G and +276G>T in the human adiponectin gene were detected in real-time PCR with LightCycler. No association was found with the +45T>G SNP. The +276G>T SNP was associated with higher BMI (P<0.01), plasma insulin (P<0.02) and HOMA(IR) (P<0.02). To analyse the possible interaction between BMI and the adiponectin gene on insulin resistance, the study group was divided into two subgroups, according to the BMI below or above the median of 26.2 kg/m(2). In both subgroups, subjects carrying the +276G>T SNP had higher HOMA(IR); however, the difference was highly significant among leaner (P<0.001), but not among heavier individuals, indicating that BMI status and the adiponectin gene interact in modulating insulin resistance. Among individuals with BMI <26.2 kg/m(2), the relative risk of insulin resistance was 9.7 (CI: 1.32-87.7, P<0.035). In a subgroup of 67 subjects, carriers of the +276G>T SNP had significantly (P<0.05) lower mean serum adiponectin levels (25.7 ng/ml) compared to noncarriers (37.0 ng/ml), suggesting a possible influence of the +276G>T SNP on adiponectin levels. In summary, we observed an association between the +276G>T SNP in the adiponectin gene and insulin resistance. In particular, among leaner individuals, the adiponectin gene appears to determine an increased risk to develop insulin resistance.

Adiponectin↗
PubMed2004

The common PPAR-gamma2 Pro12Ala variant is associated with greater insulin sensitivity.

Several genetic variants of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) have been identified, among which Pro12Ala, a missense mutation in exon 2, is highly prevalent in Caucasian populations. Up to now, conflicting results with regard to the association between this mutation and complex traits, such as obesity, insulin sensitivity and Type 2 diabetes, have been reported. We investigated the influence of the Pro12Ala polymorphism of PPAR-gamma2 on insulin sensitivity in a large Italian population sample, n=1215, in whom extensive clinical and biochemical analyses were performed. To estimate the insulin sensitivity status, the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated; in the obese/overweight subjects an oral glucose tolerance test (OGTT) was also performed and the Matsuda insulin sensitivity index (ISI) calculated. The insulin secretion index (homeostasis model assessment of percent beta-cell function, HOMA-beta%) was utilized to evaluate beta-cell function. The effect of the Pro12Ala polymorphism on quantitative variables was tested using multiple linear regression analysis. X12Ala (either Pro12Ala or Ala12Ala) genotype was associated with significantly lower fasting insulin levels compared to Pro/Pro (P=0.01 after correction for multiple comparisons) in all subjects. Consistent with this finding, significantly lower HOMA-IR was observed in X12Ala carriers (P=0.013 after correction for multiple comparisons) in all cohort. Moreover, no significant interaction effect was observed between body mass index and X12Ala polymorphism and between gender and X12Ala polymorphism in modulating insulin sensitivity. Our observations substantially extend previous findings and demonstrated that X12Ala variant is significantly associated with greater insulin sensitivity.

Amino Acid Substitution↗