Manisha Chandalia

Publications (40)170.34 Total impact

• Article: Joint Effect of Insulin Signaling Genes on Insulin Secretion and Glucose Homeostasis.

  Sabrina Prudente, Eleonora Morini, Lorella Marselli, Roberto Baratta, Massimiliano Copetti, Christine Mendonca, Francesco Andreozzi, Manisha Chandalia, Fabio Pellegrini, Diego Bailetti, Federica Alberico, Hetal Shah, Nicola Abate, Giorgio Sesti, Lucia Frittitta, Piero Marchetti, Alessandro Doria, Vincenzo Trischitta
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  ABSTRACT: Context:Reduced insulin signaling in insulin secreting β-cells causes defective insulin secretion and hyperglycemia in mice.Objective:We investigated whether functional polymorphisms affecting insulin signaling (ie, ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; and TRIB3 Q84R, rs2295490) exert a joint effect on insulin secretion and abnormal glucose homeostasis (AGH).Design:Insulin secretion was evaluated by 1) the disposition index (DI) from an oral glucose tolerance test (OGTT) in 829 individuals; or 2) insulin secretion stimulation index (SI) in islets from nondiabetic donors after glucose (n = 92) or glibenclamide (n = 89) stimulation. AGH (including impaired fasting glucose and/or impaired glucose tolerance or type 2 diabetes; T2D) was evaluated in case-control studies from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) Consortium (n = 6607).Results:Genotype risk score, obtained by totaling individual weighted risk allele effects, was associated with the following: 1) DI (P = .005); 2) glucose and glibenclamide SI (P = .046 and P = .009); or 3) AGH (odds ratio 1.08, 95% confidence interval 1.03-1.13; P = .001). We observed an inverse relationship between genetic effect and age at AGH onset, as indicated by a linear correlation between AGH-genotype risk score odds ratios and age-at-diagnosis cutoffs (R(2) = 0.80, P < .001).Conclusions:Functional polymorphisms affecting insulin signaling exert a joint effect on both in vivo and in vitro insulin secretion as well as on early-onset AGH. Our data provide further evidence that abnormal insulin signaling reduces β-cell function and impairs glucose homeostasis.
  The Journal of clinical endocrinology and metabolism 04/2013; · 6.50 Impact Factor
• Article: Heterogeneity in Subcutaneous Adipose Tissue Morphology and Metabolic Complications in Overweight and Obese Women.

  Gracie Vargas, Manisha Chandalia, Yongquan Jiang, Himara Davila, Massoud Motamedi, Nicola Abate
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  ABSTRACT: Abstract Objective: The aim of this study was to assess morphological features of intact adipose tissue (AT) ex vivo from both subcutaneous (s.c.) abdominal and gluteal areas using a novel approach of multiphoton autofluorescence microscopy (MPAM) combined with second harmonic generation microscopy (SHGM), and to assess the relationship between morphological features in the two AT sites and insulin resistance to peripheral glucose disposal. Method: This study was a cross-sectional evaluation of AT morphology feature and peripheral insulin resistance. Subjects: Fourteen overweight/obese premenopausal women underwent body composition studies, hyperinsulinemic-euglycemic clamps, and needle biopsy of both the s.c. abdominal and gluteal AT areas. MPAM combined with SHGM was used to measure adipocyte maximal diameter and collagen fiber bundle thickness within a sampled image volume after three-dimensional visualization. Results: Higher body mass index (BMI) was associated with larger adipocyte diameter in s.c. abdominal, but not gluteal, AT. Higher adipocyte diameter was associated with higher pericellular collagen thickness. Adipocyte diameter in s.c. abdominal, but not gluteal, AT was associated positively with leptin and negatively with adiponectin plasma levels and peripheral glucose disposal rate. The latter correlation was no longer significant after adjustment for collagen thickness. Conclusion: In overweight/obese premenopausal women, larger adipocyte diameter in s.c. abdominal, but not gluteal, AT associates with low plasma adiponectin and systemic insulin resistance, and suggests that increased collagen thickness (obesity-related scarring) could contribute to these findings.
  Metabolic syndrome and related disorders 04/2013;
• Article: Adipose Tissue Dysfunction in Humans: A Potential Role for the Transmembrane Protein ENPP1.

  Manisha Chandalia, Himara Davila, Wentong Pan, Magdalena Szuszkiewicz, Demidmaa Tuvdendorj, Edward H Livingston, Nicola Abate
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  ABSTRACT: Context:Adipose tissue (AT) helps to regulate body fat partitioning and systemic lipid/glucose metabolism. We have recently reported lipid/glucose metabolism abnormalities and increased liver triglyceride content in an AT-selective transgenic model overexpressing ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), the AdiposeENPP1-Tg mouse.Objective:The aim of the study was to test the translational hypothesis that AT-ENPP1 overexpression associates with AT dysfunction (changes in AT gene expression, plasma fatty acid, and adipokine levels), increased liver triglyceride deposition, and systemic insulin resistance in humans.Design/Setting/Participants:A total of 134 young normoglycemic men and women were subjected to body composition studies, hyperinsulinemic-euglycemic clamps, and AT needle biopsy. Twenty men also had liver/muscle nuclear magnetic resonance spectroscopy.Main Outcome Measures:Predetermined measures included AT expression of ENPP1 and other lipid metabolism/inflammation genes, plasma adipokines, and nonesterified fatty acid (NEFA) levels, liver/muscle triglyceride content, and the systemic glucose disposal rate.Results:After statistical adjustment for body fat content, increasing AT-ENPP1 was associated with up-regulation of genes involved in NEFA metabolism and inflammation, increased postabsorptive NEFA levels, decreased plasma adiponectin, increased liver triglyceride content, and systemic insulin resistance in men. In women, there were no changes in plasma adiponectin, NEFAs, or glucose disposal rate associated with increasing AT-ENPP1, despite increased expression of lipid metabolism and inflammation genes in AT.Conclusions:Increased AT-ENPP1 is associated with AT dysfunction, increased liver triglyceride deposition, and systemic insulin resistance in young normoglycemic men. These findings are concordant with the AdiposeENPP1-Tg phenotype and identify a potential target of therapy for health complications of AT dysfunction, including type 2 diabetes and cardiovascular disease.
  The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
• Article: Role of subcutaneous adipose tissue in metabolic complications of obesity.

  Nicola Abate, Manisha Chandalia
  Metabolic syndrome and related disorders 07/2012; 10(5):319-20.
• Article: Fat distribution and insulin resistance in young adult nonobese asian Indian women.

  Magdalene Szuszkiewicz-Garcia, Rong Li, Scott M Grundy, Nicola Abate, Manisha Chandalia
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  ABSTRACT: Abstract Although Asian Indian (people of Indian subcontinent descent) men are shown to have higher total and truncal body fat as well as greater insulin resistance compared to white men matched for total body fat and age, data in women are not conclusive. The objective of this study was to compare total and regional fat distribution and insulin sensitivity between healthy young premenopausal Asian Indian and white women of similar body mass index (BMI). Twenty Asian Indian women (65% immigrants and 35% first generation living in Dallas) and 31 white women of similar age and BMI [age 24±3 vs. 25±4; BMI 22±4 vs. 23±5; mean±standard deviation (SD) in Asian Indian and white, respectively] without diabetes were evaluated with anthropometric measurements, underwater weighing for percentage of total body fat mass, magnetic resonance imaging of whole abdomen for measurement of abdominal subcutaneous and intraperitoneal fat mass, and euglycemic-hyperinsulinemic clamp study for measurement of insulin sensitivity. There were no differences in waist or hip circumference, total body subcutaneous abdominal or intraperitoneal fat mass, fasting plasma glucose, and insulin levels between Asian Indian women and white women. The peripheral glucose disposal rate (Rd) during hyperinsulinemic-euglycemic clamp was found to be almost identical in the two study groups (median value of 6.9 and 6.8 mg/min per kg of body weight, for Asian Indians and whites, respectively). For similar total or regional fat content, the glucose disposal rate was comparable in the two study groups. In conclusion, we demonstrate that young Asian Indian women do not have excess abdominal or intraperitoneal fat or insulin resistance for similar BMI compared to white women of European descent.
  Metabolic syndrome and related disorders 06/2012; 10(5):326-30.
• Article: The challenge of coronary heart disease in South Asians who have migrated to Europe and the United States

  Manisha Chandalia, Nicola Abate
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  ABSTRACT: Certain populations, such as migrant South Asians from the Indian subcontinent to westernized countries, have excess burden of coronary heart disease compared with Caucasians of European descent despite a lower prevalence of traditional risk factors (except insulin resistance and type 2 diabetes). Recent studies did not show excess visceral fat in South Asians but did show larger adipocytes and abnormal adipokines that were associated with increased insulin resistance compared with Caucasians matched for total and regional fat mass. We propose that genetic predisposition to an adipocyte maturation defect when challenged with an obesogenic environment may precipitate adipose tissue dysfunction at much lower body fat content, as seen in South Asians. The shift in our thinking from excess fat mass—visceral or otherwise—to adipose tissue dysfunction being a cause of metabolic complications of obesity is warranted, especially for populations such as South Asians, to better target screening and prevention strategies.
  Current Cardiovascular Risk Reports 04/2012; 3(3):168-174.
• Article: Metabolic consequences of ENPP1 overexpression in adipose tissue.

  Wentong Pan, Ester Ciociola, Manish Saraf, Batbayar Tumurbaatar, Demidmaa Tuvdendorj, Sneha Prasad, Manisha Chandalia, Nicola Abate
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  ABSTRACT: Ectonucleotide pyrophosphate phosphodiesterase (ENPP1) has been shown to negatively modulate insulin receptor and to induce cellular insulin resistance when overexpressed in various cell types. Systemic insulin resistance has also been observed when ENPP1 is overexpressed in multiple tissues of transgenic models and attributed largely to tissue insulin resistance induced in skeletal muscle and liver. Another key tissue in regulating glucose and lipid metabolism is adipose tissue (AT). Interestingly, obese patients with insulin resistance have been reported to have increased AT ENPP1 expression. However, the specific effects of ENPP1 in AT have not been studied. To better understand the specific role of AT ENPP1 on systemic metabolism, we have created a transgenic mouse model (C57/Bl6 background) with targeted overexpression of human ENPP1 in adipocytes, using aP2 promoter in the transgene construct (AdiposeENPP1-TG). Using either regular chow or pair-feeding protocol with 60% fat diet, we compared body fat content and distribution and insulin signaling in adipose, muscle, and liver tissues of AdiposeENPP1-TG and wild-type (WT) siblings. We also compared response to intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT). Our results show no changes in Adipose ENPP1-TG mice fed a regular chow diet. After high-fat diet with pair-feeding protocol, AdiposeENPP1-TG and WT mice had similar weights. However, AdiposeENPP1-TG mice developed fatty liver in association with changes in AT characterized by smaller adipocyte size and decreased phosphorylation of insulin receptor Tyr(1361) and Akt Ser(473). These changes in AT function and fat distribution were associated with systemic abnormalities of lipid and glucose metabolism, including increased plasma concentrations of fatty acid, triglyceride, plasma glucose, and insulin during IPGTT and decreased glucose suppression during ITT. Thus, our results show that, in the presence of a high-fat diet, ENPP1 overexpression in adipocytes induces fatty liver, hyperlipidemia, and dysglycemia, thus recapitulating key manifestations of the metabolic syndrome.
  AJP Endocrinology and Metabolism 08/2011; 301(5):E901-11. · 4.75 Impact Factor
• Chapter: Ethnic Differences in the Metabolic Syndrome

  Nicola Abate, Manisha Chandalia
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  ABSTRACT: The prevalence of the metabolic syndrome has been shown to differ in various populations around the world and among ethnic groups within the same geographical areas. For example, whereas about 25% of the entire US population has the metabolic syndrome, a much larger prevalence is observed in Hispanic Americans, Native Americans, and blacks. These differences contribute to the excessive risk for type 2 diabetes and cardiovascular disease reported in US minority groups. Details on the mechanisms for ethnic differences in the prevalence of the metabolic syndrome are not yet completely elucidated. However, susceptibility to central obesity and insulin resistance may play a major contributing role.
  03/2011: pages 195-206;
• Article: The ACCORD LIPID trial.

  Nicola Abate, Manisha Chandalia
  Metabolic syndrome and related disorders 10/2010; 8(5):373-4.
• Article: ENPP1/PC-1 K121Q and other predictors of posttransplant diabetes.

  Magdalene Szuszkiewicz, Jason Bell, Miguel Vazquez, Beverley Adams-Huet, Scott M Grundy, Manisha Chandalia, Nicola Abate
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  ABSTRACT: Diabetes mellitus is a major cause of morbidity and mortality among transplanted patients. This study evaluated the role of the ENPP1 K121Q polymorphism and other variables known to affect diabetes risk in 115 nondiabetic and unrelated patients who underwent kidney transplant at our institution and had consented for use of genetic material (30% whites, 48% blacks, and 22% Hispanics). Thirty-six of these patients (30%) developed posttransplant diabetes mellitus (PTDM) within 1 year of observation from transplant. Black race, ENPP1 K121Q polymorphism, age, body mass index (BMI), and immunosuppressive medications were found to have the strongest associations with PTDM in the logistic regression and receiver operator characteristic (ROC) analysis. However, because ENPP1 K121Q is more common in Hispanics and in blacks, who also have higher PTDM prevalence, the studied genetic polymorphism did not exert independent predictive effect, whereas ethnicity, specifically black versus non-black, was the most robust predictor of PTDM. The model with the largest ROC area under the curve (AUC) of 0.80 was comprised of black/non-black, age, BMI, and tacrolimus treatment as significant predictors. A reduced model containing only ethnicity (black/non-black) and age as predictors yielded similar results (ROC AUC 0.78). We conclude that black race and age are major and not modifiable risk factors for PTDM. The specific role of ENPP1 K121Q on ethnic susceptibility to PTDM deserves further investigation in larger cohorts of transplanted patients.
  Metabolic syndrome and related disorders 10/2010; 9(1):25-9.
• Article: Indices of cholesterol metabolism and relative responsiveness to ezetimibe and simvastatin.

  Susan G Lakoski, Fang Xu, Gloria L Vega, Scott M Grundy, Manisha Chandalia, Chun Lam, Robert S Lowe, Michael E Stepanavage, Thomas A Musliner, Jonathan C Cohen, Helen H Hobbs
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  ABSTRACT: Context: The level and duration of exposure to circulating low-density lipoprotein-cholesterol (LDL-C) are major contributors to coronary atherosclerosis. Therefore, optimal prevention will require long-term LDL-C reduction, making it important to select the most effective agent for each individual. Objective: We tested the hypothesis that individuals with high fractional absorption of cholesterol respond better to the cholesterol absorption inhibitor ezetimibe than to simvastatin, whereas low absorbers, who have elevated rates of cholesterol synthesis, respond better to simvastatin. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled, crossover trial was performed in 215 African- and European-American men. Intervention: Participants were randomized to placebo, ezetimibe (10 mg/d), simvastatin (10 mg/d), and both drugs for 6 wk each. Main Outcome: Plasma levels of LDL-C, surrogate markers for cholesterol absorption (campesterol) and synthesis (lathosterol), and proprotein convertase subtilisin-like kexin type 9 were measured at baseline and after treatment. Results: LDL-C levels were reduced by 19% (ezetimibe), 25% (simvastatin), and 41% (ezetimibe+simvastatin) from a baseline of 146 +/- 20 mg/dl; results were similar between ethnic groups. Reduction in LDL-C correlated poorly with baseline levels of noncholesterol sterols and proprotein convertase subtilisin-like kexin type 9. Although individual responses varied widely, change in LDL-C on ezetimibe correlated with response to simvastatin (r = 0.46, P < 0.001). Combination therapy lowered LDL-C by 15% or greater in more than 95% of participants. Conclusions: Baseline cholesterol absorption and synthesis did not predict responsiveness to LDL-lowering drugs. Responsiveness to simvastatin and ezetimibe were highly correlated, suggesting that factors downstream of the primary sites of action of these drugs are a major determinant of response.
  The Journal of clinical endocrinology and metabolism 12/2009; 95(2):800-9. · 6.50 Impact Factor
• Source

  Available from: PubMed Central

  Article: Effect of a high-fiber diet compared with a moderate-fiber diet on calcium and other mineral balances in subjects with type 2 diabetes.

  Meena Shah, Manisha Chandalia, Beverley Adams-Huet, Linda J Brinkley, Khashayar Sakhaee, Scott M Grundy, Abhimanyu Garg
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  ABSTRACT: High levels of dietary fiber, especially soluble fiber, are recommended to lower serum cholesterol levels and improve glycemic control in patients with type 2 diabetes. It is not clear, however, how high levels of fiber affect mineral balance. In a randomized crossover study, 13 patients with type 2 diabetes were fed a high-fiber (50 g total and 25 g soluble fiber) and a moderate-fiber (24 g total and 8 g soluble fiber) diet of the same energy, macronutrient, calcium, magnesium, and phosphorus content for 6 weeks each. Intestinal calcium absorption was determined by fecal recovery of (47)Ca. Stool weight and mineral content were assessed during 3 days, and 24-h urinary mineral content and serum chemistry were assessed over 5 days at the end of each phase. The results were compared by repeated-measures ANOVA. Compared with the moderate-fiber diet, the high-fiber diet increased stool weight (165 +/- 53 vs. 216 +/- 63 g/day, P = 0.02) and reduced 24-h urinary calcium (3.3 +/- 1.7 vs. 2.4 +/- 1.2 mmol/day, P = 0.003) and phosphorus (29.2 +/- 5.5 vs. 26.0 +/- 3.2 mmol/day, P = 0.003) excretion and serum calcium concentration (2.33 +/- 0.06 vs. 2.29 +/- 0.07 mmol/l, P = 0.04). Calcium absorption, stool calcium, magnesium, and phosphorus content and serum phosphorus concentration were not significantly different with the two diets. A high-fiber diet rich in soluble fiber has a small impact on calcium and phosphorus balance in subjects with type 2 diabetes. It may be prudent to ensure adequate intake of calcium and other minerals in individuals consuming a high-fiber diet.
  Diabetes care 04/2009; 32(6):990-5. · 8.09 Impact Factor
• Article: Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI.

  Tayeba Khan, Eric S Muise, Puneeth Iyengar, Zhao V Wang, Manisha Chandalia, Nicola Abate, Bei B Zhang, Paolo Bonaldo, Streamson Chua, Philipp E Scherer
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  ABSTRACT: Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.
  Molecular and cellular biology 01/2009; 29(6):1575-91. · 6.06 Impact Factor
• Article: The TRIB3 Q84R polymorphism and risk of early-onset type 2 diabetes.

  Sabrina Prudente, Daniela Scarpelli, Manisha Chandalia, Yuan-Yuan Zhang, Eleonora Morini, Silvia Del Guerra, Francesco Perticone, Rong Li, Christine Powers, Francesco Andreozzi, Piero Marchetti, Bruno Dallapiccola, Nicola Abate, Alessandro Doria, Giorgio Sesti, Vincenzo Trischitta
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  ABSTRACT: The prevalence of type 2 diabetes (T2D), particularly among young adults, has been rising steadily during the past 2 decades. T2D, especially in its early-onset subtype, is under genetic control. TRIB3 inhibits insulin-stimulated Akt phosphorylation and subsequent insulin action. A TRIB3 gain-of-function polymorphism, Q84R (rs2295490), impairs insulin signaling. The objective of the study was to verify the association of TRIB3 Q84R with: 1) T2D, either subtyped or not according to age at diagnosis (early-onset, <45 yr, or >or= 45 yr); 2) insulin secretion and sensitivity in nondiabetic individuals; or 3) in vitro insulin secretion from isolated human islets. Four different case-control samples comprising a total of 5,469 whites were examined. Insulinogenic and insulin sensitivity indexes and their interplay (disposition index) were assessed in 645 nondiabetic individuals at oral glucose tolerance test, glucose (16.7 mmol/liter)-induced in vitro insulin secretion was assessed in islets isolated from 54 nondiabetic donors. In the whole sample, the R84 variant was nominally associated with T2D (odds ratio 1.17, 95% confidence interval 1.00-1.36, P = 0.04). When stratifying according to age of diabetes onset, R84 carriers had an increased risk of early-onset T2D (odds ratio 1.32, 95% confidence interval 1.10-1.58, P = 0.002). Among 645 nondiabetic subjects, R84 carriers had higher glucose levels (P = 0.005) and lower insulinogenic (P = 0.03) and disposition index (P = 0.02) during the oral glucose tolerance test. R84 islets were more likely to display relatively low glucose-stimulated insulin release (P = 0.04). The TRIB3 R84 variant is associated with early-onset T2D in whites. Alteration in the insulin secretion/insulin sensitivity interplay appears to underlie this association.
  Journal of Clinical Endocrinology &amp Metabolism 12/2008; 94(1):190-6. · 6.50 Impact Factor
• Article: Effects of N-3 fatty acids on hepatic triglyceride content in humans.

  Gloria Lena Vega, Manisha Chandalia, Lidia S Szczepaniak, Scott M Grundy
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  ABSTRACT: Because dietary N-3 fatty acids reduce plasma triglycerides, they may also decrease hepatic triglyceride content. If so, N-3 fatty acids might constitute a therapy for fatty liver. Twenty-two subjects were recruited into a study designed to test the effects of N-3 fatty acids on liver fat content. Seventeen completed the trial that had a sequential design of 4-week placebo followed by an 8-week treatment with 9 g/d of fish oil. Liver fat was measured during placebo and treatment by magnetic resonance spectroscopy. Compliance was assessed by capsule count at the end of each study phase and measurement of fatty acid composition in plasma triglyceride and phospholipid. Plasma lipoproteins and adiponectin were also measured. Treatment with fish oils reduced significantly levels of plasma triglyceride by 46% (P <.03), very low-density lipoprotein + intermediate density lipoprotein cholesterol by 21% (P <.03), total apolipoprotein B by 15% (P <.03). In contrast to the changes in plasma triglycerides, hepatic triglyceride content was not significantly reduced by fish oil treatment. N-3 fatty acids at high doses lower plasma triglyceride levels, but there are no significant decreases in hepatic content of triglyceride for the group as a whole. Whereas the triglyceride lowering is uniform, the liver response is more variable.
  Journal of Investigative Medicine 06/2008; 56(5):780-5. · 1.96 Impact Factor
• Article: Ethnic difference in sex gap in high-density lipoprotein cholesterol between Asian Indians and Whites.

  Manisha Chandalia, Viswanathan Mohan, Beverley Adams-Huet, Raj Deepa, Nicola Abate
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  ABSTRACT: To study whether low plasma high-density lipoprotein cholesterol (HDL-C) reported in Asian Indians is common in both men and women when compared with whites and whether it is related to increased body mass index (BMI) and plasma triglyceride concentration. We evaluated the lipid profile and prevalence of low HDL-C (<40 mg/dL in men and <50 mg/dL in women) in the following cohorts of normoglycemic 1404 men and 1817 women: Asian Indians living in rural India; urban Chennai, India; and Dallas, TX; and whites living in Dallas, TX. After adjustment for age, BMI, and smoking, HDL-C was not significantly different in Asian Indian men compared with whites. However, Asian Indian women had lower HDL-C compared with white women, and rural Asian Indian women had the lowest HDL-C even in the absence of high triglycerides. Lean Asian Indian women with BMI of less than 23 kg/m had higher frequency of low HDL-C compared with lean white women with BMI of less than 25 kg/m (72%, 56%, 48%, and 25% in rural, urban, and Dallas Asian Indian and white women, respectively) and lean men (52%, 42%, 28%, and 35% in rural, urban, and Dallas Asian Indian and white men, respectively). Sex differences in HDL-C was estimated as 6.6+/-0.5 mg/dL for Asian Indians and 15.3+/-1.1 mg/dL for whites (P<0.0001 for sex difference in the 2 ethnic groups). Increased prevalence of low HDL-C independently of obesity or hypertriglyceridemia is observed in women but not in men of Asian Indian origin. The sex gap in HDL-C is significantly smaller in Asian Indians compared with whites independent of geographical location.
  Journal of Investigative Medicine 03/2008; 56(3):574-80. · 1.96 Impact Factor
• Article: Metabolic correlates of nonalcoholic fatty liver in women and men.

  Gloria Lena Vega, Manisha Chandalia, Lidia S Szczepaniak, Scott M Grundy
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  ABSTRACT: Nonalcoholic hepatic steatosis associates with a clustering of metabolic risk factors and steatohepatitis. One risk factor for hepatic steatosis is obesity, but other factors likely play a role. We examined metabolic concomitants of hepatic steatosis in nonobese and obese men and women. Sixty-one obese women and 35 obese men were studied; both those with and without hepatic steatosis were compared against each other and against nonobese controls (17 women and 32 men) without hepatic steatosis. Obesity (defined as >or=25% body fat in men and >or=35% in women), was identified by x-ray absorptiometry, whereas hepatic steatosis (>or=5.5% liver fat) was detected by magnetic resonance spectroscopy. The primary endpoint was a difference in insulin sensitivity. Obese groups with and without steatosis had similar body fat percentages. Compared with obese women without hepatic steatosis, those with steatosis were more insulin resistant; the same was true for men, although differences were less striking. Obese subjects with hepatic steatosis had higher ratios of truncal-to-lower body fat and other indicators of adipose tissue dysfunction compared with obese subjects without steatosis. CONCLUSION: These results support the concept that obesity predisposes to hepatic steatosis; but in addition, insulin resistance beyond that induced by obesity alone and a relatively high ratio of truncal-to-lower body fat usually combined with obesity to produce an elevated liver fat content.
  Hepatology 09/2007; 46(3):716-22. · 11.66 Impact Factor
• Source

  Available from: Nicola Abate

  Article: Screening and biochemical analysis of GATA4 sequence variations identified in patients with congenital heart disease.

  Marie K Schluterman, Amanda E Krysiak, Irfan S Kathiriya, Nicola Abate, Manisha Chandalia, Deepak Srivastava, Vidu Garg
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  ABSTRACT: Few known monogenic causes of non-syndromic congenital heart disease (CHD) have been identified. Mutations in NKX2.5 were initially implicated in familial cases of cardiac septal defects and subsequently, functionally significant NKX2.5 mutations were found in diverse forms of non-syndromic CHD. Similarly, mutations in GATA4, which encodes a cardiac transcription factor, were first identified in familial cases of cardiac septal defects. We hypothesize that individuals with non-syndromic CHD may harbor GATA4 mutations and that these mutations alter the biochemical properties of the protein. The coding region encompassing the six exons of GATA4 was screened in a study population of 157 patients with CHD. We identified several sequence variations in GATA4. We tested these novel sequence variations that altered evolutionarily conserved amino acids and other previously reported GATA4 mutations in various biochemical assays. The novel sequence variations had no biochemical deficits while a previously reported, but unstudied, missense mutation in GATA4 (S52F) functioned as a hypomorph in transactivation assays. We did not identify any novel GATA4 mutations in our patient population with non-syndromic CHD. Consistent with previous findings, GATA4 mutations that result in deficits in transactivation ability are consistently associated with CHD suggesting that normal transactivation properties of GATA4 are required for proper cardiac development.
  American Journal of Medical Genetics Part A 05/2007; 143A(8):817-23. · 2.39 Impact Factor
• Source

  Available from: Nicola Abate

  Article: Ethnicity, type 2 diabetes & migrant Asian Indians.

  Nicola Abate, Manisha Chandalia
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  ABSTRACT: The rapid increase of diabetes prevalence in the US population and across all westernized world has been associated with environmental changes that promote obesity. However, studies conducted in various ethnic groups within the US population have pointed out differences in susceptibility to diabetes within the same environmental pressure. Of particular interest is the growing evidence that Asian Indians, i.e., persons originating from the Indian Subcontinent, are at uniquely heightened risk for type 2 diabetes when compared to other populations. The elucidation of the mechanisms responsible for the heterogeneous relationship between obesity and type 2 diabetes in various ethnic groups, and particularly in Asian Indians, may give important contributions to better understand the complex mechanisms involved in the development of type 2 diabetes. This review examines epidemiological and pathophysiological aspects of the interaction between environment and ethnic predisposition to type 2 diabetes in Asian Indians migrated to the US.
  The Indian journal of medical research 04/2007; 125(3):251-8. · 1.84 Impact Factor
• Source

  Available from: Nicola Abate

  Article: Role of ENPP1 on adipocyte maturation.

  Jian Liang, Mingui Fu, Ester Ciociola, Manisha Chandalia, Nicola Abate
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  ABSTRACT: It is recognized that the ability of adipose tissue to expand in response to energy excess, i.e. adipocyte maturation, is important in determining systemic abnormalities in glucose and lipid metabolism. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1, also known as PC-1) has been recently reported to be involved in the pathogenesis of insulin resistance and related diseases. However, its role on adipose tissue physiology as a mechanism of systemic insulin resistance is not understood. This study was performed to evaluate whether ENPP1 is regulated during adipogenesis and whether over-expression in adipocytes can affect adipocyte maturation, a potential novel mechanism of ENPP1-related insulin resistance. ENPP1 expression was found down-regulated during 3T3-L1 maturation, and over-expression of human ENPP1 in 3T3-L1 (pQCXIP-ENPP1 vector) resulted in adipocyte insulin resistance and in defective adipocyte maturation. Adipocyte maturation was more efficient in mesenchymal embryonal cells from ENPP1 knockout mice than from wild-type. We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the pathogenesis of insulin resistance in absence of obesity.
  PLoS ONE 02/2007; 2(9):e882. · 4.09 Impact Factor