Richard N Bergman

Cedars-Sinai Medical Center, Los Angeles, California, United States

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Publications (372)2951.46 Total impact

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    ABSTRACT: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis
    Nature 02/2015; 518(7538). DOI:10.1038/nature14177 · 42.35 Impact Factor
  • Orison O Woolcott, Marilyn Ader, Richard N Bergman
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    ABSTRACT: Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease, as more than 400 million people worldwide reside above 1,500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and a better glucose tolerance compared with those who live near sea level. There is also emerging evidence of lower prevalences of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1,500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalences of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis.
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    ABSTRACT: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
    Nature 02/2015; 518(7538-7538):187-96. DOI:10.1038/nature14132 · 42.35 Impact Factor
  • Orison Woolcott, Marilyn Ader, Richard Bergman
    Endocrine reviews 02/2015; er20141063. · 19.36 Impact Factor
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    ABSTRACT: Objectives To determine whether a selective increase of visceral adipose tissue content will result in insulin resistance.Methods Sympathetic denervation of the omental fat was performed under general inhalant anesthesia by injecting 6-hydroxydopamine in the omental fat of lean mongrel dogs (n = 11). In the conscious animal, whole-body insulin sensitivity was assessed by the minimal model (SI) and the euglycemic hyperinsulinemic clamp (SICLAMP). Changes in abdominal fat were monitored by magnetic resonance. All assessments were determined before (Wk0) and 2 weeks (Wk2) after denervation. Data are medians (upper and lower interquartile).ResultsDenervation of omental fat resulted in increased percentage (and content) of visceral fat [Wk0: 10.2% (8.5-11.4); Wk2: 12.4% (10.4-13.6); P < 0.01]. Abdominal subcutaneous fat remained unchanged. However, no changes were found in SI [Wk0: 4.7 (mU/l)−1 min−1 (3.1-8.8); Wk2: 5.3 (mU/l)−1 min−1 (4.5-7.2); P = 0.59] or SICLAMP [Wk0: 42.0 × 10−4 dl kg−1 min−1 (mU/l)−1 (41.0-51.0); Wk2: 40.0 × 10−4 dl kg−1 min−1 (mU/l) −1 (34.0-52.0); P = 0.67].Conclusions Despite a selective increase in visceral adiposity in dogs, insulin sensitivity in vivo did not change, which argues against the concept that accumulation of visceral adipose tissue contributes to insulin resistance.
    Obesity 01/2015; 23(1). DOI:10.1002/oby.20906 · 4.39 Impact Factor
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    ABSTRACT: Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components although few studies have examined their genetic architecture or their influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multi-cohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently-sampled intravenous glucose tolerance test (4 cohorts) or euglycemic clamp (3 cohorts) and random effects models were used to test association between loci and quantitative traits, adjusting for age, gender, and admixture proportions (Discovery). Analysis revealed significant (P<5.00x10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P<0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D cases and 9,232 controls of Mexican ancestry (Translation). Non-parametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive risk for T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 12/2014; DOI:10.2337/db14-0732 · 8.47 Impact Factor
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    ABSTRACT: Context: Metabolomic profiling of amino acids and acylcarnitines has revealed consistent patterns associated with metabolic disease. Objective: Use metabolomic profiling to identify analytes associated with insulin sensitivity (SI) and conversion to type 2 diabetes (T2D). Design: Insulin Resistance Atherosclerosis Study. Setting: Community-based. Patients: A total of 196 subjects (European American, Hispanic, and African American) were selected to represent extremes of the SI distribution and conversion to T2D between baseline and follow-up exams. Main Outcome: Mass spectrometry-based profiling of 69 metabolites. Subjects participated in a frequently sampled intravenous glucose tolerance test to measure SI and acute insulin response (AIR). T2D status was determined by a 2-hour oral glucose tolerance test. Results: Logistic regression analysis from 72 high and 75 low SI subjects, revealed significantly decreased glycine and increased valine, leucine, phenylalanine, and combined glutamine and glutamate (P=0.0079-7.7×10(-6)) in insulin resistant subjects. Ethnic-stratified results were strongest in European Americans. Comparing amino acid profiles between subjects that converted to T2D (76 converters; 70 non-converters) yielded a similar pattern of associations: decreased glycine and increased valine, leucine, and combined glutamine and glutamate (P=0.016-0.00010). Importantly, beta-cell function as a covariate revealed a similar pattern of association. Conclusions: A distinct pattern of differences in amino acids were observed when comparing subjects with high and low levels of SI. This pattern was associated with conversion to T2D, remaining significant when accounting for beta-cell function, emphasizing a link between this metabolic profile and insulin resistance. These results demonstrate a consistent metabolic signature associated with insulin resistance and conversion to T2D, providing potential insight into underlying mechanisms of disease pathogenesis.
    Journal of Clinical Endocrinology &amp Metabolism 11/2014; 100(3):jc20142357. DOI:10.1210/jc.2014-2357 · 6.31 Impact Factor
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    ABSTRACT: Background: Previous human studies reported inconsistent effects of dietary protein and branched-chain amino acids (BCAAs) on insulin action and glucose metabolism. Similarly, it is unclear whether saturated fat (SF) intake influences these metabolic variables. Objective: The objective of this study was to test the effects of high [30% of energy (%E)] vs. moderate (20%E) intakes of protein (primarily whey) on insulin action and lipid and lipoprotein concentrations in the context of both high (15%E) and low (7%E) SF diets. Methods: The study was conducted as a randomized controlled trial in 158 overweight and obese men and women. After a 4-wk baseline diet [55%E carbohydrate, 15%E protein, 30%E fat (7%E SF)), participants were randomly assigned to 4 wk of either the baseline diet or 1 of 4 test diets containing 35%E carbohydrate and either 20%E or 30%E protein and either 7%E or 15%E SF. Frequently sampled iv. glucose tolerance tests were administered after each dietary period. Results: Other than significantly higher fasting glucose concentrations for high vs. moderate protein intakes with a low-fat diet (difference +/- SE: 0.47 +/- 0.14 mmol/L; P = 0.001), there were no significant effects of dietary protein or SF on glucose metabolism, plasma insulin, or concentrations of lipids and lipoproteins. Changes in plasma BCAAs across all diets were negatively correlated with changes in the metabolic clearance rate of insulin (rho = -0.18, P = 0.03) and positively correlated with changes in the acute insulin response to glucose (rho = 0.15, P = 0.05). Conclusions: These findings suggest that short-term intake Of BCAAs can influence insulin dynamics. However, in this group of overweight and obese individuals, neither high protein nor SF intake affected insulin sensitivity or plasma concentrations of lipids and lipoproteins. This trial was registered at clinicaltrials.gov as NCT00508937.
    Journal of Nutrition 11/2014; 144(11):1753-9. DOI:10.3945/jn.114.197624 · 4.23 Impact Factor
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    ABSTRACT: Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to cause glucose uptake, but this is blocked in insulin resistance. As glucotoxicity is associated with endothelial dysfunction, the observed hyperglycemia in diet-induced obese dogs may inhibit insulin access to muscle cells, and exacerbate insulin resistance. Here we asked whether interstitial insulin diffusion is reduced in modest hyperglycemia, similar to that induced by a high fat diet.Methods During normoglycemic (100 mg/dl) and moderately hyperglycemic (120 mg/dl) clamps in anesthetized canines, sequential doses of insulin were injected into the vastus medialis of one hindlimb; the contra-lateral limb served as a control. Plasma samples were collected and analyzed for insulin content. Lymph vessels of the hind leg were also catheterized, and lymph samples were analyzed as an indicator of interstitial insulin concentration.ResultsInsulin injection increased lymph insulin in normoglycemic animals, but not in hyperglycemic animals. Muscle glucose uptake was elevated in response to hyperglycemia, however the insulin-mediated glucose uptake in normoglycemic controls was not observed in hyperglycemia. Modest hyperglycemia prevented intra-muscularly injected insulin from diffusing through the interstitial space reduced insulin-mediated glucose uptake.Conclusion Hyperglycemia prevents the appearance of injected insulin in the interstitial space, thus reducing insulin action on skeletal muscle cells.
    Metabolism 11/2014; 64(2). DOI:10.1016/j.metabol.2014.10.036 · 3.61 Impact Factor
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    ABSTRACT: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
    Nature Genetics 10/2014; DOI:10.1038/ng.3097 · 29.65 Impact Factor
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    ABSTRACT: Objective To determine whether geographical elevation is inversely associated with diabetes, while adjusting for multiple risk factors.Methods This is a cross-sectional analysis of publicly available online data from the Behavioral Risk Factor Surveillance System, 2009. Final dataset included 285,196 US adult subjects. Odds ratios were obtained from multilevel mixed-effects logistic regression analysis.ResultsAmong US adults (≥20 years old), the odds ratio for diabetes was 1.00 between 0 and 499 m of altitude (reference), 0.95 (95% confidence interval, 0.90-1.01) between 500 and 1,499 m, and 0.88 (0.81-0.96) between 1,500 and 3,500 m, adjusting for age, sex, body mass index, ethnicity, self-reported fruit and vegetable consumption, self-reported physical activity, current smoking status, level of education, income, health status, employment status, and county-level information on migration rate, urbanization, and latitude. The inverse association between altitude and diabetes in the US was found among men [0.84 (0.76-0.94)], but not women [1.09 (0.97-1.22)].Conclusions Among US adults, living at high altitude (1,500-3,500 m) is associated with lower odds of having diabetes than living between 0 and 499 m, while adjusting for multiple risk factors. Our findings suggest that geographical elevation may be an important factor linked to diabetes.
    Obesity 09/2014; 22(9). DOI:10.1002/oby.20800 · 4.39 Impact Factor
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    ABSTRACT: The hepato-portal area is an important glucohomeostatic metabolic sensor, sensing hypoglycemia, hyperglycemia, and hormones such as glucagon- like peptide-1 (GLP-1). We have previously reported that activation of hepato-portal sensors by intraportal infusion of glucose and GLP-1, or by subcutaneous administration of GLP-1-receptor activator exenatide and of intraportal glucose, improved glycemia independent of corresponding changes in pancreatic hormones. It is not clear if this effect is mediated via the portal vein (PV) or by direct action on the liver itself. To test whether receptors in the PV mediate exenatide's beneficial effect on glucose tolerance, we performed a) paired oral glucose tolerance tests (OGTT) with and without exenatide and b) intravenous glucose tolerance tests before and after PV denervation in canines. Denervation of the portal vein affected oral glucose tolerance: post-denervation OGTT glucose and insulin AUC were 50% higher than before denervation (p=0.01). However, portal denervation did not impair exenatide's effect to improve oral glucose tolerance (exenatide effect: 48±12 mmol/l*min before vs. 64±26 mmol/l*min after, p=0.67). There were no changes in insulin sensitivity or secretion during IVGTTs. Portal vein sensing might play a role in controlling oral glucose tolerance during physiological conditions, but not in pharmacological activation of GLP-1 receptors by exenatide.
    AJP Endocrinology and Metabolism 08/2014; 307(8). DOI:10.1152/ajpendo.00244.2014 · 4.09 Impact Factor
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    ABSTRACT: Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. Arq Bras Endocrinol Metab. 2014;58(6):600-9.
    Arquivos Brasileiros de Endocrinologia & Metabologia 08/2014; 58(6):600-609. DOI:10.1590/0004-2730000003223 · 0.68 Impact Factor
  • Richard N Bergman, Darko Stefanovski, Stella P Kim
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    ABSTRACT: Prevalence of Type 2 diabetes has increased at an alarming rate, highlighting the need to correctly predict the development of this disease in order to allow intervention and thus, slow progression of the disease and resulting metabolic derangement. There have been many recent 'advances' geared toward the detection of pre-diabetes, including genome wide association studies and metabolomics. Although these approaches generate a large amount of data with a single blood sample, studies have indicated limited success using genetic and metabolomics information alone for identification of disease risk. Clinical assessment of the disposition index (DI), based on the hyperbolic law of glucose tolerance, is a powerful predictor of Type 2 diabetes, but is not easily assessed in the clinical setting. Thus, it is evident that combining genetic or metabolomic approaches for a more simple assessment of DI may provide a useful tool to identify those at highest risk for Type 2 diabetes, allowing for intervention and prevention.
    Current Opinion in Biotechnology 06/2014; 28C:165-170. DOI:10.1016/j.copbio.2014.05.007 · 8.04 Impact Factor
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    ABSTRACT: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.
    Biochemical and Biophysical Research Communications 04/2014; 446(4). DOI:10.1016/j.bbrc.2014.03.075 · 2.28 Impact Factor
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    ABSTRACT: Objective: We describe the GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI). Design and Methods: GUARDIAN is comprised of seven cohorts, consisting of 4336 Mexican-American individuals in 1346 pedigrees. Insulin sensitivity (SI ), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3925 individuals) using variance components. Results: Across studies, age and gender-adjusted heritability of insulin sensitivity (SI , M, M/I) ranged from 0.23-0.48 and of MCRI from 0.35-0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to 0.59 for AIRg and MCRI (all P<0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P<0.0001); and -0.16 to -0.36 for AIRg and MCRI (P <0.0001-0.06). Conclusions: These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.
    Obesity 04/2014; 22(4). DOI:10.1002/oby.20639 · 4.39 Impact Factor
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    ABSTRACT: Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10−6), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (−0.17 s.d., P = 4.6 × 10−4). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
    Nature Genetics 03/2014; · 29.65 Impact Factor

Publication Stats

31k Citations
2,951.46 Total Impact Points

Institutions

  • 2012–2015
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Angeles, California, United States
    • University of Pittsburgh
      • Division of Endocrinology and Metabolism
      Pittsburgh, Pennsylvania, United States
    • University of Oxford
      • Wellcome Trust Centre for Human Genetics
      Oxford, ENG, United Kingdom
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2014
    • The University of Warwick
      • Division of Metabolic and Vascular Health
      Coventry, England, United Kingdom
  • 1979–2014
    • University of Southern California
      • • Department of Physiology and Biophysics
      • • Keck School of Medicine
      • • Department of Biomedical Engineering
      Los Ángeles, California, United States
  • 1981–2012
    • University of California, Los Angeles
      • • Department of Medicine
      • • Department of Physiology
      Los Ángeles, California, United States
  • 2008
    • University of Virginia
      • Department of Public Health Sciences
      Charlottesville, VA, United States
  • 2004–2008
    • Wake Forest School of Medicine
      • • Department of Biochemistry
      • • Division of Public Health Sciences
      Winston-Salem, NC, United States
  • 2002–2008
    • Keck School of Medicine USC
      Los Ángeles, California, United States
    • University of Texas at San Antonio
      San Antonio, Texas, United States
  • 2006–2007
    • University of Helsinki
      • Department of Dental Public Health
      Helsinki, Uusimaa, Finland
    • Medical University of Graz
      Gratz, Styria, Austria
  • 2005
    • Laval University
      • Département de Kinésiologie
      Québec, Quebec, Canada
  • 2003–2005
    • University of Pennsylvania
      • School of Veterinary Medicine
      Philadelphia, PA, United States
  • 1992–2005
    • Pennington Biomedical Research Center
      • Human Genomics Laboratory
      Baton Rouge, Louisiana, United States
  • 1999–2004
    • National Human Genome Research Institute
      Maryland, United States
    • University of Michigan
      • Department of Biostatistics
      Ann Arbor, MI, United States
  • 1990–2003
    • University of Texas Health Science Center at San Antonio
      • Division of Hospital Medicine
      San Antonio, TX, United States
    • University of Illinois at Chicago
      • Section of Endocrinology, Diabetes and Metabolism
      Chicago, IL, United States
  • 2001
    • Novo Nordisk
      København, Capital Region, Denmark
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
  • 1998
    • Joslin Diabetes Center
      Boston, Massachusetts, United States
    • University of South Carolina
      • Department of Epidemiology & Biostatistics
      Columbia, SC, United States
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 1996
    • University of Melbourne
      Melbourne, Victoria, Australia
    • Wake Forest University
      • Department of Public Health Sciences
      Winston-Salem, North Carolina, United States
  • 1994
    • University of Kuopio
      • Department of Medicine
      Kuopio, Eastern Finland Province, Finland
  • 1989–1994
    • University of Washington Seattle
      • Department of Medicine
      Seattle, WA, United States
  • 1991
    • Harbor-UCLA Medical Center
      Torrance, California, United States