William V Tamborlane

Yale-New Haven Hospital, New Haven, Connecticut, United States

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Publications (363)2783.5 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of cardiovascular risk factors in children with type 1 diabetes and elevated BMI in the USA is poorly defined. We aimed to test the hypothesis that children with type 1 diabetes who are overweight or obese have increased frequencies of hypertension, dyslipidemia, and micro-/macroalbuminuria compared to their healthy weight peers. We studied 11,348 children 2 to <18 years of age enrolled in T1D Exchange between September 2010 and August 2012 with type 1 diabetes for ≥1 year and BMI ≥ 5th age-/sex-adjusted percentile (mean age 12 years, 49 % female, 78 % non-Hispanic White). Overweight and obesity were defined based on Centers for Disease Control and Prevention criteria. Diagnoses of hypertension, dyslipidemia, and micro-/macroalbuminuria were obtained from medical records. Logistic and linear regression models were used to assess factors associated with weight status. Of the 11,348 participants, 22 % were overweight and 14 % obese. Hypertension and dyslipidemia were diagnosed in 1.0 % and 3.8 % of participants, respectively; micro-/macroalbuminuria was diagnosed in 3.8 % of participants with available data (n = 7,401). The odds of either hypertension or dyslipidemia were higher in obese than healthy weight participants [OR 3.5, 99 % confidence interval (CI) 2.0-6.1 and 2.2, 99 % CI 1.6-3.1, respectively]. Obese participants tended to be diagnosed with micro-/macroalbuminuria less often than healthy weight participants (OR 0.6, 99 % CI 0.4-1.0). Obese children with type 1 diabetes have a higher prevalence of hypertension and dyslipidemia than healthy weight children with type 1 diabetes. The possible association of obesity with lower micro-/macroalbuminuria rates warrants further investigation.
    Acta Diabetologica 06/2015; DOI:10.1007/s00592-015-0785-1 · 3.68 Impact Factor
  • William T Cefalu, William V Tamborlane, Jay S Skyler
    Diabetes care 06/2015; 38(6):968-70. DOI:10.2337/dc15-0615 · 8.57 Impact Factor
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    ABSTRACT: To examine the overall state of metabolic control and current use of advanced diabetes technologies in the U.S., we report recent data collected on individuals with type 1 diabetes participating in the T1D Exchange clinic registry. Data from 16,061 participants updated between 1 September 2013 and 1 December 2014 were compared with registry enrollment data collected from 1 September 2010 to 1 August 2012. Mean hemoglobin A1c (HbA1c) was assessed by year of age from <4 to >75 years. The overall average HbA1c was 8.2% (66 mmol/mol) at enrollment and 8.4% (68 mmol/mol) at the most recent update. During childhood, mean HbA1c decreased from 8.3% (67 mmol/mol) in 2-4-year-olds to 8.1% (65 mmol/mol) at 7 years of age, followed by an increase to 9.2% (77 mmol/mol) in 19-year-olds. Subsequently, mean HbA1c values decline gradually until ∼30 years of age, plateauing at 7.5-7.8% (58-62 mmol/mol) beyond age 30 until a modest drop in HbA1c below 7.5% (58 mmol/mol) in those 65 years of age. Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain all too common complications of treatment, especially in older (SH) and younger patients (DKA). Insulin pump use increased slightly from enrollment (58-62%), and use of continuous glucose monitoring (CGM) did not change (7%). Although the T1D Exchange registry findings are not population based and could be biased, it is clear that there remains considerable room for improving outcomes of treatment of type 1 diabetes across all age-groups. Barriers to more effective use of current treatments need to be addressed and new therapies are needed to achieve optimal metabolic control in people with type 1 diabetes. © 2015 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 care 06/2015; 38(6):971-8. DOI:10.2337/dc15-0078 · 8.57 Impact Factor
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    ABSTRACT: Type 2 diabetes (T2D) in youth is recognized as a pediatric disease, but few reports describe the characteristics during diagnosis. We describe the clinical presentation of 503 youth with T2D. The Pediatric Diabetes Consortium (PDC) T2D Clinic Registry enrolled T2D participants from eight pediatric diabetes centers in the USA. Clinical and laboratory characteristics at the time of diagnosis were analyzed. In total 67% presented with symptoms of diabetes and confirming laboratory data, but 33% were identified by testing at risk children, 11% presented with diabetic ketoacidosis (DKA), and 2% with hyperglycemic hyperosmolar state (HHS). The mean age was 13.1 ± 2.3 yr (range, 4.6-19.8 yr) with 38 (8%) less than 10 yr of age at diagnosis. The majority was female (65%), Hispanic (54%) and had a family history of T2D (92%). The median body mass index (BMI) z-score was 2.3 (interquartile range 2.0-2.6). Fewer than half (46%) lived with both parents, only 30% had parents with education beyond high school, and 43% lived in a household with an income of <$25 000 per year. In the initial month after diagnosis, almost all (92%) were treated with insulin (30%), metformin (31%), or a combination of insulin and metformin (32%); 7% were treated with lifestyle modification alone. The demographics of T2D in youth indicate significant social vulnerability which may affect outcomes. Metformin and insulin were the initial treatment in most youth. Importantly, T2D may occur at younger ages than previously thought and should be considered in all high-risk children presenting with diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Pediatric Diabetes 05/2015; DOI:10.1111/pedi.12281 · 2.13 Impact Factor
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    ABSTRACT: To describe C-peptide levels in a large cohort of children with type 2 diabetes T2D and examine associations with demographic and clinical factors. The Pediatric Diabetes Consortium (PDC) T2D Registry has collected clinical and biologic data from youth with T2D cared for at eight US Pediatric Diabetes Centers. In this study, we assessed C-peptide levels in 331 youth with T2D (mean age, 16.1 ± 2.5 yr; median T2D duration, 2.4 yr). Median (interquartile range) for 90 fasted C-peptide measurements was 3.5 ng/mL (2.3-4.8 ng/mL) [1.2 nmol/L (0.8-1.6 nmol/L)] and for 241 random non-fasted C-peptide measurements were 4.2 ng/mL (2.6-7.0 ng/mL) [1.4 nmol/L (0.9-2.3 nmol/L)]. C-peptide levels were lower with insulin therapy (p < 0.001), lower body mass index (p < 0.001), hemoglobin A1c ( HbA1c) ≥9% (p < 0.001), and T2D duration ≥ 6 yr (p = 0.04). Among those with duration ≥6 yr being treated with insulin and with a HbA1c level ≥9.0% (75 mmol/L), 75% of the fasted and 80% of the non-fasted C-peptide values were above 0.2 nmol/L. In youth with T2D, a decline in C-peptide is associated with deterioration of metabolic control and the need for insulin treatment. C-peptide levels decrease over time. However, even insulin-treated patients with 6 or more years of T2D and elevated HbA1c levels retain substantial endogenous insulin secretion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    Pediatric Diabetes 05/2015; DOI:10.1111/pedi.12280 · 2.13 Impact Factor
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    ABSTRACT: To describe changes in weight and body mass index (BMI) during the first year following diagnosis of type 1 diabetes (T1D) and associations with demographic and clinical characteristics. The Pediatric Diabetes Consortium includes 7 US centers with prospective longitudinal data from initial T1D diagnosis. This analysis includes 530 youth with diabetes duration of ≥1 year and measures of BMI at 3 and 12 months after diagnosis. BMI trajectory of participants and relationships between the change in BMI z-score from baseline (3 months) to 12 months with demographic characteristics, hemoglobin A1c at baseline, and insulin delivery mode at baseline were evaluated. As a group, BMI z-scores increased sharply from diagnosis for 1-3 months but remained relatively stable from +0.51 at 3 months to +0.48 at 12 months. Children aged 2-<5 years experienced a significant positive change in BMI z-score between 3 and 12 months, and there was a similar trend among girls that did not reach statistical significance. No significant differences were found for race, socioeconomic status, or insulin delivery mode. These data suggest that increased BMI during the first year of treatment of most youth with T1D reflects regain of weight lost before diagnosis. There is, however, a propensity toward additional weight gain in younger children and girls. Copyright © 2015 Elsevier Inc. All rights reserved.
    The Journal of pediatrics 05/2015; 166(5):1265-1269.e1. DOI:10.1016/j.jpeds.2015.02.036 · 3.74 Impact Factor
  • Diabetes 04/2015; 64(5):1770-1779. DOI:10.2337/db14-1445 · 8.47 Impact Factor
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    ABSTRACT: Delays in the time-action profiles of premeal boluses of rapid-acting insulin analogs contribute to early postmeal hyperglycemia in patients with diabetes. We tested whether applying local heat to skin around the injection site to increase the rate of insulin absorption reduces postprandial hyperglycemia in patients with type 2 diabetes. Fourteen patients with type 2 diabetes (4 females; age 61.6 ± 8.4 years, HbA1c 8.42 ± 1.13%; BMI 29.10 ± 5.61 kg/m(2)) on intensified insulin therapy underwent 5-hour meal tolerance tests (MTTs) with a standardized liquid meal after an overnight fast on 2 study days. Subjects injected 0.2 U/kg of insulin aspart or lispro subcutaneously into the abdominal skin on both days with and without the use of the InsuPad device. Following the premeal bolus injection of rapid-acting insulin analog, infusion site warming led to a rise in plasma insulin levels to peak concentrations that were significantly earlier than without skin warming (mean ± SD 52 ± 26.7 vs 80 ± 51.3 minutes, P < .005) as well as increase in plasma insulin levels during the first hour after injection (mean ± SD 63.5 ± 32.7 IU vs 48.0 ± 25.0 uU.min/ml, P = .019). As a result, the area under the curve of the postprandial glucose excursion during the first 2 hours (the primary study outcome) and the entire 5 hours after the meal were significantly reduced (P = .007 and P = .03, respectively) with skin warming around the injection site. Use of the InsuPad to increase the rate of insulin absorption provides an effective means to achieve better control of postmeal glucose excursions in type 2 diabetic patients receiving premeal injections of rapid-acting insulin analogs. © 2015 Diabetes Technology Society.
    Journal of diabetes science and technology 04/2015; 9(3). DOI:10.1177/1932296815578881
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    ABSTRACT: The aim of this work was to assess the association between continuous glucose monitoring (CGM) data, HbA1c, insulin-dose-adjusted HbA1c (IDAA1c) and C-peptide responses during the first 2 years following diagnosis of type 1 diabetes. A secondary analysis was conducted of data collected from a randomised trial assessing the effect of intensive management initiated within 1 week of diagnosis of type 1 diabetes, in which mixed-meal tolerance tests were performed at baseline and at eight additional time points through 24 months. CGM data were collected at each visit. Among 67 study participants (mean age [± SD] 13.3 ± 5.7 years), HbA1c was inversely correlated with C-peptide at each time point (p < 0.001), as were changes in each measure between time points (p < 0.001). However, C-peptide at one visit did not predict the change in HbA1c at the next visit and vice versa. Higher C-peptide levels correlated with increased proportion of CGM glucose values between 3.9 and 7.8 mmol/l and lower CV (p = 0.001 and p = 0.02, respectively) but not with CGM glucose levels <3.9 mmol/l. Virtually all participants with IDAA1c < 9 retained substantial insulin secretion but when evaluated together with CGM, time in the range of 3.9-7.8 mmol/l and CV did not provide additional value in predicting C-peptide levels. In the first 2 years after diagnosis of type 1 diabetes, higher C-peptide levels are associated with increased sensor glucose levels in the target range and with lower glucose variability but not hypoglycaemia. CGM metrics do not provide added value over the IDAA1c in predicting C-peptide levels.
    Diabetologia 03/2015; 58(6). DOI:10.1007/s00125-015-3559-y · 6.88 Impact Factor
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    ABSTRACT: Previous research has documented racial/ethnic disparities in diabetes treatments and outcomes. It remains controversial whether these disparities result from differences in socioeconomic status (SES) or other factors. We examined racial/ethnic disparities in therapeutic modalities and diabetes outcomes among the large number of pediatric participants in the T1D Exchange Clinic Registry. The cohort included 10 704 participants aged <18 years with type 1 diabetes for ≥1 year (48% female; mean age: 11.9 ± 3.6 years; diabetes duration: 5.2 ± 3.5 years). Diabetes management and clinical outcomes were compared among 8841 non-Hispanic white (white) (83%), 697 non-Hispanic black (black) (7%), and 1166 Hispanic (11%) participants. The population included 214 high-income black and Hispanic families. Insulin pump use was higher in white participants than in black or Hispanic participants (61% vs 26% and 39%, respectively) after adjusting for gender, age, diabetes duration, and SES (P < .001). Mean hemoglobin A1c was higher (adjusted P < .001) in black participants than in white or Hispanic participants (9.6%, 8.4%, and 8.7%). More black participants experienced diabetic ketoacidosis and severe hypoglycemic events in the previous year than white or Hispanic participants (both, P < .001). There were no significant differences in hemoglobin A1c, diabetic ketoacidosis, or severe hypoglycemia between white and Hispanic participants after adjustment for SES. Even after SES adjustment, marked disparities in insulin treatment method and treatment outcomes existed between black versus Hispanic and white children within this large pediatric cohort. Barriers to insulin pump use and optimal glycemic control beyond SES should be explored in all ethnic groups. Copyright © 2015 by the American Academy of Pediatrics.
    Pediatrics 02/2015; 135(3). DOI:10.1542/peds.2014-1774 · 5.30 Impact Factor
  • Diabetes Technology &amp Therapeutics 02/2015; 17:A13-A14. · 2.29 Impact Factor
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    ABSTRACT: Objective The objectives were to (i) describe the characteristics of a large ethnically/racially and geographically diverse population of adolescents with recent-onset type 2 diabetes (T2D), and (ii) assess the effects of short-term diabetes education and treatment with metformin on clinical and biochemical parameters in this cohort.Research design and methodsDescriptive characteristics were determined for subjects screened for Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) who met criteria for diagnosis of T2D (n = 1092). Changes in clinical and biochemical parameters were determined for those who completed at least 8 wk of the run-in phase of the trial, which included standardized diabetes education and treatment with metformin. Further analysis determined whether these changes differed according to the treatment at screening.Main outcome measuresDemographic, biochemical measurements, and anthropometrics at screening and changes over 8 wk of run-in were the outcome measures.ResultsSubjects screened for TODAY had a median age of 14 yr and median hemoglobin A1c (HbA1c) of 6.9% (52 mM/M), 2/3 were female, and ethnic/racial minorities were overrepresented. Dyslipidemia and hypertension were common comorbidities. During run-in, HbA1c, body mass index, low-density lipoprotein cholesterol, triglycerides, and blood pressure significantly improved. Nearly all participants on insulin therapy at screening were able to attain target HbA1c following insulin discontinuation.Conclusions Treatment with metformin and diabetes education provided short-term improvements in glycemic control and cardiometabolic risk factors in a large adolescent T2D cohort. Nearly all insulin-treated youth could be successfully weaned off insulin with continued improvement in glycemic control.
    Pediatric Diabetes 02/2015; DOI:10.1111/pedi.12264 · 2.13 Impact Factor
  • PEDIATRICS 02/2015; in press. · 5.30 Impact Factor
  • Diabetes Technology &amp Therapeutics 02/2015; 17:A15-A15. · 2.29 Impact Factor
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    ABSTRACT: Abstract Aims Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. Methods Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. Results Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15–24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. Conclusion These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.
    Diabetic Medicine 12/2014; Accepted manuscript online: 15 DEC 2014 10:12AM EST | DOI: 10.1111/dme.12676. DOI:10.1111/dme.12676 · 3.06 Impact Factor
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    ABSTRACT: Objectives The aim of the study was to characterize glucose levels and variability in young children with type 1 diabetes (T1D).MethodsA total of 144 children of 4–10 yr old diagnosed with T1D prior to age 8 were recruited at five DirecNet centers. Participants used a continuous glucose monitor (CGM) every 3 months during an 18-month study. Among the 144 participants, 135 (mean age 7.0 yr, 47% female) had a minimum of 48 h of CGM data at more than five of seven visits and were included in analyses. CGM metrics for different times of day were analyzed.ResultsMean hemoglobin A1c (HbA1c) at the beginning and end of the study was 7.9% (63 mmol/mol). Fifty percent of participants had glucose levels >180 mg/dL (10.0 mmol/L) for >12 h/d and >250 mg/dL (13.9 mmol/L) for >6 h/d. Median time <70 mg/dL (3.9 mmol/L) was 66 min/d and <60 mg/dL (3.3 mmol/L) was 39 min/d. Mean amplitude of glycemic excursions (MAGE) was lowest overnight (00:00–06:00 hours). The percent of CGM values 71–180 mg/dL (3.9–10.0 mmol/L) and the overall mean glucose correlated with HbA1c at all visits. There were no differences in CGM mean glucose or coefficient of variation between the age groups of 4 and <6, 6 and <8, and 8 and <10.Conclusions Suboptimal glycemic control is common in young children with T1D as reflected by glucose levels in the hyperglycemic range for much of the day. New approaches to reduce postprandial glycemic excursions and increase time in the normal range for glucose in young children with T1D are critically needed. Glycemic targets in this age range should be revisited.
    Pediatric Diabetes 12/2014; DOI:10.1111/pedi.12248 · 2.13 Impact Factor
  • Diabetes Research and Clinical Practice 12/2014; 106(3):643-4. DOI:10.1016/j.diabres.2014.11.003 · 2.54 Impact Factor
  • Diabetes Care 10/2014; 37(10):2665-7. DOI:10.2337/dc14-0494 · 8.57 Impact Factor
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    ABSTRACT: Objectives Reduction of cardiovascular risk in children with type 1 diabetes requires aggressive management of hypertension (HTN). However, the frequency of diagnosing and effectively treating HTN in youth with type 1 diabetes has not been established. To address this question, we used the data collected in >9000 youth with type 1 diabetes who enrolled in the T1D Exchange Clinic Registry.Research design and methodsThis analysis included data from medical records of 9362 individuals with enrolment and 1-yr follow-up visits (age 3 to <18 yr, disease duration ≥ 1 yr at follow-up). Data included the prevalence of a documented diagnosis of HTN, elevated blood pressure (BP) (systolic or diastolic ≥95th percentile for age, gender, and height), and treatment with angiotensin converting enzyme (ACE)-receptor inhibitor (ACE-I)/angiotensin receptor blocker (ARB) therapy.ResultsHTN was diagnosed in only 1% (113/9362) of participants; yet, elevated BP was recorded at one of the two visits in 17% and at both visits in 4%. Among those with diagnosed HTN, only 52% (59/113) were receiving ACE-I/ARB therapy and only 32% (19 of 59) of those treated were at goal BP. Children with diagnosed HTN had higher HbA1c (adjusted p < 0.001) and higher BMI (p < 0.001) when compared with children without HTN.ConclusionsHTN is likely under diagnosed and undertreated even in pediatric diabetes clinics. The relatively low proportion of hypertensive children receiving ACE-I therapy and reaching BP goals probably identifies an important area for improving care in children with type 1 diabetes.
    Pediatric Diabetes 10/2014; DOI:10.1111/pedi.12231 · 2.13 Impact Factor
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    ABSTRACT: Aims/hypothesis The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old. Methods Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (<7.5% [<58 mmol/mol]) and ADA (<8.5% [<69 mmol/mol]) were compared. Results Insulin pump use was more frequent (74% vs 50%, p < 0.001) and HbA1c levels lower in the Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX) (mean 7.4% vs 8.2%, p < 0.001). A lower HbA1c level was seen in the DPV compared with the T1DX for both pump users (p < 0.001) and injection users (p < 0.001). More children from DPV were meeting the recommended HbA1c goals, compared with children from T1DX (HbA1c <7.5%: 56% vs 22%, p < 0.001; HbA1c <8.5%: 90% vs 66%, p < 0.001). The adjusted odds of having an HbA1c level <7.5% or <8.5% were 4.2 (p < 0.001) and 3.6 (p < 0.001) higher for the DPV than the T1DX, respectively. The frequency of SH did not differ between registries or by HbA1c, whereas the frequency of DKA was higher for the T1DX and greater in those with higher HbA1c levels. Conclusions/interpretation DPV data indicate that an HbA1c of <7.5% can frequently be achieved in children with type 1 diabetes who are under 6 years old. An improved metabolic control of type 1 diabetes in young patients appears to decrease the risk of DKA without increasing SH. The greater frequency of suboptimal control in young patients in the T1DX compared with the DPV is not fully explained by a less frequent use of insulin pumps and may relate to the higher HbA1c targets that are recommended for this age group in the USA.
    Diabetologia 08/2014; 57(8). DOI:10.1007/s00125-014-3272-2 · 6.88 Impact Factor

Publication Stats

16k Citations
2,783.50 Total Impact Points


  • 1978–2015
    • Yale-New Haven Hospital
      • • Endocrinology and Diabetes Program
      • • Department of Laboratory Medicine
      New Haven, Connecticut, United States
    • Yale University
      • • Department of Pediatrics
      • • School of Medicine
      • • Department of Internal Medicine
      New Haven, Connecticut, United States
  • 2003–2014
    • University of New Haven
      New Haven, Connecticut, United States
  • 2005–2013
    • Jaeb Center for Health Research
      Tampa, Florida, United States
  • 2012
    • University of Colorado
      • Barbara Davis Center for Childhood Diabetes
      Denver, CO, United States
  • 2010
    • Vanderbilt University
      • Department of Medicine
      Nashville, MI, United States
  • 2004
    • University of Massachusetts Medical School
      • Graduate School of Nursing
      Worcester, Massachusetts, United States
  • 2000
    • Abbott Laboratories
      • Diagnostics Division (ADD)
      North Chicago, IL, United States
  • 1996–1998
    • King Faisal Specialist Hospital and Research Centre
      • Department of Pediatrics
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia
  • 1992
    • Wesleyan University
      • Department of Psychology
      Middletown, CT, United States