R. Paul Wadwa
University of Colorado Denver
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Featured researches published by R. Paul Wadwa.
Diabetes Care | 2006
Beatriz L. Rodriguez; Wilfred Y. Fujimoto; Elizabeth J. Mayer-Davis; Giuseppina Imperatore; Desmond E. Williams; Ronny A. Bell; R. Paul Wadwa; Shana L. Palla; Lenna L. Liu; Ann K. Kershnar; Stephen R. Daniels; Barbara Linder
OBJECTIVE—The purpose of this study was to determine the prevalence and correlates of selected cardiovascular disease (CVD) risk factors among youth aged <20 years with diabetes. RESEARCH DESIGN AND METHODS—The analysis included 1,083 girls and 1,013 boys examined as part of the SEARCH for Diabetes in Youth study, a multicenter, population-based study of youth 0–19 years of age with diabetes. Diabetes type was determined by a biochemical algorithm based on diabetes antibodies and fasting C-peptide level. CVD risk factors were defined as follows: HDL cholesterol <40 mg/dl; age- and sex-specific waist circumference >90th percentile; systolic or diastolic blood pressure >90th percentile for age, sex, and height or taking medication for high blood pressure; and triglycerides >110 mg/dl. RESULTS—The prevalence of having at least two CVD risk factors was 21%. The prevalence was 7% among children aged 3–9 years and 25% in youth aged 10–19 years (P < 0.0001), 23% among girls and 19% in boys (P = 0.04), 68% in American Indians, 37% in Asian/Pacific Islanders, 32% in African Americans, 35% in Hispanics, and 16% in non-Hispanic whites (P < 0.0001). At least two CVD risk factors were present in 92% of youth with type 2 and 14% of those with type 1A diabetes (P < 0.0001). In multivariate analyses, age, race/ethnicity, and diabetes type were independently associated with the odds of having at least two CVD risk factors (P < 0.0001). CONCLUSIONS—Many youth with diabetes have multiple CVD risk factors. Recommendations for weight, lipid, and blood pressure control in youth with diabetes need to be followed to prevent or delay the development of CVD as these youngsters mature.
Diabetes Care | 2009
John Guy; Lorraine G. Ogden; R. Paul Wadwa; Richard F. Hamman; Elizabeth J. Mayer-Davis; Angela D. Liese; Ralph B. D'Agostino; Santica M. Marcovina; Dana Dabelea
OBJECTIVE—The purpose of this study was to compare the lipid profile and the prevalence of lipid abnormalities in youth with and without type 1 diabetes and explore the role of glycemic control on the hypothesized altered lipid profile in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS—We conducted a cross-sectional analysis of 512 youth with type 1 diabetes (mean duration 4.22 years) and 188 healthy control subjects aged 10–22 years in Colorado and South Carolina. SEARCH for Diabetes in Youth (SEARCH) participants with type 1 diabetes and healthy control subjects recruited from primary care offices in the same geographic regions were invited to attend a research visit. Fasting lipid profiles were compared between youth with type 1 diabetes (stratified according to categories of optimal [A1C <7.5%] and suboptimal [A1C ≥7.5%] glycemic control) and healthy nondiabetic youth, using multiple linear and logistic regression. RESULTS—Youth with type 1 diabetes and optimal A1C had lipid concentrations that were similar (total cholesterol, LDL cholesterol, and LDL particle size) or even less atherogenic (HDL cholesterol, non-HDL cholesterol, triglyceride, and triglyceride–to–HDL cholesterol ratio) than those observed in nondiabetic youth, whereas youth with suboptimal glycemic control had elevated standard lipid levels (total cholesterol, LDL cholesterol, and non-HDL cholesterol). Youth with type 1 diabetes also had significantly elevated apolipoprotein B levels and more small, dense LDL particles than nondiabetic youth, regardless of glycemic control. CONCLUSIONS—Youth with type 1 diabetes have abnormal lipid levels and atherogenic changes in lipoprotein composition, even after a relatively short disease duration. As in adults, glycemic control is an important mediator of these abnormalities.
The Journal of Pediatrics | 2010
Elaine M. Urbina; R. Paul Wadwa; Cralen Davis; Beverly M. Snively; Lawrence M. Dolan; Stephen R. Daniels; Richard F. Hamman; Dana Dabelea
OBJECTIVE To discuss vascular stiffness commonly encountered in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN We examined 535 subjects with T1DM (14.6 years; 53% male, 88% non-Hispanic white) and 241 healthy control subjects (17.8 years; 42% male, 39% non-Hispanic white). Abnormalities in brachial distensibility (BrachD), pulse wave velocity, and augmentation index corrected to a HR of 75 (AIx-75) were examined. RESULTS Subjects with T1DM had higher body mass index, LDL-cholesterol, fasting glucose, and blood pressure than control subjects. Diabetic subjects had lower BrachD and higher AIx-75 indicating increased stiffness. Age-adjusted pulse wave velocity-trunk (aorto-femoral) was higher in cases (all P <or= < .05). Increased peripheral stiffness was more common than central stiffness in subjects with T1DM (low BrachD in 33% vs high PWV-trunk in 9.9%). Male subjects with type 1 diabetes had a higher prevalence of VS abnormalities than females. Presence of T1DM, male sex, and increased mean arterial pressure were the most consistent independent determinants of vascular stiffness. CONCLUSIONS Increased vascular stiffness is present in youth with T1DM with peripheral abnormalities predominating especially in males. Traditional risk factors are important correlates. Identifying early vascular abnormalities in youth with T1DM will allow for implementation of more aggressive risk factor management.
Pediatric Diabetes | 2014
Kim C. Donaghue; R. Paul Wadwa; Linda A. DiMeglio; Tien Yin Wong; Francesco Chiarelli; M. Loredana Marcovecchio; Mona Salem; Jamal Raza; Paul Hofman; Maria E. Craig
Kim C Donaghuea,b, R Paul Wadwac, Linda A Dimegliod, Tien Y Wonge, Francesco Chiarellif, M Loredana Marcovecchiof, Mona Salemg, Jamal Razah, Paul L Hofmani and Maria E Craiga,b,j aInstitute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, Australia; bDiscipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia; cBarbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Denver, CO, USA; dPediatric Endocrinology and Diabetology, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA; eSingapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore; fDepartment of Paediatrics, University of Chieti, Chieti, Italy; gDepartment of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt; hNational Institute of Child Health, Karachi, Pakistan; iLiggins Institute, University of Auckland, Auckland, New Zealand and jSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia
Diabetes Care | 2013
Mamta Jaiswal; Elaine M. Urbina; R. Paul Wadwa; Jennifer W. Talton; Ralph B. D’Agostino; Richard F. Hamman; Tasha E. Fingerlin; Stephen R. Daniels; Santica M. Marcovina; Lawrence M. Dolan; Dana Dabelea
OBJECTIVE This study compared heart rate variability (HRV) parameters in youth with and without type 1 diabetes and explored potential contributors of altered HRV. RESEARCH DESIGN AND METHODS HRV parameters were measured among 354 youth with type 1 diabetes (mean age 18.8 years, diabetes duration 9.8 years, and mean A1C 8.9%) and 176 youth without diabetes (mean age 19.2 years) participating in the SEARCH CVD study. Multiple linear regression was used to assess the relationship between diabetes status and HRV parameters, adjusting for covariates. RESULTS Compared with control subjects, youth with type 1 diabetes had reduced overall HRV (10.09 ms lower SD of NN intervals [SDNN]) and markers of parasympathetic loss (13.5 ms reduced root mean square successive difference of NN intervals [RMSSD] and 5.2 normalized units (n.u.) reduced high frequency [HF] power) with sympathetic override (5.2 n.u. increased low frequency [LF] power), independent of demographic, anthropometric, and traditional cardiovascular risk factors. Older age, female sex, higher LDL cholesterol and triglyceride levels, and presence of microalbuminuria were independently associated with lower HRV but did not account for the observed differences between youth with and without diabetes. Youth with type 1 diabetes and A1C levels ≥7.5% had significantly worse HRV parameters than control subjects; however, in youth with optimal glycemic control (A1C <7.5%), HRV parameters did not differ significantly from control subjects. CONCLUSIONS Youth with type 1 diabetes have signs of early cardiac autonomic neuropathy: reduced overall HRV and parasympathetic loss with sympathetic override. The main driver of these subclinical abnormalities appears to be hyperglycemia.
The Journal of Pediatrics | 2013
David M. Maahs; Dana Dabelea; Ralph B. D'Agostino; Jeannette S. Andrews; Amy S. Shah; Nancy A. Crimmins; Elizabeth J. Mayer-Davis; Santica M. Marcovina; Giuseppina Imperatore; R. Paul Wadwa; Steven R. Daniels; Kristi Reynolds; Richard F. Hamman; Lawrence M. Dolan
OBJECTIVE To test the hypothesis that a change in glycated hemoglobin (A1c) over a follow-up interval of approximately 2 years would be associated with concomitant changes in fasting lipids in individuals with type 1 diabetes (T1D). STUDY DESIGN All subjects with T1D diagnosed in 2002-2005 in the SEARCH for Diabetes in Youth study with at least 2 study visits ∼12 and ∼24 months after an initial visit were included (age at initial visit, 10.6 ± 4.1 years; 48% female; diabetes duration, 10 ± 7 months; 76% non-Hispanic white; A1c = 7.7% ± 1.4%). Longitudinal mixed models were fit to examine the relationship between change in A1c and change in lipid levels (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], log triglycerides [TG], and non-HDL-c) with adjustment for possible confounders. RESULTS Change in A1c over time was significantly associated with changes in TC, HDL-c, LDL-c, TG, and non-HDL-c over the range of A1c values. For example, for a person with an A1c of 10% and then a 2% decrease in A1c 2 years later (to 8%), the model predicted concomitant changes in TC (-0.29 mmol/L, -11.4 mg/dL), HDL-c (0.03 mmol/L, 1.3 mg/dL), LDL-c (-0.23 mmol/L, -9.0 mg/dL), and non-HDL-c (-0.32 mmol/L, -12.4 mg/dL) and an 8.5% decrease in TG (mmol/L). CONCLUSIONS Improved glucose control over a 2-year follow-up was associated with a more favorable lipid profile but may be insufficient to normalize lipids in dyslipidemic T1D youth needing to decrease lipids to goal.
Diabetes Care | 2013
Mamta Jaiswal; Elaine M. Urbina; R. Paul Wadwa; Jennifer W. Talton; Ralph B. D’Agostino; Richard F. Hamman; Tasha E. Fingerlin; Stephen R. Daniels; Santica M. Marcovina; Lawrence M. Dolan; Dana Dabelea
OBJECTIVE Reduced heart rate variability (HRV) and increased arterial stiffness (AS) are both present in youth with type 1 diabetes. However, it is unclear whether they are associated and whether their association is independent of cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS The SEARCH Cardiovascular Disease (SEARCH CVD) study explored the cross-sectional relationships between HRV and several measures of AS in youth with (n = 344) and without (n = 171) type 1 diabetes. The SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure HRV using SD of normal R-R interval (SDNN), as well as AS, using pulse wave velocity in the carotid to femoral segment (PWV-trunk) and augmentation index adjusted to a heart rate of 75 bpm (AIx75). Brachial distensibility (BrachD), another index of AS, was measured with a DynaPulse instrument (Pulse Metric, San Diego, CA). Multiple linear regression analyses explored the associations between HRV and each of the three AS measures, after adjusting for demographic characteristics and traditional CVD risk factors (blood pressure, lipids, obesity, microalbuminuria, and smoking) separately, for youth with and without type 1 diabetes. RESULTS Among youth with type 1 diabetes, lower SDNN was associated with peripheral AS (lower BrachD, P = 0.01; r2 = 0.30) and central AS (higher PVW-trunk, P < 0.0001; r2 = 0.37; and higher AIx75, P = 0.007; r2 = 0.08). These associations were attenuated with adjustment for CVD risk factors, but remained statistically significant for BrachD and PWV-trunk. While a similar association between HRV and BrachD was present in control youth, lower HRV was not associated with increased central AS or with AIx75. CONCLUSIONS Longitudinal studies are needed to understand the pathways responsible for these associations.
Reviews in Endocrine & Metabolic Disorders | 2007
R. Paul Wadwa
In the United States, cardiovascular disease is the leading cause of mortality in adults with diabetes over age 30 years. Studies in persons without diabetes have shown that atherosclerosis, a central factor in cardiovascular disease, begins in childhood and the presence of cardiovascular disease risk factors in youth lead to increased cardiovascular disease risk in adults. Therefore, youth with diabetes are at increased risk for developing cardiovascular disease as adults and there is a role for risk factor screening and addressing modifiable factors to lower cardiovascular disease risk starting in childhood. This paper reviews the literature on traditional cardiovascular disease risk factors in youth with diabetes including hyperglycemia, hypertension, dyslipidemia, smoking, obesity and family history of cardiovascular disease with an emphasis on type 1 diabetes as well as current American Diabetes Association guidelines for screening and treatment of modifiable risk factors. Current roles of inflammatory markers and measures of subclinical vascular changes such as arterial stiffness are also discussed.
Diabetes Care | 2015
David M. Maahs; Daniel J. DeSalvo; Laura Pyle; Trang T. Ly; Laurel Messer; Paula Clinton; Emily Westfall; R. Paul Wadwa; Bruce Buckingham
Acetaminophen (paracetamol) interferes with continuous glucose monitor (CGM) sensing, resulting in falsely elevated CGM glucose values in both sensors currently approved by the U.S. Food and Drug Administration (FDA). In amperometric glucose biosensors, particularly those measuring hydrogen peroxide, acetaminophen’s phenolic moiety is oxidized at the sensing electrode, producing an electrochemical signal not related to glucose (1). Limited published data exist documenting the magnitude of the effect of acetaminophen on CGM glucose (2), especially in the outpatient setting with contemporary sensor technology. Currently, the FDA recommends that insulin dosing decisions are based on blood glucose (BG) meter values, not CGM glucose values. Given the common use of acetaminophen, its interference with CGM sensing has significant clinical implications for patients who use CGM. To better understand this effect, we performed an acetaminophen challenge as part of an outpatient study designed to investigate the potential challenges to closed-loop systems, which use CGM sensor …
Diabetes Care | 2013
Dana Dabelea; Jennifer W. Talton; Ralph B. D’Agostino; R. Paul Wadwa; Elaine M. Urbina; Lawrence M. Dolan; Stephen R. Daniels; Santica M. Marcovina; Richard F. Hamman
OBJECTIVE To evaluate if presence of cardiovascular (CV) risk factors and their clustering as metabolic syndrome (MetS) is associated with increased arterial stiffness and accelerated progression over time among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS Longitudinal study of 298 youth with type 1 diabetes (age 14.5 years; 46.3% female; duration 4.8 years), with two research visits conducted 5 years apart. CV factors included: waist circumference, blood pressure (BP), fasting lipids (HDL cholesterol, LDL cholesterol [LDL-c], triglycerides), albumin/creatinine ratio, and HbA1c. MetS was based on Adult Treatment Panel III criteria modified for youth. Pulse wave velocity (PWV) in the carotid–femoral segment was measured by tonometry. Mixed models were used to assess the rate of progression in PWV and the association between CV factors and PWV over time. RESULTS PWV increased significantly over time (0.145 m/s/year; P < 0.0001). MetS (P = 0.0035), large waist (P < 0.0001), and elevated BP (P = 0.0003) at baseline were each associated with worse PWV over time. These baseline factors, however, did not significantly influence the rate of progression. Increases in waist circumference (P < 0.0001), LDL-c levels (P = 0.0156), and declining glucose control (HbA1c; P = 0.0419) were independently associated with higher PWV over time. CONCLUSIONS Presence, clustering, and worsening of CV risk factors are associated with increased arterial stiffness over time in youth with type 1 diabetes. Whether improvement in CV risk factors early in life will slow the progression of arterial stiffness and reduce the burden of CV disease in this population requires further study.