Diabetes

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21681

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    Unveiling the Factors Driving Plasma Water T2 as a Biomarker for Early Insulin Resistance Syndrome
    (2017-03-14) Deodhar, Sneha; Cistola, David; Mishra, Ina
    Background: Approximately 86 million US adults have prediabetes, putting them at high risk for type 2 diabetes mellitus and cardiovascular disease. Prediabetes is a state of impaired glucose tolerance or moderate hyperglycemia where up to 70% of pancreatic β-cell capacity has been lost irreversibly. It is preceded by an often-undetected phase, early insulin resistance syndrome (EIRS), which consists of compensatory hyperinsulinemia, dyslipidemia, subclinical inflammation and electrolyte abnormalities. Early identification is important to preserve pancreatic function and prevent diabetes and pre-diabetes. In previous work, we showed that plasma water transverse relaxation time T2, measured using benchtop NMR relaxometry, provides a sensitive measure of EIRS in asymptomatic, normoglycemic subjects. Plasma water T2 detected EIRS in 15% of this cohort, which was undetected by fasting glucose or HbA1c. Our hypothesis is that shifts in the levels of specific acute phase proteins and lipoproteins drive plasma water T2 values lower in EIRS. Purpose: To quantify the contributions from the most abundant plasma proteins and lipoproteins to plasma water T2 by determining relaxivity values (r, slope of 1/T2 vs. concentration). Higher relaxivity means greater influence on water T2. Methods: Purified plasma protein fractions were obtain from Millipore-Sigma, Inc. and Athens, Inc., and lipoprotein fractions were prepared from human plasma using density-gradient ultracentrifugation. Two sets of serial dilutions were made for each protein and lipoprotein fraction: (1) in phosphate-buffered saline, to determine r value in buffer alone, and 2) in a mixture of human serum albumin and gamma globulin, to determine r in a background that mimics human plasma. Protein concentrations were quantified using a Pierce BCA assay, and total cholesterol and triglyceride concentrations, using kits from Wako Diagnostics. Linear regression was used to quantify and compare r values. Results: The highest relaxivity values were observed for ceruloplasmin, haptoglobin, apo-transferrin and complement C3, whereas surprisingly low values were observed for triglyceride-rich lipoproteins. Albumin, IgG and α2-macroglobulin yielded intermediate r values. Conclusions: This study unveils the factors driving plasma water T2 as a biomarker for early insulin resistance syndrome. Plasma water T2 is a promising tool for population screening and metabolic health assessment for diabetes and prediabetes prevention.
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    Association of Elevated Liver Enzymes with Non-Invasive Risk Factors for Type II Diabetes Mellitus in Children
    (2017-03-14) Habiba, Nusrath; Hamby, Tyler; Basha, Riyaz; Shah, Deep; Bowman, Paul; Chatrath, Amritpaul
    Purpose: The obesity epidemic has led to an increased incidence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) in children. This relationship is significant as the liver is intimately involved in blood glucose homeostasis as insulin resistance triggers glycogenolysis in the liver. However, there is limited research on the association between elevated liver enzymes and risk factors for T2DM in children. The purpose of this study was to assess the prevalence of elevated liver enzymes and their association with non-invasive risk factors for T2DM in non-diabetic children between the ages of 10-14 years without chronic diseases. The liver enzymes studied were alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT). The non-invasive risk factors for T2DM are 1) Body Mass Index (BMI) [greater than] 85th percentile for age and gender, 2) blood pressure [greater than] 95th percentile for height and gender, 3) acanthosis nigricans, 4) race or ethnicity of high risk, and 5) history of T2DM in the family. A race or ethnicity of high risk includes African Americans, Hispanics, American Indians, and Asian/Pacific Islanders. Methods: Following IRB approval, the study was conducted at the outpatient clinics of the University of North Texas Health Science Center, Fort Worth. Children with elevated blood glucose levels, chronic medical conditions, or those who had received systemic corticosteroid therapy within the last year were excluded. Participation was voluntary and 151 children participated in the study who were from the representative races and ethnicities attending the clinics. Results: Results indicated that those with elevated GGT levels had marginally higher BMI (p=0.06) and were significantly more likely to have acanthosis nigricans (p Conclusions: These results suggest that there are meaningful relationships between elevated liver enzymes and non-invasive risk factors for T2DM.
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    Is Diabetes a Risk Factor for Blindness in Males 35 and Older?
    (2017-03-14) Smith, Christine PA-S; Salo, Danielle PA-S; Gamble, Morgan PA-S; Jessica, Hartos PhD; Hamilton, Madison PA-S
    Introduction: The incidence of blindness has reached an all time high and is expected to increase exponentially within the next forty years (1). Previous studies have found that diabetes is the most common cause of blindness in working age adults (2). However, blindness due to diabetes has also shown a multi-peak age distribution, peaking in young adults and over 60 years old. The purpose of this study was to assess whether diabetes is a risk factor for blindness in males 35 and older. Methods: BRFSS data from 2014 was used for men 35 and older from New Mexico, Kentucky, Montana and Mississippi in this cross-sectional analysis. Multiple logistic regression analysis was performed to assess the relationship between diabetes and blindness, while controlling for weight status, education level, health care access, lifetime diagnosis of stroke, chronic health problems and ethnicity/ race. Results: A low percentage of males age 35 and older reported blindness (5-10%) or diabetes (11-18%). In multiple logistic regression analysis, blindness was significantly related to diabetes in Kentucky, New Mexico and Montana (moderate to large effect sizes) and significantly related to chronic health problems in all four states (large effect sizes). Conclusions: Although this study was unable to determine temporal relations, we found that blindness was related to diabetes and chronic health problems in general population samples of males 35 and older. Even though diabetes and blindness may have a low prevalence in primary care, providers should expect them to be related and should screen for both if male patients 35 and older present with symptoms of either, which is common practice. Chronic health problems (52-65%) are more prevalent than blindness and diabetes in males 35 and older, and if present, patients should be screened for vision loss.
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    Benchtop NMR Relaxometry in Clinical Diagnostics: Whole Human Blood
    (2017-03-14) Deodhar, Sneha; Mishra, Ina; Cistola, David; Patel, Vipulkumar
    Purpose: Benchtop NMR relaxometry is a promising technology for metabolic heath screening and assessment. Unlike spectrometry and imaging, NMR relaxometry uses compact and inexpensive devices, making it practical for clinical laboratories and point-of-care settings. In previous work, we reported that the water transverse relaxation time (T2) of human blood plasma is a sensitive and specific marker for early insulin resistance syndrome. Here, we investigated whether whole human blood could be analyzed directly, thus avoiding the centrifugation step and saving time and expense. During sample equilibration, anticoagulated whole blood sediments spontaneously inside the NMR tube, creating a cell pellet and a plasma supernatant. We exploited this phenomenon and designed experiments to measure the T2 values of the pellet and supernatant simultaneously. The goal of this study was to quantify the association of whole blood T2 values with over 200 established blood biomarkers in order to assess information content of the T2 data. Methods: We recruited 45 asymptomatic, non-diabetic human volunteers through an IRB-approved protocol. Blood samples were collected after an overnight fast, and NMR relaxation times were measured using a Bruker Minispec mq20 and a modified Carr-Purcell-Meiboom-Gill pulse scheme. The exponential decay curves were analyzed using a discrete inverse Laplace transform algorithm, as implemented in XpFIT (Alango, Ltd.), to extract T2 values. In addition, diagnostic testing was performed on each blood sample, mostly by Quest Diagnostics, Inc. and Atherotech, Inc. Results: The settled blood gives two distinct T2 values corresponding to supernatant (T2S) and cell pellet (T2P). Surprisingly, supernatant T2S correlates with red blood cell and hemoglobin markers, even though it lacks both red blood cell and hemoglobin after sedimentation. Therefore, we hypothesized that the paramagnetic deoxyhemoglobin from the cell pellet exerts a long-range influence on the plasma supernatant. This hypothesis was tested by a simulated hematocrit experiment that varied the height of the blood cell pellet, and a gadolinium experiment that altered the relaxation of samples that were physically separated. The cell pellet T2P correlates with insulin and lipid biomarkers from the blood. Conclusions: The results demonstrate that whole blood T2 values report on insulin resistance status, as well as hematocrit and hemoglobin levels.
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    Readmission Rates for Children with Diabetic Ketoacidosis (DKA)
    (2017-03-14) Jarvis, Todd; Thornton, Paul; Gonzalez, Jose; Hsieh, Susan; Wilson, Don; Hamilton, Luke M.S.
    Background: Ketoacidosis is a potentially life threatening complication of diabetes mellitus. Emergency Departments (ED) are usually the first point of contact. Criteria for admission varies and could influence the rate of readmissions. Objective: To describe the population and compare readmission rates of patients treated at Cook Children’s ED for DKA. Methods: A retrospective chart review was preformed of children seen in the Cook Children’s Medical Center ED from September 2011 – August 2014. No attempt was made to classify patients as T1 vs T2. APR-DRG 420 (diabetic ketoacidosis) was used for subject selection. Results: 313 children were seen in the ED with a diagnosis of DKA. Of the total patients seen in the ED, 14% were discharged for home management after initial assessment and treatment; 86% were admitted to the hospital. Of the patients discharged, a median 5.2 hours was spent in the ED. Discharged patients had a median glucose of 285 mg/dL (nl. 74-120 mg/dL), median pH of 7.3 (nl. 7.35-7.45), and median HCO3 of 20.4 mEq/L (nl. 22-28 mEq/L). Of the patients admitted, a median 3.6 hours was spent in the ED. Admitted patients had a median glucose of 437 mg/dL, median pH of 7.2, and median HCO3 of 11.2 mEq/L. Conclusions: DKA is defined as 1) metabolic acidosis (pH 3 200 mg/dL); and 3) ketonemia/ketonuria. It occurs frequently among youth with diabetes and is the main cause of mortality in individuals with diabetes Of the 313 children seen in the ED from September 2011 — August 2014, a large majority were admitted from the ED. Glucose levels of admitted patients (437 mg/dL) were 53% higher than discharged patients (285 mg/dL). Admitted patients HCO3 levels (11.2 mEq/L) were 45% lower than discharged patients (20.4 mEq/L). Of the 45 discharged from the ED, 16% returned to the ED within 90 days for DKA, while only 7% of the 268 children admitted returned. In the US, DKA is present in up to 40% of youth with new-onset diabetes. A recent study found 1 in 5 children were re-admitted for DKA within 1 year of a previous occurrence, with large variations in treatment for DKA within Children’s Hospitals located in the US. These studies illustrate the need to identify children who are at risk for DKA and to develop effective interventions for prevention of DKA. A better understanding of the characteristics of children with DKA and treatment/disposition strategies used by ED physicians can help improve care of those treated in the ED.
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    Use of Frozen vs. Fresh Plasma to Assess Early Insulin Resistance Syndrome
    (2017-03-14) Patel, Vipulkumar; Mishra, Ina; Deodhar, Sneha; Cistola, David; Jones, Clint
    Background: Insulin resistance is defined as the blunted response to insulin by tissues and can progress to prediabetes and type 2 diabetes. About 86 million US adults were identified with pre-diabetes in 2012. By the time prediabetes develops, approximately 70% of β-cell secretory function has been lost irreversibly. Thus, it is imperative to detect insulin resistance at an earlier stage in order to preserve pancreatic function and prevent progression to diabetes. Prior work revealed that water proton transverse relaxation time (T2) measured by NMR relaxometry using fresh human plasma samples provides a sensitive and specific biomarker for early insulin resistance syndrome. Purpose: The objective of this study was to compare T2 values of frozen plasma samples with those from fresh plasma to assess the feasibility of analyzing bio-banked samples from longitudinal population studies. Hypothesis: Freezing at -80oC will have little or no impact on measured T2 values and their correlation with insulin resistance markers. Methods: We recruited 45 asymptomatic, non-diabetic human volunteers though an IRB approved protocol. Blood samples were collected after an overnight fast and were processed and analyzed immediately, with the remaining samples stored at -80oC. In addition, over 200 blood biomarkers were measured on each fresh blood sample – many by outside laboratories including Quest Diagnostics, Inc. and Atherotech, Inc. After several months in the freezer, the NMR measurements were performed on the once-frozen, once-thawed samples. All NMR measurements were performed at 37oC using a Bruker mq20 Minispec instrument and a modified CPMG pulse scheme. The associations between frozen and fresh T2 values and metabolic biomarkers were quantified using the Pearson’s product moment and concordance correlation coefficients. Results: Plasma water T2 from frozen samples showed a strong, statistically significant correlation with fresh plasma water T2 values (Pearson r=0.85, Concordance correlation coefficient=0.74). However, the frozen plasma water T2 were 5% lower, on average, than fresh samples. Nevertheless, this difference did not impact the overall pattern of association between T2 and metabolic biomarkers of early insulin resistance syndrome. Conclusions: These findings establish the feasibility of using frozen bio-banked specimens for the validation of plasma water T2 as a metabolic biomarker and screening tool for diabetes risk assessment.
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    For General Health, Does Diabetes Status Differ by Veteran Status in Males Ages 25 to 45?
    (2017-03-14) Ihediwa, Chiamaka; Holmes, Victor L.; Hartos, Jessica; Salaices, Veronica
    Introduction: Diabetes mellitus is a chronic medical condition in the U.S. population and in the veteran population, but little information is available for the relationship between diabetes and veteran status for different age groups. Thus, the purpose of this study was to assess whether diabetes status differs by veteran status in males ages 25 to 45. Methods: This cross sectional analysis used 2014 BRFSS data for males ages 25 to 45 from Alabama, Georgia, and Texas. Multiple logistic regression analysis was used to assess the relationship between diabetes status and veteran status, while controlling for age, ethnicity/race, weight status, mental health, heart disease, tobacco use, and alcohol use. Results: Across states, few males ages 25-45 reported diabetes (4-7%) or veteran status (14-19%). After controlling for psychosocial and demographic factors, diabetes status was not significantly related to veteran status in any of the 3 states. Conclusions: Overall, diabetes was not related to veteran status in representative samples of males ages 25 to 45. Additionally, the prevalence of both diabetes status and veteran status was low. The study was limited by the dichotomous measurement of the variables which did not provide additional pertinent information about their diagnosis or military role. It is recommended that clinicians screen for diabetes in this age group if there are symptoms, especially in those that are older as diabetes may become more prevalent as men age.
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    Is Binge Drinking a Risk Factor for Diabetes in Middle Aged Males?
    (2017-03-14) Bengston, Emily; Armstrong, Hailey; Dorth, Jaime; Hartos, Jessica; Runeberg, Taylor
    Introduction: Diabetes is a major health issue in the United States with multiple behavioral and genetic risk factors, but little is known about the relationship between binge drinking and the development of diabetes in different age and gender groups. The purpose of this study was to assess whether binge drinking is a risk factor for diabetes in middle aged males. Methods: This cross-sectional analysis used data from the 2014 BRFSS for males aged 30-50 from Arkansas, Mississippi, New Mexico, and Tennessee. The relationship between diabetes status and binge drinking was analyzed using multiple logistic regression controlling for age, ethnicity/race, educational level (SES), weight status, exercise, and smoking status. Results: Few participants in the target population reported ever being diagnosed with diabetes (7-9%), and about one-fifth reported binge drinking (19-24%). After controlling for behavioral risk factors and demographics, binge drinking and diabetes were not significantly related in any state, but obesity was positively related (large effect size) to diabetes in three of four states. Conclusions: Overall, binge drinking was not related to diabetes in middle aged men but was significantly related to weight status. While this study is restricted by cross sectional study design and limited measurement of variables, it is recommended that practitioners understand the relationship between diabetes and obesity and educate their patients about the many comorbid and detrimental effects it can have on a patient’s overall health. Additionally, because one in five participants reported binge drinking, patient education about the health risks associated with excessive drinking should continue to occur by practitioners.
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    Acanthosis Nigricans - A reliable diagnostic indicator of insulin resistance and type 2 Diabetes Mellitus in obese youth and adolescents
    (2017-03-14) Shah, Taksh; Kolluru, Samyuktha; Rich, Alisa; Barve, Amruta
    Background: Over the last few decades, there has been an increasing prevalence of Type 2 diabetes mellitus (DM) in youth with obesity. Acanthosis Nigricans (AN) is frequently associated with obesity and is a reliable risk indicator for developing type 2 diabetes. Although the risk for obesity is elevated in African American populations in general, there is a 2-fold increased risk in African Americans having AN to develop non-insulin dependent diabetes mellitus (NIDDM). AN once considered a rare dermatological condition is now frequently observed among obese youths and adolescents across ethnicities. Objective: The aim of this study is to evaluate AN as a diagnostic indicator; and its correlation to insulin resistance, obesity, and increased risk for development of diabetes in obese youth and adolescents. Methods: A systematic review of databases (Pubmed, Scopus, and Medline) resulted in 1743 publications related to AN, and Type 2 DM. Cross referencing AN, and Type 2 DM with obesity resulted in 679 publications since 2000. Search was narrowed using keywords AN, type 2 DM, insulin resistance, obesity, risk, youth and screening which resulted in 27 referenced papers. Abstracts of the papers were retrieved and reviewed for relevance resulting in 22 papers retrieved in full and evaluated. Studies, where AN presents with drug induced, autoimmune (systemic lupus erythematosus) or syndromic (hyperandrogenism) conditions, were excluded. Results: Results of the study confirm AN is associated with insulin resistance in obese youth and adolescents. Reports indicate a strong association of AN with insulin resistance, hyperinsulinemia, and risk for developing diabetes. Hyperpigmentation of the skin in AN is generally symmetrically distributed in the neck area, but can also be present in the forehead and folds of the skin (groin, armpits, and bends of the arms and knees). Research confirmed a positive and independent association between ethnicity, family history of diabetes, high body mass index (BMI), obesity, hyperinsulinemia, insulin resistance and AN. Conclusions: AN is strongly associated with obesity, hyperinsulinemia, insulin resistance and type 2 DM, which can be used as a reliable index for insulin resistance and to identify diabetes risk. It provides a valuable tool to primary care providers for prediabetes identification and secondary prevention. Screening programs for AN can be conducted in schools to identify children at the highest risk of developing type 2 DM associated with obesity. Intervention programs should incorporate AN screening, an easily performed and noninvasive technique along with other important risk factors for identifying obese adolescents at risk for type 2 diabetes. Adopting lifestyle changes along with early detection of AN and other risk markers may reduce the prevalence, incidence, and burden of type 2 DM in obese youth and adolescents.