Ann K. Cashion

Nurses transforming health care using genetics and genomics

Nurses are well positioned to incorporate genetic and genomic information across all aspects of the United States (U.S.) health care system. Nurses, the most trusted health professionals [1], make unique contributions to the field of human genetics and genomics and complement the work of other health care providers to improve the health of the public. Health care benefits greatly from the unprecedented and ongoing work elucidating the genetic/genomic basis of health, illness, disease risk, and treatment response. The progress in genetics and genomics is applicable to the entire spectrum of health care and all health professionals and as such to the entire nursing profession (2.9 million) [2] in the United States regardless of role, clinical specialty, or academic preparation. The majority of disease risk, health conditions and the therapies used to treat those conditions have a genetic and/or genomic element influenced by environmental, lifestyle, and other factors therefore impacting the entire nursing profession [3]. Nurses have intimate knowledge of the patient’s, family’s, and community’s perspectives; an understanding of biologic underpinnings; experience with genetic/genomic technologies and information; skills in communication and building coalitions; and most importantly, the public’s trust. Across the lifespan, nursing focuses on health promotion and disease prevention, which is an integral component of genetic/genomic health care practices. Awareness of nurses’ strengths and skills, together with the recognition that prevention is the hallmark of genetic/genomic health care, will inform public policymaking groups as they address issues that affect heath care practice in the area of genetics/genomics. Policy making process will be informed with new insights will be gained with inclusion of nurses and professional nursing organizations. These policies can facilitate the ability of U.S. health care systems to use genetic/genomic knowledge to promote health and manage disease.

Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects

Obese African-American (AA) subjects have higher resting and stimulated insulin concentrations than obese Caucasians (C), which could not be explained by the severity of obesity or the degree of insulin sensitivity. We investigated whether differences in glucagon-like peptide-1 (GLP-1), the most potent incretin that regulates insulin secretion, might explain racial differences in insulin response. Accordingly, we measured fasting and stimulated glucose, insulin, and GLP-1 levels during a 3-h oral glucose tolerance test (OGTT) in 26 obese C (age 38±2 y, body mass index 44±1 kg/m2) and 16 obese AA (age 36±2 y, BMI 46±2 kg/m2) subjects. Corrected insulin response (CIR30), a measure of β-cell activity, whole body insulin sensitivity index (WBISI), and area under the curve (AUC) for insulin, GLP-1, and C-peptide/insulin ratio were computed from the OGTT.Glucose levels, fasting and during the OGTT, were similar between racial groups; 32% of the C and 31% of the AA subjects had impaired glucose tolerance. With a similar WBISI, AAs had significantly higher CIR30 (2.3±0.4 vs 1.01±0.1), insulin response (IAUC: 23 974±4828 vs 14 478±1463), and lower insulin clearance (0.07±0.01 vs 0.11±0.01) than C (all, P<0.01). Obese AAs also had higher fasting GLP-1 (6.7±2.5 vs 4.5±1.1) and GLP-1AUC (1174.7±412 vs 822.4±191) than C (both, P<0.02). Our results indicate that obese AAs had higher concentrations of GLP-1 both at fasting and during the OGTT than obese C. The increased GLP-1 concentration could explain the greater insulin concentration and the increased prevalence of hyperinsulinemia-associated disorders including obesity and type 2 diabetes in AAs.

Changes in patterns of 24-hr heart rate variability after kidney and kidney-pancreas transplant.

BACKGROUND Transplantation has been shown to improve cardiorespiratory reflex measures of autonomic function. However, there are limited data on how kidney or kidney-pancreas transplantation influence continuous autonomic modulation of heart rate and the clinical utility of 24-hr heart rate variability (HRV) monitoring. METHODS Ninety nondiabetic kidney and 30 diabetic kidney-pancreas transplant recipients underwent 24-hr Holter monitoring before and again at 6 and 12 months posttransplantation. Tapes were submitted for determination of HRV including interbeat variability (the proportion of adjacent R-R intervals having a difference <50 msec, the SD of all R-R intervals for the entire recording, and the SD of the averages of R-R intervals calculated over 5-min blocks for the entire recording) which is associated with vagal function, sudden death, and circadian function, respectively. Power spectral analysis quantified total neural, sympathetic, and parasympathetic modulation of the heart in ln(msec2). RESULTS Nondiabetic kidney recipients showed improvement (P< or =0.05) in the SD of the averages of R-R intervals calculated over 5-min blocks (83.2 vs. 95.7 msec) and the SD of all R-R intervals (94.5 vs. 104.4 msec) by 6 months and all groups showed improvement by 12 months. Kidney-pancreas recipients also showed improved total neural (4.35 vs. 4.64) and sympathetic modulation (2.70 vs. 3.13). Kidney-pancreas recipients had significantly poorer values for each measure (P< or =0.05) at all time points. CONCLUSIONS Cardiac autonomic neuropathy arises in the presence of uremia and diabetes, with severe dysfunction seen when these conditions occur concomitantly. Improvement in cardiac autonomic function follows both kidney and kidney-pancreas transplantation with more pronounced improvement in the circadian measures. Therefore, circadian measures of 24-hr HRV could be used to monitor the restoration of cardiac autonomic function.

Gastroparesis following kidney/pancreas transplant

Abstract:  This pilot study examined associations among patterns of gastric myoelectrical activity, symptoms of gastroparesis, years of diabetes, months of dialysis, and use of gastrointestinal medications in gastroparetic kidney‐pancreas (KP) transplant recipients. Electrogastrography (EGG) and gastric symptom data were obtained from 42 transplant recipients before and after transplant (6, 12, and 24 months). Recipients were 38 ± 7 yr of age, 88% Whites, and 60% male; 97% had hypertension. All had functioning grafts post‐transplant (mean creatinine, 1.59 ± 0.66 mg/dL, and serum glucose 91.97 ± 24.92 mg/dL). Sixteen subjects had normal EGG (2.7–3.2 cycles per minute, cpm); two were tachygastric (>3.2 cpm) at all time points; one remained bradygastric (<2.7 cpm) throughout the study period. Following transplant, symptoms lessened and were associated with 6‐month normalization of EGG (r = 0.41, p = 0.02). A small change in the percentage of patients with normal EGG was observed from baseline to 24 months (67% vs. 69% respectively); however, there was a shift from bradygastria (29% to 15% respectively) to tachygastria (5% to 15% respectively). Prescribed prokinetic and antisecretory medications use increased over the study period from 13 (31%) subjects at baseline to 32 (86%) at 6 months; 21 (78%) at 12 months; and 12 (92%) at 24 months. Although symptoms diminish following transplant, gastroparesis remains a significant problem for transplant patients. Normalization of EGG and shifts from bradygastria to tachygastria occur post‐transplant. Our results suggest that serial EGGs and frequent assessment of symptoms can be used to follow gastroparesis in KP recipients.

An Overview of the Genomics of Metabolic Syndrome

PURPOSE This article provides a brief overview of the diagnostic criteria and genomic risk factors for the components of metabolic syndrome (MetS). ORGANIZING CONSTRUCTS Contributions of cardiovascular, obesity, and diabetes genomic risk factors to the development of MetS as reported in the literature have been reviewed. FINDINGS The genomic risk factors for the development of MetS are strongly linked to the genomic risk factors that make up the components of the disease. Many of the cardiovascular and renal genomic risk factors for MetS development are similar to those found in the development of hypertension and dyslipidemia. Obesity may act as a master trigger to turn on the gene expression changes necessary for the other components of the disease. Studies in the genomics of type 2 diabetes show a number of overlapping genes and polymorphisms that influence both the development of diabetes and MetS. CONCLUSIONS Although health practitioners now have some insights into the genomics of risk factors associated with MetS, the overall understanding of MetS remains inadequate. Clinical applications based on some of the discussed genomic risk factors are being developed but are not yet available for the diagnosis and treatment of MetS. CLINICAL RELEVANCE A broad knowledge of the genomic contributions to disease processes will enable the clinician to better utilize genomics to assess and tailor management of patients.

Cardiovascular Dysautonomia of Patients With End-Stage Renal Disease and Type I or Type II Diabetes

BACKGROUND End-stage renal disease and diabetes mellitus are known to cause autonomic dysfunctions that are responsible for poor outcomes. Studies suggest that 24-hour heart rate variability with power spectral analysis is more sensitive to early changes in autonomic function than laboratory-evoked measures. OBJECTIVES To evaluate cardiovascular autonomic function in patients (a) awaiting kidney or pancreas-kidney transplantation, (b) without diabetes (NonDM), (c) with Type I insulin dependent diabetes mellitus (IDDM), and (d) with Type II noninsulin dependent diabetes mellitus (NIDDM), and to compare the results of the laboratory-evoked cardiovascular autonomic tests with those from 24-hour heart rate variability monitoring with power spectral analysis. METHOD This cross-sectional study examined autonomic function in prekidney transplant patients with and without diabetes (N=96), comparing laboratory-evoked measures to 24-hour measures. RESULTS The nondiabetic group had a normal change in heart rate with deep breathing, Valsalva ratio, and change in systolic blood pressure with tilt. Both diabetic groups had poorer values for all measures of heart rate variability; demonstrated abnormal changes in heart rate with deep breathing and borderline Valsalva ratios; demonstrated a greater decrease in circadian rhythmicity; and had lower SDNNS, pNN50s, and rMSSDs than the nondiabetic group. CONCLUSIONS Results showed that 24-hour measures are more sensitive, that patients with end-stage renal disease and diabetes regardless of type experience significantly poorer function than do patients without diabetes, and that these values approach those associated with sudden cardiac death.

Correlation of genetic markers of rejection with biopsy findings following human pancreas transplant.

Abstract:  Acute rejection after pancreas transplantation remains a significant problem and contributes to immunologic graft loss. No clinical markers of pancreas rejection have been universally accepted. Recent studies have identified several cytotoxic genes as possible markers of acute rejection in renal and islet cell transplant recipients. However, these markers of rejection have not been evaluated in pancreas transplant recipients. This study evaluated the differential expression of granzyme B, perforin, and human leukocyte antigen (HLA)‐DRA in peripheral blood between patients with and without biopsy‐proven pancreas rejection (n = 7 per group). Gene expression levels were analyzed using real time reverse transcriptase polymerase chain reaction assays. Expression of these genes in controls (n = 17) with and without type 1 diabetes was also analyzed. Patients with biopsy‐proven pancreas rejection had higher levels of granzyme B, perforin, and HLA‐DRA than patients who did not have rejection, although the difference was not statistically significant. Moreover, patients with biopsy‐proven pancreas rejection had a significantly higher level of granzyme B than control subjects with type 1 diabetes (p ≤ 0.03). Our findings suggest that, with additional evaluation of a larger number of patients as well as a longitudinal approach, analyses of granzyme B expression levels in peripheral blood may be shown to be a non‐invasive method of monitoring pancreas allograft rejection.

Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults.

OBJECTIVE: This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR®Depot; Novartis) on the enteroinsular axis in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct β-cell effect and through mediating a glucagon-like peptide 1 (GLP-1) response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations.DESIGN: Prospective, open-label trial using a pre–post test design.SETTING: Single university, clinical research center.SUBJECTS: In all, 42 healthy, severely obese Caucasian and African-American (AA) adults (93% female, 64% Caucasian, age=37.8±1.2 y, weight=123±4.2 kg, BMI=44.5±1 kg/m2), recruited through physician referral and newspaper ads, participated in the study.INTERVENTIONS: Indices of β-cell activity, insulin and GLP-1 response before and during a 75-gm oral glucose tolerance test were determined before and after 24 weeks of octreotide-LAR.RESULTS: AA exhibited higher β-cell activity, and insulin and GLP-1 concentrations than Caucasians. Octreotide-LAR suppressed the insulin and GLP-1 levels in both groups.

Characterizing dietary intake and physical activity affecting weight gain in kidney transplant recipients

Context— Weight gain after kidney transplantation affects 50% to 90% of kidney transplant recipients. Factors leading to weight gain in recipients are thought to include a change in lifestyle (eg, dietary intake and physical activity), age, race, sex, and immunosuppressant medications. Objective— To examine dietary intake and physical activity of kidney transplant recipients at baseline and 3 and 6 months after transplantation to identify contributing factors to weight gain. Design— Descriptive, correlational study using secondary data from a larger parent study examining genetic and environmental contributors to weight gain after kidney transplantation. Participants and Setting— Forty-four kidney transplant recipients at a mid-South university hospital-based transplant institute who had dietary intake, physical activity, and clinical data at baseline and 3 and 6 months were included. Main Outcome Measures— Dietary intake, physical activity, weight, and body mass index. Results— Mean weight gain increased by 6% from baseline to 6 months. Interestingly, dietary intake did not change significantly from baseline to 6 months. Hours of sleep per day decreased during the same period (P = .02). Dietary intake, physical activity, age, race, sex, and immunosuppression showed no significant relationship to weight gain at 6 months. Conclusion— Little consideration has been given to dietary intake and physical activity of kidney transplant recipients and the effects of these variables on weight gain. Further studies with a larger sample are needed, as weight gain after transplantation is a significant risk factor for diminished long-term outcomes.

Advanced nursing practice and research contributions to precision medicine.

BACKGROUND Genomic discoveries in the era of precision medicine hold the promise for tailoring healthcare, symptom management, and research efforts including targeting rare and common diseases through the identification and implementation of genomic-based risk assessment, treatment, and management. However, the translation of these discoveries into tangible benefits for the health of individuals, families, and the public is evolving. PURPOSE In this article, members of the Genetics Expert Panel identify opportunities for action to increase advanced practice nursing and research contributions toward improving genomic health for all individuals and populations. DISCUSSION Identified opportunities are within the areas of: bolstering genomic focused advanced practice registered nurse practice, research and education efforts; deriving new knowledge about disease biology, risk assessment, treatment efficacy, drug safety and self-management; improving resources and systems that combine genomic information with other healthcare data; and advocating for patient and family benefits and equitable access to genomic healthcare resources.