Stephanie J. Fonda

Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation

Excessive retinal vascular permeability contributes to the pathogenesis of proliferative diabetic retinopathy and diabetic macular edema, leading causes of vision loss in working-age adults. Using mass spectroscopy–based proteomics, we detected 117 proteins in human vitreous and elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I–induced alkalinization of vitreous increased kallikrein activity and its generation of factor XIIa, revealing a new pathway for contact system activation. CA-I–induced retinal edema was decreased by complement 1 inhibitor, neutralizing antibody to prekallikrein and bradykinin receptor antagonism. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema.

Short- and Long-Term Effects of Real-Time Continuous Glucose Monitoring in Patients With Type 2 Diabetes

OBJECTIVE To determine whether short-time, real-time continuous glucose monitoring (RT-CGM) has long-term salutary glycemic effects in patients with type 2 diabetes who are not on prandial insulin. RESEARCH DESIGN AND METHODS This was a randomized controlled trial of 100 adults with type 2 diabetes who were not on prandial insulin. This study compared the effects of 12 weeks of intermittent RT-CGM with self-monitoring of blood glucose (SMBG) on glycemic control over a 40-week follow-up period. Subjects received diabetes care from their regular provider without therapeutic intervention from the study team. RESULTS There was a significant difference in A1C at the end of the 3-month active intervention that was sustained during the follow-up period. The mean, unadjusted A1C decreased by 1.0, 1.2, 0.8, and 0.8% in the RT-CGM group vs. 0.5, 0.5, 0.5, and 0.2% in the SMBG group at 12, 24, 38, and 52 weeks, respectively (P = 0.04). There was a significantly greater decline in A1C over the course of the study for the RT-CGM group than for the SMBG group, after adjusting for covariates (P < 0.0001). The subjects who used RT-CGM per protocol (≥48 days) improved the most (P < 0.0001). The improvement in the RT-CGM group occurred without a greater intensification of medication compared with those in the SMBG group. CONCLUSIONS Subjects with type 2 diabetes not on prandial insulin who used RT-CGM intermittently for 12 weeks significantly improved glycemic control at 12 weeks and sustained the improvement without RT-CGM during the 40-week follow-up period, compared with those who used only SMBG.

Changes in Diabetes Distress Related to Participation in an Internet-Based Diabetes Care Management Program and Glycemic Control:

Background: This article investigated how changes in diabetes distress relate to receiving care management through an Internet-based care management (IBCM) program for diabetes and level of participation in this program. Further, it examined the relationship between diabetes distress and changes in glycemic control. Methods: We enrolled patients of the Veterans Affairs Boston Healthcare System with diabetes who had hemoglobin A1c (HbA1c) levels of ≥9.0%. Subjects were randomized to usual care (n = 52) or IBCM (n = 52) for 1 year. We measured diabetes distress at baseline and quarterly thereafter using the Problem Areas in Diabetes (PAID) questionnaire. Glycemic control was determined by baseline and quarterly HbA1c. For subjects randomized to IBCM, we measured participation by observing frequency and consistency of their usage of the IBCM patient portal over 12 months. Linear mixed models were used to analyze THE data. Results: PAID scores declined over time for both treatment groups. Among subjects randomized to IBCM, the decline in PAID scores over time was significant for sustained users of the IBCM patient portal but not for nonusers. Moreover, subjects whose usage of the patient portal was sustained throughout the study had lower PAID scores at baseline. With respect to changes in glycemic control, HbA1c reduced individual differences in PAID scores by 44%; a lower baseline HbA1c was associated with lower baseline PAID scores, and over time, the decrease in HbA1c was associated with further decreases in the PAID score. Conclusions: Participation in IBCM varies by initial diabetes distress, with people with less distress participating more. For people who participate, IBCM further mitigates diabetes distress. There is also a relationship between achievements in glycemic control and subsequent lowering of diabetes distress. Future research should identify how to maximize fit between patient needs and the provisions of IBCM, with the aim of increasing patient engagement in the active management of their health using this care modality. A key to maximizing fit might be first addressing metabolic control aggressively and then using IBCM for sustainment of health.

A Randomized Comparison of Online- and Telephone-Based Care Management with Internet Training Alone in Adult Patients with Poorly Controlled Type 2 Diabetes

AIMS Care management may improve the quality of diabetes care by enhancing contact between high-risk patients and their providers. This prospective, longitudinal, randomized trial sought to investigate whether telephone or online care management improves diabetes-related outcomes over time compared with usual care supplemented with Internet access and training. SUBJECTS AND METHODS One hundred fifty-one adult subjects with type 2 diabetes mellitus and an elevated hemoglobin A1c (A1c) level (≥8.5%) were randomly assigned to online care management (n=51), telephone-based care management (n=51), or Web training (n=49) groups. Online and telephone participants interacted with a care manager through a diabetes education and care management Web site and by telephone, respectively. The Web training group was provided with online diabetes self-management resources but no care management support. The primary outcome measure was A1c measured every 3 months for a year. RESULTS A1c declined significantly and substantially in all groups over 12 months. A1c declined linearly at a rate of 0.32% (P<0.0001) per quarter for the online group, 0.36% (P<0.0001) for the telephone group, and 0.41% for the Web training group (P<0.0001). The rate of change over time did not differ significantly among groups. The groups converged at 12 months with average absolute A1c difference of -1.5%. The number of interactions with care providers was not significantly associated with the change in A1c. Blood pressure, weight, lipid levels, and diabetes distress did not differ among groups over time. CONCLUSIONS Online, telephone-based care management, and Web training for diabetes patients with elevated A1c were each associated with a substantial improvement in A1c over a 1-year period. Internet access and training alone may be as effective as care management in patients with poorly controlled diabetes.

Relationship of Body Mass and Net Worth for Retirement-Aged Men and Women:

This article examines linkages between body weight and socioeconomic status (SES) among Americans at or near retirement age. The authors hypothesize that (a) body weight relates negatively to SES, (b) this relationship is greater for women than men, and (c) the relationship attenuates when health, employment, and marital status are controlled. We use the 1992 Health and Retirement Study for this examination. SES is measured as net worth. Body weight is measured as body mass index and categorized as normal weight, overweight, and obese. Results indicate that, for women, overweight and obesity relate to lower logged networth. This relationship attenuates once covariates are considered. For men, overweight and obesity relate to higher logged net worth, even when covariates are considered. The findings suggest that greater weight has different meanings for men and women in this cohort; it might be related to success for men but a sociocultural detriment for women.

Use of an IRT-based latent variable model to link different forms of the CES-D from the Health and Retirement Study.

Abstract.Background:The goal of this study was to calibrate depressive symptoms collected using different versions of the Centers for Epidemiologic Studies—Depression (CES-D) instrument in different waves of the Health and Retirement Study (HRS).Method:The HRS is a prospective and nationally representative cohort study. This analysis included a sample of HRS participants, adults aged 23–85 years in 1992 who had complete data on depressive symptoms at initial 2- and 4-year follow-up interviews (N = 5,734). Depressive symptoms were assessed with the CES-D. Symptom coverage and response categories varied across study wave. The first wave (1992) used a four-category response, whereas subsequent waves (1994 and 1996) used a two-category response. A structural equations model (SEM) based in Item Response Theory (IRT) was used to calibrate symptoms and generate linked depressive symptom burden scores.Results:Linked depressive symptom burden scores, derived from calibrated symptoms, were distributed similarly across HRS wave.Conclusion:Our results demonstrate the applicability of an IRT-based SEM to address a common challenge in prospective studies: changes in the content and context of symptom assessment. Future investigations may make use of our linked syndrome scores to further explore other aspects of depression from a longitudinal perspective.

Patterns of body weight in middle-aged and older Americans, by gender and race, 1993–2000

SummaryObjectives: Despite evidence of poor health outcomes associated with excessive weight gain or loss, longitudinal patterns of body weight over the adult life course have not been fully described. This article seeks to address this by examining body weight patterns for middle-aged and older adults. Methods: Panel data from the Health and Retirement Study (HRS) original cohort and the original cohort of the Asset and Health Dynamics Among the Oldest Old (AHEAD) study are used to compare, by social group, characteristics of respondents and non-respondents, baseline weight (1993 and 1994) to year 2000 weight, and explore various weight change trajectories over time. Results: Overall, a greater proportion of middle-aged adults are heavier over time than at baseline and a greater proportion of older adults lose weight over time compared to baseline. Examining the transitions across weight trajectories for all of the social groups suggests considerable variability. Conclusions: These findings suggest that differing physiologic and social or environmental experiences may have implications for body weight patterns. Understanding these patterns by race/ethnicity and gender could provide insight into health disparities among different social groups.

Combining iGoogle and Personal Health Records to Create a Prototype Personal Health Application for Diabetes Self-Management

OBJECTIVE The aim of this project is to create a prototype for a personal health application (PHA) for patients (i.e., consumers) with diabetes by employing a user-centered design process. This article describes the design process for and resulting architecture, workflow, and functionality of such a PHA. MATERIALS AND METHODS For the design process, we conducted focus groups with people who have diabetes (n = 21) to ascertain their needs for a PHA. We then developed a prototype in response to these needs, and through additional focus groups and step-by-step demonstrations for people with diabetes as well as healthcare providers, we obtained feedback about the prototype. The feedback led to changes in the PHAs presentation and function. RESULTS Focus group participants said they wanted a tool that could give them timely, readily available information on how diabetes-related domains interact, how their behaviors affect them, and what to do next. Thus, the prototype PHA is Internet-based, retrieves data for diabetes self-management from a personal health record, displays those data using gadgets in the consumers iGoogle page, and makes the data available to a decision-support component that provides lifestyle-oriented advice. Manipulation of the data enables consumers to anticipate the results of future actions and to see interrelationships. CONCLUSIONS A user-centered design process resulted in a PHA that uses technology that is publicly available, employs a personal health record, and is Internet based. This PHA can provide the backbone for a decision support system that can bring together the cornerstones of diabetes self-management and integrate them into the life of the person with diabetes.

A Head-to-Head Comparison of the Postprandial Effects of 3 Meal Replacement Beverages Among People With Type 2 Diabetes:

Purpose The purpose of this study was to compare the effects of 3 meal replacement beverages on glycemic response among people with type 2 diabetes. Methods The study examined Glucerna® Weight Loss Shake, Slim-Fast® Shake, and Ensure® with Fiber Shake, using a prospective, 3-way, cross-over design. Eighteen subjects with type 2 diabetes drank the beverages in random order on different weeks. The volume of each beverage was adjusted to include 50 grams of carbohydrates. Glucose was measured 0 to 180 minutes postprandial. Analyses included 2-factor analysis of variance (ANOVA) for repeated measures on both factors, calculation of area under the curve (AUC), and 1-way repeated measures ANOVA of AUC. Results The postprandial glucose profiles of the shakes differed. Glucerna® had the best profile as indicated by the graph of mean postprandial glucose levels and its lower incremental AUC. Despite the superiority of Glucerna®, 2-hour postprandial blood glucose values exceeded the ADA’s recommended upper limit for 22% of the subjects. Conclusions Meal replacement beverages are a popular and potentially effective option for people trying to lose or maintain weight; however, it is unknown to what degrees they affect postprandial blood glucose in people with type 2 diabetes. Because postprandial glycemic excursion is linked to cardiovascular disease, identifying a meal replacement beverage with the lowest glycemic response may mitigate some of the risks in patients with diabetes. Of the meal replacements observed in this study, Glucerna® had the smallest effect on postprandial glucose. Glycemic response to meal replacements should be monitored given product and individual variability.

Prevalence of diabetic retinopathy and diabetic macular edema in a primary care-based teleophthalmology program for American Indians and Alaskan Natives

Background Diabetes and its complications are more common in American Indians and Alaska Natives (AI/AN) than other US racial/ethnic populations. Prior reports of diabetic retinopathy (DR) prevalence in AI/AN are dated, and research on diabetic macular edema (DME) is limited. This study characterizes the recent prevalence of DR and DME in AI/AN using primary care-based teleophthalmology surveillance. Methods This is a multi-site, clinic-based, cross-sectional study of DR and DME. The sample is composed of AI /AN patients with diabetes (n = 53,998), served by the nationally distributed Indian Health Service-Joslin Vision Network Teleophthalmology Program (IHS-JVN) in primary care clinics of US Indian Health Service (IHS), Tribal, and Urban Indian health care facilities (I/T/U) from 1 November 2011 to 31 October 2016. Patients were recruited opportunistically for a retinal examination using the IHS-JVN during their regular diabetes care. The IHS-JVN used clinically validated, non-mydriatic, retinal imaging and retinopathy assessment protocols to identify the severity levels of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), DME, and sight threatening retinopathy (STR; a composite measure). Key social-demographic (age, gender, IHS area), diabetes-related health (diabetes therapy, duration of diabetes, A1c), and imaging technology variables were examined. The analysis calculated frequencies and percentages of severity levels of disease. Results Prevalence of any NPDR, PDR, DME, and STR among AI/AN patients undergoing DR teleophthalmology surveillance by IHS-JVN was 17.7%, 2.3%, 2.3%, and 4.2%, respectively. Prevalence was lowest in Alaska and highest among patients with A1c >/ = 8%, duration of diabetes > 10 years, or using insulin. Conclusions Prevalence of DR in this cohort was approximately half that in previous reports for AI/AN, and prevalence of DME was less than that reported in non-AI/AN populations. A similar reduction in diabetes related end-stage renal disease in the same population and time period has been reported by other researchers. Since these two diabetic complications share a common microvasculopathic mechanism, this coincident change in prevalence may also share a common basis, possibly related to improved diabetes management.