Kirstie K. Danielson

Minimally Invasive Robotic Kidney Transplantation for Obese Patients Previously Denied Access to Transplantation

Epidemiological data indicate that 20-50% of patients on dialysis for end-stage renal disease (ESRD) are obese (body mass index [BMI] ≥30 kg/m2) (1). Obese patients with chronic renal failure have longer wait times until kidney transplantation (2) and inferior patient outcomes (3-7). In the US, for example, patients with a BMI 40 kg/m2 (2). Higher BMIs in kidney transplant recipients are associated with excess risk of surgical site infections (SSIs), which negatively impact graft survival (8). Obesity is also associated with comorbidities such as diabetes, although data on whether obesity increases mortality in kidney transplanted patients remains unclear (8,9). Provider perceptions of these risks accompanied by the expectation of some centers to give obese patients time to lose weight are the main reasons why a number of transplant centers are reluctant to list obese patients for transplantation (2,10). Unfortunately, many of these obese patients have diabetes and hypertension likely secondary to their obesity (11) and such patients who remain on dialysis have a very high mortality rate. The 5-year mortality rate for diabetic and hypertensive dialysis patients is 75 and 70%, respectively (1). A recent study demonstrated that obese patients who did not present with any SSIs had the same kidney transplant success rate as patients with a normal BMI (8). If surgical procedures could be developed that prevent SSIs and demonstrate successful outcomes, transplant centers may become less reluctant to list obese patients for kidney transplantation. Although any benefit would still have to be weighed against potential increased risks from obesity-related comorbidities. The prevalence of obesity and ESRD is higher among racial and ethnic minority populations, including African-Americans and Hispanics, compared to Non-Hispanic whites (12-15). These observations suggest developing kidney transplantation options for obese patients with ESRD may also help to reduce health disparities in racial and ethnic minorities. We therefore developed a new, minimally invasive, robotic-assisted kidney transplantation method using a short epigastric incision. This method avoids any incision in the infection prone lower quadrants of the abdomen. We hypothesized a priori that the robotic approach would reduce SSIs and improve outcomes in obese kidney transplant patients. Herein, we present our experience and outcomes of the patients undergoing minimal invasive, robotic kidney transplantation at a single institution compared to patients who underwent the conventional open procedure.

Systematic Analysis of Donor and Isolation Factor’s Impact on Human Islet Yield and Size Distribution

Islet transplantation is a promising therapy for T1DM. Key factors influencing islet yield have been identified with conflicting results. In this study, we analyzed 276 isolations to identify variables for islet yield and, additionally, islet size and size distribution. Pearson correlation analyses demonstrated that BMI had a positive correlation with pancreas size, actual islet count (AIC), and islet equivalent (IEQ)/g (all p ≤0.009), while CIT had a negative correlation with AIC and IEQ/g (all p ≤0.003). In mixed linear regression, BMI also had a positive correlation with islet size but only for shorter digestion times (≤15 min); there was no association between BMI and islet size for longer digestion times (>15 min). CIT was not associated with islet size. Donor age, sex, and preservation solutions were shown to have no correlation with islet yields or size distribution. Pancreas size had a positive correlation with AIC and a negative association with IEQ/g; it also had positive association with islet size but only for females, not males. Overdigestion was positively associated with islet counts; however, there was also a greater proportion of smaller islets when digestion rate was >74% (p = 0.005). Of the three collagenases analyzed, Sigma V had the lowest digestion rate (mean = 65%), approximately 5% or 10% lower than Roche Liberase HI (p = 0.04) and Serva NB1 (p = 0.0003), respectively; however, the Sigma V group showed better islet size preservation. Yet, the enzymes resulted in similar IEQ/g digested tissue. Of the isolated islets, 70.2% were smaller than 150 μm and contributed only 20.4% to the total IEQ, while 7.4% of the islets were larger than 250 μm but contributed 42.4% to the total IEQ. In summary, BMI, pancreas size, and CIT are useful variables for predicting islet yield, but selection of enzyme and balancing digestion time and rate are also important.

Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+

Qi M, Mørch Y, Lacík I, Formo K, Marchese E, Wang Y, Danielson KK, Kinzer K, Wang S, Barbaro B, Kolláriková G, Chorvát D Jr, Hunkeler D, Skjåk‐Bræk G, Oberholzer J, Strand BL. Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+. Xenotransplantation 2012; 19: 355–364.

Reduction in Carotid Intima-Media Thickness After Pancreatic Islet Transplantation in Patients With Type 1 Diabetes

OBJECTIVE Determine the impact of islet transplantation on carotid intima-media thickness (CIMT), a marker for atherosclerosis, in type 1 diabetes without kidney disease. RESEARCH DESIGN AND METHODS Consecutive case series of 15 adults (mean age [SD], 49 years [10 years]; 87% female) with type 1 diabetes for ≥5 years (mean duration [SD], 30 years [12 years]; mean HbA1c [SD], 7.2% [0.9%]), without kidney disease, presenting with severe hypoglycemic unawareness to undergo allogeneic pancreatic islet transplant(s) (one to three each) in a phase 1/2 and 3 clinical trial. Current follow-up ranges from 1 to 5 years (2005–2011). CIMT of the common and internal carotid arteries was measured before and every 12–16 months after the first transplant (two to six CIMTs each) by one ultrasonographer and one blinded reader. CIMT was analyzed as change from baseline to 12- and 50-month follow-up; a combined CIMT score was calculated as the sum of the standardized IMT scores (SD units [SDs]) of both arteries. RESULTS All patients achieved insulin independence after one to three transplants. CIMT decreased at 12 months (n = 15) for the common carotid (−0.058 mm; P = 0.006) and combined score (−1.28 SDs; P = 0.004). In those with 50-month follow-up (n = 7), the decrease in the combined score continued from 12 (−1.59 SDs; P = 0.04) to 50 months (−0.77 SDs; P = 0.04). During follow-up, the decreasing slope of change in CIMT was associated with decreasing slopes of change in HbA1c, lipoproteins, and cardiovascular/inflammatory markers. CONCLUSIONS Islet transplantation may ameliorate diabetes-related atherosclerosis through improved glycemic control consequent to restoring endogenous insulin secretion, and optimal lipid management posttransplant also contributes.

Racial and Ethnic Differences in an Estimated Measure of Insulin Resistance Among Individuals With Type 1 Diabetes

OBJECTIVE Insulin resistance is greater in racial/ethnic minorities than in non-Hispanic whites (NHWs) for those with and without type 2 diabetes. Because previous research on insulin resistance in type 1 diabetes was limited to NHWs, racial/ethnic variation in an estimated measure of insulin resistance in type 1 diabetes was determined. RESEARCH DESIGN AND METHODS The sample included 79 individuals with type 1 diabetes diagnosed at age <18 years (32.9% NHWs, 46.8% non-Hispanic black [NHB], 7.6% other/mixed, and 12.7% Hispanic) and their families. Estimated glucose disposal rate (eGDR) (milligrams per kilogram per minute; a lower eGDR indicates greater insulin resistance) was calculated using A1C, waist circumference, and hypertension status. RESULTS Mean current age was 13.5 years (range 3.2–32.5) and diabetes duration was 5.7 years (0.1–19.9). eGDR was inversely associated with age. Compared with that in NHWs, age-adjusted eGDR was significantly lower among nonwhites (NHB, other/mixed, and Hispanic: Δ = −1.83, P = 0.0006). Age-adjusted eGDR was negatively associated with body fat, triglycerides, urinary albumin/creatinine, acanthosis nigricans, parental obesity, and parental insulin resistance and positively related to HDL and sex hormone–binding globulin. In multivariable analysis, lower eGDR was significantly associated with older age, nonwhite race/ethnicity, acanthosis, and lower HDL. CONCLUSIONS Minorities with type 1 diabetes are significantly more insulin resistant, as measured by eGDR, than NHWs. Exploring potential mechanisms, including disparities in care and/or physiological variation, may contribute to preventing racial/ethnic differences in insulin resistance–associated outcomes.

Insufficient sleep in young patients with diabetes and their families.

Objective: We examined sleep in families of individuals with type 1 diabetes and the relationship of sleep with obesity, diabetes, and insulin resistance. Methods: Probands with type 1 diabetes diagnosed before age 18 and first- and second-degree relatives were included (n = 323). Demographic, anthropometric and clinical variables, and self-reported sleep duration and napping were assessed. Results: On average, adults (≥20 years) slept 7.5 (SD 1.5) hr, whereas children (5–11 years) and adolescents (12–19 years) slept 9.8 (SD 1.1) and 8.5 (SD 1.9) hr, respectively (p < .01). Based on national recommendations, 40.9% of participants slept insufficiently, particularly young people (vs. adults, p < .01). In age-group stratified analysis, there were no significant associations of insufficient sleep or sleep duration with obesity, diabetes status, or insulin resistance after adjustment for age, race/ethnicity, and gender. In all, 42% of participants reported napping regularly (≥1/week), with adolescents significantly more likely to do so (vs. adults, odds ratio [OR] = 1.95, p < .01). Non-Hispanic Blacks and Hispanics also had higher odds of regular napping (vs. non-Hispanic Whites, OR = 3.74, p < .01 and OR = 2.52, p = .03, respectively). In adjusted analysis, leaner (vs. obese) adolescents, whether measured by body mass index, percentage body fat, or waist circumference, were significantly more likely to nap regularly. Conclusions: We found that insufficient sleep was significantly more likely in children and adolescents compared with adults in families with type 1 diabetes. Lower adiposity was associated with regular napping in adolescents. The high prevalence of insufficient sleep in young patients with type 1 diabetes and their relatives detected in the current study may have significant health consequences.

The trajectory of IGF-1 across age and duration of type 1 diabetes.

Individuals with type 1 diabetes may have low IGF‐1, related to insulinopenia and insulin resistance. There are few longitudinal studies of IGF‐1 levels to establish its pattern in type 1 diabetes with duration and age, and to examine whether IGF‐1 tracks within individuals over time. We examine age and duration trends, and the relationship of IGF‐1 to gender, glycaemic control, insulin level and other factors.

Diabetes Island: Preliminary Impact of a Virtual World Self-Care Educational Intervention for African Americans With Type 2 Diabetes

Background Diabetes is a serious worldwide public health challenge. The burden of diabetes, including prevalence and risk of complications, is greater for minorities, particularly African Americans. Internet-based immersive virtual worlds offer a unique opportunity to reach large and diverse populations with diabetes for self-management education and support. Objective The objective of the study was to examine the acceptability, usage, and preliminary outcome of a virtual world intervention, Diabetes Island, in low-income African Americans with type 2 diabetes. The main hypotheses were that the intervention would: (1) be perceived as acceptable and useful; and (2) improve diabetes self-care (eg, behaviors and barriers) and self-care related outcomes, including glycemic control (A1C), body mass index (BMI), and psychosocial factors (ie, empowerment and distress) over six months. Methods The evaluation of the intervention impact used a single-group repeated measures design, including three assessment time points: (1) baseline, (2) 3 month (mid intervention), and (3) 6 month (immediate post intervention). Participants were recruited from a university primary care clinic. A total of 41 participants enrolled in the 6 month intervention study. The intervention components included: (1) a study website for communication, feedback, and tracking; and (2) access to an immersive virtual world (Diabetes Island) through Second Life, where a variety of diabetes self-care education activities and resources were available. Outcome measures included A1C, BMI, self-care behaviors, barriers to adherence, eating habits, empowerment, and distress. In addition, acceptability and usage were examined. A series of mixed-effects analyses, with time as a single repeated measures factor, were performed to examine preliminary outcomes. Results The intervention study sample (N=41) characteristics were: (1) mean age of 55 years, (2) 71% (29/41) female, (3) 100% (41/41) African American, and (4) 76% (31/41) reported annual incomes below US

Cell population in spleens during antibody-mediated rejection: Pathologic and clinical findings

20,000. Significant changes over time in the expected direction were observed for BMI (P<.02); diabetes-related distress (P<.02); global (P<.01) and dietary (P<.01) environmental barriers to self-care; one physical activity subscale (P<.04); and one dietary intake (P<.01) subscale. The participant feedback regarding the intervention (eg, ease of use, interest, and perceived impact) was consistently positive. The usage patterns showed that the majority of participants logged in regularly during the first two months, and around half logged in each week on average across the six month period. Conclusions This study demonstrated promising initial results of an immersive virtual world approach to reaching underserved individuals with diabetes to deliver diabetes self-management education. This intervention model and method show promise and could be tailored for other populations. A large scale controlled trial is needed to further examine efficacy.

Disparities in completion rates of the medical prerenal transplant evaluation by race or ethnicity and gender

Background In the treatment of refractory antibody-mediated rejection (AMR), splenectomy has been associated with surprisingly rapid recovery of renal function. The mechanism is still unclear. Methods We review 11 recipients, who underwent rescue splenectomy (RS) as a treatment of AMR within 3 months after kidney transplantation. At transplantation, all patients had undergone desensitization for initially positive crossmatch to their prospective donors. The cellular populations of the spleen were analyzed by immunohistochemistry. For comparison, we obtained spleen specimens from eight controls who were nontransplantation patients. Results Rejection occurred in all the patients early after transplantation (mean [SD], 7.1 [5.7] days). One graft was lost 4 weeks after kidney transplantation. A significantly higher number of plasma cells (PCs) (P=0.049) and lower number of T and B lymphocytes (P=0.02 and P=0.005, respectively) were detected in the RS group compared with the control group. By analyzing the PC variations in the RS group, significantly lower numbers of PCs were detected in the spleens of patients who received rituximab before splenectomy (P=0.0004). In contrast, a higher number of PCs were found in patients (n=3) who did not respond to splenectomy and subsequently underwent bortezomib treatment and recovered their renal function (P=0.02). Conclusions Splenectomy may reverse AMR by debulking PCs. Our analysis suggests that patients with a very high load of PCs may not be rescued by splenectomy alone and may need additional treatments.