CHECK UP: A student-designed model for creating innovative patient education materials that your patients will actually use.

OBJECTIVE: As appointments become more rushed, it is crucial that primary care clinicians consider new and effective ways to provide preventive health education to patients. Currently, patient education is often handouts printed from the electronic medical record system; however, these pieces of paper often do not have the desired impact. Well-established advertising methods reveal that repeated exposure is key in recall and swaying consumer decisions. The Creating Health Education for Constructive Knowledge in Underserved Populations (CHECK UP) Program is a medical student-led program that aims to improve patient recall of health information, health promoting behaviors and health outcomes by applying modified advertising concepts to the delivery of health education. METHODS: Patients were given large magnets containing health education information. These patients were interviewed 3-4 months afterwards to assess use and effectiveness of magnets as a means to provide health education. RESULTS: In total, 25 of the 28 patients given CHECK UP magnets agreed to participate. The majority of participants (23/25) kept the magnets and reported that they, as well as others in their households, see the magnets daily. All 23 participants recalled at least 1 health tip from 1 of the magnets. CONCLUSIONS: The use of non-traditional materials for patient education allowed for repeated exposure and recall of health information. Consideration for modified use of evidence-based advertising and marketing strategies for the delivery of patient education may be an easy and effective way to provide information to patients outside of the clinical setting and promote health behavioral changes.

A Student-Driven Community Engagement Model for School Nutrition Education Programs.

BACKGROUND: Parental engagement in nutrition education programs often focuses on direct communication with parents. While this is an important component for the success of nutrition education, the role that students can play in connecting the program to their home is often overlooked. METHODS: Feedback from students participating in a nutrition education program was used to develop an intervention that allowed students to take snacks they prepared in class home to their families. Change in parental awareness and family communication about the program was assessed in response to this intervention. A total of 257 third-grade students and 80 of their parents completed surveys to assess communication and interest in learning more about nutrition through the program. RESULTS: A significant increase in family awareness and communication about the nutrition program was reported in response to the intervention that gave the students the ability to share food they made in class with their families. CONCLUSIONS: Community engagement for school nutrition education programs is effective in stimulating family conversation about nutrition when methods are cognizant of students potential and motivation for driving these conversations. Our model for student-centered community engagement can be used by nutrition education programs to increase parental engagement.

Pancreatic alpha-cell mass across adult human lifespan.

AIM: To establish pancreatic alpha-cell mass in lean, non-diabetic humans over the adult lifespan, performed as a follow-up study to beta-cell mass across the adult human lifespan. METHODS: We examined human pancreatic autopsy tissue from 66 lean, non-diabetic individuals aged from 30 to 102 years, grouped into deciles: 3rd (30-39 years), 4th (40-49 years), 5th (50-59 years), 6th (60-69 years), 7th (70-79 years), 8th (80-89 years) and 9th deciles (90+ years). Sections of pancreas were immunostained for glucagon and analyzed for fractional alpha-cell area. Population-based pancreatic volume data were used to calculate alpha-cell mass. RESULTS: With advanced age, the exocrine pancreas undergoes atrophy demonstrated by increased fat area (as % exocrine area) (0.05 ± 0.01 vs 1.6 ± 0.7% fat area of total exocrine pancreas, 3rd vs 9th decile, P < 0.05). Consequently, islet density increases with age (2.7 ± 0.4 vs 10.5 ± 3.3 islets/mm2, 3rd vs 9th decile, P < 0.05). Alpha-cell fractional area increases with advanced age (0.34 ± 0.05% vs 0.73 ± 0.26%, 3rd vs 9th decile, P < 0.05). However, alpha-cell mass remains constant at ~190 mg throughout the adult lifespan in lean, non-diabetic humans. Within islets, alpha-cell distribution between mantle and core is unchanged across deciles (1862 ± 220 vs 1945 ± 200 vs 1948 ± 139 alpha cells in islet mantle/mm2, 3rd vs 6th vs 9th decile, P = 0.93 and 1912 ± 442 vs 1449 ± 123 vs 1514 ± 168 alpha cells in islet core/mm2, 3rd vs 6th vs 9th decile, P = 0.47), suggesting that human islets retain their structural organization in the setting of age-related exocrine atrophy. CONCLUSIONS: Consistent with our previous findings for beta-cell mass, alpha-cell mass remains constant in humans, even with advanced age. Pancreatic endocrine cells are much more robustly preserved than exocrine cells in aged humans, and islets maintain their structural integrity throughout life.

An Increase in Chromogranin A-Positive, Hormone-Negative Endocrine Cells in Pancreas in Cystic Fibrosis.

We sought to establish whether an increase in chromogranin A-positive, hormone-negative (CPHN) endocrine cells occurs in the pancreas of patients with cystic fibrosis (CF), as potential evidence of neogenesis. Pancreata were obtained at autopsy from nondiabetic patients with CF (n = 12) and age-matched nondiabetic control subject (CS) individuals without CF (n = 12). In addition, pancreas from three diabetic patients with CF was obtained. Pancreas sections were stained for chromogranin A, insulin, and a cocktail of glucagon, somatostatin, pancreatic polypeptide, and ghrelin and evaluated for the frequency of CPHN cells. There was a higher frequency of CPHN cells in islets of the patients with CF compared with the CS group. Moreover, CPHN cells occurring as single cells or clusters scattered in the exocrine pancreas were also more frequent in patients with CF. The increased frequency of CPHN cells in pancreas of patients with CF may indicate an attempt at endocrine cell regeneration.

Characterization of Non-hormone Expressing Endocrine Cells in Fetal and Infant Human Pancreas.

Context: Previously, we identified chromograninA positive hormone-negative (CPHN) cells in high frequency in human fetal and neonatal pancreas, likely representing nascent endocrine precursor cells. Here, we characterize the putative endocrine fate and replicative status of these newly formed cells. Objective: To establish the replicative frequency and transcriptional identity of CPHN cells, extending our observation on CPHN cell frequency to a larger cohort of fetal and infant pancreas. Design, Setting, and Participants: 8 fetal, 19 infant autopsy pancreata were evaluated for CPHN cell frequency; 12 fetal, 24 infant/child pancreata were evaluated for CPHN replication and identity. Results: CPHN cell frequency decreased 84% (islets) and 42% (clusters) from fetal to infant life. Unlike the beta-cells at this stage, CPHN cells were rarely observed to replicate (0.2 ± 0.1 vs. 4.7 ± 1.0%, CPHN vs. islet hormone positive cell replication, p < 0.001), indicated by the lack of Ki67 expression in CPHN cells whether located in the islets or in small clusters, and with no detectable difference between fetal and infant groups. While the majority of CPHN cells express (in overall compartments of pancreas) the pan-endocrine transcription factor NKX2.2 and beta-cell specific NKX6.1 in comparable frequency in fetal and infant/child cases (81.9 ± 6.3 vs. 82.8 ± 3.8% NKX6.1+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.9; 88.0 ± 4.7 vs. 82.1 ± 5.3% NKX2.2+-CPHN cells of total CPHN cells, fetal vs. infant/child, p = 0.4), the frequency of clustered CPHN cells expressing NKX6.1 or NKX2.2 is lower in infant/child vs. fetal cases (1.2 ± 0.3 vs. 16.7 ± 4.7 clustered NKX6.1+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01; 2.7 ± 1.0 vs. 16.0 ± 4.0 clustered NKX2.2+-CPHN cells/mm2, infant/child vs. fetal, p < 0.01). Conclusions: The frequency of CPHN cells declines steeply from fetal to infant life, presumably as they differentiate to hormone-expressing cells. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells. Precis : CPHN cell frequency declines steeply from fetal to infant life, as they mature to hormone expression. CPHN cells represent a non-replicative pool of endocrine precursor cells, a proportion of which are likely fated to become beta-cells.

Increased Chromogranin A-Positive Hormone-Negative Cells in Chronic Pancreatitis.

Context: Chronic pancreatitis (CP) is characterized by inflammation, fibrosis, and a loss of pancreatic acinar cells, which can result in exocrine and eventually endocrine deficiency. Pancreatitis has been reported to induce formation of new endocrine cells (neogenesis) in mice. Our recent data have implicated chromogranin A-positive hormone-negative (CPHN) cells as potential evidence of neogenesis in humans. Objective: We sought to establish if CPHN cells were more abundant in CP in humans. Design, Setting, and Participants: We investigated the frequency and distribution of CPHN cells and the expression of the chemokine C-X-C motif ligand 10 (CXCL10) and its receptor chemokine C-X-C motif receptor 3 in pancreas of nondiabetic subjects with CP. Results: CPHN cell frequency in islets was increased sevenfold in CP [2.1% ± 0.67% vs 0.35% ± 0.09% CPHN cells in islets, CP vs nonpancreatitis (NP), P < 0.01], as were the CPHN cells found as scattered cells in the exocrine areas (17.4 ± 2.9 vs 4.2 ± 0.6, CP vs NP, P < 0.001). Polyhormonal endocrine cells were also increased in CP (2.7 ± 1.2 vs 0.1 ± 0.04, CP vs NP, % of polyhormonal cells of total endocrine cells, P < 0.01), as was expression of CXCL10 in α and ß cells. Conclusion: There is increased islet endogenous expression of the inflammation marker CXCL10 in islets in the setting of nondiabetic CP and an increase in polyhormonal (insulin-glucagon expressing) cells. The increase in CPHN cells in CP, often in a lobular distribution, may indicate foci of attempted endocrine cell regeneration.

Pancreatic Nonhormone Expressing Endocrine Cells in Children With Type 1 Diabetes.

It has been proposed that the deficit in ß-cell mass in type 1 diabetes (T1D) may be due, in part, to ß-cell degranulation to chromogranin-positive hormone-negative (CPHN) cells. The frequency and distribution of pancreatic CPHN cells were investigated in 19 children with T1D compared with 14 non-diabetic (ND) children. We further evaluated these cells for replication and expression of endocrine lineage markers Nkx6.1 and Nkx2.2, and compared these frequencies with those previously reported in CPHN cells in adults with T1D. In contrast to adults' cells, pancreatic CPHN cells were comparably abundant (percentage of endocrine cells ± standard error of the mean, 1.4 ± 0.2 vs 1.0 ± 0.2 in patients with T1D vs ND subjects, respectively; P = not significant) and comparably distributed in children with T1D vs ND donors. Replication of CPHN cells was detected but unchanged in children with T1D vs ND children, as was the percentage of CPHN cells expressing Nkx6.1 or NKx2.2. In children with T1D, the frequency of pancreatic CPHN cells was not increased, and this differed from adults with T1D.

Increased Frequency of Hormone Negative and Polyhormonal Endocrine Cells in Lean Individuals With Type 2 Diabetes.

CONTEXT: It has been suggested that beta cell loss in type 2 diabetes (T2D) may be due to beta cell degranulation and/or altered cell identity. While shown to have a minor role in obese T2D, this has not been evaluated in lean T2D. OBJECTIVE: To establish the contribution of altered beta cell identity in lean T2D and, using a rodent model of lean T2D, whether changes in beta cell identity precede hyperglycemia. DESIGN, SETTING, AND PARTICIPANTS: We investigated the frequency of chromogranin A positive hormone negative (CPHN) and polyhormonal endocrine cells in pancreas from 10 lean nondiabetic and 10 lean T2D subjects and in pancreas from wild-type and human IAPP transgenic rats at the prediabetic and diabetic stages. RESULTS: CPHN cells and polyhormonal-expressing cells were comparably increased in lean T2D and human IAPP transgenic rats, in the latter both before and at onset of diabetes. However, the extent of these cells could only account for approximately 2% of beta cell loss. CONCLUSION: Degranulation and altered identity play at most a minor role in the beta cell deficit in lean T2D. Because the increase in CPHN and polyhormonal cells precede diabetes onset, these changes are likely a response to stress rather than hyperglycemia, and may reflect attempted regeneration.

Increased Hormone-Negative Endocrine Cells in the Pancreas in Type 1 Diabetes.

CONTEXT AND OBJECTIVE: Type 1 diabetes (T1D) is characterized by a ß-cell deficit due to autoimmune inflammatory-mediated ß-cell destruction. It has been proposed the deficit in ß-cell mass in T1D may be in part due to ß-cell degranulation to chromogranin-positive, hormone-negative (CPHN) cells. DESIGN, SETTING, AND PARTICIPANTS: We investigated the frequency and distribution of CPHN cells in the pancreas of 15 individuals with T1D, 17 autoantibody-positive nondiabetic individuals, and 17 nondiabetic controls. RESULTS: CPHN cells were present at a low frequency in the pancreas from nondiabetic and autoantibody-positive, brain-dead organ donors but are more frequently found in the pancreas from donors with T1D (islets: 1.11% ± 0.20% vs 0.26% ± 0.06 vs 0.27% ± 0.10% of islet endocrine cells, T1D vs autoantibody positive [AA+] vs nondiabetic [ND]; T1D vs AA+, and ND, P < .001). CPHN cells are most commonly found in the single cells and small clusters of endocrine cells rather than within established islets (clusters: 18.99% ± 2.09% vs 9.67% ± 1.49% vs 7.42% ± 1.26% of clustered endocrine cells, T1D vs AA+ vs ND; T1D vs AA+ and ND, P < .0001), mimicking the distribution present in neonatal pancreas. CONCLUSIONS: From these observations, we conclude that CPHN cells are more frequent in T1D and, as in type 2 diabetes, are distributed in a pattern comparable with the neonatal pancreas, implying a possible attempted regeneration. In contrast to rodents, CPHN cells are insufficient to account for loss of ß-cell mass in T1D.

ß-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of ß-Cell Dedifferentiation and Degranulation.

CONTEXT: Type 2 diabetes is characterized by a ß-cell deficit and a progressive defect in ß-cell function. It has been proposed that the deficit in ß-cells may be due to ß-cell degranulation and transdifferentiation to other endocrine cell types. OBJECTIVE: The objective of the study was to establish the potential impact of ß-cell dedifferentiation and transdifferentiation on ß-cell deficit in type 2 diabetes and to consider the alternative that cells with an incomplete identity may be newly forming rather than dedifferentiated. DESIGN, SETTING, AND PARTICIPANTS: Pancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases. RESULTS: Whereas there was a slight increase in islet endocrine cells expressing no hormone in type 2 diabetes (0.11 ± 0.03 cells/islet vs 0.03 ± 0.01 cells/islet, P < .01), the impact on the ß-cell deficit would be minimal. Furthermore, we established that the deficit in ß-cells per islet cannot be accounted for by an increase in other endocrine cell types. The distribution of hormone negative endocrine cells in type 2 diabetes (most abundant in cells scattered in the exocrine pancreas) mirrors that in developing (embryo and neonatal) pancreas, implying that these may represent newly forming cells. CONCLUSIONS: Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in ß-cells in type 2 diabetes but may reflect, in part, attempted ß-cell regeneration.