Noninsulinoma pancreatogenous hypoglycemia syndrome: quantitative and immunohistochemical analyses of islet cells for insulin, glucagon, somatostatin, and pancreatic and duodenal homeobox protein.

OBJECTIVE: To present a case of an elderly man with noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) and to determine the pathogenesis of this syndrome. METHODS: The pancreas of our patient with NIPHS was immunocytochemically stained for insulin-, glucagon-, and somatostatin-secreting cells and pancreatic and duodenal homeobox protein (PDX-1). The clinical findings and morphologic and immunocytochemical analyses of the islets of our patient are described, along with a review of related published reports. RESULTS: A 78-year-old man presented with hyperinsulinemic hypoglycemia, with episodes unrelated to meals or fasting. An insulinoma could not be localized by preoperative imaging or by intraoperative ultrasonography or palpation. He underwent a 70% distal pancreatectomy. For assessment of the possibility that a nuclear transcription factor regulating islet beta-cell growth and development is overexpressed in this disease and is responsible for diffuse islet hyperfunction and proliferation of beta-cells, pancreatic sections from our patient were stained immunocytochemically for PDX-1, insulin, glucagon, and somatostatin. Morphologic findings were compared with pancreatic sections from normal control patients and normative data reported in the literature. Clinical findings and morphologic analyses were consistent with NIPHS. Islets were arranged in long clusters, both in the pancreatic tissue and in peripancreatic adipose tissue. Islets were small but increased in number, and insulin, glucagon, and somatostatin were present in the islets. The relative intensity of insulin staining was increased in our patient in comparison with that in the control patients, and PDX-1 was not overexpressed. CONCLUSION: The etiopathogenesis of NIPHS in this patient involved (1) an increased number of islets with development of ectopic islets in the peripancreatic adipose tissue; (2) alpha- and delta- as well as beta-cell proliferation; and (3) an early step in the development of the islet not involving overexpression of PDX-1.

Accessibility of home blood pressure monitors for blind and visually impaired people.

BACKGROUND: The prevalence of hypertension comorbid with diabetes is a significant health care issue. Use of the home blood pressure monitor (HBPM) for aiding in the control of hypertension is noteworthy because of benefits that accrue from following a home measurement regimen. To be usable by blind and visually impaired patients, HBPMs must have speech output to convey all screen information, an easily readable visual display, identifiable controls that are easy to use, and an accessible user manual. METHODS: Data on the physical aspects and the features and functions of nine Food and Drug Administration-approved HBPMs (eight of which were recommended by the British Hypertension Society) were tabulated and analyzed for usability by blind and visually impaired individuals. Video Electronics Standards Association standards were used to measure contrast modulation in the displays of the HBPMs. Ten persons who are blind or visually impaired and who have diabetes were surveyed to determine how they monitor their blood pressure and to learn their ideas for improvements in usability. RESULTS: Physical controls were found to be easy to identify, and operating procedures were found to be relatively simple on all of the HBPMs, but user manuals were either inaccessible or minimally accessible to blind persons. The two HBPMs that have speech output do not voice all of the information that is displayed on the screen. Some functions that are standard in the HBPMs without speech output, such as the feature for automatically setting cuff inflation volume and memory, were lacking in the HBPMs with speech output. These features were mentioned as desirable in interviews with legally blind persons who are diabetic and who monitor their blood pressure at home. Visual display output was large and adequate in all of the HBPMs. Michelson contrast for numeric digits in the HBPM displays was also measured, ranging from 55 to 75% for characters with dominant spatial frequency components lying in the range of 0.5-1.0 cycles/degree. CONCLUSIONS: Home blood pressure monitors are easy-to-use devices that do not present accessibility barriers that are difficult to surmount, either technically or operationally. Two HBPMs with voice output were found to have a significant degree of accessibility, but they were not found to offer as many features as those HBPMs that were less accessible. Recommendations were made to improve accessibility, including the development of visual display standards that specify a minimally acceptable level of Michelson contrast.

Vitamin A deficiency impairs fetal islet development and causes subsequent glucose intolerance in adult rats.

To determine the role of vitamin A in fetal islet development, beta- and alpha-cell mass, apoptosis, and alpha- and beta-cell replication were measured in rats using a model of marginal vitamin A deficiency. Female rats before and during pregnancy and their offspring postweaning were fed a diet containing retinol as retinyl palmitate at a low marginal (LM, 0.25 mg/kg diet) or a sufficient (SUFF, 4.0 mg/kg diet) level. Fetal islet size, replication, apoptosis, and offspring glucose tolerance were examined. Both beta-cell area and number per islet were reduced approximately 50% in fetuses from dams fed an LM vitamin A diet compared with those from dams fed the SUFF vitamin A diet. The alpha-cell area and number per fetal islet were not affected by vitamin A deficiency. Apoptosis was not increased. The percentage of newly replicated beta-cells in the LM fetal pancreas was 42% less than that of SUFF offspring, but alpha-cell replication was not affected. To determine whether this decrease in beta-cell area affected adult glucose tolerance and insulin secretion, 65-d-old offspring were subject to glucose tolerance tests. LM rats had a 55% lower plasma insulin level and a 76% higher serum glucose than SUFF rats. The same pattern could be seen in 35-d-old rats. These findings show that vitamin A deficiency decreases beta-cell mass and this reduction can be attributed to a reduced rate of fetal beta-cell replication in LM offspring. This may contribute to impaired glucose tolerance later in adult life.

Accessibility of insulin pumps for blind and visually impaired people.

BACKGROUND: Continuous subcutaneous insulin infusion using an insulin pump (IP) more closely mimics the normal pancreas than multiple insulin injections. It is an effective, and often a preferred, means of maintaining normal blood glucose levels, but IPs were not designed to be fully accessible to blind or visually impaired people. This study will identify accessibility issues related to the design of IPs and focus on the key improvements required in the user interface to provide access for people who are blind or visually impaired. METHODS: IPs that are commercially available were evaluated, and features and functions such as operating procedures, user interface design, and user manuals were tabulated and analyzed. Potential failures and design priorities were identified through a Failure Modes and Effects Analysis (FMEA). RESULTS: Although the IPs do provide some limited audio output, in general, it was found to be of minimal use to people who are blind or visually impaired. None of the IPs uses high-contrast displays with consistently large fonts preferred by people who are visually impaired. User manuals were also found to be of minimal use. Results of the FMEA emphasize the need to focus design improvements on communicating and verifying information so that errors and failures can be detected and corrected. CONCLUSIONS: The most important recommendation for future IP development is speech output capability, which, more than any other improvement, would break down accessibility barriers and allow blind and visually impaired people to take advantage of the benefits of IP technology.