Associations of health literacy with diabetic foot outcomes: a systematic review and meta-analysis.

BACKGROUND: People with diabetes have low health literacy, but the role of the latter in diabetic foot disease is unclear. AIM: To determine, through a systematic review and meta-analysis, if health literacy is associated with diabetic foot disease, its risk factors, or foot care. METHODS: We searched PubMed, EMBASE, CINAHL, Web of Science, Scopus and Science Direct. All studies were screened and data extracted by two independent reviewers. Studies in English with valid and reliable measures of health literacy and published tests of association were included. Data were extracted on the associations between the outcomes and health literacy. Meta-analyses were performed using random effects models. RESULTS: Sixteen articles were included in the systematic review, with 11 in the meta-analysis. In people with inadequate health literacy, the odds of having diabetic foot disease were twice those in people with adequate health literacy, but this was not statistically significant [odds ratio 1.99 (95% CI 0.83, 4.78); two studies in 1278 participants]. There was no statistically significant difference in health literacy levels between people with and without peripheral neuropathy [standardized mean difference -0.14 (95% CI -0.47, 0.18); two studies in 399 participants]. There was no association between health literacy and foot care [correlation coefficient 0.01 (95% CI -0.07, 0.10); seven studies in 1033 participants]. CONCLUSIONS: There were insufficient data to exclude associations between health literacy and diabetic foot disease and its risk factors, but health literacy appears unlikely to have a role in foot care. The contribution of low health literacy to diabetic foot disease requires definitive assessment through robust longitudinal studies.

Feasibility of a multi-modal exercise program on cognition in older adults with Type 2 diabetes - a pilot randomised controlled trial.

BACKGROUND: Type 2 Diabetes (T2D) is associated with increased risk of dementia. We aimed to determine the feasibility of a randomised controlled trial (RCT) examining the efficacy of exercise on cognition and brain structure in people with T2D. METHODS: A 6-month pilot parallel RCT of a progressive aerobic- and resistance-training program versus a gentle movement control group in people with T2D aged 50-75 years (n = 50) at the University of Tasmania, Australia. Assessors were blinded to group allocation. Brain volume (total, white matter, hippocampus), cortical thickness and white matter microstructure (fractional anisotrophy and mean diffusivity) were measured using magnetic resonance imaging, and cognition using a battery of neuropsychological tests. Study design was assessed by any changes (during the pilot or recommended) to the protocol, recruitment by numbers screened and time to enrol 50 participants; randomisation by similarity of characteristics in groups at baseline, adherence by exercise class attendance; safety by number and description of adverse events and retention by numbers withdrawn. RESULTS: The mean age of participants was 66.2 (SD 4.9) years and 48% were women. There were no changes to the design during the study. A total of 114 people were screened for eligibility, with 50 participants with T2D enrolled over 8 months. Forty-seven participants (94%) completed the study (23 of 24 controls; 24 of 26 in the intervention group). Baseline characteristics were reasonably balanced between groups. Exercise class attendance was 79% for the intervention and 75% for the control group. There were 6 serious adverse events assessed as not or unlikely to be due to the intervention. Effect sizes for each outcome variable are provided. CONCLUSION: This study supports the feasibility of a large scale RCT to test the benefits of multi-modal exercise to prevent cognitive decline in people with T2D. Design changes to the future trial are provided. TRIAL REGISTRATION: ANZCTR 12614000222640 ; Registered 3/3/2014; First participant enrolled 26/6/2014, study screening commenced 1/9/2014; Australian and New Zealand Clinical Trial Registry.

Novel approaches to the treatment of hyperglycaemia in type 2 diabetes mellitus.

Control of hyperglycaemia is a fundamental therapeutic goal in patients with type 2 diabetes. The progressive nature of ß-cell dysfunction in type 2 diabetes leads to the need for escalating anti-hyperglycaemic treatment, including insulin, in most patients. Given the prevalence of complications such as weight gain and hypoglycaemia associated with traditional anti-hyperglycaemic agents (AHA), including sulphonylureas and insulin, it is unsurprising that recent years have seen the development of novel agents to treat hyperglycaemia. With increasing evidence supporting the need for a multi-faceted approach to the prevention of adverse cardiovascular events in people with type 2 diabetes, a patient-centred and individualised management strategy addressing lifestyle, cardiovascular risk factor modification and glycaemic control remains critical in improving outcomes in these patients.

Admission blood glucose predicts mortality and length of stay in patients admitted through the emergency department.

BACKGROUND: Hyperglycaemia has been associated with adverse outcomes in several different hospital populations. AIM: The aim of this study was to investigate the relationship between admission blood glucose level (BGL) and outcomes in all patients admitted through the emergency department. METHODS: This study was a retrospective observational cohort study from an Australian tertiary referral hospital. Patients admitted in the first week of each month from April to October 2012 had demographic data, co-morbidities, BGL, intensive care unit admission, length of stay and dates of death recorded. Factors associated with outcomes were assessed by multi-level mixed-effects linear regression. RESULTS: Admission BGL was recorded for 601 admissions with no diagnosis of diabetes and for 219 admissions diagnosed with type 2 diabetes (T2DM). In patients with no diagnosis of diabetes, admission BGL was associated with in-hospital and 90-day mortality (P < 0.001). After multivariate analysis, BGL greater than 11.5 mmol/L was significantly associated with increased mortality at 90 days (P < 0.05). In patients with T2DM increased BGL on admission was not associated with in-hospital or 90-day mortality but was associated with length of hospital stay (ß: 0.22 days/mmol/L; 95% confidence interval 0.09-0.35; P < 0.001), although this association was lost on multivariable analysis. In patients with T2DM, increased coefficient of variation of BGL was also positively associated with length of hospital stay in an almost dose-dependent fashion (P < 0.001). CONCLUSION: Admission BGL was independently associated with increased mortality in patients with no diagnosis of diabetes. Glycaemic variability was associated with increased length of hospital stay in patients with T2DM.

Healthcare professional requirements for the care of adult diabetes patients managed with insulin pumps in Australia.

BACKGROUND: Healthcare professional (HCP) time supporting insulin pump therapy (IPT) has not been documented, yet it is important in planning and allocating resources for effective care. AIM: This study aims to determine HCP time spent in IPT patient care to inform resource planning for optimal IPT delivery. METHODS: Twenty-four Australian adult IPT-experienced institutions (14 government funded, seven private, three both) collected data between April 2012 and January 2013 prospectively, including: patient demographics, HCP classification, purpose of HCP-patient interaction, interaction mode and HCP time with the patient. A subset of patients was tracked from pre-pump education until stable on IPT. RESULTS: Data on 2577 HCP-adult patient interactions (62% face-to-face, 29% remote, 9% administrative) were collected over 12.2 ± 6.4 weeks for 895 patients; age 35.4 ± 14.2 years; 67% female; 99% type 1 diabetes, representing 25% of all IPT patients of the institutions. Time (hours) spent on IPT interactions per centre per week were: nurses 5.4 ± 2.8, dietitians 0.4 ± 0.2 and doctors 1.0 ± 0.5. IPT starts accounted for 48% of IPT interaction time. The percentage of available diabetes clinic time spent on outpatient IPT interactions was 20.4%, 4.6% and 2.7% for nurses, dietitians and doctors respectively. Fifteen patients tracked from pre-pump to stabilisation over 11.8 ± 4.5 weeks, required a median (range) of 9.2 (3.0-20.9), 2.4 (0.5-6.0) and 1.8 (0.5-5.4) hours per patient from nurses, dietitians and doctors respectively. CONCLUSIONS: IPT patient care represents a substantial investment in HCP time, particularly for nurses. Funding models for IPT care need urgent review to ensure this now mainstream therapy integrates well into healthcare resources.

22q11.2 deletion presenting with severe hypocalcaemia, seizure and basal ganglia calcification in an adult man.

We report a 40-year-old man who was found to have profound hypocalcaemia and hypoparathyroidism when investigated for multiple, generalized, tonic/clonic seizures and a chest infection. Computed tomography scan of the brain revealed extensive symmetric bilateral calcification within the cerebellum, thalamus and basal ganglia. Molecular cytogenetic testing by fluorescent in situ hybridization using the commercial Vysis LSI DiGeorge/VCFS dual colour probe set showed a deletion of 22q11.2. The extraordinary feature of this case is the adult presentation of hypocalcaemia, hypoparathyroidism and basal ganglia calcification due to 22q11.2 deletion.

Trends in diabetes management practices of patients from an Australian insulin-treated diabetes register.

AIMS: To compare diabetes management practices in 2001 among individuals from Tasmania, Australia, with a previous management survey conducted in 1995-7. METHODS: Subjects were ascertained through the Tasmanian Insulin-Treated Diabetes Register. General demographic data were collected by telephone interview, and participants mailed a questionnaire on their diabetes management practices. RESULTS: The response rate in 2001 was 80.8% (n=1336). There was a trend to more frequent blood glucose self-monitoring, notably in those less than 25 years (P<0.001 for monitoring >2 times/day), together with continued uptake of the pen system of insulin administration. More intensive shared management by general practitioner and diabetes specialist was noted, including a greater proportion visiting their doctor more than five times per year (P=0.006 for those <50 years). Most patients continue to be appropriately screened for hypertension and retinopathy. Dietitian visits declined overall (P=0.03 for at least annual visits), and there appeared to be an inadequate level of foot examination by patients and doctors. CONCLUSIONS: The survey indicated that most patients were taking greater responsibility for their metabolic control, and intensive management practices and more convenient methods of administration may be contributors. Two areas of possible concern are access to dietitian services, and patient and health provider education on appropriate foot care.

A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males.

OBJECTIVE: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Single school in northwest Tasmania. PARTICIPANTS: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y). INTERVENTIONS: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. RESULTS: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. CONCLUSIONS: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.

Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1).

BACKGROUND: The majority of reports describing the natural history and prognosis of multiple endocrine neoplasia type 1 (MEN 1) utilize phenotypic rather than molecular genetic criteria to establish a diagnosis of MEN 1. OBJECTIVES AND PATIENTS: We sought to determine the spectrum of endocrine abnormality amongst 152 members (64 gene carriers and 88 noncarriers) of a large MEN 1 family in whom a determination of MEN 1 status had previously been made by phenotype screening. The predictive utility of both clinical and molecular screening techniques are described. RESULTS: A novel IVS2-3 (C-G) MEN1 mutation was identified in affected members of this family. Seven (10%) of 71 individuals satisfying clinical diagnostic criteria for MEN 1 were found to be genetically negative (excluded by mutation analysis and haplotyping) for MEN 1. These cases of MEN 1 phenocopy comprised four cases of primary hyperparathyroidism, two 'nonsecretory' pituitary adenoma and one case of coincident prolactinoma and hyperparathyroidism. Three of the patients with hyperparathyroidism had previously required parathyroidectomy and each had achieved normocalcaemia following parathyroid resection. Predictive genetic testing prospectively identified three children with the MEN 1 genotype. Serum calcium was normal at the time of their initial molecular genetic diagnosis. In each case hyperparathyroidism subsequently developed during adolescence. CONCLUSION: Multiple endocrine neoplasia type 1 phenocopy is an important differential diagnosis in patients exhibiting an multiple endocrine neoplasia type 1 phenotype. This is a relevant consideration, particularly when the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but nonspecific, criteria such as mild hyperparathyroidism, pituitary micoadenoma, and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to confirm clinical diagnoses of multiple endocrine neoplasia type 1.

Preoperative sestamibi scanning and surgical findings at bilateral, unilateral, or minimal reoperation for recurrent hyperparathyroidism after subtotal parathyroidectomy in patients with multiple endocrine neoplasia type 1.

HYPOTHESES: Preoperative parathyroid radioisotope scanning is of little or no value in patients with multiple endocrine neoplasia type 1 when 4 or more hypertrophied glands are present. Scanning using technetium Tc 99m sestamibi and single photon emission computed tomography will achieve a high level of sensitivity and specificity after 3 or more glands have previously been removed, justifying limited surgical reexploration. DESIGN: In a prospective study, the preoperative documented report of the predicted site of residual parathyroid was compared with the surgical findings in 13 patients having 19 scans and 17 reoperations. SETTING: All patients belonged to one family, previously described as Tasman family 1, and were confirmed by genetic testing as having multiple endocrine neoplasia type 1. In 10 of 13 patients, reexploration was being undertaken more than 10 years after the first operation. MAIN OUTCOME MEASURES: Scanning was regarded as successful when the documented preoperative report correctly predicted the side and quadrant in which a gland was found at surgery. Surgery was regarded as successful when calcium levels decreased to or below normal levels and were maintained. RESULTS: All 13 scans before first reexploration were successful in identifying the location of a residual parathyroid. From a statistical viewpoint, this equates to 100% sensitivity and 92% specificity. However, despite accurate localization of 1 residual gland in every patient, 7 supernumerary glands in 4 patients and 1 parathyroid remnant in a fifth patient were not localized so that sensitivity in locating all glands in every patient was only 61%. Scans performed for persistent hypercalcemia 48 to 72 hours after reexploration in 2 patients were unsuccessful in demonstrating any residual parathyroid. Scans performed 3 months after surgery in the same 2 patients and a third patient were successful, with sensitivity and specificity of 100%. Apart from patient 11, who awaits reexploration, normocalcemia was eventually achieved in every patient, with 11 of 12 having an initial period of hypocalcemia. CONCLUSIONS: Three months after reexploration and trimming or resection with transplant of half a gland left at first operation, sestamibi scanning achieved sensitivity and specificity of 100% in locating supernumerary parathyroids in patients with multiple endocrine neoplasia type 1 and persistent hypercalcemia. Before first reexploration, however, scans rarely provided new information, predominantly showing only the hypertrophied half-gland remnant.

Vitamin D deficiency and secondary hyperparathyroidism: clinical and biochemical associations in older non-institutionalised Southern Tasmanians.

AIM: To determine the prevalence and associations of vitamin D (25-OHD) deficiency in a sample of older Tasmanian subjects. METHODS: A cross-sectional survey of: 109 patients with a mean age of 79 years (range 60-101 years) consecutively admitted to a short stay geriatric rehabilitation ward; 52 community dwelling subjects with a mean age of 75 years (range 64-88 years). Subjects answered a questionnaire, had anthropometric measurements and underwent venepuncture. RESULTS: The main outcome measure was 25 hydroxy vitamin D (25-OHD) level with deficiency defined as <28 nmol/L. Vitamin D deficiency was found in 67% and secondary hyperparathyroidism in 49% of the hospitalised group. Vitamin D deficiency was also found in 17% of the community group, in particular one in three residents of Independent Living Units was deficient. Subjects who were deficient were older (80 years vs 76 years [p<0.001]), had lower body mass index (23.7 kg/m2 vs 25.9 kg/m2 [p<0.001]) and had a lower serum albumin (35 gm/L vs 39 gm/L [p<0.001]). Deficient subjects had poorer physical functional status (p=0.02) and lower activity levels (p<0.001) and reported less habitual sun exposure (p<0.001). Biochemical measures such as parathyroid hormone, alkaline phosphatase and calcium were weakly predictive of vitamin D levels. By stepwise multiple regression analysis, the only significant predictors of vitamin D levels were the Frenchay Activity Index, albumin and calcium. CONCLUSION: Vitamin D deficiency and secondary hyperparathyroidism is common in community living older people who are hospitalised in Southern Tasmania and is associated with increasing age, poor physical function and activity and low reported sun exposure.

Refractory amiodarone-associated thyrotoxicosis: an indication for thyroidectomy.

BACKGROUND: Tasmania is an area of endemic iodine deficiency. Amiodarone is a class III anti-arrhythmic drug that is widely used for the management of ventricular and supraventricular tachydysrhythmias. Individuals from areas of endemic iodine deficiency appear more likely to manifest hyperthyroidism following amiodarone therapy, whereas hypothyroidism is a more frequent complication in iodine-replete communities. METHODS: Cases series. The clinical and biochemical response to medical and surgical management of five consecutive Tasmanian patients presenting with severe type-II amiodarone-associated thyrotoxicosis was reviewed. RESULTS: Five patients were identified. Combinations of antithyroid therapy including propylthiouracil, lithium carbonate, dexamethasone and cholestyramine were used. Thyroidectomy was required in two cases (40%) due to severe unremitting thyrotoxicosis despite combined drug regimens. Anaesthesia and total thyroidectomy were undertaken without complication despite the presence of severe hyperthyroidism at the time of surgery. In both cases thyroid histopathology demonstrated degenerative and destructive follicular lesions with multinuclear cell infiltrate and focal fibrosis. CONCLUSION: Amiodarone-associated thyrotoxicosis may be severe and refractory to medical therapy. Despite the potential risks of anaesthesia associated with uncontrolled thyrotoxicosis, thyroidectomy should be considered in the setting of life-threatening thyrotoxicosis.

Vitamin D levels in prepubertal children in Southern Tasmania: prevalence and determinants.

OBJECTIVE: To describe the prevalence and determinants of 25-hydroxy D3(25(OH)D) in children. DESIGN: Cross-sectional study. SETTING: Southern Tasmania between June and November 1997. SUBJECTS: Two hundred and one 8-y old male and female children taking part in a cohort study whose principal endpoints were blood pressure and high-density lipoprotein (HDL) cholesterol. RESULTS: The mean 25(OH)D level was 79 nmol/l (s.d. 29.5, median 73, range 12-222). Boys had higher levels than girls (82.1 vs 72.8 nmol/l, P=0.02). 25(OH)D was associated with sunlight exposure in winter school holidays (r=0.20, P=0.005) and winter weekends (r=0.16, P=0.02), the month after school holidays (87.5 vs 69.5 nmol, P<0.0001) and body mass index (r=-0.23, P=0.001). Dietary intake of vitamin D was low (mean 40 IU/day, range 5.2-384) and was not associated with 25(OH)D levels (r=0.01, P=0.91). Variation in skin melanin density was weakly associated with 25(OH)D (r=0.09, P=0.19). CONCLUSIONS: Sunlight is the major determinant of vitamin D stores in our population. Neither variation in skin type within Caucasians nor diet modified this association to any significant extent. Extrapolation of these findings to sunlight bone mass associations in a very similar population suggests that a minimum level of around 50 nmol/l in the population is required for optimal bone development in prepubertal children but this needs to be confirmed with further controlled trials of vitamin D supplementation and bone mass. SPONSORSHIP: Arthritis Foundation of Australia, Roche Pharmaceuticals.

Octreotide improves biochemical, radiologic, and symptomatic indices of gastroenteropancreatic neoplasia in patients with multiple endocrine neoplasia type 1 (MEN-1). Implications for an integrated model of MEN-1 tumorigenesis.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant tumor syndrome associated with parathyroid, gastroenteropancreatic (GEP), and pituitary neoplasia. Gastrinoma and GEP malignancy are common life-threatening endocrine complications of MEN-1. An effective management strategy for these disorders remains to be determined. The authors attempted to determine the role of the somatostatin analogue, octreotide, in ameliorating features of hypergastrinemic GEP neoplasia associated with MEN-1. METHODS: Five MEN-1 patients with hypergastrinemia and either symptoms of GEP neoplasia or hepatic metastases received a trial of octreotide, 100 microg subcutaneously, three times daily for 3 months. RESULTS: Treatment with octreotide was associated with a rapid symptomatic and biochemical response. In all patients serum gastrin fell to < 25% of the pretreatment value. The serum glycoprotein-alphasubunit (a marker of enterochromaffin-like [ECL] cell hyperplasia, gastric carcinoidosis, and disseminated enteropancreatic malignancy) was elevated at baseline in three patients. In each case the serum glycoprotein-alphasubunit normalized after treatment with octreotide. Hepatic metastases were present in two patients at baseline. The size of the metastases diminished by up to 15% during the period of octreotide treatment. Four patients reported symptoms prior to treatment: lethargy, easy fatigability, and generalized musculoskeletal discomfort. A marked symptomatic improvement occurred in each case. No patient experienced side effects related to octreotide therapy and all elected to remain on treatment after completion of the trial. CONCLUSIONS: Octreotide is a safe and effective adjunct to surgical strategies for the management of GEP neoplasia in hypergastrinemic MEN-1 patients.

Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy.

BACKGROUND: Sporadic primary hyperparathyroidism (PHPT) occurs most frequently in postmenopausal women. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal-dominant disease in which mild to moderate PHPT develops in most gene carriers by 20 years of age. Primary hyperparathyroidism associated with MEN 1 is typically recurrent, despite initially successful subtotal parathyroidectomy. Osteoporosis is considered a complication of sporadic PHPT and an indication for parathyroidectomy. In the setting of MEN 1, however, the relationship of bone mass to PHPT, fracture risk, and parathyroidectomy is unknown. HYPOTHESIS: Parathyroidectomy improves bone mineral density for patients with primary hyperparathyroidism in the setting of MEN 1. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Twenty-nine women with MEN 1 belonging to a single family with a history of MEN 1. INTERVENTIONS: Parathyroidectomy. MAIN OUTCOME MEASURES: Bone mineral density (BMD) and history of skeletal fracture. RESULTS: Osteopenia and osteoporosis were diagnosed in 41% and 45% of patients, respectively. Forty-four percent of patients with uncontrolled PHPT had severe osteopenia (T score, <-2.0) by 35 years of age. Reduction in BMD was greatest at the femoral neck. Reduced BMD was associated with an increased likelihood of skeletal fracture (P = .05). Patients with uncontrolled PHPT had lower femoral neck and lumbar spine BMDs than those in whom PHPT was controlled by parathyroidectomy (P = .005 and .02, respectively). Successful parathyroidectomy improved femoral neck and lumbar spine BMDs by a mean +/- SEM of 5.2% +/- 2.5% and 3.2% +/- 2.9%, respectively. CONCLUSIONS: Osteoporosis is a frequent and early complication of PHPT in MEN 1. Despite difficulty in achieving a cure of PHPT in MEN 1, parathyroidectomy has an important role in the optimization of BMD for patients with MEN 1.

Management of insulin-treated diabetes in Tasmania.

OBJECTIVE: To evaluate patterns of self-management, healthcare utilisation and screening for major complications among Tasmanians with insulin-treated diabetes. MAIN OUTCOME MEASURES: Frequency of self-monitoring of blood glucose, health care utilisation and screening for diabetic complications. DESIGN AND SETTING: A questionnaire survey of 1517 people listed on the Tasmanian Diabetes Register in 1995-1997. RESULTS: Response rate was 79.5%. Self-monitoring of blood glucose was reported by 98% of respondents, daily self-monitoring by 74%. About 41% of respondents were being managed jointly by GPs and diabetes specialists, 29% solely by GPs and 25% solely by diabetes specialists. Over 96% visited the doctor treating their diabetes more than once a year, but 21% reported they had never visited a diabetes educator and 43% reported they had never visited a dietitian. Most respondents aged > or = 25 years (90%) reported having an eye examination within the past two years, almost all by an eye specialist. Blood pressure was commonly assessed, but most adults indicated that the doctor treating their diabetes did not routinely examine their feet. Nearly 19% of respondents smoked cigarettes. CONCLUSIONS: Some aspects of diabetes self-care and medical care have improved in Tasmania since the 1984 survey (eg, frequency of self-monitoring of blood glucose rose from 50% to 98%). However, our findings suggest that further improvements are needed to increase daily self-monitoring of blood glucose, attendance at diabetes educator and dietitian services, and foot examinations by doctors. Additional efforts are also needed to lower the prevalence of smoking.

Enteropancreatic malignancy associated with multiple endocrine neoplasia type 1: risk factors and pathogenesis.

BACKGROUND: Enteropancreatic malignancy is an important cause of morbidity and mortality associated with multiple endocrine neoplasia type 1 (MEN 1). However, the risk factors and mechanisms of the tumorigenesis of this malignancy are poorly understood. METHODS: The authors conducted a retrospective study of factors associated with the development of malignant enteropancreatic tumor in 69 patients with MEN 1 belonging to a single family. RESULTS: Metastatic enteropancreatic tumor and gastrinoma were identified in 20% and 36% of patients, respectively. Compared with MEN 1 patients who did not have an immediate family history of enteropancreatic malignancy, MEN 1 patients with a first-degree relative affected by enteropancreatic malignancy had an increased risk of developing disseminated tumor (odds ratio, 3.7; P < 0.05). In addition, hypergastrinemia and advanced age were both associated with a significant increase in the risk of enteropancreatic malignancy. Elevated serum glycoprotein alpha subunit levels were associated with enterochromaffin-like cell hyperplasia, gastric carcinoid formation, and disseminated enteropancreatic tumor in hypergastrinemic patients (P < 0.05). CONCLUSIONS: Disease modifier factors act in concert with the MEN 1 gene to modulate the development of enteropancreatic neoplasia. It is possible to identify MEN 1 patients at high risk for developing aggressive enteropancreatic tumors. Heritable disease modifier factor(s) affecting enteropancreatic malignancy appear to reside at loci distinct from that of the MEN 1 gene.