Sensor-augmented CSII therapy with predictive low-glucose suspend following total pancreatectomy.

Pancreatogenic diabetes is characterised by recurrent severe hypoglycaemia due to changes in both endocrine and exocrine functions. There are no guidelines to manage these individuals. Herein, we describe the post-operative management of two people who developed pancreatogenic diabetes following total pancreatectomy for neuroendocrine malignancy. In both individuals, diabetes was managed using sensor-augmented predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII). We demonstrate the benefit of sensor-augmented CSII in averting hypoglycaemia whilst optimising glycaemic control. Expected rates of severe hypoglycaemia in individuals with pancreatogenic diabetes can be averted with the use of continuous glucose monitoring (CGM) technology, optimising quality of life and reducing the risk of diabetes-related complications. LEARNING POINTS: There are no clear guidelines to manage people with pancreatogenic diabetes.We describe the use of CGM with predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII) in the management of two individuals post-pancreatectomy.Predictive low-glucose suspend technology can achieve excellent glycaemic control whilst avoiding recurrent and severe hypoglycaemia in people with pancreatogenic diabetes.Predictive low-glucose suspend CGM should be considered as an effective therapeutic option for the management of pancreatogenic diabetes.

Gaps and barriers in health-care provision for co-morbid diabetes and chronic kidney disease: a cross-sectional study.

BACKGROUND: Patients with diabetes and chronic kidney disease (CKD) are a complex subset of the growing number of patients with diabetes, due to multi-morbidity. Gaps between recommended and received care for diabetes and chronic kidney disease (CKD) are evident despite promulgation of guidelines. Here, we document gaps in tertiary health-care, and the commonest patient-reported barriers to health-care, before exploring the association between these gaps and barriers. METHODS: This cross-sectional study recruited patients with diabetes and CKD (eGFR < 60 mL/min/1.73 m2) across 4 large hospitals. For each patient, questionnaires were completed examining clinical data, recommended care, and patient-reported barriers limiting health-care. Descriptive statistics, subgroup analyses by CKD stage and hospital, and analyses examining the relationship between health-care gaps and barriers were performed. RESULTS: 308 patients, of mean age 66.9 (SD 11.0) years, and mostly male (69.5%) and having type 2 diabetes (88.0%), participated. 49.1% had stage 3, 24.7% stage 4 and 26.3% stage 5 CKD. Gaps between recommended versus received care were evident: 31.9% of patients had an HbA1c ≥ 8%, and 39.3% had a measured blood pressure ≥ 140/90 mmHg. The commonest barriers were poor continuity of care (49.3%), inadequate understanding/education about CKD (43.5%), and feeling unwell (42.6%). However, barriers associated with a failure to receive items of recommended care were inadequate support from family and friends, conflicting advice from and poor communication amongst specialists, the effect of co-morbidities on self-management and feeling unmotivated (all p < 0.05). CONCLUSIONS: Barriers to health-care varied across CKD stages and hospitals. Barriers associated with a deviation from recommended care were different for different items of care, suggesting that specific interventions targeting each item of care are required.

Mortality associated with primary hyperparathyroidism.

561 patients with primary hyperparathyroidism were followed between 1961 and 1994. Relative survival was compared to that of the Australian population studied during the same time interval. Mortality was significantly greater in the hyperparathyroid population (P<0.001). Mortality was not greater in the patients with serum calcium levels >3.00 mmol/L compared to those with a serum calcium levels <3.00 mmol/L. 113 patients did not have parathyroid surgery. Their relative survival was not significantly different from those who had surgery but their mean serum calcium and parathyroid hormone (PTH) levels were significantly lower than those who had surgery. A re-analysis of the 453 patients followed between 1972 and 2011 was carried out and a 20-year survival analysis made of those diagnosed between 1972 and 1981 and those diagnosed between 1982 and 1991. The latter group had significantly worse relative mortality than the former group (P<0.001) but was significantly older at the time of diagnosis (56.94 ± 14.83 vs 52.01 ± 13.58, P<0.001). The serum calcium and serum PTH levels were not significantly different between these two groups.

Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized, double-blind, placebo-controlled study.

BACKGROUND: Although postmenopausal combined hormone replacement therapy reduces the risk of hip fracture, long-term use may be associated with an increased risk of breast cancer, and in women more than 10 years after menopause it is associated with an increased risk of cardiovascular disease. Isoflavones, because of preferential binding to estrogen receptor beta, may retain the beneficial effects on bone but lessen the adverse effects on the breast. OBJECTIVE: The objective of this study was to study the effects of an isoflavone obtained from red clover (Rimostil) on bone mineral density, and on low-density lipoprotein (LDL) cholesterol. DESIGN: In a double-blind, randomized, placebo-controlled trial, 50 mg of Rimostil was given to women who were menopausal for at least 1 year. Bone mineral density of the spine, femoral neck and forearm and serum LDL cholesterol were measured at baseline and at 6-month intervals. The duration of follow-up was 2 years. RESULTS: There was no beneficial effect of Rimostil on bone density at any site. There was a 12% fall in serum LDL cholesterol in the Rimostil-treated arm, which was significantly greater than the 2% drop seen in the control arm (P=0.005).

Use of dermal injection of activated protein C for treatment of large chronic wounds secondary to pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum (PG) is a systemic disease that presents with cutaneous necrotizing ulceration, producing deep necrotic ulcers, usually with a raised, undermined, violaceous border. Treatment typically involves high dose immunosuppressive drugs, but more recently anti-tumour necrosis factor and monoclonal antibodies have been used. Activated protein C (APC) stimulates wound healing in patients with treatment-refractory skin ulcers, possibly by stimulating angiogenesis and re-epithelialization, and preventing inflammation. AIM: To investigate whether APC may be beneficial as a treatment for ulcers related to cutaneous PG. METHODS: Two patients were recruited with a clinical history and physical and histopathological evidence of acute PG. A total of 400 µg (1.0 mL) of APC was injected subcutaneously into the dermal edge of necrotic PG ulcers weekly for a total treatment period of 6 weeks. Photographs were taken, and clinical progress, ulcer size and pain score were monitored during this period and after the cessation of treatment, at weeks 8 and 12. RESULTS: Over the 12 weeks of the trial, APC led to a reduction in wound size from 3.8 cm(2) to 0.8 cm(2) in patient 1 (78.9% decrease) and from 41 cm(2) to 16 cm(2) in patient 2 (70.0% decrease, respectively), and a reduction in pain scores from 10 to 0 (100% decrease) in both patients. CONCLUSION: Although this study has limited because of its small sample size and lack of a true placebo group, it does indicate that APC has potential as a therapeutic option for patients with chronic skin ulcers from PG.

The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism.

OBJECTIVE: This study was undertaken to evaluate the effects of varying doses of phytoestrogens on lipid and bone metabolism in postmenopausal women. DESIGN: A novel red clover isoflavone preparation (Rimostil) containing genistein, daidzein, formononetin, and biochanin was administered to 46 postmenopausal women in a double-blind protocol after a single-blind placebo phase and followed by a single-blind washout phase. Patients were randomized to receive either 28.5 mg, 57 mg, or 85.5 mg of phytoestrogens daily for a 6-month period. RESULTS: At 6 months, the serum high-density lipoprotein cholesterol had risen significantly by 15.7-28.6% with different doses (p = 0.007, p = 0.002, p = 0.027), although the magnitude of the response was independent of the dose used. The serum apolipoprotein B fell significantly by 11.5-17.0% with different doses (p = 0.005, p = 0.043, p = 0.007) and the magnitude of the response was independent of the dose used. The bone mineral density of the proximal radius and ulna rose significantly by 4.1% over 6 months with 57 mg/day (p = 0.002) and by 3.0% with 85.5 mg/day (p = 0.023) of isoflavones. The response with 28.5 mg/day of isoflavones was not significant. There was no significant increase in endometrial thickness with any of the doses of isoflavone used. CONCLUSION: These results show that the administration of an isoflavone combination extracted from red clover was associated with a significant increase in high-density lipoprotein cholesterol, a significant fall in apolipoprotein B, and a significant increase in the predominantly cortical bone of the proximal radius and ulna after 6 months of treatment. Interpretation of the results is undertaken cautiously because of the absence of a simultaneously studied control group.

Effect of venesection on bone mineral density in an eugonadal woman with haemochromatosis.

BACKGROUND: A 41-year-old premenopausal woman with newly diagnosed haemochromatosis was found to have osteopenia on screening bone mineral densitometry. METHODS AND RESULTS: Liver biopsy showed grade 3 haemochromatosis with an hepatic iron index of 4. Investigation for secondary factors for osteopenia revealed no cause. The patient was clinically and biochemically eugonadal. Following venesection of 8 L blood (4 g iron) over 17 months and calcium supplementation, her bone density rose significantly. Neck of femur bone density increased by 6.0% over 13 months and lumbar vertebral bone density increased by 7.2%. There are no previous reports of response of bone density to venesection in eugonadal patients or in women with haemochromatosis.

Patients undergoing coronary artery bypass graft surgery are at high risk of impaired glucose tolerance and diabetes mellitus during the first postoperative year.

This study demonstrates that patients who have undergone coronary artery bypass graft (CABG) surgery have a high prevalence of abnormal glucose tolerance 3 months and 1 year later. Although only 6% were known to have diabetes mellitus (DM) preoperatively, a further 4% were classified DM at two oral glucose tolerance tests (OGTTs) over the subsequent year and a further 18% were classified as having impaired glucose tolerance (IGT) at 12 months. Reproducibility of the 120-minute plasma glucose level in the 75-g OGTT was estimated from a repeat test performed within 10 days. The coefficient of variation (CV) of 120-minute glucose was between 14% and 18%. The observed changes in class of glucose tolerance observed at OGTTs repeated 6 and 12 months after surgery differed from the predicted changes based purely on the estimated variability of 120-minute glucose measurement. There was evidence of regression to the mean for the IGT group. However, there was also evidence of deteriorating glucose tolerance in some subjects. Between 4% and 9% of those with IGT 3 months after CABG surgery developed DM by 12 months, and 26 (13%) of those with initially normal glucose tolerance (NGT) developed IGT. Insulin and glucose responses in the OGTT and estimates of insulin resistance and beta-cell function from fasting samples show that insulin resistance was the principal abnormality in IGT subjects, whereas in DM subjects, both insulin resistance and beta-cell dysfunction contributed. Analysis of preoperative patient characteristics showed that the presence of either a systolic blood pressure of 140 mm Hg or body mass index (BMI) of more than 25 kg/m2 identified 51% of the subjects who would at 1 year after surgery include all those who would be classified DM and 67% of those who would have IGT. Further analyses including insulin levels identified groups at particularly high risk of DM, but no combination of readily available preoperative measures identified all those destined to be classified IGT.

Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man.

1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained. 2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h-1 kg-1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion. 3. On the Intralipid study day serum triacylglycerol (2.24 +/- 0.20 versus 0.67 +/- 0.10 mmol/l), plasma nonesterified fatty acid (395 +/- 13 versus 51 +/- 1 mumol/l), blood glycerol (152 +/- 2 versus 11 +/- 1 mumol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64-104) versus 4 (3-5) mumol/l] were all significantly higher (all P less than 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 +/- 0.07 versus 0.27 +/- 0.08 mg min-1 kg-1, P less than 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 +/- 0.77 to 6.17 +/- 0.71 mg min-1 kg-1, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

The patient with newly diagnosed diabetes mellitus.

This outline is based on dietary advice, regular exercise, diabetes education (including glucose monitoring) and, if necessary, an oral hypoglycaemic agent or insulin. Precipitating factors such as dietary indiscretions, infections, drugs, thyrotoxicosis and haemochromatosis should be sought, and associated cardiovascular risk factors such as obesity, hyperlipidaemia, hypertension and a history of smoking should receive attention.

Coronary artery bypass surgery--impact upon the patient's spouse.

The spouses of 65 coronary artery bypass graft surgery (CAGS) patients were assessed to determine levels of psychological symptoms and social impairment both before and 12 months after surgery. There was substantial psychological morbidity in spouses pre-operatively, with from one-third to one-half having clinically significant levels of depression and/or anxiety symptoms. Pre-operatively there was also significant global psychosocial impairment in the spouse. Of the specific domains of psychosocial adjustment, recreational and psychological adjustment was most severely affected, vocational/domestic adjustment and sexual adjustment being less impaired, and extended family relationships showing minimal impairment. There was significant improvement in spouses' psychological and global psychosocial adjustment at 12 months, with recreational adjustment showing the greatest improvement. Significant improvements also occurred in vocational adjustment but not in domestic or sexual adjustment. Neither physical, psychological nor social adjustment variables preoperatively in either the patient or spouse were predictive of psychological morbidity in the spouse (anxiety or depression) at 12 months. Similarly there were no significant patient or spouse preoperative predictors of social adjustment in the spouse at 12 months. However, the patients post-operative psychological morbidity and the spouses social and psychological morbidity were related.

A prospective evaluation of the psychosocial effects of coronary artery bypass surgery.

Eighty-nine patients were prospectively studied to determine psychological and psychosocial impairment prior to and after coronary artery graft surgery (CAGS). Psychological morbidity prior to surgery was high, with one-third having clinically significant levels of depression and/or anxiety symptoms. Scores on the Psychosocial Adjustment to Illness Scale indicated a generally high level of psychosocial impairment pre-operatively, with vocational and domestic functioning being most severely affected, social and sexual functioning being less impaired, and extended family relationships being largely unaffected. In general, there was a significant reduction in psychological morbidity and an improvement in psychosocial functioning at 6 months, which remained at 12 months. Vocational and domestic functioning showed the greatest improvement. Sexual and social functioning showed modest improvements overall, with significant numbers reporting residual impairment due to their heart disease. These findings add to a growing body of evidence demonstrating generally favourable psychological and social outcome following CAGS.