Association of type 2 diabetes with prolonged hospital stay and increased rate of readmission in patients with lower limb cellulitis.

BACKGROUND/AIMS: Lower limb (LL) cellulitis-related hospitalisations are prevalent in type 2 diabetes subjects. We assess its costs and factors associated with length of stay and readmissions. METHODS: A retrospective case-control study at an urban hospital servicing a multi-ethnic population in New Zealand, where 7% of the adult population is estimated to have diabetes. Admissions with LL cellulitis in 2008-2013 were identified using coding records. Subsequent hospitalisations after 1 month with the same diagnosis were classified as readmissions. Glycaemic control was assessed by HbA1c measured within 6 months of the index admission. RESULTS: There were 4600 admissions with LL cellulitis in 3636 patients, including 719 patients (20%) with type 2 diabetes. Hospital stay was longer for type 2 diabetes patients (median 5.3 vs 3.0 days, P < 0.001), independent of age, ethnicity and HbA1c. Accompanying LL ulceration was more frequent in type 2 diabetes patients (50% vs 17%, P < 0.001); however, admissions remained longer for type 2 diabetes patients without ulceration (median 3.4 vs 2.8 days, P < 0.001). Readmission rates were also higher in type 2 diabetes patients compared to non-diabetes patients (HR 1.7, P < 0.001), even in the absence of ulceration (HR 2.2, P < 0.001). Age, HbA1c and ethnicity did not distinguish those prone to readmissions in the type 2 diabetes cohort. Type 2 diabetes patients accounted for a fifth of all admissions and one third of the estimated costs. CONCLUSIONS: A high proportion of patients with type 2 diabetes was admitted with LL cellulitis. They had significantly longer admissions and higher readmission rates. Age, HbA1c and ethnicity did not predict length of stay or recurrence.

Ethnicity and risk of lower limb amputation in people with Type 2 diabetes: a prospective cohort study.

AIM: Lower limb amputation is a serious complication of diabetic foot disease and there are unexplained ethnic variations in incidence. This study investigates the risk of amputation among different ethnic groups after adjusting for demographic, socio-economic status and clinical variables. METHODS: We used primary care data from a large national multi-ethnic cohort of patients with Type 2 diabetes in New Zealand and linked hospital records. The primary outcome was time from initial data collection to first lower limb amputation. Demographic variables included age of onset and duration since diabetes diagnosis, gender, ethnicity and socio-economic status. Clinical variables included smoking status, height and weight, blood pressure, HbA1c , total cholesterol/HDL ratio and albuminuria. Cox proportional hazards models were used. RESULTS: There were 892 lower limb amputations recorded among 62 002 patients (2.11 amputations per 1000 person-years), followed for a median of 7.14 years (422 357 person-years). After adjusting for demographic and socio-economic variables and compared with Europeans, Maori had the highest risk [hazard ratio (HR) 1.84 (95%CI:1.54-2.19)], whereas East Asians [HR 0.18, (0.08-0.44)] and South Asians [HR 0.39 (0.22-0.67)] had the lowest risk. Adjusting for available clinical variables reduced the differences but they remained substantial [HR 1.61 (1.35-1.93), 0.23 (0.10-0.56) and 0.48 (0.27-0.83), respectively]. CONCLUSIONS: Ethnic groups had significantly different risk of lower limb amputation, even after adjusting for demographic and some major clinical risk factors. Barriers to care should be addressed and intensive prevention strategies known to reduce the incidence of lower limb amputations could be prioritized to those at greatest risk.

New onset diabetes after transplantation: Not another acronym!

New onset diabetes after transplantation is the onset of diabetes in previously non-diabetic individuals extending beyond the first month post-transplantation.

The Diabetes Excess Weight Loss (DEWL) Trial: a randomised controlled trial of high-protein versus high-carbohydrate diets over 2 years in type 2 diabetes.

AIMS/HYPOTHESIS: To compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss, using group-based interventions, among overweight people with type 2 diabetes. Study design Multicentre parallel (1:1) design, blinded randomised controlled trial. METHODS: Individuals with type 2 diabetes aged 30­75 years and a BMI >27 kg/m2 were randomised, by an independent statistician using sequentially numbered sealed envelopes, to be prescribed either a low-fat high-protein (30% of energy as protein, 40% as carbohydrate, 30% as fat) or a low-fat high carbohydrate(15% of energy as protein, 55%as carbohydrate,30% as fat) diet. Participants attended 18 group sessions over 12 months. Primary outcomes were change in weight and waist circumference assessed at baseline, 6 and 12 months.Secondary outcomes were body fatness, glycaemic control,lipid profile, blood pressure and renal function. A further assessment was undertaken 12 months after the intervention.Research assessors remained blinded to group allocation throughout. Intention-to-treat analysis was performed. RESULTS: A total of 419 participants were enrolled (mean±SDage 58±9.5 years,BMI 36.6±6.5 kg/m2 and HbA1c 8.1±1.2%(65 mmol/mol)). The study was completed by 70%(294/419).No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up. Both groups had lost weight (2­3 kg, p<0.001) and reduced their waist circumference (2­3 cm, p<0.001) by 12 months and largely maintained this weight loss for the following 12 months. By 6 months, the difference in self-reported dietary protein between groups was small (1.1%total energy; p<0.001). No significant differences between groups were found in secondary outcomes: body fatness, HbA1c, lipids, blood pressure and renal function.There were no important adverse effects. CONCLUSIONS/INTERPRETATION: In a 'real-world' setting, prescription of an energy-reduced low-fat diet, with either increased protein or carbohydrate, results in similar modest losses in weight and waist circumference over 2 years

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

AIMS/HYPOTHESIS: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. METHODS: Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. RESULTS: During fenofibrate run-in, plasma creatinine increased by 10.0 µmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 µmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). CONCLUSIONS/INTERPRETATION: Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. TRIAL REGISTRATION: ISRCTN64783481.

Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: We investigated effects of renal function and albuminuria on cardiovascular outcomes in 9,795 low-risk patients with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. METHODS: Baseline and year 2 renal status were examined in relation to clinical and biochemical characteristics. Outcomes included total cardiovascular disease (CVD), cardiac and non-cardiac death over 5 years. RESULTS: Lower estimated GFR (eGFR) vs eGFR ≥90 ml min⁻¹ 1.73 m⁻² was a risk factor for total CVD events: (HR [95% CI] 1.14 [1.01-1.29] for eGFR 60-89 ml min⁻¹ 1.73 m⁻²; 1.59 [1.28-1.98] for eGFR 30-59 ml min⁻¹ 1.73 m⁻²; p < 0.001; adjusted for other characteristics). Albuminuria increased CVD risk, with microalbuminuria and macroalbuminuria increasing total CVD (HR 1.25 [1.01-1.54] and 1.19 [0.76-1.85], respectively; p = 0.001 for trend) when eGFR ≥90 ml min⁻¹ 1.73 m⁻². CVD risk was further modified by renal status changes over the first 2 years. In multivariable analysis, 77% of the effect of eGFR and 81% of the effect of albumin:creatinine ratio were accounted for by other variables, principally low HDL-cholesterol and elevated blood pressure. CONCLUSIONS/INTERPRETATION: Reduced eGFR and albuminuria are independent risk factors for cardiovascular events and mortality rates in a low-risk population of mainly European ancestry. While their independent contributions to CVD risk appear small when other risk factors are considered, they remain excellent surrogate markers in clinical practice because they capture risk related to a number of other characteristics. Therefore, both should be considered when assessing prognosis and treatment strategies in patients with diabetes, and both should be included in risk models.

Glycated haemoglobin and cardiovascular outcomes in people with Type 2 diabetes: a large prospective cohort study.

AIMS: To investigate the association between long-term glycaemic control, measured by glycated haemoglobin (HbA(1c)), and time to first cardiovascular disease (CVD) event for people with Type 2 diabetes in New Zealand. METHODS: A prospective cohort study including people with Type 2 diabetes but no previous CVD. The primary outcome measure was time to first recorded fatal or non-fatal CVD event (ischaemic heart disease, cerebrovascular accident, transient ischaemic attack or peripheral vascular disease) as identified from linked primary care, hospital and mortality records between January 2000 and December 2005. A Cox proportional hazards model was used to examine the association between HbA(1c) and time to CVD event, adjusting for age at diagnosis, duration of diabetes, gender, ethnicity, socio-economic status, smoking, blood pressure (BP), serum total cholesterol : high-density lipoprotein ratio, body mass index (BMI) and urine albumin : creatinine ratio. RESULTS: Participants included 48 444 people with Type 2 diabetes. Fifty-one per cent (n = 24 721) were women, median age 60 years. Median duration of diabetes was 3 years, median BMI 31 kg/m(2), median HbA(1c) 7.1% and mean BP was 138/81 mmHg. During the study period (median follow-up 2.4 years), there were 5667 first CVD events (11.7% of cohort). Each 1% increase in HbA(1c) was associated with an increase in hazard ratio (HR) for CVD of 1.08 (95% confidence interval 1.06-1.10, P < 0.001), myocardial infarction [HR 1.08 (1.04, 1.11)] and stroke [HR 1.09 (1.04, 1.13)]. CONCLUSION: This study has confirmed in a large prospective cohort that increased HbA(1c) is an independent risk factor for cardiovascular disease after controlling for traditional risk factors.

An association between ethnicity and cardiovascular outcomes for people with Type 2 diabetes in New Zealand.

AIMS: To investigate the association between ethnicity and risk of first cardiovascular (CV) event for people with Type 2 diabetes in New Zealand. METHODS: A prospective cohort study using routinely collected data from a national primary health care diabetes annual review programme linked to national hospital admission and mortality data. Ethnicity was recorded as European, Maori, Pacific, Indo-Asian, East-Asian or Other. A Cox proportional hazards model was used to investigate factors associated with first CV event. Data was collected from 48,444 patients with Type 2 diabetes, with first data collected between 1 January 2000 and 20 December 2005, no previous cardiovascular event at entry and with complete measurements. Risk factors included ethnicity, gender, socio-economic status, body mass index, smoking, age at diagnosis, duration of diabetes, systolic blood pressure, serum lipids, glycated haemoglobin and urine albumin : creatinine ratio. The main outcome measures were time to first fatal or non-fatal CV event. RESULTS: Median follow-up was 2.4 years. Using combined European and Other ethnicities as a reference, hazard ratios for first CV event were 1.30 for Maori (95% confidence interval 1.19-1.41), 1.04 for Pacific (0.95-1.13), 1.06 for Indo-Asian (0.91-1.24) and 0.73 for East-Asian (0.62-0.85) after controlling for all other risk factors. CONCLUSIONS: Ethnicity was independently associated with time to first CV event in people with Type 2 diabetes. Maori were at 30% higher risk of first CV event and East-Asian 27% lower risk compared with European/Other, with no significant difference in risk for Pacific and Indo-Asian peoples.

Fatty acid composition of milk of refugee Karen and urban Korean mothers. Is the level of DHA in breast milk of Western women compromised by high intake of saturated fat and linoleic acid?

BACKGROUND: Lower proportions of docosahexaenoic acid (DHA) and total n-3 metabolites have been reported in breast milk of European, Australian and North American women compared with milk of mothers from non-Western countries. This difference is not always explained by intakes of marine products. OBJECTIVE: We investigated the possibility that the relative composition of DHA and total n-3 metabolites in breast milk of non-Western mothers with low fat intakes is higher than the levels commonly reported in their Western counterparts. SUBJECTS: Mature milk of refugee Karen women from two different camps in Thailand (n=26 and n=53), and transition milk from urban Korean mothers (n=12) in Seoul was collected. In common with their respective community, the mothers have low fat intake, which is predominately of plant origin. RESULTS: The percentage levels of DHA and n-3 metabolites in the milk of the Karen mothers were 0.52 +/- 0.14 and 0.85 +/- 0.24 (camp 1) and 0.54 +/- 0.22 and 0.92 +/- 0.42 (camp 2). In the Korean milk, DHA was 0.96 +/- 0.21 and total n-3 metabolites 1.51 +/- 0.3. CONCLUSION: We postulate that the levels of DHA and total n-3 metabolites may be compromised in breast milk of mothers on the Western high fat diet. This calls into question the use of DHA composition of such milk as a reference for the formulation of milk designed, for infant feed or, to test the function of DHA in neuro-visual development.

[Emergent pathogens, international surveillance and international health regulations (2005)]. / Les pathogènes émergents, la veille internationale et le Règlement sanitaire international (2005).

In order to address the vitality of the microbial world, to detect emerging infectious diseases, to determine their potential threat to public health, and to establish effective interventions, the World Health Organization (WHO) has developed and coordinates the Global Outbreak Alert and Response Network (GOARN) which connects several surveillance networks. Some of these networks are specific to epidemic-prone diseases, such as influenza, dengue, yellow fever or meningitis. Others were especially designed to track unusual events--such as the emergence of SARS--that are naturally-occurring, accidental, or deliberately created (biological weapons, bio-terrorism). Lastly, a special effort is being made at the international level to modernize the International Health Regulations, now obsolete, and to support all the countries in the reinforcement of their outbreak alert and response capacity.

Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease, partly owing to dyslipidaemia, which can be amenable to fibrate therapy. We designed the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study to assess the effect of fenofibrate on cardiovascular disease events in these patients. METHODS: We did a multinational, randomised controlled trial with 9795 participants aged 50-75 years, with type 2 diabetes mellitus, and not taking statin therapy at study entry. After a placebo and a fenofibrate run-in phase, we randomly assigned patients (2131 with previous cardiovascular disease and 7664 without) with a total-cholesterol concentration of 3.0-6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0-5.0 mmol/L to micronised fenofibrate 200 mg daily (n=4895) or matching placebo (n=4900). Our primary outcome was coronary events (coronary heart disease death or non-fatal myocardial infarction); the outcome for prespecified subgroup analyses was total cardiovascular events (the composite of cardiovascular death, myocardial infarction, stroke, and coronary and carotid revascularisation). Analysis was by intention to treat. The study was prospectively registered (number ISRCTN 64783481). FINDINGS: Vital status was confirmed on all but 22 patients. Averaged over the 5 years' study duration, similar proportions in each group discontinued study medication (10% placebo vs 11% fenofibrate) and more patients allocated placebo (17%) than fenofibrate (8%; p<0.0001) commenced other lipid treatments, predominantly statins. 5.9% (n=288) of patients on placebo and 5.2% (n=256) of those on fenofibrate had a coronary event (relative reduction of 11%; hazard ratio [HR] 0.89, 95% CI 0.75-1.05; p=0.16). This finding corresponds to a significant 24% reduction in non-fatal myocardial infarction (0.76, 0.62-0.94; p=0.010) and a non-significant increase in coronary heart disease mortality (1.19, 0.90-1.57; p=0.22). Total cardiovascular disease events were significantly reduced from 13.9% to 12.5% (0.89, 0.80-0.99; p=0.035). This finding included a 21% reduction in coronary revascularisation (0.79, 0.68-0.93; p=0.003). Total mortality was 6.6% in the placebo group and 7.3% in the fenofibrate group (p=0.18). Fenofibrate was associated with less albuminuria progression (p=0.002), and less retinopathy needing laser treatment (5.2%vs 3.6%, p=0.0003). There was a slight increase in pancreatitis (0.5%vs 0.8%, p=0.031) and pulmonary embolism (0.7%vs 1.1%, p=0.022), but no other significant adverse effects. INTERPRETATION: Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events. It did reduce total cardiovascular events, mainly due to fewer non-fatal myocardial infarctions and revascularisations. The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit.

A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget's disease of bone.

Second and third generation bisphosphonates are the treatment of choice for Paget's disease of bone. These drugs are more effective than calcitonin and etidronate, but there have been no head to head, randomized controlled trials comparing potent bisphosphonates. We conducted a 2-year, randomized, open-label trial comparing oral alendronate and intravenous pamidronate in 72 subjects with Paget's disease. Randomization was stratified according to baseline plasma total alkaline phosphatase (ALP) and previous bisphosphonate treatment (yes or no). All previously treated patients had received pamidronate but not alendronate. Assigned treatments were pamidronate (60 mg) every 3 months as a single infusion or alendronate (40 mg) daily in 3-month blocks, continued until biochemical remission (defined as both ALP and urine deoxypyridinoline (DPD)/creatinine ratio in the reference range) or a clear plateau effect was observed. At 1 year, nonresponders to pamidronate were crossed over to alendronate treatment. At 1 year, 31/36 (86%) subjects randomized to alendronate achieved biochemical remission compared with 21/36 (56%) for pamidronate (P = 0.017). There was a significantly greater reduction in ALP (P < 0.001) and DPD/creatinine ratio (P < 0.001) for alendronate compared with pamidronate treatment. In previously untreated patients, alendronate resulted in remission in 20/22 (91%) subjects compared with 19/22 (86%) of pamidronate-treated subjects, which was not significantly different; however, alendronate resulted in a significantly greater reduction in ALP (P = 0.014) and DPD/creatinine ratio (P < 0.001). In previously treated patients, alendronate resulted in remission in 11/14 (79%) subjects compared with 2/14 (14%) for pamidronate (P < 0.001), with a significantly (P < 0.001) greater reduction in both ALP and DPD/creatinine ratio. Of subjects crossed over from pamidronate to alendronate, 10/14 (71%) achieved remission, including 9/11 (82%) previously treated patients. We conclude that, in patients with previously untreated Paget's disease of bone, alendronate and pamidronate have similar efficacy in achieving biochemical remission. In patients previously treated with pamidronate, alendronate is more effective.

The influence of piglet birth weight on physical and behavioural development in early life.

The objective of this study was to determine whether body weight at birth influences the physical and behavioural development of the neonatal pig. Sixteen sows and their litters were randomly allocated into four treatment groups. From the normal distribution curve of their birth weight, piglets were sub-divided into three groups: (1) low (<10th percentile) (2) normal (10-90th percentile) and (3) high (>90th percentile). To assess behavioural development, each litter was exposed to a ball placed in the creep area for a period of 1,800 s, and evaluated once over a 3-day period starting on either 5, 7, 14 or 21 days of postnatal life. Their response to, and interaction with, an object was used to calculate a numerical index of piglet behavioural development. Teat order was calculated following observations during consecutive suckling on days 11, 13 and 15 of life, and dominance hierarchy was assessed on day 12, 14 and 16. Individual body weight was recorded on days 0, 5, 7, 14 and 21 of postnatal life. Statistical differences between groups were analysed using general linear model, analysis of variance. Regression analyses were used to determine relationships between physical and behavioural development with teat order and dominance. There was a significant (p < 0.001) relationship between birth weight, growth performance and behavioural development. Behavioural developmental index (BDI) significantly improved (p < 0.001) with age and was also influenced by the day on which the ball was introduced (p < 0.01). Body weight on day 1 of the test was significantly (p < 0.001) correlated to BDI and age at test. Piglets demonstrating compensatory growth were more dominant and exhibited an improved behavioural developmental score than their slower growing littermates. In conclusion, compromised growth in utero can have a detrimental effect on the physical and behavioural development of the neonate. Animals with an enhanced developmental index in conjunction with a higher dominance value exhibited a improved neonatal growth performance.

A randomized trial comparing hormone replacement therapy (HRT) and HRT plus calcitriol in the treatment of postmenopausal osteoporosis with vertebral fractures: benefit of the combination on total body and hip density.

We report a prospective, randomized, multicenter, open-label 2-year trial of 81 postmenopausal women aged 53-79 years with at least one minimal-trauma vertebral fracture (VF) and low (T-score below - 2) lumbar bone mineral density (BMD). Group HRT received piperazine estrone sulfate (PES) 0.625 - 1.25 mg/d +/- medroxyprogesterone acetate (MPA) 2.5 - 5 mg/d; group HRT/D received HRT plus calcitriol 0.25 microg bd. All with a baseline dietary calcium (Ca) of < 1 g/ d received Ca carbonate 0.6 g nocte. Final data were on 66 - 70 patients. On HRT/D, significant (P < 0.001) BMD increases from baseline by DXA were at total body - head, trochanter, Ward's, total hip, intertrochanter and femoral shaft (% group mean delta 4.2, 6.1, 9.3, 3.7, 3.3 and 3.3%, respectively). On HRT, at these 6 sites, significant deltaS were restricted to the trochanter and Wards. Significant advantages of HRT/D over HRT were in BMD of total body (- head), total hip and trochanter (all P = 0.01). The differences in mean delta at these sites were 1.3, 2.6 and 3.9%. At the following, both groups improved significantly -lumbar spine (AP and lateral), forearm shaft and ultradistal tibia/fibula. The weightbearing, site - specific benefits of the combination associated with significant suppression of parathyroid hormone-suggest a beneficial effect on cortical bone. Suppression of bone turnover was significantly greater on HRT/D (serum osteocalcin P = 0.024 and urinary hydroxyproline/creatinine ratio P = 0.035). There was no significant difference in the number of patients who developed fresh VFs during the trial (HRT 8/36, 22%; HRT/D 4/34, 12% - intention to treat); likewise in the number who developed incident nonvertebral fractures. This is the first study comparing the 2 treatments in a fracture population. The results indicate a significant benefit of calcitriol combined with HRT on total body BMD and on BMD at the hip, the major site of osteoporotic fracture.

An unusual cause of hyperinsulinaemic hypoglycaemia syndrome.

Endogenous hyperinsulinism as a cause for hypoglycaemia can be attributed to a number of different causes including insulinoma, sulphonylurea drugs and the newly described disorder non-insulinoma pancreatogenous hypoglycaemia (NIPH). The calcium stimulation test is increasingly used as a method for not only localizing insulinoma but also for distinguishing the above entities. We describe a case in which felonious sulphonylurea administration was used to mimic either an insulinoma or NIPH. Importantly, this case demonstrates that, contrary to previous reports, the insulin response to calcium stimulation in such cases may be uniformly positive and should alert the physician to possible surreptitious sulphonylurea ingestion.

A randomized trial of sodium fluoride (60 mg) +/- estrogen in postmenopausal osteoporotic vertebral fractures: increased vertebral fractures and peripheral bone loss with sodium fluoride; concurrent estrogen prevents peripheral loss, but not vertebral fractures.

Postmenopausal Caucasian women aged less than 80 years (n = 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (-E study), age 70.8 +/- 0.8 years (mean +/- SEM) were all treated with calcium (Ca) 1.0-1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on, 3 months off, initial dose 60 mg/day; group F CaD, n = 34) or no NaF (group CaD, n = 31). In the second study 34 patients, age 65.5 +/- 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n = 17; E CaD, n = 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to +/- NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p = 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft -7.3% (p = 0.005); femoral shaft -7.1% (p = 0.004); distal forearm -4.0% (p=0.004); total hip -4.1% (p = 0.003); and femoral neck -3.5% (p = 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p < 0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox's proportional hazards model, in the -E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p = 0.008, 95% CI 2.3-255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: -23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups; there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts, if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor.