Impact of type 2 diabetes on hospitalization and mortality in people with malignancy.

AIM: To compare the characteristics of and outcomes for people with malignancies with and without a co-diagnosis of diabetes. METHODS: Emergency department and hospital discharge data from a single centre for the period between 1 January 2015 and 31 December 2017 were used to identify people with a diagnosis of a malignancy and diabetes. Multivariate Cox regression models were used to estimate the effect of diabetes on all-cause mortality. A truncated negative binomial regression model was used to assess the impact of diabetes on length of hospital inpatient stay. Prentice-Williams-Peterson total time models were used to assess the effect of diabetes on number of emergency department re-presentations and inpatient re-admissions. RESULTS: Of 7004 people identified with malignancies, 1195 (17.1%) were also diagnosed with diabetes. A diagnosis of diabetes was associated with a greater number of inpatient re-admissions [adjusted hazard ratio 1.13 (95% CI 1.03, 1.24)], a greater number of emergency department re-presentations [adjusted hazard ratio 1.13 (95% CI 1.05, 1.22)] and longer length of stay [adjusted incidence rate ratio 1.14 (95% CI 1.04, 1.25)]. A co-diagnosis of diabetes was also associated with a 48% increased risk of all-cause mortality [adjusted hazard ratio 1.48 (95% CI 1.22-1.76)]. CONCLUSIONS: People with malignancies and diabetes had significantly more emergency department presentations, more inpatient admissions, longer length of hospital stay and higher rates of all-cause mortality compared to people with a malignancy without diabetes.

Marteilia refringens and Marteilia pararefringens sp. nov. are distinct parasites of bivalves and have different European distributions.

Marteilia refringens causes marteiliosis in oysters, mussels and other bivalve molluscs. This parasite previously comprised two species, M. refringens and Marteilia maurini, which were synonymized in 2007 and subsequently referred to as M. refringens 'O-type' and 'M-type'. O-type has caused mass mortalities of the flat oyster Ostrea edulis. We used high throughput sequencing and histology to intensively screen flat oysters and mussels (Mytilus edulis) from the UK, Sweden and Norway for infection by both types and to generate multi-gene datasets to clarify their genetic distinctiveness. Mussels from the UK, Norway and Sweden were more frequently polymerase chain reaction (PCR)-positive for M-type (75/849) than oysters (11/542). We did not detect O-type in any northern European samples, and no histology-confirmed Marteilia-infected oysters were found in the UK, Norway and Sweden, even where co-habiting mussels were infected by the M-type. The two genetic lineages within 'M. refringens' are robustly distinguishable at species level. We therefore formally define them as separate species: M. refringens (previously O-type) and Marteilia pararefringens sp. nov. (M-type). We designed and tested new Marteilia-specific PCR primers amplifying from the 3' end of the 18S rRNA gene through to the 5.8S gene, which specifically amplified the target region from both tissue and environmental samples.

Asymmetric changes in circulating insulin levels after an increase compared with a reduction in insulin pump basal rate in people with Type 1 diabetes.

AIMS: To investigate circulating insulin profiles after a clinically relevant insulin pump basal rate increase vs a reduction, and the associated glucose responses. METHODS: A cohort of 12 adults with Type 1 diabetes undertook this two-stage university hospital study using Accu-Chek pumps (Roche Diagnostics, Mannheim, Germany) and insulin aspart. An insulin basal rate change of 0.2 unit/h (increase in first stage, reduction in second stage) was implemented at ~09:30 h, after a single overnight basal rate (without bolus insulin), while fasting participants rested. Frequent venous samples for the assessment of plasma free insulin, glucose and cortisol were collected from 60 min before until 300 min after rate change. The primary outcome was time to steady-state insulin. RESULTS: The 0.2-unit/h rate change represented a mean ± sd alteration of 23 ± 6%. After the rate increase, the median (interquartile range) times to 80% and 90% steady-state insulin were 170 (45) min and 197 (87) min, respectively. By contrast, after rate reduction, 80% steady-state insulin was not achieved. After the rate increase, mean ± se insulin levels increased by 4.3 ± 3.1%, 12.0 ± 2.9% and 25.6 ± 2.6% at 60, 120 and 300 min, respectively (with no significant difference until 180 min). After the rate reduction, insulin decreased by 8.3 ± 3.0% at 300 min (with no significant difference until 300 min). After rate reduction, glucose levels paradoxically declined by 17.4 ± 3.7% after 300 min; cortisol levels also fell during observation (P = 0.0003). CONCLUSIONS: The time to circulating insulin change after a 0.2-unit/h basal rate change was substantial, and was greater after a reduction than after an increase. Counter-regulatory hormone circadian variation may affect glycaemia when implementing minor changes at low basal rates. Both direction of basal rate change, and time of day, warrant consideration when anticipating the clinical effects of basal rate changes.

Multicenter Australian trial of islet transplantation: improving accessibility and outcomes.

Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim of this single-arm, multicenter study was to evaluate an immunosuppressive protocol of initial antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching to sirolimus and MMF. Islets were cultured for 24 h prior to transplantation. The primary end-point was an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥ 12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 6 (35%) remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2 nmol/L had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. The combination of islet culture, ATG, tacrolimus and MMF is a viable alternative for islet transplantation.

Metabolic modeling using statistical and spreadsheet software: Application to the glucose minimal model.

Kinetic non-linear metabolic models are used extensively in medical research and increasingly for clinical diagnostic purposes. An example of such a model is the Glucose Minimal Model by Bergman and colleagues [1]. This model is similar to pharmacokinetic/pharmacodynamic models in that like pharmacokinetic/pharmacodynamic models, it is based on a small number of fairly simple ordinary differential equations and it aims to determine how the changing concentration of one blood constituent influences the concentration of another constituent. Although such models may appear prima facie, to be relatively simple, they have gained a reputation of being difficult to fit to data, especially in a consistent and repeatable fashion. Consequently, researchers and clinicians have generally relied on dedicated software packages to do this type of modeling. This article describes the use of statistical and spreadsheet software for fitting the Glucose Minimal Model to data from an insulin modified intravenous glucose tolerance test (IM-IVGTT). A novel aspect of the modeling is that the differential equations that are normally used to describe insulin action and the disposition of plasma glucose are first solved and expressed in their explicit forms so as to facilitate the estimation of Glucose Minimal Model parameters using the nonlinear (nl) optimization procedure within statistical and spreadsheet software. The most important clinical parameter obtained from the Glucose Minimal Model is insulin sensitivity (SI). Using IM-IVGTT data from 42 horses in one experiment and 48 horses in a second experiment, we demonstrate that estimates of SI derived from the Glucose Minimal Model fitted to data using STATA and Excel, are highly concordant with SI estimates obtained using the industry standard software, MinMod Millennium. This work demonstrates that there is potential for statistical and spreadsheet software to be applied to a wide range of kinetic non-linear modeling problems.

Application of the intravenous glucose tolerance test and the minimal model to patients with insulinoma: insulin sensitivity (Si) and glucose effectiveness (Sg) before and after surgical excision.

BACKGROUND: The unmodified frequently sampled intravenous glucose tolerance test (FSIGT) has not previously been used to assess insulin/glucose kinetics in patients with insulinoma. OBJECTIVE: To measure insulin sensitivity (Si) and glucose effectiveness (Sg) by means of the FSIGT in patients with insulinoma, before and after surgical removal of the tumour. SUBJECTS AND METHODS: FSIGTs were performed in five patients, before and approximately 3 months post-surgery, and in 11 controls. Si and Sg were estimated using Minimal Model computer analysis of dynamic glucose and insulin data. RESULTS: Si was lower in insulinoma patients before, compared with after surgery (3.37 +/- 0.62 vs. 6.24 +/- 1.09 SE [x10(-4)] min(-1)microU(-1) ml, P < 0.05). Sg was similar in patients pre- and post-surgery (3.0 +/- 0.67 vs. 2.4 +/- 0.6 [x10(-2)] min(-1), NS). CONCLUSIONS: Insulin sensitivity improves after excision of an insulinoma. Glucose effectiveness is not influenced by chronic hyperinsulinaemia and hypoglycaemia.

Animals as an energy source in third world agriculture.

Agricultural development programs have so far been largely unable to meet the food needs of the world's poorest. Increased food production can be achieved only from more intensive agriculture, which requires greater energy inputs per farm worker. Problems of technological infrastructure and escalating oil prices appear to preclude the spread of mechanization to Third World agriculture at this time. Efficient utilization of grazing animals in specific integrated farming systems could not only increase energy inputs through draft and transportation but also increase the yield of high-grade products and by-products from the renewable energy of biomass. An approach to development based on animal agriculture systems is suggested that might initiate a self-sustaining, more productive agriculture requiring only small inputs of fossil-fuel energy.

Beef production options and requirements for fossil fuel.

A large percentage of the feed resources used in beef production cannot be used by man or most other animals. These noncompetitive feeds could be used in different ways to increase beef production, but fossil fuel consumption by the beef industry would not be greatly reduced.

Automated vehicles and older drivers in Canada.

INTRODUCTION: As seniors represent a growing proportion of the driving population, research about how automated vehicles can help improve older driver safety and mobility is highly relevant. This paper examines the knowledge, attitudes and perceptions of older drivers towards limited self-driving vehicles (LSDVs), and how these variables can influence the likelihood that they will rely on this technology. METHOD: The study includes data from a previous national survey (N = 2662) about automated vehicle technology, with new analyses to test hypothetical models using structural equation modeling. Results of the first model were confirmed and built upon with a second more complex model that incorporated the construct "behavioral adaptation." Focus groups with older drivers were also conducted (N = 38) to help reveal nuances in older drivers' knowledge, attitudes, perceptions, and behaviors regarding this technology. RESULTS: Survey results demonstrated that feelings of safety and knowledge about LSDVs are positively related to perceived ease of use and adoption of the technology. The positive association between safety and perceived ease of use was further highlighted when comparing responses of older drivers to those of younger age groups, as older drivers were significantly less likely to agree that LSDVs were easy to use and were significantly less agreeable about feeling safe using them. Focus groups results confirmed that safety and knowledge of LSDVs are essential to the likelihood of adopting this technology, and revealed a high receptivity among older drivers to educational strategies and tools to increase their knowledge of LSDVs. Implications for educational strategies and safety benefits for older drivers are discussed. Practical applications: Results provide insight into strategies to encourage the early adoption of automated vehicles by older drivers and facilitate a safer transition towards automated vehicles that is lead by a cohort of safety-conscious drivers.

Canadian wildlife-vehicle collisions: An examination of knowledge and behavior for collision prevention.

OBJECTIVES: This study examines drivers' responses to wildlife on Canadian roads. The objective of this paper is to demonstrate that knowledge of what to do when encountering wildlife on the road does not always translate into the appropriate behavior to avoid a collision. METHODS: Data from the Traffic Injury Research Foundation's (TIRF) 2016 Road Safety Monitor (RSM) and data from TIRF's National Fatality Database from 2000 to 2014 were analyzed to test hypotheses based on the theory of planned behavior. Logistic regression and piecewise linear regression were used. RESULTS: Analyses of the data showed that the prevalence of fatal WVCs has remained relatively consistent, and that the majority of persons killed in WVCs died in crashes that involved large mammals. The majority of fatalities occurred in the summer (182 or 38.4%) and fall (163 or 34.4%). The RSM data revealed that 60.9% [50.5, 70.4] of respondents who previously hit an animal indicated that drivers should slow down and steer straight when confronted with wildlife, while 47.3% [37.1, 57.6] of respondents indicated this was the action they took when they hit wildlife. Comparatively, 59.5% [56.6, 62.4] of respondent who have not hit an animal indicated this was an appropriate response. Additionally, 33.2% [24, 44] of respondents who previously hit an animal indicated that drivers should swerve to avoid a collision with wildlife, while 37.5% [28.2, 47.8] of respondents indicated this was the action they took when they hit wildlife. CONCLUSIONS: Many drivers are unaware of what the safest method of WVC prevention is. Further, while a subgroup of drivers may have the knowledge and intention to slow down and steer straight even if the animal is directly in the path, i.e., the safest possible behavior, they are not necessarily adopting this behavior. Practical applications: Recommendations are formulated to address this discrepancy, as well as practical applications.

Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. A novel compensatory mechanism.

20 normoglycemic first degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients were compared with 20 matched subjects without any family history of diabetes using the intravenous glucose tolerance test with minimal model analysis of glucose disappearance and insulin kinetics. Intravenous glucose tolerance index (Kg) was similar in both groups (1.60 +/- 0.14 vs 1.59 +/- 0.18, x 10(-2) min-1, NS). However, insulin sensitivity (Si) was reduced (3.49 +/- 0.43 vs 4.80 +/- 0.61, x 10(-4) min-1 per mU/liter, P = 0.05), whereas glucose effectiveness (Sg) was increased (1.93 +/- 0.14 vs 1.52 +/- 0.16, x 10(-2) min-1, P < 0.05) in the relatives. Despite insulin resistance neither fasting plasma insulin concentration (7.63 +/- 0.48 vs 6.88 +/- 0.45, mU/liter, NS) nor first phase insulin responsiveness (Phi1) (3.56 +/- 0.53 vs 4.13 +/- 0.62, mU/liter min-1 per mg/dl, NS) were increased in the relatives. Phi1 was reduced for the degree of insulin resistance in the relatives so that the Phi1 x Si index was lower in the relatives (11.5 +/- 2.2 vs 16.7 +/- 2.0, x 10(-4) min-2 per mg/dl, P < 0.05). Importantly, glucose effectiveness correlated with Kg and with basal glucose oxidation but not with total glucose transporter 4 (GLUT4) content in a basal muscle biopsy. In conclusion we confirm the presence of insulin resistance in first degree relatives of NIDDM patients. However, insulin secretion was altered and reduced for the degree of insulin resistance in the relatives, whereas glucose effectiveness was increased. We hypothesize that increased glucose effectiveness maintains glucose tolerance within normal limits in these "normoinsulinemic" relatives of NIDDM patients.

An evaluation of Nova Scotia's alcohol ignition interlock program.

Alcohol ignition interlock programs for offenders aim to reduce recidivism among convicted drink drivers. This study presents an evaluation of Nova Scotia's interlock program implemented in 2008 in order to assess its effectiveness to reduce impaired driving and to help identify areas for improvement. Data used include conviction and crash records of individual participants; provincial monthly counts of alcohol-related charges, convictions and fatal and serious crashes; and interlock logged events. Methods used include descriptive statistics, survival analysis, time series and logistic regression analysis. With respect to specific deterrence (i.e., preventing recidivism) there was a 90% reduction in recidivism among voluntary participants since participation in the interlock program and a 79% reduction after these participants exited from the program. With respect to general deterrence (i.e., referring to a preventative effect on the entire population of drivers in Nova Scotia) there were temporary decreases in the numbers of alcohol-related charges (13.32%) and convictions (9.93%) and a small significant decrease in the number of fatal and serious injury alcohol-related crashes, following the implementation of the program. The evidence suggests the interlock program was better at preventing harm due to alcohol-impaired driving than the alternative of not using the interlock program. Recommendations were formulated supporting the continuation of the interlock program in Nova Scotia.

Prevalence and trends of drugged driving in Canada.

OBJECTIVES: This study evaluates prevalence and trends in drugged driving in Canada based on multiple indicators collected from the Road Safety Monitor (RSM) and Canada's National Fatality Database maintained by the Traffic Injury Research Foundation (TIRF). The objective of this paper is to identify the state of drug-positive driving in Canada, as well as to make comparisons with data from previous years to determine whether changes have occurred. METHODS: Available data from the RSM on self-reported drugged driving behaviours were collected and analyzed using multivariate techniques in various years spanning from 2002 to 2015. Data from TIRF's National Fatality Database from 2000 to 2012 were also analyzed to evaluate trends and prevalence of drugs in fatally injured drivers across Canada. Additionally, differences among drugged drivers with respect to gender and age were studied. RESULTS: Analyses of the RSM data and of the National Fatality Database showed that, as a whole, the prevalence of drugged driving has remained relatively stable over the past decade, with some changes noticed in specific years for some drug types. Specifically from the RSM, there was a 62.5% increase from the 1.6% of drivers reporting driving within two hours of using marijuana in 2013 to 2.6% in 2015. The analyses of the fatality data revealed a 16.9% increase in the percentage of fatally injured drivers testing positive for drugs between 2000 and 2012 (from 33.56% to 39.24%). Cocaine-positive fatally injured drivers increased from 3.6% in 2000 to 6.2% in 2012. Similarly, marijuana-positive fatally injured drivers increased from 12.8% in 2000 to 19.7% in 2012. Results showed varying characteristics with respect to gender and age among self-reported and fatally injured drugged drivers. CONCLUSIONS: Drugged driving behaviours remain prevalent among Canadian drivers and drugs continue to be found in over one-third of tested fatally injured drivers. Although self-reported behaviours have neither decreased nor increased overall in the past decade according to RSM data, with the exception of driving within two hours of using marijuana, data from fatally injured drivers reveal that small, but significant increases in some behaviours have occurred.

Structure of the human erythrocyte insulin receptor.

The structure of the insulin receptor in intact human erythrocytes was defined using the techniques of disuccinimidyl suberate (DSS) cross-linking of 125I-insulin and surface [125I]iodination followed by receptor immunoprecipitation. In contrast to a recent report, we found the erythrocyte insulin receptor to be similar in structure to that in classic target tissues for insulin, consisting of at least three species of molecular weight approximately 295,000, 265,000, and 245,000, containing disulfide-linked subunits of molecular weight approximately 130,000 and 95,000. The interconversion of the three oligomeric forms could mediate changes in receptor affinity as postulated in other tissues. The 95,000 subunit was detected by immunoprecipitation only if surface iodination was performed in a Tris/Hepes buffer using lodogen and not if phosphate-buffered saline or lactoperoxidase iodination was used. These findings indicate that the lack of a bioeffect of insulin in erythrocytes is not explained by a gross defect in the structure of their insulin receptors. The apparent identity of the insulin receptor structure in erythrocytes and insulin target tissues provides a firmer basis for the use of erythrocytes in some circumstances to reflect insulin receptor status.

Pulsatile insulin has greater hypoglycemic effect than continuous delivery.

The relative hypoglycemic effects of pulsatile versus steadily infused insulin have been examined in six normal subjects in whom pancreatic insulin output was suppressed by somatostatin-14. Soluble insulin was infused continuously overnight on one occasion and on another occasion the same quantity was given in pulses of 2-min duration with a gap of 11 min. The mean plasma glucose concentrations were lower when pulsed insulin was given [mean for the last hour: 4.66 +/- 0.08 mmol/L (+/- SEM) versus 5.53 +/- 0.06 mmol/L (+/- SEM) for steady infusion], diverging significantly (P less than 0.05 paired t test) 7 h after the start of the study. The specific binding of 125I(A14)mono-iodo-insulin to monocytes was greater after pulsed insulin (2.9% with pulsed versus 2.4% with steadily infused insulin at tracer-only point; P less than 0.02 paired t test). Thus, intravenous insulin has greater hypoglycemic effect when pulsed, possibly mediated by greater insulin receptor binding.

Pulsatile, synchronous basal insulin and glucagon secretion in man.

The basal plasma insulin, glucagon, and glucose concentrations of 28 normal subjects were measured at 1-min intervals for periods of 45-120 min. Regular plasma insulin and/or glucagon cycles were detected in 11 subjects by autocorrelation (mean periods 13.1 and 13.7 min, respectively). Individual plasma insulin cycles were defined in all subjects (mean period 10.7 min, amplitude 1.1 mU/L), and were associated, after averaging, with plasma glucagon (amplitude 5.5 pg/ml) and plasma glucose (0.02 mmol/L) cycles. There was a significant correlation between the amplitudes of simultaneous plasma insulin and glucagon cycles (r = 0.23, P = less than 0.05, N = 124). Cross-correlation demonstrated a delay of 2 min between the changes in plasma insulin and glucagon. No comparable oscillations in plasma pancreatic polypeptide were detected. The synchronous pulsatile secretion of glucagon and insulin may be a mechanism by which insulin's hepatic effects are limited, thereby maintaining hepatic glucose production but allowing sufficient peripheral insulin concentrations to inhibit excessive catabolism. The simultaneous pulses of insulin and glucagon may be stimulated by a pacemaker, with the A-B intercellular connections producing insulin and glucagon synchrony.

Effects of prolonged pulsatile hyperinsulinemia in humans. Enhancement of insulin sensitivity.

Prolonged near-physiological pulsatile insulin infusion has a greater hypoglycemic effect than continuous insulin infusion. We have previously shown that continuous hyperinsulinemia induces insulin insensitivity. This study examines the mechanisms responsible for the greater hypoglycemic effect of pulsatile insulin administration, in particular, whether prolonged pulsatile hyperinsulinemia induces insulin insensitivity. Basally and 1 h after cessation of a 20-h pulsatile infusion of insulin (0.5 mU.kg-1.min-1), eight nondiabetic human subjects were assessed for 1) glucose turnover with [3-3H]glucose, 2) insulin sensitivity by minimal-model analysis of intravenous glucose tolerance tests, and 3) monocyte insulin-receptor binding. The time-averaged plasma insulin levels were 30 +/- 5 mU/L (mean +/- SE) during the infusion, which was similar to the levels achieved in our previous continuous hyperinsulinemia study. However, the average rate of glucose infusion to maintain euglycemia was 55% greater than in the previous study. Hepatic glucose production was -5.2 +/- 1.4 mumol.kg-1.min-1 during the infusion but returned to preinfusion levels 1 h after the infusion was stopped. Insulin sensitivity (Sl) and glucose tolerance (rate of glucose disappearance, Kg) showed changes opposite in direction to our previous continuous hyperinsulinemia study (pre- vs. postinfusion Kg 1.5 +/- 0.1 vs. 1.7 +/- 0.2 min-1 x 10(2), NS; pre- vs. postinfusion Sl 8.4 +/- 2.3 vs. 11.8 +/- 3.7 min-1.mU-1.L x 10(4), P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute and chronic counterregulatory hormone infusions on glucose tolerance and insulin sensitivity in diabetic dogs.

The effects of elevated EPI and CORT levels on KG, SI, and SG were studied in dogs with alloxan-induced diabetes. Conscious dogs received SAL, EPI 20 ng.kg-1.min-1 for 30 min (short EPI) or 72 h (long EPI), or CORT 200 micrograms.kg-1.min-1 for 60 min (short CORT) or 72 h (long CORT) before assessment of glucose metabolism by rapid sampling for glucose and insulin levels after 300 mg/kg i.v. glucose and exogenous insulin infusion designed to simulate the normal secretory pattern. With EPI infusion, KG fell acutely from 2.9 +/- 0.4 to 2.0 +/- 0.2%/min (SAL vs. short EPI, P < 0.05), but rose to 3.4 +/- 0.4%/min during long EPI. Minimal-model analysis of the glucose response with the insulin data as input showed that SI decreased acutely from 4.7 +/- 1.8 to 2.5 +/- 0.6 x 10(-5) min-1/pM (SAL vs. short EPI, P < 0.05), but rose to 4.5 +/- 2.5 x 10(-5) min-1/pM during long EPI. The effects of EPI on SG paralleled the results for KG and SI, with acute decline from 3.9 +/- 0.4 to 2.1 +/- 0.4 x 10(-2) min-1 (SAL vs. short EPI, P < 0.05) and recovery to 3.3 +/- 0.3 x 10(-2) min-1 during long EPI. During CORT infusion, KG tended to fall (SAL 2.9 +/- 0.4 vs. short CORT 2.5 +/- 0.5 vs. long CORT 2.2 +/- 0.5%/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Fenfluramine increases insulin action in patients with NIDDM.

These studies examined the effect of fenfluramine on insulin action and insulin secretion in healthy subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). In the first study, a double-blind crossover design was used in healthy subjects to compare the effect of short-term fenfluramine therapy (60 mg orally for 3 days) with placebo. Insulin secretion and whole-body insulin sensitivity (determined by frequently sampled intravenous glucose tolerance tests with analysis by the minimal-model method) were unchanged by fenfluramine. In the second study, involving patients with NIDDM inadequately controlled on submaximal to maximal doses of oral hypoglycemic agents, a double-blind crossover strategy was used to compare baseline studies (conducted after a run-in period) with fenfluramine (60 mg orally) or placebo for 4 wk. There was a significant fall in fasting blood glucose after therapy with fenfluramine compared with the baseline study period (13.0 +/- 1.2 vs. 8.4 +/- 0.89 mM, mean +/- SE, P less than .01) with no significant fall in fasting serum insulin (20 +/- 2 vs. 24 +/- 3 microU/ml) or C-peptide (1.3 +/- 0.2 vs. 1.3 +/- 0.1 nM). During euglycemic-hyperinsulinemic (1 mU.kg-1.min-1) clamp studies there was a significant increase in insulin action from 12.7 +/- 2.3 to 17.3 +/- 1.8 min-1.10(3) microU.ml-1 (P less than .05), although clamp insulin levels were lower after fenfluramine treatment (136 +/- 14 vs. 96 +/- 9 microU/ml, P less than .02), reflecting an enhanced metabolic clearance rate for insulin (12.7 +/- 1.5 vs. 20.1 +/- 2.1 ml.kg-1.min-1, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinic- rather than self-monitoring of home blood samples: relevance of day-to-day variability to decision making.

The day-to-day variability of blood glucose concentrations in juvenile diabetes means that it is often more reasonable to aim to achieve a generally good pattern of blood glucose control, rather than regularly to assess the next insulin dose after each blood glucose measurement. This means that immediate assessment by the patient of his blood glucose concentrations is not always necessary. We have investigated control in 22 insulin-requiring diabetic patients by means of a monthly series of four blood samples taken during a day into collector bottles and transported to a laboratory for blood glucose assay. The overall means before breakfast, before lunch, before dinner, and before bed were 6.1, 5.8, 7.3, and 7.2 mmol/L, respectively. In many patients, sufficiently good control can be obtained by this method so that it is not necessary to ask them to measure their own blood glucose concentrations or to ask them to obtain the fairly expensive meters for reading glucose oxidase strips. Control would then probably be best assessed by a series of three daily profiles taken once per month, with, if necessary, the results being discussed with the patient. On the other hand, in more unstable diabetes, home assessment by patients of blood glucose measurements is indicated.