Search

A wearable device for the acquisition, processing and storage of the signal from needle-type glucose sensors has been designed and developed as part of a project aimed at developing a portable artificial pancreas. The device is essential to assess the operational characteristics of miniaturized sensors in vivo. It can be connected to sensors operating at a constant potential of 0.65 Volts, and generating currents in the order of 10–9Amp. It is screened and equipped with filters that permit data recording and processing even in the presence of electrical noise. It can operate with sensors with different characteristics (1–200 nA full scale). The device has been designed to be worn by patients, so its weight and size have been kept to a minimum (250 g; 8.5 × 14.5 × 3.5 cm). It is powered by rechargeable Ni/Cd batteries allowing continuous operation for 72 h. The electronics consists of an analog card with operational amplifiers, and a digital one with a microprocessor (Intel 80C196, MCS-96 class, with internal 16-bit CPU supporting programs written in either C or Assembler language), a 32 Kb EPROM, and an 8 Kb RAM where the data are stored. The microprocessor can run either at 5 or 10 Mhz and features on-chip peripherals: an analog/digital (AID) converter, a serial port (used to transfer data to a Personal Computer at the end of the 72 h), input-output (I/O) units at high-speed, and two timers. The device is programmed and prepared to operate by means of a second hand-held unit equipped with an LCD display and a 16-key numeric pad. The hand-held unit is easily connected to the wearable one to calibrate the sensor, display alarms and system fault messages.

The intracerebroventricular injection of eledoisin (ELE), or of other tachykinins with potent agonist activity at neurokinin B (NK-3) receptors, increases plasma vasopressin in the rat. The effect is antagonized by saralasin pretreatment, thus suggesting that it is mediated by angiotensin receptor activation. Since the magnocellular part of the hypothalamic paraventricular nucleus (PVN) is very rich in NK-3 receptors, the present study was aimed at investigating the role of this nucleus in the effect of ELE on plasma vasopressin. Direct injection of ELE into the PVN increased plasma vasopressin levels more potently than the injection of the same doses into the lateral ventricle. Lesioning of the magnocellular part of the PVN completely abolished the increase in plasma vasopressin induced by the injection of ELE 100 ng/rat into the lateral ventricle. Pretreatment into the PVN either with saralasin or with captopril resulted in a marked suppression of the effect of ELE on plasma vasopressin. These findings indicate the PVN as a site of action for the central effect of tachykinins on plasma vasopressin and suggest that the angiotensin mediation of the effect might take place in the same nucleus.

UX Arietis is an active binary system with an orbital period of 6.44 days. The presence of long lasting large spots on the surface of the more active star has been deduced from optical observations (Vogt & Hatzes 1991).The observations presented here have been performed from December 1992 until October 1994 using the Effelsberg 100 m telescope. The instrument was available for this program in the gaps between previously scheduled observations. For this reason our observations span a frequency interval between 1.4 GHz (21 cm) and 43 GHz (7 mm), depending on the scheduled receiver at each observing time. These data, which are an extension of those published by Neidhöfer et al. (1993), are shown in Fig. 1, plotted in terms of the known orbital period (6.44 days). The search for different periodicities (by using the Phase Dispersion Minimization method) has shown the existence of two main other periods: at 156 days and at 24 days (Massi et al., in preparation).

The 24-h profiles of some metabolites [glucose, nonesterified fatty acids (NEFA), ketone bodies] and hormones [insulin, glucagon, Cortisol, growth hormone (GH)] have been compared in two groups of insulin-dependent diabetics, during conventional subcutaneous (sc) insulin therapy (n = 9) and during artificial endocrine pancreas [glucose continuous insulin infusion system (GCIIS), Biostator®] treatment (n = 6) respectively. A third group of 7 normal subjects was examined as control. Blood glucose was continuously monitored throughout the study in all subjects. Blood samples for determination of NEFA, acetoacetate, 3-β-OH-butyrate, free insulin, glucagon, Cortisol and growth hormone were withdrawn at frequent intervals. Mean blood glucose profiles in the diabetic sc treated patients ranged between 90 ± 30 and 250± 105 mg/dl (mean ± SD). In the patients treated with Biostator® mean blood glucose profiles were maintained in a physiological pattern, between 87 ± 15 and 146 ± 17 mg/dl, but mean blood glucose, mean amplitude of glycemie excursions and M values were significantly higher than in normal subjects. During Biostator® treatment plasma NEFA and ketone body profiles showed significantly lower values than in diabetic subjects under sc insulin therapy and quite similar to those of normal subjects. In the Biostator® treated patients free insulin levels (range 10 ± 3 and 148 ± 102 μU/ml) were significantly higher than free insulin levels of sc treated patients (range 13, 8 ± 10 and 31 ± 26 μU/ml) and insulin levels of normal subjects (range 8 ± 2 and 60 ± 38 μU/ml). Plasma glucagon concentrations were similar in diabetics under Biostator treatment (range 100 ± 54 and 147 ± 39 pg/ml) and in normal subjects (range99 ± 30 and 170 ± 108 pg/ml); higher values, although not statistically significant, were noted in the sc treated patients. GH levels fluctuated abnormally in both groups of diabetic patients, while no difference was observed in either of the three groups of subjects examined for plasma cortisol.

Twenty-four hour plasma free insulin and blood glucose and intermediary metabolite profiles have been measured in 6 C-peptide deficient 'brittle' diabetic patients, during continuous sc and im insulin infusion. During sc infusion free insulin profiles were erratic and unpredictable. Mean 24 h blood glucose levels were raised at 12.6 ± 2.1 (se) mmol/l, and 3-hydroxybutyrate at 0.24 ± 0.08 mmol/1. Blood lactate (1.88 ± 0.18 mmol/l) and glycerol (0.084 ± 0.007) were also elevated. Insulin (im) restored free insulin profiles to the normal pattern as found in 'stable' diabetics on sc infusion, with characteristic post-meal peaks (49 ± 7, 103 ± 35, and 95 ± 34 mU/l) and stable night-time levels. Mean 24 h blood glucose was 6.7 ± 1.1 mmol/l (P < 0.05 compared to sc infusion) and 3-hydroxybutyrate 0.07 ± 0.02 mmol/l (P < 0.05). Blood lactate (1.67 ± 0.08 mmol/l) and glycerol (0.10 ± 0.02 mmol/l) levels remained abnormal. The ratio of plasma free insulin to insulin dose administered was significantly higher during im infusion. In the 6 'stable' diabetics on sc insulin infusion good blood glucose control (7.1 ± 0.9 mmol/l) was accompanied by clear post-prandial insulin peaks, and stable nocturnal levels. The results strongly suggest that in one category of 'brittle' diabetics there is defective and erratic sc insulin absorption.

Glucose tolerance and insulin and glucagon secretion were investigated in two groups of uremic patients, respectively on conservative and hemodialytic treatment. For this purpose, a glucose infusion was performed in the fasting state. Glucose intolerance was observed in uremic patients; hemodialysis improved, but did not normalize the glucose disposal. In uremic patients both on conservative and dialytic treatment plasma insulin and glucagon levels were higher than in the control group; the pattern of glucagon suppression was well maintained. The data obtained suggest that glucose intolerance in uremia is related mainly to peripheral insulin resistance and is not due to hyperglucagonemia.

In order to verify whether or not insulininduced blood glucose control can acutely lower glycosylated haemoglobin levels, HbAI (a+b+c) (HbAI) was measured in 11 diabetics before, during and after 3 days of treatment with an “artificial endocrine pancreas” (Biostator). Initially 5 patients were in fair glycaemic control (group A), while the other 6 showed poor control (group B). HbAI levels decreased significantly after 3 days in both groups A (from 9.6 ± 0.2% to 8.5 ± 0.3%, mean ± SEM, p < 0.05) and B (from 13.7 ± 0.2% to 12.6 ± 0.3%, p < 0.05). A further HbAI decrease was observed until day 60 following Biostator treatment, during which period glycaemic control inproved, as assessed by fasting and post-lunch plasma glucose values and daily glycosuria determined every 10 days.

The activity of semi-synthetic human insulin has been compared with porcine insulin in normal man using an euglycaemic glucose clamp at two different insulin infusion rates. In the two hour infusion insulin levels plateaued for both types of insulin at 44-48 mU/l (infusion rate 0.05 U kg body weight-1 h-1) and 22-24 mU/1 (0.02 U kg-1 h-1), giving identical metabolic clearance rates. The glucose delivery required to maintain euglycaemia in the second hour of insulin infusion was 13.9 +/- 2.1 g (mean +/- SEM) and 14.7 +/- 1.5 g (NS) at the lower dose for porcine and human insulins respectively, and 27.1 +/- 2.5 and 28.0 +/- 2.9 g (NS) at the higher dose. The potency ratio for human, compared with porcine, insulin was 1.06 +/- 0.12. No differences were seen in the time of onset of action of the insulins, serum half-life or distribution space. The responses of blood lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were identical. No untoward reactions occurred. The activity and disposal of this semi-synthetic human insulin are indistinguishable from porcine insulin in normal euglycaemic man.

The glucose clamp technique has been used to evaluate the metabolic activity of NPH biosynthetic insulin in diabetic subjects free from anti-insulin antibodies. After overnight blood glucose normalization with a glucose-controlled insulin infusion system (Biostator), an s.c. injection of NPH insulin was given in the abdominal region. The insulin dose (0.236 +/- 0.05 U/kg body wt) was related to the usual intermediate-acting insulin requirement in the morning. Glucose was clamped at 100 mg/dl by a feedback i.v. glucose infusion. The end of the action of s.c. injected insulin considered conventionally to be the time of the spontaneous rise of blood glucose to 110 mg/dl. Free insulin levels were higher and the length of action was longer after NPH porcine than after NPH biosynthetic human insulin (BHI) (area under the free insulin curve: porcine 1423 +/- 556 mU/L/h; BHI 1045 +/- 338 mU/L/h, P less than 0.05; length of action: porcine 16.0 +/- 3.2 h; BHI 13.7 +/- 0.9 h, P less than 0.05); the glucose requirement was higher after porcine (76.8 +/- 13.5 g) than after BHI (58.5 +/- 14.6 g) without reaching statistical significance. However, the metabolic activity of the bioavailable insulin (index of plasma free insulin activity) was similar for the two insulins (porcine 381 +/- 77.4, BHI 342.8 +/- 54.2 mU/L/g of glucose/h). We conclude that a difference in pharmacokinetics exists between NPH BHI and porcine NPH insulin, which makes the latter metabolically more active. The different behavior does not seem to be related to the insulin molecule itself but could be a consequence of the unequal content of protamine in the two pharmacologic preparations.

The safety, reproducibility, and reliability of an insulin infusion test for assessment of adequate glucose counterregulation were evaluated in 18 patients with type I (insulin-dependent) diabetes mellitus. When the test (a 60-min, 30-mU/m2/min insulin infusion) was administered on three separate occasions at 3–4-wk intervals, coefficients of variation for plasma glucose and counterregulatory hormone (glucagon, epinephrine, cortisol, and growth hormone) responses averaged less than 8%. No patient experienced symptoms requiring discontinuation of the test and plasma glucose concentrations increased spontaneously after stopping the insulin infusion. Using objective criteria based on plasma glucose nadirs or postnadir rates of plasma glucose recovery, no patient judged to have adequate glucose counterregulation by the test (post-nadir rates of plasma glucose recovery or plasma glucose nadir above 0.4 mg/dl/min and 45 mg/dl) developed severe hypoglycemia (plasma glucose < 40 mg/dl) during up to 7 mo of intensive insulin therapy, whereas nearly all patients with inadequate counter-regulation did. We conclude that this test, when performed in standardized conditions, is safe and reproducible and can reliably predict those patients with type I diabetes who are at risk of developing severe hypoglycemia during intensive insulin therapy.

Aims Critical appraisal of secondary data made available by the OECD for the time frame 2000–2011. Methods Comparison of trends and variation of amputations in people with diabetes across OECD countries. Generalized estimating equations to test the statistical significance of the annual change adjusting for major potential confounders. Results A total of 26 OECD countries contributed to the OECD data collection for at least 1 year in the reference time frame, showing a decline in rates of over 40 %, from a mean of 13.2 (median 9.4, range 5.1–28.1) to 7.8 amputations per 100,000 in the general population (9.9, 1.0–18.4). The multivariate model showed an average decrease equal to −0.27 per 100,000 per year (p = 0.015), adjusted by structural characteristics of health systems, showing lower amputation rates for health systems financed by public taxation (−4.55 per 100,000 compared to insurance based, p = 0.002) and non-ICD coding mechanisms (−7.04 per 100,000 compared to ICD-derived, p = 0.001). Twelve-year decrease was stronger among insurance-based financing systems (tax based: −0.16 per 100,000, p = 0.064; insurance based: −0.36 per 100,000; p = 0.046). Conclusions In OECD countries, amputation rates in diabetes continuously decreased over 12 years. Still, in 2011, one amputation every 7 min could be directly attributed to diabetes. Although interesting, these results should be taken with extreme caution, until common definitions are improved and data quality issues, e.g., a different ability in capturing diabetes diagnoses, are fully resolved.

AimTo estimate type 2 diabetes mellitus (T2DM) prevalence in Russian adults.MethodsNATION is a national, epidemiological, cross-sectional study, conducted in Russia. In adults (aged 20–79 years), recruitment was stratified by age, sex, geographic region and settlement type to obtain a representative sample. Recruitment was in public areas with high numbers of people. T2DM was diagnosed by glycated haemoglobin A1c (HbA1c) levels (diabetes: HbA1c ≥6.5% [≥48mmol/mol]; pre-diabetes: HbA1c ≥5.7 to

We report the features of a sensor for determining L-lactate. An oxygen sensor, coupled to a nylon net with chemically bound L-lactate oxidase (EC 1.1.3.2), is inserted into an artificial pancreas (Biostator, Miles) "downstream" from the glucose sensor. We used the sensor to continuously monitor the L-lactate concentration in blood after a "glucose clamp" experiment with a diabetic patient. L-Lactate determinations in blood drawn from the patient every 15 min agreed well with results obtained by use of the L-lactate sensor.

1. In response to furosemide-induced sodium depletion pigeons showed a robust salt appetite. Following the 1st depletion they started to ingest 3% NaCl after a latency of 373 +/- 69 s and in 24 h they took 21.16 +/- 3.07 ml of this solution (vs. a daily mean intake of 1-2 ml prior to the depletion). 2. The appetite was selective as shown by the fact that when, after depletion, 0.34 M-CaCl2 was offered (which is equiosmotic to 3% NaCl) pigeons took just a trivial amount of it. 3. Analysis of sodium losses following the natriuretic treatment revealed that pigeons respond to sodium depletion with an excessive overconsumption of NaCl solution. In the 2 h after access to salt they took about 3 times the amount of sodium lost. 4. Repeated sodium depletions sharply reduced the latency to the ingestion of salt and produced larger intakes. However, the overall amount of salt taken in 24 h after the later depletions was very similar and statistically indistinguishable from that taken following the 1st depletion. 5. Subchronic deoxycorticosterone acetate treatment (2 mg pigeon-1 day-1 I.M.) increased daily 3% NaCl intake, but large variability was observed in the response. 4 mg pigeon-1 day-1 evoked a reliable 3% NaCl intake which was particularly marked from the 5th day of the treatment. 6. Pulse intracerebroventricular (I.C.V.) injection of purified hog renin evoked water intake within about 1 min of injection, followed (about 6 h later) by increased salt intake. In the 24 h after renin injection pigeons took 16.58 +/- 2.89 ml of 3% NaCl. On the 2nd day following injection salt intake was still higher than in controls. 7. In conclusion, our results show that pigeons respond to sodium depletion with a robust salt appetite. Moreover, salt appetite can be evoked by deoxycorticosterone acetate as well as by renin. These findings suggest that in the pigeon salt appetite may be an endocrine-induced behaviour controlled by mineralocorticoids and by the renin-angiotensin system.

The activity of biosynthetic human insulin (BHI) has been compared with that of pork insulin using the glucose clamp technique in normal subjects. After a baseline period, insulin was infused at 0.02 U/kg/h for 2 h, then 0.032 U/kg/h for 2 h, and finally 0.05 U/kg/h for 2 h. Glucose was clamped at baseline values using a glucose-controlled insulin infusion system (Biostator) and the amount of glucose infused to maintain normoglycemia calculated for each insulin dose for the two insulins. C-peptide levels decreased with both insulins, suggesting suppression of endogenous insulin secretion. Serum insulin levels attained were the same for both insulins. There were no significant differences in either total glucose infused or glucose infused during the last 30 or 60 min at each insulin dose for the two insulins. Intermediary metabolite responses to the infusion of the two insulins were similar. We conclude that in normal human beings, BHI shows identical metabolic activity with pork insulin.

The effect on water intake, urine flow and vasopressin release of intracranial injections of substance P, physalaemin and eledoisin was studied in Wistar and Brattleboro, homozygous and heterozygous, rats. The tachykinins strongly inhibited water intake both in Wistar and in Brattleboro, homozygous and heterozygous, rats. Physalaemin and eledoisin reduced urine flow in Wistar and heterozygous, but not in homozygous, Brattleboro rats. Substance P never affected urine elimination. Physalaemin and eledoisin produced a dose-dependent, long lasting release of vasopressin in Wistar rats. Substance P did not affect the release of vasopressin. The results suggest that both substance P and physalaemin could influence brain mechanisms which control water intake, acting as thirst inhibitors, and that physalaemin could also participate in body fluid control by conserving water through vasopressin release.

Eledoisin cured corneal lesions produced in the rabbit by cocaine but failed to heal those produced by sodium hydroxide. The effect was probably due to accelerated epithelial proliferation.

Twenty-four hour profiles of blood hormones and intermediary metabolites were obtained in seven 'brittle' diabetic subjects during their usual insulin therapy and during feedback intravenous insulin infusion from an artificial pancreas (GCIIS). The results were compared to those in matched stable diabetics and normal controls. Although routine insulin doses were higher in the brittle group than in the stable group (164 +/- 32 (mean +/- SE) vs. 58 +/- 8 U/day, P less than 0.005) during routine therapy, plasma free insulin levels were equal (35 +/- 12 vs. 31 +/- 6 mU/l). In the brittle group feedback i.v. insulin infusion reduced daily requirements to normal levels (80 +/- 13 U/day, P less than 0.025; stable group 71 +/- 4 U/day, NS). On routine therapy blood glucose levels were not different in the two groups (brittle 10.5 +/- 1.6, stable 10.8 +/- 0.6 mmol/l) and were similarly corrected by the GCIIS (6.9 +/- 0.3 and 6.9 +/- 0.3 mmol/l, respectively). Blood lactate and pyruvate levels were markedly abnormal in the brittle group during routine therapy (lactate: brittle group 1.93 +/- 0.27 mmol/l, stable group 0.91 +/- 0.07 mmol/l, P less than 0.025), and this abnormality was not corrected by the GCIIS (1.75 +/- 0.32 and 0.88 +/- 0.08 mmol/l, P less than 0.005). Abnormalities were also found in profiles of blood alanine and glycerol, and serum cortisol. Blood ketone body levels did not differ between the two groups of patients. The results suggest a defect in insulin delivery from subcutaneous tissue into the plasma. These patients have a characteristic metabolic abnormality, unresponsive to short-term normoglycaemia, either as the result of long-term disturbance of diabetic control, or as a marker for the underlying hormonal or biochemical abnormality.