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Combining the selective arterial calcium injection test and intraoperative blood glucose monitoring for multiple insulinomas: report of two cases.

To date, no precise methods of preoperatively localizing multiple insulinomas or intraoperatively confirming their complete removal have been established. We describe herein the effectiveness of combining the selective arterial calcium injection (SACI) test to locate tumors preoperatively, with intraoperative continuous blood glucose monitoring (IOBGM) to confirm their complete removal. During the 8-year period from 1990 to 1997, we experienced two patients with multiple insulinomas. The first patient required resection of a residual tumor in the remnant pancreas for persistent hyperinsulinemia after a distal pancreatectomy performed under conventional diagnostic procedures. In the second patient, a SACI test was performed in addition to other diagnostic imaging procedures, and while computed tomography scan, endoscopic ultrasonography, and arteriography demonstrated multiple tumors in the body and tail of pancreas, the SACI test suggested that there were also tumors in the head of pancreas. Intraoperative ultrasonography showed a tumor measuring 5 mm in diameter on the surface of the head of the pancreas, apart from the multiple tumors in the body and tail of the pancreas. Complete removal of all tumors was assessed by the hyperglycemic rebound after resection of the tumors, determined by IOBGM. Based upon our experience, we believe that the SACI test and IOBGM are helpful for establishing precise localization and achieving complete removal of multiple insulinomas.

Blood Glucose↗

[Insulin therapy by insulin pump: continuous or conventional self-blood glucose monitoring? ].

Use of portable pumps is increasing to achieve intensive insulin treatment. Beside unpredictable insulin absorption and insufficient reactivity to changes of insulin flow rate due to the subcutaneous route, this therapy is however limited by the lack of information on blood glucose level provided by self-blood glucose monitoring. Thus, patient interpretation only leads to speculative adaptation of pump flow rate. The lack of alert toward the risk of hypoglycemia or hyperglycemic ketogenic deviations can lead to the occurrence of deleterious metabolic distorsions, among which severe hypoglycemia stands in first rank. Starting experiences of continuous recording of interstitial glucose level by portable systems using glucose-oxidase allow on short time durations the identification of daily periods of poor metabolic control. Retrospective availability of information gives the possibility of more adequate treatment adaptations than conventional capillary blood glucose monitoring, but does not allow immediate prevention of metabolic events. Only devices providing real time or near-real time information to the patient can fulfill this function. However, the absence of tight parallelism between variations of interstitial and blood glucose levels may lead to erroneous decisions. A true continuous real time information on blood glucose level on long-term seems only expectable from implantable glucose sensors. Still under investigation, these systems should be able to insure vigilance toward the risk of hypo- and hyperglycemia on weekly or monthly periods. Initially used as complementary to capillary self-monitoring, their reliability should allow their use as substitutes for conventional monitoring, except for measurements aimed at signal calibration. Pump control by the sensor signal is conceivable if it corresponds to a direct, continuous, real time measurement of blood glucose, and subject to a simultaneous improvement of insulin infusion modes.

Blood Glucose↗

Appetite and blood glucose profiles in humans after glycogen-depleting exercise.

Regulatory functions of glycogen stores and blood glucose on human appetite, particularly relating to exercise, are not fully understood. Ten men (age 20-31 yr) performed glycogen-depleting exercise in an evening, ate a low-carbohydrate dinner, and stayed overnight in the laboratory. The next day, blood glucose was monitored continuously for 517 +/- 23 (SE) min. Subjects had access to high-fat and high-carbohydrate foods after baseline glucose and respiratory quotient were determined. In the afternoon, 1 h of moderate exercise was performed. Baseline respiratory quotient was 0. 748 +/- 0.008, plasma free fatty acids were 677 +/- 123 micromol/l, insulin was 4.8 +/- 0.5 microU/ml, and leptin was 1.9 +/- 0.3 ng/ml. Postabsorptively, 8 of 10 meals were initiated during stability in blood glucose. Postprandially, the association between meal initiation and blood glucose declines became significant (chi(2) = 7. 82). During moderate exercise, blood glucose initially decreased but recovered before completion. When the glycogen buffer is depleted, meal initiation can occur during blood glucose stability; the relationship between blood glucose declines and meal initiation reestablishes with refeeding.

Adult↗

Pendra goes Dutch: lessons for the CE mark in Europe.

The development of a truly non-invasive continuous glucose sensor is an elusive goal. We describe the rise and fall of the Pendra device. In 2000 the company Pendragon Medical introduced a truly non-invasive continuous glucose-monitoring device. This system was supposed to work through so-called impedance spectroscopy. Pendra was Conformité Européenne (CE) approved in May 2003. For a short time the Pendra was available on the Dutch direct-to-consumer market. A post-marketing reliability study was performed in six type 1 diabetes patients. Mean absolute difference between Pendra glucose values and values obtained through self-monitoring of blood glucose was 52%; the Pearson's correlation coefficient was 35.1%; and a Clarke error grid showed 4.3% of the Pendra readings in the potentially dangerous zone E. We argue that the CE certification process for continuous glucose sensors should be made more transparent, and that a consensus on specific requirements for continuous glucose sensors is needed to prevent patient exposure to potentially dangerous situations.

Blood Glucose↗

Management strategies for brittle diabetes.

Type 1 diabetes is an intrinsically unstable condition. However, the term "brittle diabetes" is reserved for those cases in which the instability, whatever its cause, results in disruption of life and often recurrent and/or prolonged hospitalization. It affects 3/1000 insulin-dependent diabetic patients, mainly young women. Its prognosis is poor with lower quality of life scores, more microvascular and pregnancy complications and shortened life expectancy. Three forms have been described: recurrent diabetic ketoacidosis, predominant hypoglycemic forms and mixed instability. Main causes of brittleness include malabsorption, certain drugs (alcohol, antipsychotics), defective insulin absorption or degradation, defect of hyperglycemic hormones especially glucocorticoid and glucagon, and above all delayed gastric emptying as a result of autonomic neuropathy. Psychosocial factors are very important and factitious brittleness may lead to a self-perpetuating condition. The assessment of brittle diabetes requires quantification of the variability of blood glucose levels. To quantify instability, measures which have been developed, include Mean Amplitude of the largest Glycemic Excursions (MAGE), Mean Of Daily Differences (MODD), Lability Index (LI), Low Blood Glucose Index (LBGI), Clarke's score, Hyposcore, and continuous blood glucose monitoring. Once psychogenic problems have been excluded, therapeutic strategies require firstly, the treatment of underlying organic causes of the brittleness whenever possible and secondly optimising standard insulin therapy using analogues, multiple injections and consideration of Continuous Subcutaneous Insulin Infusion. Alternative approaches may still be needed for the most severely affected patients. Isolated islet transplantation (IIT), which restores glucose sensing, should be considered in cases of hypoglycaemic unawareness and/or lability especially if the body mass index is < 25, but with current immunosuppressive protocols patients must have normal renal function and preferably no plans for pregnancy. Implantable pumps have advantages for patients who either weigh more than 80 kgs or have abnormalities of kidney or liver function or are highly sensitised.

Diabetes Mellitus, Type 1↗

Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception.

In a study of the impact of aspartame, fat, and carbohydrate on appetite, we monitored blood glucose continuously for 431 (SE 16) min. Ten healthy males (19-31 years) participated in three time-blinded visits. As blood glucose was monitored, appetite ratings were scored at randomized times. On the first meal initiation, volunteers consumed one of three isovolumetric drinks (aspartame, 1 MJ simple carbohydrate, and 1 MJ high-fat; randomized order). High-fat and high-carbohydrate foods were available ad libitum subsequently. Blood glucose patterns following the carbohydrate drink (+1.78 (SE 0.28) mmol/l in 38 (SE 3) min) and high-fat drink (+0.83 (SE 0.28) mmol/l in 49 (SE 6) min) were predictive of the next intermeal interval (R 0.64 and R 0.97 respectively). Aspartame ingestion was followed by blood glucose declines (40% of subjects), increases (20%), or stability (40%). These patterns were related to the volunteers' perception of sweetness of the drink (R 0.81, P = 0.014), and were predictive of subsequent intakes (R -0.71, P = 0.048). For all drinks combined, declines in blood glucose and meal initiation were significantly associated (chi 2 16.8, P < 0.001), the duration of blood glucose responses and intermeal intervals correlated significantly (R 0.715, P = 0.0001), and sweetness perception correlated negatively with hunger suppression (R -0.471, P = 0.015). Effects of fat, carbohydrate, and aspartame on meal initiation, meal size, and intermeal interval relate to blood glucose patterns. Varied blood glucose responses after aspartame support the controversy over its effects, and may relate to sweetness perception.

Adult↗

Disease management in the young diabetic patient: glucose monitoring, coping skills, and treatment strategies.

Type 1 diabetes mellitus was thought to be the prevalent type of diabetes in children and adolescents; however, increasing numbers of juvenile patients appear to have type 2 diabetes. Management of all diabetes in young patients should include regular assessment, careful monitoring for glycemic control and the presence of hypoglycemia, and educational training on disease management. Hypoglycemic episodes, especially nocturnal events, are frequent in the young diabetic patient. Improvements in glycemic control and nocturnal hypoglycemia have been observed with continuous subcutaneous insulin infusion and insulin glargine. A continuous glucose-monitoring system can provide important insight into 24-hour glycemic control. Overall, careful management, monitoring, and education can improve glycemic control and yield positive treatment outcomes in the child or adolescent with diabetes.

Adaptation, Psychological↗

Technology choice, glycemic control and patient-reported outcome measures in adults with type 1 diabetes: A randomized crossover trial comparing a smart insulin pen with an automated insulin delivery system (EBIACE-1).

AIMS: To compare glycemic outcomes and patient-reported outcome measures (PROMs) between smart insulin pens (SIP) and an automated insulin delivery (AID) system in adults with type 1 diabetes (T1D), and to identify individuals able to maintain near-optimal glycemic control using SIP. METHODS: EBIACE-1 was a randomized, open-label, crossover trial including 31 adults with T1D. Participants received SIP (InPen&#x2122;) and AID (MiniMed&#x2122; 780G) for 6&#xa0;months each. Co-primary outcomes were time in range (TIR 70-180 mg/dL) and HbA1c. Treatment effects were assessed using longitudinal models in intention-to-treat (ITT) and per-protocol (PP) analyses. Predictors of near-optimal glycemic control with SIP were evaluated using multivariable logistic regression. RESULTS: AID improved glycemic control versus SIP, with higher TIR (81&#xa0;% vs 66&#xa0;%; +15&#xa0;%, 95&#xa0;% CI 10-19; P&#xa0;<&#xa0;0.001) and lower HbA1c (6.9&#xa0;% [52&#xa0;mmol/mol] vs 7.3&#xa0;% [56&#xa0;mmol/mol]; -0.4&#xa0;%, 95&#xa0;% CI&#xa0;-&#xa0;0.6 to&#xa0;-&#xa0;0.3; P&#xa0;<&#xa0;0.001). Near-optimal glycemic control with SIP was achieved by 12 of 26 participants (46&#xa0;%). In exploratory analyses, higher baseline diabetes-related life interference was associated with a lower probability of achieving this outcome. CONCLUSIONS: AID provides superior glycemic control, although nearly half of participants achieved near-optimal control with SIP, supporting a personalized approach to technology selection.

Adult↗

Treatment options for insulin-dependent diabetes mellitus: a comparison of the artificial endocrine pancreas, continuous subcutaneous insulin infusion, and multiple daily insulin injections.

The essential components of an intensive insulin therapy program are maintenance of stable basal concentrations of insulin between meals and appropriate, timely increases in the concentration of circulating insulin after ingestion of meals. Closed-loop systems that both continuously monitor the plasma glucose concentration and continuously infuse insulin intravenously can reproducibly achieve near-normal glycemia in patients with insulin-dependent diabetes mellitus. Near-normal glycemia can also be achieved with use of a continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) of regular insulin combined with a single injection of slowly absorbable insulin in properly selected, compliant and cooperative patients. The frequency of hypoglycemia is similar with CSII and MDI. The risks of catheter-associated problems and ketoacidosis, however, are greater with CSII than with MDI. In contrast, the basal concentration of insulin can be more reproducibly and rapidly regulated with CSII than with MDI. The ratio of risk versus benefit associated with intensive insulin therapy with either CSII or MDI is currently unknown.

Blood Glucose↗

Hypoglycaemia and counterregulation during childhood.

Hypoglycaemia is particularly common in young children with type 1 diabetes mellitus yet the normal protective counterregulatory responses have been little studied in this age group. The studies reported have shown conflicting results, in part related to prior glycaemic control and also to the method of investigation used. Counterregulatory hormone responses during both spontaneous and experimentally induced episodes of nocturnal hypoglycaemia do appear to be blunted, which may be a function of sleep itself. Although studies of cognitive function have consistently shown defects in certain areas of neurocognitive performance, particularly in those children with early-onset diabetes or a prior history of severe hypoglycaemia, the contribution of nocturnal hypoglycaemia to the development of these impairments has not been evaluated. In young adults and adolescents, nocturnal hypoglycaemia has been linked to cardiac arrhythmia and the risk of sudden death. The development of new techniques for continuous subcutaneous glucose monitoring may allow detailed study of counterregulatory responses and symptom recognition in young children. Effective intensification of insulin therapy without an increased risk of hypoglycaemia may be possible using new insulin analogues or continued subcutaneous intravenous infusion (CSII), thus improving patient compliance and overall quality of clinical care.

Adolescent↗

A fully implantable subcutaneous glucose sensor array: enhanced accuracy from multiple sensing units and a median-based algorithm.

Although continuous electrochemical glucose monitoring holds promise in the management of diabetes, its utility is limited in part because of error of unclear origin. The use of redundant glucose sensors in an array might reduce such error. We hypothesized that in a subcutaneously implanted array, a median-based continuous computation that excludes outlying data would lead to more accurate glucose measurement than averaging of all signals. Each rat was implanted with an array of four sensing units, and each unit transmitted data independently to an external monitoring device. Animals underwent perturbation of glucose by insulin infusions in diabetic animals and glucose infusions in nondiabetic animals, and in both, capillary glucose monitoring was performed frequently. Repeat glucose perturbation studies were performed every 1-2 weeks. We observed that a median-based technique, the Z-score with Median Absolute Deviation (ZMAD), consistently led to greater sensing accuracy as compared with signal averaging. The ZMAD technique yielded a correlation coefficient of 0.93, and 96% of values fell in the A and B regions of the Clarke error grid, demonstrating a high degree of accuracy of the unified signal. When tested in an implanted array of glucose sensors, a median-based technique (ZMAD) yields an accurate unified signal, and its accuracy is superior to signal averaging.

Algorithms↗

Effect of digestible carbohydrates on glucose control in insulin-dependent diabetic patients.

Recent studies have demonstrated that high-carbohydrate-high-fiber diets may improve the metabolic control in diabetes. To evaluate the influence of dietary carbohydrates separate from dietary fiber on blood glucose control, six insulin-dependent diabetic patients (IDD) were assigned in random order to two weight-maintaining diets for consecutive periods of 10 days. The diets differed in carbohydrate (41% in diet A and 60% in diet B) and fat content (41% and 20%, respectively) but were identical in calories, proteins, simple sugars, and fiber. After each dietary period blood glucose was continuously monitored for 24 h (Biostator GCIIS, Life Science Instruments, Miles Laboratories, Elkhart, Indiana). The M value was 48 +/- 20 after diet A and 96 +/- 27 after diet B (t = 3.83, P less than 0.025); the mean daily blood glucose was 152 +/- 5 mg/dl after diet A and 206 +/- 11 mg/dl after diet B (t = 7.50, P less than 0.001). Similarly, the blood glucose level for the 3-h period after each of the three main meals was lower after diet A than after diet B (analysis of variance: F = 5.2, P less than 0.05). No significant difference in fasting serum cholesterol, triglycerides, or serum lipoprotein composition was observed between the two diets. In order to separate the influence of dietary carbohydrate and fat on postprandial blood glucose concentration, an additional test meal experiment was performed in eight insulin-dependent diabetic patients. In random order on consecutive days they were given two standard meals that were identical in carbohydrate and protein content and differed only in the amount of olive oil added to the meals (12 g versus 36 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of insulin on sodium reabsorption in hypertensive patients.

The effect of insulin on sodium reabsorption was studied with the hyperinsulinemic euglycemic clamp technique, using lithium clearance as a marker of sodium reabsorption in the proximal tubule. The subjects were 12 nondiabetic hypertensive patients who were divided into two groups. In the first group, the effect of insulin on sodium and lithium reabsorption was examined. The second group served as a control. Blood glucose was continuously monitored from 9 AM to 10 AM (baseline period). Hyperinsulinemic euglycemic clamp was performed with an artificial endocrine pancreas by infusing insulin at a rate of 2 mU/kg.min from 10 AM to noon. In the control group the protocol was exactly the same except that glucose clamp was not performed. Urine was collected hourly from 9 AM to noon. In the glucose clamp group, urinary sodium excretion (UNaV) decreased by 42% during the second hour of the glucose clamp (P < .02). Clearance of lithium (CLi) and fractional distal sodium reabsorption [(CLi-CNa)/CLi] increased, and CNa/CLi decreased significantly during the glucose clamp. In the control group, UNaV and (CLi-CNa)/CLi remained unchanged, and CLi decreased significantly. As shown by the increase of CLi and (CLi-CNa/CLi, and the decrease of UNaV and CNa/CLi in the glucose clamp group, insulin decreases urinary sodium excretion by increasing distal sodium reabsorption, whereas it inhibits sodium reabsorption in the proximal tubule.

Absorption↗

Insulin pump therapy in type 1 diabetes mellitus.

OBJECTIVES: To review the current experience with insulin pump therapy in children and adolescents in order to guide pediatricians regarding indications and complications. SOURCES OF DATA: Systematic review of articles published in the literature referring to the use of insulin pump therapy, indications, complications and response to treatment. All articles published between 1995 and 2005 and appearing in the MEDLINE and LILACS databases were reviewed. The keywords were: insulin pump, type 1 diabetes mellitus and diabetes mellitus. The articles covering the subject of interest and referring to children and adolescents were selected. SUMMARY OF THE FINDINGS: Insulin pump therapy is not required for all patients with type 1 diabetes, since intensive treatments produce very similar results in terms of glycated hemoglobin and control of complications over the medium and long terms. However, the pump allows for greater comfort for patients, with less rigid meal schedules and better quality of life. The first requirement for patients intending to use the pump is getting used to having a device attached to the body and following strict glucose control; otherwise, pump therapy is not advantageous. Complications are rare due to the technologies currently available. The cost, however, is greater than with conventional treatments. CONCLUSION: The development of infusion pumps and glucose monitors, including continuous monitoring systems, will lead to "intelligent pumps," so that a true "artificial pancreas" will be available, which can even be implanted in the patient, allowing non-diabetic persons to lead a normal life.

Adolescent↗

Human eating: evidence for a physiological basis using a modified paradigm.

The aim of these studies was to determine if meal requests and changes in hunger ratings in humans were related to spontaneous changes in blood glucose concentration. In our first study, 18 healthy subjects were acutely isolated from food ant time cues. Blood glucose was continuously monitored online and visual analog ratings of hunger were obtained following an overnight fast. Spoken meal requests, if they occurred, were also recorded. In 83% of the subjects, both the perception and behavioral expression of hunger, as assessed by changes in hunger ratings and meal requests, were preceded by, and correlated with, brief, transient declines in blood glucose (nadir: -10% at 27 min). The pattern, magnitude and time course of these declines was similar to those observed in rats. This significant association, between increased expression of hunger and declines in blood glucose, is being tested in a second, ongoing study using acute insulin infusions to mimic spontaneous transient declines in blood glucose. Each subject was studied twice: either insulin or saline was infused while hunger ratings were obtained. Preliminary results in five subjects indicate that hunger ratings increased after insulin-induced transient declines in blood glucose. No change in hunger ratings occurred when blood glucose concentration was stable. These results suggest that this temporal pattern of blood glucose reflects an antecedent physiological event or provides a signal related to the expression of hunger in humans. Further understanding of human eating may result from investigation of the complex interaction of physiological and other factors in an experimental setting that allows the expression the behavior under study.

Adult↗

Long-range negative correlation of glucose dynamics in humans and its breakdown in diabetes mellitus.

Diurnal fluctuations in glucose levels continuously monitored during normal daily life are investigated using an extended random walk analysis, referred to as detrended fluctuation analysis (DFA), in 12 nondiabetic subjects and 15 diabetic patients. The DFA exponent alpha = 1.25 +/- 0.29 for healthy individuals in the "long-range" (>2 h) regime is shown to be significantly (P < 0.01) smaller than the reference "uncorrelated" value of alpha = 1.5, suggesting that the instantaneous net effects of the dynamical balance of glucose flux and reflux, causing temporal changes in glucose concentration, are long-range negatively correlated. By contrast, in diabetic patients, the DFA exponent alpha = 1.65 +/- 0.30 is significantly (P < 0.05) higher than that in nondiabetic subjects, evidencing a breakdown of the long-range negative correlation. It is suggested that the emergence of such positive long-range glucose correlations in diabetic patients-indicating that the net effects of the flux and reflux persist for many hours-likely reflects pathogenic mechanisms of diabetes, i.e., the lack of long-term stability of blood glucose and that the long-range negatively correlated glucose dynamics are functional in maintaining normal glucose homeostasis.

Adaptation, Physiological↗

[Late hypoglycaemia in chemical diabetes. Abnormalities of pancreatic glucagon secretion and effect of pectine (author's transl)].

Nineteen patients suffering from chemical diabetes either with (group A, ten cases) or without (group B, nine cases) reactive hypoglycaemia were included in the study and compared with seven control (group C). The following variables were measured over a 5 hour period during a standard oral glucose tolerance test (OGTT): (i) blood glucose by continuous monitoring; (ii) plasma insulin and glucagon levels by radioimmunoassay. Furthermore, in five diabetics of group A, the data from the standard OGTT were compared with those from a pectin-supplemented OGTT (9 g per square meter of body surface). Although the insulin response was similar glucagon levels were significantly higher (45.1 +/- 11.8 pmol/l) (p less than 0.01) in group B than in group A (9.6 +/- 1.3) and C (8.1 +/- 1.4 at 30 minutes). The high glucagon levels noted in group B may explain the absence of reactive hypoglycaemia. The pectin supplementation improved the OGTT pattern by blunting the blood glucose peak (p less than 0.05), and avoiding the reactive hypoglycaemia (p less than 0.01). The addition of pectin did not produce any significant effect on the insulin response while a significant increase in glucagon concentrations (p less than 0.05) was observed beyond the 150th minute. Therefore, the data suggest that pectin may improve the OGTT pattern by increasing the glucagon response in the late period of the test. The development of postprandial reactive hypoglycaemia seldom coincides with a plasma glucagon peak, while the absence of reactive hypoglycaemia tends to be associated with high levels of glucagon, as is the case in overt diabetes mellitus.

Adult↗