Blood glucose discrimination training with insulin-dependent diabetics: a clinical note

Two insulin-dependent diabetic adults were exposed to a blood glucose discrimination training program. Following baseline, during which subjects estimated their blood glucose levels twice daily, subjects received immediate feedback regarding the accuracy of their estimates. The procedure resulted in a large increase in accuracy of blood glucose level estimation. The implications of the findings were discussed.     

Accuracy of subjective blood glucose estimation by patients with insulin-dependent diabetes

A between-groups design using a baseline, treatment, follow-up procedure was used to investigate the accuracy of 20 patients with insulin-dependent diabetes when subjectively estimating their blood glucose levels. Patients were encouraged to attend to their mood for cues when making estimates of their blood glucose. Their capacity for reducing estimation errors when given immediate or delayed feedback of actual blood glucose was examined. The results showed that neither delayed nor immediate feedback produced a significant improvement in the mean estimation accuracy of these groups of patients or in their ability to predict whether their blood glucose was in the acceptable or unacceptable range. Patients were particularly inaccurate in detecting Low [less than 4.0 mmol/L (less than 72.0 mg/dl)] and Very High [greater than 16.0 mmol/L (greater than 288.0 mg/dl)] blood glucose levels. Examination of mood-blood glucose relationships revealed consistent patterns for individual subjects and considerable differences between subjects.     

Blood glucose discrimination training in patients with type II diabetes

This study was designed to determine whether patients with Type II diabetes could be taught to discriminate blood glucose after experiencing a variety of blood glucose levels and receiving feedback on the accuracy of their estimates. Thirty-six subjects (18 on oral agents and 18 on insulin) were randomly assigned to one of two feedback conditions: (1) current feedback, which received accurate information regarding their blood glucose levels, (2) noncurrent feedback, which received blood glucose levels from the preceding session. Subjects were exposed to a wide range of blood glucose values in six training sessions by ingesting drinks with three different caloric loads. In pre/post comparisons using several indices of accuracy, both groups showed significant improvement in estimating blood glucose levels. However, feedback on current blood glucose levels did not produce greater improvement than noncurrent. Accuracy was unrelated to the degree to which subjects reported associating internal sensations to their estimates. Failure to find differences between the two feedback conditions may have been due to the noncurrent feedback group's receiving fairly accurate information, to the difficulty of the discrimination task, and to the limited number of training trials.     

Blood glucose discrimination training in patients with Type II diabetes

This study was designed to determine whether patients with Type II diabetes could be taught to discriminate blood glucose after experiencing a variety of blood glucose levels and receiving feedback on the accuracy of their estimates. Thirty-six subjects (18 on oral agents and 18 on insulin) were randomly assigned to one of two feedback conditions: (1) current feedback, which received accurate information regarding their blood glucose levels, (2) noncurrent feedback, which received blood glucose levels from the preceding session. Subjects were exposed to a wide range of blood glucose values in six training sessions by ingesting drinks with three different caloric loads. In pre/post comparisons using several indices of accuracy, both groups showed significant improvement in estimating blood glucose levels. However, feedback on current blood glucose levels did not produce greater improvement than noncurrent. Accuracy was unrelated to the degree to which subjects reported associating internal sensations to their estimates. Failure to find differences between the two feedback conditions may have been due to the noncurrent feedback group's receiving fairly accurate information, to the difficulty of the discrimination task, and to the limited number of training trials.The authors thank Marsha D. Marcus, Ph.D., for her contributions to this study.     

Accuracy of subjective blood glucose estimation by patients with insulin-dependent diabetes

A between-groups design using a baseline, treatment, follow-up procedure was used to investigate the accuracy of 20 patients with insulin-dependent diabetes when subjectively estimating their blood glucose levels. Patients were encouraged to attend to their mood for cues when making estimates of their blood glucose. Their capacity for reducing estimation errors when given immediate or delayed feedback of actual blood glucose was examined. The results showed that neither delayed nor immediate feedback produced a significant improvement in the mean estimation accuracy of these groups of patients or in their ability to predict whether their blood glucose was in the acceptable or unacceptable range. Patients were particularly inaccurate in detecting Low [<4.0 mmol/L (<72.0 mg/dl)] and Very High [>16.0 mmol/L (>288.0 mg/dl)] blood glucose levels. Examination of moodblood glucose relationships revealed consistent patterns for individual subjects and considerable differences between subjects.The authors wish to thank the consultant physician Dr. J. D. Ward, and Drs. G. Knight and A. J. M. Boulton from the Royal Hallamshire Hospital, Sheffield, for referring the patients who took part in the study. The research was funded by NIH Grant number AM28196 to Dr. C. Bradley.     

一种改进的用于PET/FDG实验的定量计算方法

在传统的ＰＥＴ／ＰＤＧ实验的定量计算方法基础上提出了一种改进的算法。与传统方法相比,本方法可以大大减不实验中的动脉抽血次数。对模拟数据和４名受试者共３３个感兴趣区的实验数据的计算结果显示,本文在４次因时的结果与传统的Ｐａｔｌａｋ方法在２２次因时的结果符合得比较好,对于４名受试者的实验数据,两种方法的平均相对误差的为６．５％,初步证实了本方法的可行性。     

Effect of D,L-carnitine, acetyl-D,L-beta-methylcholine chloride and glycine betaine on some processes of carbohydrate metabolism of humans and goats.

Oral administration of carnitine in normal and diabetic subjects showed a marked decrease in the level of blood glucose during the oral glucose tolerance test (OGTT) except for the three hour samples in diabetic subjects, while a decrease in the level of subsequent blood pyruvate samples was observed during the OGTT in normal and diabetic subjects after the administration of carnitine. During the OGTT, the peak of blood glucose and blood pyruvate level was generally delayed in the diabetic subjects. Furthermore, the mean blood pyruvate levels were elevated above those of normal subjects during the late stages of the test. The mean levels of blood glucose and blood pyruvate of all samples after the administration of carnitine were significantly higher in diabetics than the corresponding values in noramls. Carnitine administration decreased the total blood amino acid nitrogen level only in diabetic subjects. Carnitine caused a highly significant increase in the activity of serum alanine aminotransferase in normal and diabetic subjects, while it had no effect on the activity of serum aspartate aminotransferase. In goats, the level of blood glucose during the intravenous glucose tolerance test (IVGTT) was not affected by carnitine (1,3 or 6 mg/kg body weight). Carnitine in all doses used had no effect on the total blood amino acid nitrogen during the IVGTT, or on the activity of serum alanine aminotransferase and serum aspartate aminotransferase in the fasting samples. Acetyl-D,L-beta-methylcholine had no effect on the level of blood glucose, total blood amino acid nitrogen, the activity of serum alanine aminotransferase or serum aspartate aminotransferase in normal and diabetic subjects. The level of blood pyruvate decreased both in normal and diabetic subjects, in the samples that represented the peak of the curve. Glycine betaine had no effect on blood glucose, pyruvate, total blood amino acid nitrogen and the activity of serum alanine aminotransferase or serum aspartate amino transferase in normal and diabetic subjects or in goats.     

Plasma insulin and C-peptide responses to oral glucose load after physical exercise in men with normal and impaired glucose tolerance

Blood glucose, plasma insulin and C-peptide responses to oral glucose tolerance test (OGTT) were studied under basal conditions and immediately after 90-min exercise (60% VO2 max) in nondiabetic subjects with normal or impaired glucose tolerance. During the postexercise recovery blood glucose response to OGTT was increased in normal subjects and markedly decreased in those with impaired glucose tolerance, while insulin and C-peptide responses were diminished in both subgroups. The ratio of blood glucose to insulin was similarly elevated in all subjects. Comparing with basal conditions no significant changes were found in C-peptide to insulin ratio in response to OGTT after exercise, although a tendency towards an elevation of this ratio was noted in the subjects with impaired glucose tolerance. The data indicate that the reduced insulin response to OGTT during postexercise recovery in healthy subjects is due to diminished insulin secretion without any substantial changes in the hormone removal from blood, whereas in the glucose intolerant men the latter process may be enhanced.     

Effect of low blood glucose on plasma CRF, ACTH, and cortisol during prolonged physical exercise.

The effects of low blood glucose concentration during low-intensity prolonged physical exercise on the hypothalamus-pituitary-adrenocortical axis were investigated in healthy young men. In experiment 1, six subjects who had fasted for 14 h performed bicycle exercise at 50% of their maximal O2 uptake until exhaustion. At the end of the exercise, adrenocorticotropic hormone (ACTH) and cortisol increased significantly. However, this hormonal response was totally abolished when the same subjects exercised at the same intensity while blood glucose concentrations were maintained at the preexercise level. In experiment 2, in addition to ACTH and cortisol, the possible changes in plasma concentration of corticotropin-releasing factor (CRF) were investigated during exercise of the same intensity performed by six subjects. As suggested by a previous study (Tabata et al. Clin. Physiol. Oxf. 4: 299-307, 1984), when the blood glucose concentrations decreased to less than 3.3 mM, plasma concentrations of CRF, ACTH, and cortisol showed a significant increase. At exhaustion, further increases were observed in plasma CRF, ACTH, and cortisol concentrations. These results demonstrate that decreases in blood glucose concentration trigger the pituitary-adrenocortical axis to enhance secretion of ACTH and cortisol during low-intensity prolonged exercise in humans. The data also might suggest that this activation is due to increased concentration of CRF, which was shown to increase when blood glucose concentration decreased to a critical level of 3.3 mM.     

Beneficial effects of ketogenic diet in obese diabetic subjects

Objective Obesity is closely linked to the incidence of type II diabetes. It is found that effective management of body weight and changes to nutritional habits especially with regard to the carbohydrate content and glycemic index of the diet have beneficial effects in obese subjects with glucose intolerance. Previously we have shown that ketogenic diet is quite effective in reducing body weight. Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic obese subjects. In this study the effect of ketogenic diet in obese subjects with high blood glucose level is compared to those with normal blood glucose level for a period of 56 weeks. Materials and methods A total of 64 healthy obese subjects with body mass index (BMI) greater than 30, having high blood glucose level and those subjects with normal blood glucose level were selected in this study. The body weight, body mass index, blood glucose level, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined before and at 8, 16, 24, 48, and 56 weeks after the administration of the ketogenic diet. Results The body weight, body mass index, the level of blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes were more significant in subjects with high blood glucose level as compared to those with normal blood glucose level. The changes in the level of creatinine were not statistically significant. Conclusion This study shows the beneficial effects of ketogenic diet in obese diabetic subjects following its long-term administration. Furthermore, it demonstrates that in addition to its therapeutic value, low carbohydrate diet is safe to use for a longer period of time in obese diabetic subjects.     

Repeated blood glucose and plasma insulin levels in normal volunteer subjects receiving isocaloric meals, before and after chlorpropamide and glibenclamide.

The blood glucose and plasma insulin response to the two hypoglycaemic agents, chlorpropamide (Diabenese) and glibenclamide (Daonil) was determined in normal subjects under strict metabolic control in a double blind study. The subjects were admitted to hospital for the period of the study, during which time they received four isocaloric meals per day and their physical exercise was standardised. Chlorpropamide had a prolonged hypoglycaemic effect compared with the short lived response after glibenclamide. Thy hypoglycaemic characteristics of the two preparations could not be explained simply on the insulin responses. Chlorpropamide was capable of lowering blood glucose without raising plasma insulin levels, whereas glibenclamide produced a prolonged and marked increase in plasma insulin levels only to be associated with a short-lived hypoglycaemic response. The latter suggested that a degree of insulin resistance had been produced secondary to the early profound lowering of the blood glucose following glibenclamide. The data indicate therefore the need for caution in extrapolating to diabetic subjects the hypoglycaemic characteristics of an agent such as glibenclamide derived from studies in normal subjects.     

Blood glucose discrimination training in insulin-dependent diabetes mellitus (IDDM) patients

Self-management of insulin-dependent diabetes mellitus (IDDM) is dependent on a negative feedback loop of blood glucose (BG) fluctuations, which in turn directs treatment decisions to maintain normal BG. Although this feedback is typically accomplished by self-monitoring of blood glucose (SMBG), SMBG has limitations, and patients often rely on what their BG "feels" like. Two studies were performed to evaluate whether patients could learn to more accurately "feel"/discriminate their BG on the basis of internal cues or internal plus external BG cues. In Study I, BG Awareness Training significantly improved pre- to posttreatment BG estimation accuracy, relative to a control group. Study II replicated BG Awareness Training efficacy in improving BG estimation accuracy. Improvement in estimation accuracy was related only to initial accuracy; those who were initially less accurate improved the most. This improvement was represented in a 31% reduction in dangerous BG estimation errors and a 9% increase in accurate estimates. Resulting estimations were, however, still significantly less accurate than SMBG at the end of training.     

Relation of blood glucose levels to the changes in plasma levels of various hydrolytic enzymes in diabetic patients

Plasma levels of various hydrolytic enzymes in diabetic patients, as diagnosed by their blood glucose levels, were compared with those of control subjects. Most of the levels of the aminopeptidase activities examined were significantly increased, while those of angiotensin-converting enzyme (ACE) and esterase decreased, in diabetic patients. The results of multivariate analysis suggest that the increased aminopeptidase activities are related rather to secondary organ lesions than to the primary pancreatic lesion. It seems that the blood glucose level is not necessarily a good indicator of metabolic abnormalities underlying this pathological condition.     

Twenty-four-hour rhythms of plasma glucose and insulin secretion rate in regular night workers

To determine whether the ultradian and circadian rhythms of glucose and insulin secretion rate (ISR) are adapted to their permanent nocturnal schedule, eight night workers were studied during their usual 24-h cycle with continuous enteral nutrition and a 10-min blood sampling procedure and were compared with 8 day-active subjects studied once with nocturnal sleep and once with an acute 8-h-shifted sleep. The mean 24-h glucose and ISR levels were similar in the three experiments. The duration and the number of the ultradian oscillations were influenced neither by the time of day nor by the sleep condition or its shift, but their mean amplitude increased during sleep whenever it occurred. In day-active subjects, glucose and ISR levels were high during nighttime sleep and then decreased to a minimum in the afternoon. After the acute sleep shift, the glucose and ISR rhythms were split in a biphasic pattern with a slight increase during the night of deprivation and another during daytime sleep. In night workers, the glucose and ISR peak levels exhibited an 8-h shift in accordance with the sleep shift, but the onset of the glucose rise underwent a shift of only 6 h and the sleep-related amplification of the glucose and ISR oscillations did not occur simultaneously. These results demonstrate that despite a predominant influence of sleep, the 24-h glucose and ISR rhythms are only partially adapted in permanent night workers.     

Monitoring of blood glucose concentration in subjects with hypoglycaemic symptoms during everyday life.

OBJECTIVE--To study the persistence of hypoglycaemic symptoms, changes in blood glucose concentrations, and the relation between reported symptoms and measured blood glucose values in functional hypoglycaemia. DESIGN--Re-evaluation of symptoms in patients admitted consecutively with suspected hypoglycaemia followed by a case-control study. SETTING--The Steno Memorial Hospital in Gentofte, Denmark, which specialises in the diagnosis and treatment of and research on endocrine disorders, including hypoglycaemia. PATIENTS--21 Subjects admitted consecutively with hypoglycaemic symptoms that were relieved by eating in whom insulinoma and other organic disorders presenting with hypoglycaemia had been ruled out. Twelve of these subjects with persistent symptoms entered the case-control study, as did a matched control group. INTERVENTIONS--Four days of monitoring blood glucose concentrations at home, six daily samples being taken in fixed relation to meals by the finger prick method. Extra samples were taken when symptoms occurred. MAIN OUTCOME MEASURES--Blood glucose concentration, glycated haemoglobin concentration, and within subject variation in measured values. RESULTS--After one to three years of observation 19 of the 21 subjects still had symptoms. Six out of 12 subjects experienced hypoglycaemic symptoms during the controlled study. Blood glucose concentration ranged from 3.7 mmol/l to 7.5 mmol/l during these episodes. Changes in blood glucose concentration, mean blood glucose concentrations at each time point, within subject variation in the measured values, and glycated haemoglobin concentration were not significantly different in all patients compared with the control subjects and in patients with symptoms during the study compared with controls. CONCLUSION--Hypoglycaemic symptoms during everyday life in apparently healthy subjects are persistent but are not related to chemical hypoglycaemia.     

Circadian and Ultradian Rhythms in Blood Glucose and Plasma Insulin of Healthy Adults

The circadian and ultradian variations of blood glucose and plasma insulin have been characterized individually and as a group phenomenon in five healthy young adults studied while adhering as closely as possible to their usual routine of sleep, activity, meal content and timing. Three complementary methods were used to analyze the data: displaying raw data as a function of time; cosinor method according to Nelson and Halberg; and time series analyses as proposed by De Prins and Malbecq. The subjects were studied in the laboratory and their life routine were controlled, but very close to that of their habitual routine. They had mainly ultradian rhythms of blood glucose (mainly about 6 hr) and circadian rhythms of immunoreactive insulin (I.R.I.). Blood glucose ultradian rhythms seem to be mainly but not exclusively mealtime dependent, while I.R.I, circadian rhythms appear to be primarily endogenous in origin. Therefore, the role played by insulin in the control of blood glucose levels seems to be programmed on a circadian basis rather than by a time independent feedback phenomenon as postulated by the conventional homeostatic hypothesis. The advantage of this chronophysiologic approach is to consider circadian rhythms of both I.R.I. and insulin effectiveness as an adaptive phenomenon able to maintain blood sugar changes in the ultradian domain of rhythms.     

A Comparison of the Oral and Intravenous Glucose Tolerance Tests in Non-Diabetic,Possible Diabetic and Diabetic Subjects

Results of standard three-hour oral glucose tolerance tests (OGTT) and intravenous glucose tolerance tests (IVGTT), performed on the same subjects, were compared in an attempt to determine their value in the diagnosis of borderline diabetes. A total of 83 such tests were carried out on 81 subjects. Applying the U.S. Public Health Service point count method to the results of the OGTT test, there were 38 normals, 23 possible diabetics and 22 diabetics. A constant (K) was calculated from the glucose disappearance rate in the IVGTT curves.K disagreed with the OGTT classification to a significant extent, especially in the possible diabetic and non-diabetic groups. Also, the correlation coefficients between K and the OGTT values were not impressive. This does not mean that one test is superior to the other, only that the accuracy of either test in diagnosing early diabetes is doubtful.Technically, the IVGTT was more difficult and time-consuming, and six of the 81 subjects suffered from thrombophlebitis at the site of glucose injection.     

Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus.

Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin-dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin-dependent diabetes mellitus showed a significant improvement in their glucose tolerance, which paralleled the severity of their diabetes. This response seems to reflect decreased degradation of insulin rather than increased pancreatic output. These observations suggest that treatment with chloroquine or suitable analogues may be a new approach to the management of diabetes.     

Comparative Accuracy of 3 Blood Glucose Monitoring Systems that Communicate with An Insulin Pump

ObjectiveThis study compared the accuracy of the Contour® Next Link blood glucose monitoring system (BGMS) with 2 other BGMSs (OneTouch® UltraLink® and Nova Max Link™), all 3 of which can communicate wirelessly with an insulin pump.MethodsStudy staff tested fingerstick samples from 112 subjects aged ≥ 18 years with each BGMS. All BGMS results were compared to YSI 2300 STAT Plus™ Glucose Analyzer results from the same sample source. To safely obtain a wide range of glucose values, 3 blood samples were obtained from each subject (1 sample was tested fresh from the fingertip [unmodified], and the other 2 samples were modified to raise or lower the glucose concentration). The primary endpoint evaluated was difference in accuracy among the BGMSs across the entire tested glucose range (34 to 561 mg/dL). Additional comparisons were made of accuracy in the low (≤ 80 mg/dL) and high (> 180 mg/dL) glucose ranges. BGMS accuracy was assessed by mean absolute relative difference (MARD).ResultsThe Contour® Next Link BGMS had a statistically significantly lower MARD from the reference value than the other BGMSs across the entire tested glucose range, calculated using all samples as well as only unmodified (i.e., natural) samples. In the low and high glucose ranges, the Contour® Next Link also had a statistically significantly lower MARD from the reference value than the other BGMSs.ConclusionAs assessed by MARD, the Contour® Next Link BGMS was significantly more accurate than the other BGMSs evaluated, all of which can communicate wirelessly with an insulin pump. (Endocr Pract. 2014;20: 1016-1021)     

Role of Mood in Outcome of Biofeedback Assisted Relaxation Therapy in Insulin Dependent Diabetes Mellitus

Stressful life events and negative mood have been associated with elevated blood glucose and poor self-care in individuals with diabetes. The purpose of this controlled study was to determine the effect of mood state, specifically depression, anxiety, and daily hassles on the outcome of biofeedback assisted relaxation in insulin dependent diabetes mellitus. Eighteen subjects completed the study, nine in biofeedback assisted relaxation and nine in the control group. There were no significant group differences in blood glucose between those receiving biofeedback assisted relaxation and the subjects continuing usual care. Five of the nine experimental subjects and one of the nine control subjects were identified as succeeders according to an arbitrary criterion. Treatment failures were more depressed, more anxious, and took longer to complete the protocol than succeeders. Statistically significant correlations were found between high scores on inventories measuring depression, anxiety, and hassles intensity and higher blood glucose levels and smaller changes in blood glucose as a result of treatment. It is suggested that mood has an important impact on the response to biofeedback assisted relaxation. Further research is necessary to determine whether assessment of anxiety and depression followed by appropriate treatment where necessary should precede biofeedback assisted relaxation in insulin dependent diabetes.