Control In Insulin-dependent Diabetes Research Articles

Pharmacological Potential of Advance Diabetes Support Product in the Management of Insulin-Dependent Diabetes: Overviews on Case Study

Type I or Type II diabetes, once recognized as juvenile diabetes or insulin-dependent diabetes, is a chronic illness in which the pancreas produces slight or no insulin. Insulin-dependent diabetes is a syndrome of glucose homeostasis considered by autoimmune destruction of the insulin-producing pancreatic Beta-cell that gradually leads to insulin deficiency. As there is no perfect treatment for management, Gplife has thought of and developed a product that is found to be effective in the management of insulin-dependent diabetes. After 60 days of evaluation of cases, it is observed that fasting blood glucose was reduced by 62.25%, postprandial glucose levels were reduced by 62.37%, HBA1C levels were reduced by 39.57%, C Peptide levels were increased by 26.67%, also the external insulin injection requirement of the patient’s decreased by 88.57%. This case study gives an overview of the current understanding of the disease and the efficacy of advance diabetic support products in insulin-dependent diabetes. It is evident that the said product further helps to reduce insulin and OHA doses for the management of insulin-dependent diabetes. It is suggested that the advance diabetes support product should be further extensively used as a monotherapy or adjunctive therapy for the regulation, or management or control of insulin-dependent diabetes.

Spanish Consensus on the Use of Intermittently Scanned Continuous Glucose Monitoring in the Management of Patients With Insulin Therapy: The MONITOR Project.

Continuous glucose monitoring (CGM) systems are increasingly being adopted as an alternative or adjunct to self-monitoring of blood glucose (SMBG) by patients receiving insulin therapy. However, the available evidence on the role of intermittently scanned CGM or flash CGM (isCGM) remains limited. This consensus aims to evaluate the degree of agreement among Spanish experts on the role of isCGM in the evaluation of glycemic variability, reduction of glycosylated hemoglobin (HbA1c) levels, and selection and adjustment of insulin therapy. Delphi methodology was used to achieve consensus in two survey rounds. A total of 431 Spanish endocrinologists participated in the first round of a 34-item questionnaire survey on isCGM and 427 participated in the second round. Any disagreement was resolved in round 2. Consensus was reached for 32 statements, and four items were ultimately agreed upon SMBG after round 2. There was a high degree of consensus that isCGM helps to evaluate glycemic variability, improves HbA1c levels, and can guide therapeutic changes in type 1 diabetes patients. However, there was no consensus on the routine use of the interquartile range to evaluate glycemic variability or the selection of HbA1c as the main parameter for monitoring glycemic control. Most Spanish experts believe that the isCGM system is appropriate for: (1) identifying glycemic variability and facilitating its management, (2) evaluating hyperglycemia as a complement of HbA1c levels, and (3) guiding therapeutic decisions on insulin selection and dosing. The isCGM system is a useful tool for patients and health care professionals to improve glycemic control in insulin-dependent diabetes.

Kernel-based Estimate of the Insulin Action of Rapid-Acting Insulin in Home-Monitored Data

To improve glycemic control in insulin-dependent diabetes, estimates of the glucose- lowering effect of insulin-the insulin action (IA)-and the dynamics thereof are essential. The current practice relies on generic estimates of the dynamic shape of the IA and rules-of-thumb to assess the total glucose-lowering effect. In this paper we present individualized estimates based on home-monitored data, incorporating a kernel-based estimate that also accounts for the nonlinear behavior of the IA across the glucose range. The method is successfully validated on 29 patients on continuous insulin pump therapy.

Poor glycemic control induces hypertension in diabetes mellitus.

We conducted this study to test the hypothesis that hypertension is a primary consequence of poor glycemic control per se very early in insulin-dependent diabetes mellitus. Sprague-Dawley rats (n=15) were instrumented with artery and vein catheters, placed in metabolic cages, and sodium intake was clamped throughout the study. Mean arterial pressure was measured 24 h/d. After a precontrol period, streptozotocin (70 mg/kg IV) was administered, and 15 hours later a continuous intravenous infusion was begun at 4 U/rat per day. The insulin infusion was titrated on an individual rat basis to maintain good glycemic control, and after this 7-day control period, blood glucose, urinary sodium excretion, and mean arterial pressure were not different from precontrol values, averaging 8.8 +/- 0.6 mmol/L, 2.8 +/- 0.2 mmol/d, and 103 +/- 2 mm/Hg, respectively, for control days 5 through 7. Subsequently, a 4-day period of poor glycemic control was initiated by reducing the insulin infusion rate. Blood glucose, urinary sodium excretion, and mean arterial pressure began to increase on day 1; for diabetes days 3 and 4, they averaged 23.4 +/- 1.0 mmol/L, 3.6 +/- 0.1 mmol/d, and 110 +/- 2 mm Hg, respectively. All were significantly elevated. When insulin treatment was restored, all variables returned to control levels during the next 4 days. A second 4-day diabetic period yielded similar results. These results indicate that elevated blood pressure is a primary consequence of poor glycemic control in insulin-dependent diabetes, occurring before renal injury has had time to develop, and therefore, may be a factor contributing to the initiation of end-organ injury.

Response to DCCT: How Sweet Is It?

From the lack of increased referral to diabetic centers, it would appear that practicing physicians drew greatly different conclusions from the Diabetes Control and Complications Trial (DCCT) than did Brancati 1 as described in his editorial The Benefits of Tight Glycemic Control in Diabetes Mellitus. To me, the DCCT report showed that there is excellent justification for tight glycemic control in insulin-dependent diabetics, that patients should be encouraged to intensively monitor their blood glucose levels and adjust their dosage of insulin to maintain near normalization of the blood glucose levels as manifested by the hemoglobin A 1C , and that careful attention should be paid to diet. This confirmed my impression of state-of-the-art management of diabetes. I extrapolated that the same conclusions might apply to non—insulin-dependent diabetics and that aggressive management is probablyjustified. Nowhere did I draw from the DCCT the conclusion that tight diabetic control in a well-staffed diabetic unit

Therapeutic Uses of Gastrointestinal Peptides

The GI tract is one of nature's great pharmacies. Most, if not all, biologically active peptides can be found there, and it is quite likely that others remain to be discovered. Our ability to exploit this resource has expanded considerably over the past two decades. Advances in analytical techniques have allowed investigators to rapidly isolate and purify new compounds from tissue extracts. Sequencing and de novo synthesis of newly discovered peptides are now routine, and the structural modifications required to alter activity and tailor a compound to a particular use are easily made. A number of gastrointestinal peptides or their analogues for use in clinical studies are available from commercial sources (see Table 7). Somatostatin is the first gut peptide to successfully complete development and yield a pharmaceutical compound with a broad range of action. Several of the peptides discussed in this article have similar potential. TRH stands out as a candidate because of its effectiveness in the treatment of experimental spinal cord injury and a variety of shock states. Such a broad range of action in critical fields may justify the intensive development required to yield potent, long-acting, and highly specific analogues. Similarly, the antimetastatic and immunostimulant properties of the enkephalins offer promise for new therapies in the treatment of AIDS, ARC, and cancer. Studies with amylin may lead to new and more precise regimens of blood sugar control in insulin-dependent diabetics and could in turn, prevent some of the worst long-term effects of the disease. The development of effective intranasal forms of GHRH could spare children with GH-GHRH deficiency the distress of repeated injections and help to prevent excessive GH blood levels. Secretin, glucagon, or CGRP might be used one day in cardiovascular emergencies, and VIP or its analogues could prove effective in the treatment of asthma. Although preliminary results with many of these peptides are encouraging, further progress will require the development of standardized experimental models and a more rigorous approach to experimental design. Many of the studies reported here suffered from small patient numbers, a narrow or nonexistent range of doses, or the use of only one or two dosing regimens. Lack of objective criteria for determining the level of response, e.g., in studies of mental illness or degenerative diseases, and the ethical problems of withholding treatment from some patients to establish proper controls further hamper research in this area. If the questions of efficacy and safety are to be resolved, thorough, well-planned trials will be required.

Background factors, long-term complications, quality of life and metabolic control in insulin dependent diabetes

Sixty-six of 74 adults with Insulin Dependent Diabetes Mellitus (IDDM) examined earlier (1988), were followed up two years later (1990) with the aim of studying the influence of sociodemographic factors, long-term complications and quality of life on metabolic control. It was found that both non-cohabitance and a major discrepancy between quality of life change ratings made prospectively (difference in current QOL ratings made 1990 vs 1988) and retrospectively (assessed in 1990 and covering the same period) were associated with poorer metabolic control, and also that perceived somatic health was linked with better metabolic control. A majority of the persons with a major discrepancy in their quality of life ratings, seen as suggestive of difficulties in their realistically assessing their own life situation, was also found to be non-cohabitant and/or to have incipient nephropathy, indicating these persons to constitute a risk group. In addition, well-regulated subjects were found to rate their bodily health as higher than they did their quality of life, whereas for poorly regulated persons the opposite was the case. The results were seen as pointing to the need of paying special attention clinically to the group of persons characterized here by a major discrepancy in their quality of life change ratings and also as emphasizing the fact that living with IDDM is a balancing act for the individual between satisfying bodily demands to be well-regulated and living in such a way as to perceive quality of life.

Psychophysical visual function, retinopathy, and glycemic control in insulin-dependent diabetics with normal visual acuity.

We studied relations between psychophysical visual function and grade of retinopathy, glycemic control and clinical background data in 51 insulin-dependent diabetic patients, aged 17-47 years. Three separate qualities of visual function were examined, macular recovery time (nyctometry; 2 min adaptation), contrast sensitivity (Vistech 6000 chart; between 1.5 and 18 cycles per degree (cpd)) and colour vision (Fletcher DS8; protan/deutan and tritan). Only contrast sensitivity of 6 cpd was associated with the grade of retinopathy; reduced function was found in patients with retinopathy compared to those without. No correlations between macular recovery, contrast sensitivity and colour vision were found. None of the visual functions was significantly related to glycemic control, age, duration of diabetes, blood pressure, intraocular pressure, or urinary albumin excretion. Our data suggests that the neurosensory function of contrast sensitivity correlates more sensitively to the grade of diabetic retinopathy than macular recovery and colour vision. Cross-sectional assessments of different psychophysical visual functions seem to be of restricted clinical value as indicators of preceding glycemic control in diabetic patients with no or mild nonproliferative retinopathy.

Recent life events, gender, and the control of diabetes mellitus

Sixty-six outpatients with insulin-dependent diabetes mellitus (IDDM) filled in a life event questionnaire reflecting positive and negative life events perceived to have occurred over the past year. The difference in glycosylated hemoglobin (HbA1C) measures obtained before and after the 1-year period in question (Delta-HbA1C) served as a proxy measure of change in metabolic control. Among males, those reporting predominantly negative life events showed poorer metabolic control than those reporting few negative life events or none. Among females, the greater the number of events reported, especially positive ones, the greater the change for the better in HbA1C over the event year studied. These results suggest that life events may be significant to metabolic control in insulin-dependent diabetes. This only becomes apparent, however, when the two genders are analyzed separately, as various relationships found in one sex may be lacking or even opposite to the other sex. The findings also suggest the importance to the diabetic of learning of life events both the relative lack and preponderance of positive as well as negative events.

Psychosocial and psychopathologic influences on management and control of insulin-dependent diabetes.

The objective of this research was to explore the relationship of psychosocial variables to management and control of insulin-dependent diabetes, as measured by a scale of reported behavioral adherence and by glycosylated hemoglobin, respectively. The method includes a relatively large sample (127 subjects) drawn from a clinic, a broad range of psychosocial variables (depression, anxiety, family process, health locus of control), and documented reliability and validity of psychosocial measurement (alpha coefficients ranging from .63 to .95). The results show that both anxiety and depression have weak positive correlations with blood sugar. Family process variables also are weakly correlated with blood sugar. The measure of behavioral adherence is moderately correlated with blood sugar. The life stage of the diabetic appears to affect these relationships markedly. The conclusion is that there is no broad strong association of psychosocial variables with blood sugar but that there may be subgroups of diabetics, especially adolescents with recent onset, for whom the relationships may be more powerful.

The effect of dietary fiber type on glycated hemoglobin and renal hypertrophy in the adult diabetic rat

The effect of various dietary fiber sources on glycated hemoglobin and renal hypertrophy, two longterm indicators of blood glucose control, was studied in diabetic rats. Streptozotocin-treated rats were fed a fiber-free diet or diets containing 8% dietary fiber, using one of the following fiber sources: cellulose, sugar beet fiber, beet fiber treated with calcium carbonate, oat bran, rye bran, barley bran flour, wheat bran, or guar gum. After 28 days, only guar gumfeeding reduced the % glycated hemoglobin relative to the fiber-free control group. Renal hypertrophy was seen in animals from all diabetic groups and was not diminished by any of the fiber sources. In meal-fed animals there was no evidence of expansion of the intestinal contents volume by feeding of any fiber source. Guar gum substantially increased the viscosity of the intestinal contents in 3 of 4 animals. The results are consistent with the use of purified, highly viscous fiber sources for improving glycemic control in insulin-dependent diabetes.

Relationships among islet cell antibodies, residual β-cell function, and metabolic control in patients with insulin-dependent diabetes mellitus of long duration: Use of a sensitive C-peptide radioimmunoassay

Relationships among islet cell antibodies (ICA), residual β-cell function, and metabolic control were studied in 60 insulin-dependent diabetics (IDDs) of long duration (6 to 31 years). Sensitive C-peptide immunoreactivity (CPR) and ICA assays with limits of 0.017 nmol/L and 5 Juvenile Diabetes Foundation (JDF) U, respectively, demonstrated that baseline (0.16 ± 0.02 nmol/L, mean ± SE, n = 26), as well as maximum CPR values (0.34 ± 0.05 nmol/L), during 100-g oral glucose tolerance tests (OGTT) in ICA-positive IDDs were significantly higher than corresponding values in ICA-negative ones (baseline values, 0.10 ± 0.01 nmol/L, P < .05; maximum values, 0.20 ± 0.04 nmol/L, P < .01, n = 34). Negative correlation was observed between increment of serum CPR and metabolic control indices, including fasting blood glucose (FBG) and HbA 1c levels ( P < .05). In addition, ICA-positive insulin-dependent diabetes mellitus (IDDM) patients had lower values of FBG (8.2 ± 0.4 mmol/L, P < .01 v ICA-negative IDDs) and HbA 1c (9.2% ± 0.2%, P < .05 v ICA-negative IDDs) than ICA-negative ones (FBG, 9.9 ± 0.4 mmol/L; HbA 1c, 9.8% ± 0.2%). These results indicate that minute CPR responses to OGTT detected by sensitive methods may represent residual pancreatic β cells, which may contribute to ICA generation and good metabolic control in IDDs of long duration.

The influence of different insulin regimens on quality of life and metabolic control in insulin-dependent diabetics

Administration of insulin with premeal boluses of short-acting insulin using a new injection device (Novopen) was compared with a conventional three times daily injection regimen regarding aspects of quality of life and metabolic control in insulin-dependent diabetes mellitus (IDDM). Eighteen C-peptide-negative patients with IDDM (16 men, two women, aged 31.0 ± 7.4 years, duration of diabetes 13.0 ± 4.6 years; mean ± SD) participated in the study. All patients had been treated with three daily insulin injections for at least 1 year prior to the study. The patients were randomized into two groups. Group A started a 3-month treatment period with premeal injections of short-acting insulin and intermediate-acting insulin at bedtime. This period was followed by another 3 months using the initial three times daily injection regimen. Group B completed the study in the reverse order. Quality of life was assessed by using questionaires and personal interviews by the same clinical psychologist. Metabolic control was assessed by measuring the levels of glycosylated hemoglobin. The results show that both treatment groups experienced a general improvement in mood and well-being during the period with multiple insulin injection treatment. Furthermore, during the periods of insulin pen treatment, an increased experience of freedom and less dependence on fixed meal times were noted. Overall metabolic control, insulin dosage, body weight, and number of hypoglycemic episodes did not changes during the study. It is concluded that metabolic control, safety, and number of hypoglycemic episodes using premeal doses of short-acting insulin using Novopen were not different from those seen during conventional treatment. However, the experienced effects and consequences on quality of life during this treatment regimen were generally more positive with an increased feeling of freedom and improvement in mood.

Basal and stimulated insulin levels rise with advancing puberty.

We studied the effect of pubertal development on insulin secretion. Intravenous glucose tolerance tests were performed on 47 islet-cell antibody negative siblings of diabetic children and on 16 normal adults. Puberty was staged using Tanner's criteria and subjects were grouped as follows: I, stage 1 (n = 16); II, stages 2 and 3 (n = 15); III, stages 4 and 5 (n = 16); IV, adults (n = 16). Fasting insulin increased with advancing puberty (p = 0.59, P less than 0.001). The stimulated insulin response also rose with increasing pubertal development: for the 0-10 min insulin area, p = 0.46, P less than 0.001 and for the 10-60 min area, p = 0.68, P less than 0.001. There was a low positive correlation between insulin and age to 16 years but multiple regression analysis showed that this could be accounted for by puberty alone. Indeed prepubertal children and adults did not differ. There was no correlation between glucose (fasting and 0-60 min area) and puberty or age. These findings suggest that insulin resistance increases during puberty, and this may contribute to the frequency of presentation or worsening control of insulin dependent diabetes at this time.

Does physiological blood glucose control require an adaptive control strategy?

To test the hypothesis that only an adaptive algorithm would guarantee optimal feedback control of glycemia in insulin-dependent diabetes, fasting chronically diabetic dogs at rest were subjected to short-term artificial beta cell treatment. Insulin was applied intravenously and an oral glucose load was given during the experiment. Employing the same dosing algorithm, three different control strategies were employed in a random order on different days: adaptive control (minimum variance controller, Test A), fixed command control using on-line parameter estimates (Test B), and fixed command control using off-line individually optimized dosage constants (Test C). Comparison was made to nondiabetic control animals. The glycemic profiles were entirely normal in Test A and C, but were distinctly elevated in Test B. The peripheral hyperinsulinaemia could, however, not be avoided by adaptive control. It is concluded that the restoration of physiological blood glucose control in insulin-dependent diabetes requires dosage parameters which are either continually adapted to the actual situation (adaptive control) or are optimized to meet the individual's needs. In the latter case, fixed command control may be employed. Peripheral hyperinsulinaemia cannot be avoided as long as insulin is administered by a posthepatic route.

Diabetes, insulin and exercise.

The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so-called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin levels are low. Physical activity is often difficult to carry out on a precise schedule and the exercise-induced changes in demand for insulin and calories vary according to the intensity and duration of exercise, time of day, and differ within and between individuals. Thus, physical training can not be recommended as a means of improving metabolic control in insulin-dependent diabetes. However, our present knowledge and technology allows the well-informed and cooperative patient to exercise and even to reach the elite level. To achieve this, pre-exercise metabolic control should be optimal and knowledge of the patient's reaction to exercise is desirable, which necessitates frequent self-monitoring of plasma glucose. It may often be necessary to diminish the insulin dose before exercise, and/or to ingest additional carbohydrate during or after exercise. In non-insulin-dependent (type II) diabetes, exercise is associated with less risk of metabolic derangement, and in genetically disposed individuals physical training may prevent development of overt diabetes possibly by diminishing the strain on the pancreatic beta cell. The latter, however, is only achieved if exercise is not accompanied by increased caloric intake. Whether physical training in diabetes can reduce cardiovascular morbidity and mortality is at present unknown, but training has in diabetic patients been shown to lessen some risk factors for development of arteriosclerosis. However, training of diabetics (especially in the less well-regulated patient) may not lessen coronary risk factors to the same extent as in healthy subjects.

Serum fructosamine concentration as measure of blood glucose control in insulin dependent diabetes

Serum fructosamine concentration as measure of blood glucose control in insulin dependent diabetes

1190 PUBERTY AND DIABETES INDEPENDENTLY REDUCE INSULIN SENSITIVITY IN CHILDHOOD

The unstable metabolic control seen in adolescents with insulin dependent diabetes (IDD) is frequently attributed to psychosocial factors. To test the hypothesis that physiological changes of puberty play a role, we used the euglycemic, 1mU/kg.min insulin clamp technique (which raises plasma free insulin levels by ∼90uU/ml) to quantitate insulin sensitivity. 14 conventionallytreated, C-peptide negative IDD (5 Tanner I, 9 Tanner II-IV) and 5 Tanner I and 7 Tanner II-IV normal controls were studied. In the IDD neither the duration (7.2±1.3vs5.6±0.9yrs) nor the daily insulin dose (1.1±0.1 vs 1.0±0.1units/kg) differed between the groups (Tanner II-IV vs I). The glucose infusion rates (mg/kg. min) required to maintain euglycemia (91±0.6mg/dl) during the insulin clamp studies are shown below: In normal children, the onset of puberty is associated with a significant reduction in insulin-mediated glucose metabolism. A further 40% reduction in insulin sensitivity is observed in IDD at each stage of development. Conclusions: 1) Puberty causes a sharp reduction in insulin sensitivity in both normal and IDD children 2)IDD induces an additional defect in insulin sensitivity at each stage of development 3)The combined effects of puberty and IDD result in marked insulin resistance which may contribute to poor metabolic control in adolescent IDD.

Blood glucose discrimination training and metabolic control in insulin-dependent diabetics

Nine insulin-dependent diabetic adults were exposed to a blood glucose discrimination training program. Following baseline, during which Ss estimated their blood glucose levels twice daily, Ss received immediate feedback regarding the accuracy of their estimates. The procedure resulted in a large increase in accuracy of blood glucose estimation. Improvements in the ability to detect changes in blood glucose levels in the absence of chemical assessment, however, did not have a significant effect on long-term metabolic control. The implications of these findings are discussed.

Intensive attention improves glycaemic control in insulin dependent diabetes

Intensive attention improves glycaemic control in insulin dependent diabetes