scholarly journals 3D kernel-density stochastic model for more personalized glycaemic control: development and in-silico validation

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Vincent Uyttendaele ◽  
Jennifer L. Knopp ◽  
Shaun Davidson ◽  
Thomas Desaive ◽  
Balazs Benyo ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glycaemic Control ◽  
Stochastic Model ◽  
Kernel Density ◽  
Estimation Methods ◽  
Effective Control ◽  
Patient Specific ◽  
Glycaemic Variability ◽  
Glucose Levels

Abstract Background The challenges of glycaemic control in critically ill patients have been debated for 20 years. While glycaemic control shows benefits inter- and intra-patient metabolic variability results in increased hypoglycaemia and glycaemic variability, both increasing morbidity and mortality. Hence, current recommendations for glycaemic control target higher glycaemic ranges, guided by the fear of harm. Lately, studies have proven the ability to provide safe, effective control for lower, normoglycaemic, ranges, using model-based computerised methods. Such methods usually identify patient-specific physiological parameters to personalize titration of insulin and/or nutrition. The Stochastic-Targeted (STAR) glycaemic control framework uses patient-specific insulin sensitivity and a stochastic model of its future variability to directly account for both inter- and intra-patient variability in a risk-based insulin-dosing approach. Results In this study, a more personalized and specific 3D version of the stochastic model used in STAR is compared to the current 2D stochastic model, both built using kernel-density estimation methods. Fivefold cross validation on 681 retrospective patient glycaemic control episodes, totalling over 65,000 h of control, is used to determine whether the 3D model better captures metabolic variability, and the potential gain in glycaemic outcome is assessed using validated virtual trials. Results show that the 3D stochastic model has similar forward predictive power, but provides significantly tighter, more patient-specific, prediction ranges, showing the 2D model over-conservative > 70% of the time. Virtual trial results show that overall glycaemic safety and performance are similar, but the 3D stochastic model reduced median blood glucose levels (6.3 [5.7, 7.0] vs. 6.2 [5.6, 6.9]) with a higher 61% vs. 56% of blood glucose within the 4.4–6.5 mmol/L range. Conclusions This improved performance is achieved with higher insulin rates and higher carbohydrate intake, but no loss in safety from hypoglycaemia. Thus, the 3D stochastic model developed better characterises patient-specific future insulin sensitivity dynamics, resulting in improved simulated glycaemic outcomes and a greater level of personalization in control. The results justify inclusion into ongoing clinical use of STAR.

Virtual patient trials of a multi-input stochastic model for tight glycaemic control using insulin sensitivity and blood glucose data

2020 ◽  
Vol 59 ◽  
pp. 101896
Author(s):  
Shaun M. Davidson ◽  
Vincent Uyttendaele ◽  
Christopher G. Pretty ◽  
Jennifer L. Knopp ◽  
Thomas Desaive ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glycaemic Control ◽  
Stochastic Model ◽  
Virtual Patient ◽  
Tight Glycaemic Control

scholarly journals Vanadyl Sulfate Treatment Stimulates Proliferation and Regeneration of Beta Cells in Pancreatic Islets

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Samira Missaoui ◽  
Khémais Ben Rhouma ◽  
Mohamed-Tahar Yacoubi ◽  
Mohsen Sakly ◽  
Olfa Tebourbi
Keyword(s):  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Pancreatic Islets ◽  
Beta Cells ◽  
Control Level ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Blood Glucose Levels

We examined the effects of vanadium sulfate (VOSO4) treatment at 5 and 10 mg/kg for 30 days on endocrine pancreas activity and histology in nondiabetic and STZ-induced diabetic rats. In diabetic group, blood glucose levels significantly increased while insulinemia level markedly decreased. At the end of treatment, VOSO4at a dose of 10 mg/Kg normalized blood glucose level in diabetic group, restored insulinemia, and significantly improved insulin sensitivity. VOSO4also increased in a dose-dependent manner the number of insulin immunopositive beta cells in pancreatic islets of nondiabetic rats. Furthermore, in the STZ-diabetic group, the decrease in the number of insulin immunopositive beta cells was corrected to reach the control level mainly with the higher dose of vanadium. Therefore, VOSO4treatment normalized plasma glucose and insulin levels and improved insulin sensitivity in STZ-experimental diabetes and induced beta cells proliferation and/or regeneration in normal or diabetic rats.

Knowledge of Diabetes mellitus and Glycaemic Control

1997 ◽  
Vol 6 (4) ◽  
pp. 186-197
Author(s):  
David L. Robinson ◽  
Mahmoud Al-Bustan ◽  
Milad S. Bitar ◽  
Adnan Al-Asousi ◽  
Sobia Majeed
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Glycaemic Control ◽  
Hospital Admissions ◽  
Factor Model ◽  
Fasting Blood Glucose ◽  
General Factor ◽  
Diabetes Knowledge ◽  
Glucose Levels ◽  
Blood Glucose Levels

It has been claimed that lack of knowledge of diabetes mellitus has been a cause of excess admissions and morbidity. There is also some evidence that diabetic education programs can improve self-regulatory behaviour and reduce hospital admissions. In this report we test the hypothesis that greater knowledge of diabetes should be associated with better glycaemic control and lower fasting blood glucose levels. Responses to diabetes knowledge questions were provided by 420 patients attending diabetic clinics in Kuwait. In an earlier and complementary report a principal components analysis revealed that knowledge of diabetes cannot be understood in terms of a single general factor. With a subsequent Varimax rotation we obtained 12 uncorrelated knowledge factors with eigenvalues greater than unity and these would all be confounded in the simple aggregation of correct answers to diabetes knowledge questions employed in earlier studies. Results are now described which show that the 12-factor model of diabetes knowledge is better able to predict blood glucose levels than the scores obtained on a single scale by just summing the correct answers to all diabetes knowledge questions. A standard multiple linear regression with the diabetes knowledge factors age, sex and ‘years since diagnosis’ as independent variables, and fasting blood glucose levels as the dependent variable, shows that 4 of the 12 factors yield statistically significant semi-partial correlation coefficients that account for unique fractions of the total variance of blood glucose levels. The meaning of these 4 factors is discussed with special reference to glycaemic control and blood glucose levels.

scholarly journals MON-613 The Expression of TBC1 Domain Family, Member 4 (TBC1D4) in Skeletal Muscles of Insulin-Resistant Mice in Response to Sulforaphane

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nasser M Rizk ◽  
Amina Saleh ◽  
Abdelrahman ElGamal ◽  
Dina Elsayegh ◽  
Isin Cakir ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Skeletal Muscles ◽  
Glucose Disposal ◽  
Domain Family ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Blood Glucose Levels

Abstract The Expression of TBC1 Domain Family, member 4 (TBC1D4) in Skeletal Muscles of Insulin-Resistant Mice in Response to Sulforaphane. Background: Obesity is commonly accompanied by impaired glucose homeostasis. Decreased glucose transport to the peripheral tissues, mainly skeletal muscle, leads to reduced total glucose disposal and hyperglycemia. TBC1D4 gene is involved in the trafficking of GLUT4 to the outer cell membrane in skeletal muscle. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound acting by reducing blood glucose levels through mechanisms not fully understood (1). The aim of this study is to investigate the effects SFN on TBC1D4 and GLUT4 gene expression in skeletal muscles of DIO mice, in order to elucidate the mechanism(s) through which SFN improves glucose homeostasis. Methodology: C57BL/6 mice (n=20) were fed with a high fat diet (60%) for 16 weeks to generate diet induced obese (DIO) mice with body weights between 45–50 gm. Thereafter, DIO mice received either SFN (5mg/kg BW) (n=10) or vehicle (n=10) as controls daily by intraperitoneal injections for four weeks. Glucose tolerance test (1g/kg BW, IP) and insulin sensitivity test (ITT) were conducted (1 IU insulin/ g BW, IP route) at the beginning and end of the third week of the injection. At the end of 4 weeks of the injection, samples of blood and skeletal muscles of both hindlimbs were collected. The expression levels of GLUT4 and TBC1D4 genes were analyzed by qRT-PCR. Blood was also used for glucose, adiponectin and insulin measurements. Results: SFN-treated DIO mice had significantly lower non-fasting blood glucose levels than vehicle-treated mice (194.16 ± 14.12 vs. 147.44 ± 20.31 mg/dL, vehicle vs. SFN, p value=0.0003). Furthermore, GTT results indicate that the blood glucose levels at 120 minutes after glucose infusion in was (199.83±34.53 mg/dl vs. 138.55±221.78 mg/dl) for vehicle vs. SFN with p=0.0011 respectively. ITT showed that SFN treatment did not enhance insulin sensitivity in DIO mice. Additionally, SFN treatment did not significantly change the expression of TBC1D4, and GLUT4 genes in skeletal muscles compared to vehicle treatment (p values >0.05). Furthermore, SFN treatment did not significantly affect the systemic insulin (1.84±0.74 vs 1.54±0.55 ng/ml, p=0.436), or adiponectin (11.96 ±2.29 vs 14.4±3.33 ug/ml, p=0.551) levels in SFN vs. vehicle-treated DIO mice, respectively. Conclusion: SFN treatment improves glucose disposal in DIO mice, which is not linked to the gene expression of GLUT4 and TBC1D4 and its mechanism of glucose disposal in skeletal muscles. Furthermore, SFN treatment did not improve insulin level, and the insulin sensitizer hormone adiponectin as potential players for enhancing insulin sensitivity. 1. Axelsson AS, Tubbs E, Mecham B, Chacko S, Nenonen HA, Tang Y, et al. Sci Transl Med. 2017;9(394).

scholarly journals Glycaemic variability in diabetes: a tool for assessing the quality of glycaemic control and the risk of complications

2014 ◽  
Vol 17 (2) ◽  
pp. 76-82 ◽  
Author(s):  
Vadim Valer'evich Klimontov ◽  
Natalya Evgen'evna Myakina
Keyword(s):  
Blood Glucose ◽  
Glycaemic Control ◽  
Computational Methods ◽  
Temporal Structure ◽  
Vascular Complications ◽  
Vascular Lesions ◽  
Diabetic Patients ◽  
Glycaemic Variability ◽  
Hypoglycaemia Unawareness ◽  
Vascular Walls

The routine approach to evaluating the effectiveness of diabetes treatment based on the level of glycated haemoglobin (HbA. 1c) accounts for the average glucose level but does not consider the scope and frequency of its fluctuations. The development of computational methods to analyse glycaemic oscillations has made it possible to propose the concept of glycaemic variability (GV). The interest in research focused on GV increased dramatically after continuous glucose monitoring (CGM) technology was introduced, which provided the opportunity to study in detail the temporal structure of blood glucose curves. Numerous methods for assessing GV proposed over the past five decades characterize glycaemic fluctuations as functions of concentration and time and estimate the risks of hypoglycaemia and hyperglycaemia. Accumulating evidence indicates that GV may serve as a significant predictor of diabetic complications. Prospective studies demonstrate that certain GV parameters have independent significance for predicting diabetic retinopathy, nephropathy and cardiovascular diseases. There is evidence that GV correlates with the severity of atherosclerotic vascular lesions and cardiovascular outcomes in diabetic patients. The mechanisms underlying the relationship between GV and vascular complications are being intensively studied, and recent data show that the effect of GV on vascular walls may be mediated by oxidative stress, chronic inflammation and endothelial dysfunction. Average blood glucose levels and GV are considered independent predictors of hypoglycaemia. Increased GV is associated with impaired hormonal response to hypoglycaemia and is a long-term predictor of hypoglycaemia unawareness. These data allow us to conclude that computational methods for analysing GV in patients with diabetes may serve as a promising tool for personalized assessment of glycaemic control and the risk of vascular complications and hypoglycaemia. Thus, the reduction of GV can be regarded as one of the therapeutic targets to treat diabetes.

scholarly journals Sample of Aboriginal Australians, 2-hour post-load insulin concentrations are greatest between fasting plasma glucose values of 6.7-7.3 mmol/l

2018 ◽  
Vol 1 (2) ◽  
pp. 01-05
Author(s):  
Paul Aveyard
Keyword(s):  
Blood Glucose ◽  
Glycaemic Control ◽  
Routine Care ◽  
Systematic Sampling ◽  
Control Group ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Good Glycaemic Control ◽  
Blood Glucose Levels ◽  
The Impact

Background: Prevention of diabetic complications requires good glycaemic control. This study aimed to provide type 2 diabetes patients with remote active care and glycaemic control through the use of videophone technology without the need for them to attend hospital. The literature recommends additional research to study the impact of technical innovations on improved disease self-management and medical outcome. This is the only study to be conducted in Turkey concerning patient monitoring using videophone technology. The aim of the study was to establish the effectiveness of the use of videophone technology in the glycaemic control of patients with diabetes living in remote areas. Methods: This is a prospective, randomized control study using the systematic sampling method (using half ratio), in which 24 patients were chosen for the Experimental Group (EG) and another 24 for the Control Group (CG). All of the patients agreed to participate in the study. Patients in the CG received routine care, while the glycaemic control and consultations for patients in the EG were conducted using videophone technology. The patients were monitored by videophone for a total of 6 months. The HbA1c and blood glucose values recorded over the 6 month monitoring period were analyzed to determine the effectiveness of using a videophone. Results: The mean age of the individuals in the EG was 54.41 ± 8.54 years (Min=43 Max=78) and in the CG it was 57.25 ± 9.61 (Min=40 Max=77). In both groups, 50% of the individuals were men and 50% were women. When the two groups were compared, it was was found that the preprandial blood glucose levels of the diabetic patients in the EG (mean 159.48 ± 40.71mg/dl) were lower by 13.55 ± 52.89 mg / dl than the preprandial blood glucose levels of the diabetic patients in the CG (mean 173.03 ± 65.07 mg/dl). It was determined at the end of the six-month monitoring that the A1c levels of the individuals in the EG were significinatly lowered by 0.49% in total, and that the A1c levels of the individuals in the CG were higher by 0.17 % in total. Conclusions: It was shown that videophone technology can be useful in the glycaemic control of diabetic patients in Turkey.

Insulin and oral anti-hyperglycaemic agents in critical illness

2016 ◽  
Author(s):  
Roosmarijn T. M. van Hooijdonk ◽  
Marcus J. Schultz
Keyword(s):  
Blood Glucose ◽  
Critical Illness ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Insulin Infusion ◽  
Venous Catheter ◽  
Glycaemic Variability ◽  
Mortality And Morbidity ◽  
Glucose Levels ◽  
Measuring Devices

Dysglycaemia is frequently seen in the intensive care unit (ICU). Hyperglycaemia, hypoglycaemia and glycaemic variability are all independently associated with mortality and morbidity in critically-ill patients. It is common practice to treat hypergycaemia in these patients, while at the same time preventing hypoglycaemia and glycaemic variability. Insulin infusion is preferred over oral anti–hyperglycaemic agents for glucose control in the ICU because of the highly unpredictable biological availability of oral anti-hyperglycaemic agents during critical illness. Many oral anti–hyperglycaemic agents are relatively contraindicated in critically-ill patients. Intravenously-administered insulin has a predictable effect on blood glucose levels, in particular because of its short half-life. Notably, effective and safe insulin titration requires frequent blood glucose measurements, a dedicated lumen of a central venous catheter for infusion of insulin, an accurate syringe pump, and trained nurses for delicate adoptions of the infusion rate. Insulin infusion increases the risk of hypoglycaemia, which should be prevented at all times. In addition, precautions should be taken against overcorrection of hypoglycaemia, using only small amounts of glucose. Whether glycaemic variability can be kept minimal is uncertain. Use of continuous glucose measuring devices has the potential to improve glycaemic control in critically-ill patients.

scholarly journals Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice

Endocrinology ◽  
2018 ◽  
Vol 160 (1) ◽  
pp. 193-204 ◽  
Author(s):  
Isadora C Furigo ◽  
Miriam F Suzuki ◽  
João E Oliveira ◽  
Angela M Ramos-Lobo ◽  
Pryscila D S Teixeira ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Prolactin Secretion ◽  
Dopamine Receptor Agonist ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Insulin Tolerance ◽  
Promising Therapeutic Approach

Abstract Previous studies have shown that bromocriptine mesylate (Bromo) lowers blood glucose levels in adults with type 2 diabetes mellitus; however, the mechanism of action of the antidiabetic effects of Bromo is unclear. As a dopamine receptor agonist, Bromo can alter brain dopamine activity affecting glucose control, but it also suppresses prolactin (Prl) secretion, and Prl levels modulate glucose homeostasis. Thus, the objective of the current study was to investigate whether Bromo improves insulin sensitivity via inhibition of Prl secretion. Male and female ob/ob animals (a mouse model of obesity and insulin resistance) were treated with Bromo and/or Prl. Bromo-treated ob/ob mice exhibited lower serum Prl concentration, improved glucose and insulin tolerance, and increased insulin sensitivity in the liver and skeletal muscle compared with vehicle-treated mice. Prl replacement in Bromo-treated mice normalized serum Prl concentration without inducing hyperprolactinemia. Importantly, Prl replacement partially reversed the improvements in glucose homeostasis caused by Bromo treatment. The effects of the Prl receptor antagonist G129R-hPrl on glucose homeostasis were also investigated. We found that central G129R-hPrl infusion increased insulin tolerance of male ob/ob mice. In summary, our findings indicate that part of Bromo effects on glucose homeostasis are associated with decrease in serum Prl levels. Because G129R-hPrl treatment also improved the insulin sensitivity of ob/ob mice, pharmacological compounds that inhibit Prl signaling may represent a promising therapeutic approach to control blood glucose levels in individuals with insulin resistance.

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