This paper studies benefits of using simplified re-gime-switching adaptive control strategies in improving performance of insulin control for Type I diabetic patients. Typical dynamic models of glucose levels in diabe...This paper studies benefits of using simplified re-gime-switching adaptive control strategies in improving performance of insulin control for Type I diabetic patients. Typical dynamic models of glucose levels in diabetic patients are nonlinear. Using a linear time invariant controller based on an operating condition is a common method to simplify control design. On the other hand, adaptive control can potentially improve system performance, but it increases control complexity and may create further stability issues. This paper investigates patient models and presents a simplified switching control scheme using PID controllers. By comparing different switching schemes, it shows that switched PID controllers can improve performance, but frequent switching of controllers is unnecessary. These findings lead to a control strategy that utilizes only a small number of PID controllers in this scheduled adaptation strategy.展开更多
Background: Iowa Care (Iowa Medicaid in State of Iowa, USA), switched insulin glargine to detemir in subjects with Diabetes Mellitus (DM) without the knowledge or approval of healthcare providers beginning 8/2006.Impa...Background: Iowa Care (Iowa Medicaid in State of Iowa, USA), switched insulin glargine to detemir in subjects with Diabetes Mellitus (DM) without the knowledge or approval of healthcare providers beginning 8/2006.Impact of this transition in subjects with Type 1 DM is recently reported. Objective: To examine the impact of this transition on various parameters of diabetes management in Type 2 DM. Subjects and Methods: A retrospective review of the records of subjects with Type 2 DM was conducted until 8/2007 in whom the transition had occurred. Only those subjects with adequate glycemic control while receiving insulin glargine [GI] and completing at least 3 months of therapy with insulin detemir [DI] are included in this report. Ten subjects with Type 2 DM, duration 7 ± 2 years with age, 55 ± 3 years who were switched from GI to DI (Group 1) fulfilled the criteria for inclusion. Subjects were switched from GI in Q AM to DI Q HS in the same daily dose. Glycemic control (HbA1c), body weight, daily insulin dose (Units) and severe hypoglycemic events during the last 2 weeks of the period, pre switch and again at the end of 3 months post switch were assessed. Records of 8 subjects matched for age, duration of DM, glycemic control while receiving GI for additional 3 months (Group 2) during the same period were examined for comparison. All subjects were followed in the outpatient clinic at intervals of 3 months. Results Glycemic control remained stable on continuing GI AM;HbA1c;7.1 ± 0.3 to 7.1 ± 0.3%, while it worsened on switching to DI Q HS;HbA1c, 7.1 ± 0.3 to 8.1 ± 0.5 [P < 0.01]. A mild weight loss was noted in subjects on transition. No severe hypoglycemic events were reported in any subject in either group. Conclusion Abrupt transition from insulin glargine to insulin detemir in subjects with Type 2 DM is likely to result in lapse of glycemic control which may cause decreased quality of life. Furthermore, use of insulin detemir may result in increased costs due to need of the higher daily dose as well as additional equipment required for probable twice daily administration to achieve adequate glycemic control. Therefore, insulin glargine and detemir appear to be far from being bioequivalent.展开更多
The success of a specific treatment is traditionally judged according to parameters such as HbA1c. However, other, patient-reported outcomes (PRO) of (insulin) therapy, become increasingly more important. The introduc...The success of a specific treatment is traditionally judged according to parameters such as HbA1c. However, other, patient-reported outcomes (PRO) of (insulin) therapy, become increasingly more important. The introduction of (basal) insulin-analogues could possibly improve PRO, particularly “quality of life”. Direct comparative studies between once daily insulin glargine and once to twice or twice daily insulin detemir have previously shown differences in insulin dosage, dosing frequency and weight gain. Whether this leads to a difference in quality of life in patients who are transferred from insulin detemir to insulin glargine remains to be determined. To establish the effect of insulin glargine on quality of life and patient satisfaction in patients with DM2 who are in poor metabolic control with a (human) basal insulin, a large prospective, observational study in Dutch daily practice was performed. The results of the patient population switched from NPH-insulin to insulin glargine have been published previously. In this article the results of the group of patients treated with insulin detemir before the observation period are described. The results of this observational study show that changing basal insulin therapy to insulin glargine in patients with DM2 who are in poor glycemic control with insulin detemir leads to a clinically significant improvement of glycemic control as well as emotional wellbeing, despite a small increase in weight. Whether other factors such as decreased dosing frequency play a role remains to be determined by future studies.展开更多
Background: The major effect of Exenatide is attributed to lowering of post-prandial glycemia, whereas insulin glargine mainly improves fasting glycemia [FPG]. Objective: Therefore, we assessed effect of Exenatide adm...Background: The major effect of Exenatide is attributed to lowering of post-prandial glycemia, whereas insulin glargine mainly improves fasting glycemia [FPG]. Objective: Therefore, we assessed effect of Exenatide administration at 6 months and for at 1 year on glycemic control, lipids, body weight [BW], daily insulin dose and hypoglycemic events. Methods: Records of 164 subjects, 126 men and 38 women administered Exenatide between January 2011 and December 2013 are included in this report. Exenatide was initiated at 5 mcg subcutaneously twice daily [BID] in obese subjects, BMI > 30 kg/m2, with C-peptide > 1 ng/d, and HbA1c 7.5% - 9.5%, while receiving daily metformin 2000 mg, Sulfonylurea Glimepiride 8 mg and insulin Glargine [GLAR]. Exclusion criteria were creatinine > 1.5 mg/dL and liver enzymes > 2.5 times upper limit of normal. Indices of glycemic control include fasting plasma glucose levels and HbA1c. Lipids include serum concentrations of total, LDL and HDL cholesterol. Other endpoints are body weight, daily insulin dose and number of hypoglycemic events per patient during 4 weeks prior to initiation of Exenatide, at 6 months and 1 year of therapy. Results: In 37 subjects, Exenatide was discontinued within 1 - 3 weeks;29 due to onset of nausea and vomiting. Seven of these also complained of abdominal pain and in these, serum amylase and lipase were elevated indicating presence of acute pancreatitis. One subject discontinued because of chest pain. Fasting plasma Glucose remained unchanged following Exenatide administration. However, HbA1c declined significantly denoting improvement in overall glycemic control without significant changes in body weight, daily insulin dose and hypoglycemic events. Lipid panel improved as well. Conclusion: Exenatide may be an appropriate adjuvant option in obese subjects with Type 2 diabetes mellitus with lack of desirable glycemic control while receiving therapy with Metformin, Glimepiride, and insulin Glargine. Moreover, improvement in glycemic control is likely to be secondary to lowering of post prandial hyperglycemia induced by Exenatide.展开更多
The term Diabetes Mellitus (DM) comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. The Insulin therapy constitutes the pre...The term Diabetes Mellitus (DM) comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. The Insulin therapy constitutes the preferred treatment for DM, consisting of daily subcutaneous insulin injections to control blood glucose levels. The chitosan studied for Biomedicine is a biomaterial that can be used for controlled release of drugs whose release rate can be controlled by Sodium Tripolyphosphate (TPP), which is an ionic cross linker of the chitosan. Present study, therefore, was aimed to develop and evaluate membranes of chitosan and chitosan cross linked by TPP for use in controlled release of insulin system, with the purpose of obtaining an alternative to the injectable administration of this drug. The developed membranes were characterized by the techniques of Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), High Performance Liquid Chromatography (HPLC) and Evaluation of Cell Viability of Macrophages (MTT). With the FTIR technique the interaction between chitosan, tripolyphosphate and insulin was identified. Chemical elements present in chitosan, insulin and sodium tripolyphosphate membranes were detected by EDX technique. By SEM technique, the changes in the morphology of the membrane containing insulin, with the presence of granular particles of varying sizes, could be observed when compared to pure chitosan. With HPLC assay insulin was identified and it was shown that it gets separated from chitosan membrane even when the membrane was cross linked by the TPP, though at a reduced rate. The crosslinking agent was effective to control the rate of insulin release. The biocompatibility of the prepared membranes was confirmed by cell viability of macrophages using the MTT assay. The developed membranes, therefore, have potential for use as a biomaterial in controlled release systems for insulin.展开更多
While the incidence of toddlers’ diabetes is soaring,their mainstay insulins were withdrawn,namely the weak 10% or 20% insulin mixtures (WIM),which were injected only once or twice daily.Consequently,toddlers are coe...While the incidence of toddlers’ diabetes is soaring,their mainstay insulins were withdrawn,namely the weak 10% or 20% insulin mixtures (WIM),which were injected only once or twice daily.Consequently,toddlers are coerced to use an insulin pump,multi-dose insulin regime (MuDIR),mix or dilute insulins.This paper highlights the difficulties and proposes a simple solution.While an insulin pump is the best available option,it is not readily available for everyone.Mixing insulins is not sufficiently precise in small doses.Although diluting insulin would allow precise dosing and reduce the dose variability secondary to dribbling after injections,it,like insulin mixing,deprives children from using the pen and related child-friendly accessories.In MuDIR,we inject 4-5 small doses of insulin instead of 1-2 daily larger doses of WIM.Thus,on using a half unit (unit) insulin pen,a dose of 0.5,1,1.5 and 2 units are adjusted in steps of 100%,50%,33% or 25%;unlike the advisable 5%-20%.This does not easily match the tiny erratic meals of grazing toddlers.Maternal anxiety peaks on watching yo-yoing glycemia.Carers have to accept either persistently high sugar or wild fluctuation.The risks of such poor glycemic pattern are increasingly recognized.Using insulin U20 in a unit disposable pen allows deci-unit dosing,with 5%-20% dose-tuning,greater accuracy on delivering small doses and reduction of dose variability from dribbling.Deci-unit dosing may help avoid wide glycemic swings and provide the affordable alternative to insulin pumps for toddlers.Deci-unit pen materializes the Human Rights of Children,a safer and effective treatment.展开更多
Diabetes therapy is normally based on discrete insulin infusion that uses long-time interval measurements. Nevertheless, in this paper, a continuous drug infusion closed-loop control system was proposed to avoid the t...Diabetes therapy is normally based on discrete insulin infusion that uses long-time interval measurements. Nevertheless, in this paper, a continuous drug infusion closed-loop control system was proposed to avoid the traditional discrete approaches by automating diabetes therapy. Based on a continuous insulin injection model, two controllers were designed to deal with this plant. The controllers designed in this paper are: proportional integral derivative (PID), and fuzzy logic controllers (FLC). Simulation results have illustrated that the fuzzy logic controller outperformed the PID controller. These results were based on serious disturbances to glucose, such as exercise, delay or noise in glucose sensor and nutrition mixed meal absorption at meal time.展开更多
Introduction: To assess the changes in glycemic control after initiating or switching to a basal insulin analogue in patients with diabetes mellitus. Methods: A retrospective, observational analysis was conducted usin...Introduction: To assess the changes in glycemic control after initiating or switching to a basal insulin analogue in patients with diabetes mellitus. Methods: A retrospective, observational analysis was conducted using electronic data from a Hong Kong regional hospital. Data from adult patients with type 1 and 2 diabetes mellitus (T1DM and T2DM, respectively) who had been prescribed with basal insulin glargine in 2008-2010, with recorded HbA1c levels at the time of initiation, at 6 and 12 months thereafter, were analysed. Results: Data from 106 eligible patients were analysed. Substantial reduction in HbA1c and fasting sugar levels were reported in both T1DM (Δ HbA1c = 1.5%, Δ FBG = 1.3 mmol/L p < 0.05) and T2DM (Δ HbA1c = 1.2%, Δ FBG = 2.9 mmol/L p < 0.05) patients after 12 months of therapy. A total of 42% of T1DM and 26% of T2DM patients achieved HbA1c levels < 7.0%. After adjustment, T2DM patients who were insulin naive achieved a statistically greater HbA1c reduction (Δ = 1.7%) than those who previous treated with premixed or basal bolus insulin (Δ = 0.3%) (p < 0.05). Percentage of patients experiencing hypoglycaemia reduced from 69% to 62% in T1DM but increased from 26% to 36% in T2DM patients. All hypoglycaemic episodes recorded were either asymptomatic or mild and self-limiting. Only 4% of the patients discontinued treatment at the end of 12 months. Conclusions: In real life clinical practice, a single daily basal insulin analogue therapy provided effective glycemic control with an acceptable risk of mild hypoglycaemia.展开更多
This paper aims at the development of an approach integrating the fuzzy logic strategy for a glucose and insulin in diabetic human optimal control problem. To test the efficiency of this strategy, the author proposes ...This paper aims at the development of an approach integrating the fuzzy logic strategy for a glucose and insulin in diabetic human optimal control problem. To test the efficiency of this strategy, the author proposes a numerical comparison with the indirect method. The results are in good agreement with experimental data.展开更多
The effect of nutrition education using self-monitoring of blood glucose on glycemic control was investigated in the present study. Of 36 males and 25 females aged 30 - 69 years under outpatient treatment at 3 hospita...The effect of nutrition education using self-monitoring of blood glucose on glycemic control was investigated in the present study. Of 36 males and 25 females aged 30 - 69 years under outpatient treatment at 3 hospitals in Niigata prefecture, Japan, 61 non-insulin-treated obese type 2 diabetes patients with HbA1c of 6.9% - 9.3% and body mass index of 25 kg/m2 or higher were randomly allocated. Thirty and 31 patients were analyzed in intervention and control groups, respectively. The intervention group performed self-monitoring of blood glucose 2 hours after supper twice a week for 6 months and underwent nutrition education on the association between meals and postprandial blood glucose once every 2 months. The primary outcome was glycated hemoglobin, with the secondary outcome of body mass index. Stages of change for eating the appropriate supper amount were investigated to verify the process of the educational effect, and satisfaction with diabetes treatment and well-being were investigated to verify the continuity of treatment. On intention-to-treat analysis, glycated hemoglobin (mean ± SD) decreased from 7.9% ± 0.6% to 7.7% ± 0.6% in the intervention group but increased from 7.9% ± 0.6% to 8.1% ± 0.6% in the control group, showing a significant difference in the change after intervention between the groups (p = 0.027). In the intervention group, body mass index decreased from 28.9 ± 3.8 to 28.4 ± 3.7 kg/m2 (p = 0.019), the stages of change to learn the appropriate amount of supper progressed (p = 0.026), and satisfaction with diabetes treatment increased (p = 0.031).展开更多
BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to ...BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE: To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES: Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbAlc), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. RESULTS: Compared with the control group, CHF treatment significantly decreased BMI (P〈0.05), WC (P〈0.01) and WHR (P〈0.01). Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P〈0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P〈0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P〉0.05), whereas it significantly increased with CHF treatment (P〈0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P〈0.01). However, there was no significant difference between the two groups (P〉0.05). CONCLUSION: Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.展开更多
Hyperglycemia is common in critically ill patients and can be caused by various mechanisms, including nutrition, medications, and insufficient insulin. In the past, hyperglycemia was thought to be an adaptive response...Hyperglycemia is common in critically ill patients and can be caused by various mechanisms, including nutrition, medications, and insufficient insulin. In the past, hyperglycemia was thought to be an adaptive response to stress, but hyperglycemia is no longer considered a benign condition in patients with critical illnesses. Indeed, hyperglycemia can increase morbidity and mortality in critically ill patients. Correction of hyperglycemia may improve clinical outcomes. To date, a definite answer with regard to glucose management in general intensive care unit patients, including treatment thresholds and glucose target is undetermined. Meta-analyses of randomized controlled trials suggested no survival benefit of tight glycemic control and a significantly increased incidence of hypoglycemia. Studies have shown a J- or U-shaped relationship between average glucose values and mortality; maintaining glucose levels between 100 and 150 mg/dL was likely to be associated with the lowest mortality rates. Recent studies have shown glycemic control < 180 mg/d L is not inferior to near-normal glycemia in critically ill patients and is clearly safer. Glycemic variability is also an important aspect of glucose management in the critically ill patients. Higher glycemic variability may increase the mortal-ity rate, even in patients with the same mean glucose level. Decreasing glucose variability is an important issue for glycemic control in critically ill patients. Continuous measurements with automatic closed-loop systems could be considered to ensure that blood glucose levels are controlled within a specific range and with minimal variability.展开更多
In type 1 diabetes,flexible,intensive insulin management improves not only glycemic control but also dietary freedom and treatment satisfaction.Such flexibility has been made possible with the new insulin analogues(as...In type 1 diabetes,flexible,intensive insulin management improves not only glycemic control but also dietary freedom and treatment satisfaction.Such flexibility has been made possible with the new insulin analogues(as part of a basal-bolus regime) and is now gaining wide applicability,especially among children and adolescents.This approach requires appropriate individualized patient education.Especially for adolescents,the clinician should be able to guarantee insightful participation in direct response to their attitudes,wishes and needs.This patient-and-doctor collaboration is an ever-challenging duty and has the potential to change the future of the individual diabetic patient.展开更多
AIM: To assess the safety of enhanced recovery after surgery(ERAS) program in gastrectomy and influences on nutrition state and insulin-resistance. METHODS: Our ERAS program involved shortening the fasting periods and...AIM: To assess the safety of enhanced recovery after surgery(ERAS) program in gastrectomy and influences on nutrition state and insulin-resistance. METHODS: Our ERAS program involved shortening the fasting periods and preoperative carbohydrate loading. Eighty gastrectomy patients were randomly assigned to either the conventional group(CG) or ERAS group(EG). We assessed the clinical characteristics and postoperative outcomes prospectively. The primary endpoint was noninferiority in timely discharge from the hospital within 12 d. Secondary endpoints were the incidence of aspiration at anesthesia induction, incidence of postoperative complications, health related quality of life(HRQOL) using the SF8 Health Survey questionnaire, nutrition state [e.g., albumin, transthyretin(TTR), retinal-binding protein(RBP), and transferrin(Tf)], the homeostasis model assessment-insulin resistance(HOMA-R) index, postoperative urine volume,postoperative weight change, and postoperative oral intake.RESULTS: The ERAS program was noninferior to the conventional program in achieving discharge from the hospital within 12 d(95.0% vs 92.5% respectively; 95%CI:-10.0%-16.0%). There was no significant difference in postoperative morbidity between the two groups. Adverse events such as vomiting and aspiration associated with the induction of general anesthesia were not observed. There were no significant differences with respect to postoperative urine volume, weight change, and oral intake between the two groups. EG patients with preoperative HOMA-R scores above 2.5 experienced significant attenuation of their HOMA-R scores on postoperative day 1 compared to CG patients(P = 0.014). There were no significant differences with respect to rapid turnover proteins(TTR, RBP and Tf) or HRQOL scores using the SF8 method.CONCLUSION: Applying the ERAS program to patients who undergo gastrectomy is safe, and improves insulin resistance with no deterioration in QOL.展开更多
This double-blind, controlled, randomized, three-way cross-over study evaluates the effect of 40 g (D1 group) and 20 g (D2 group) of acacia gum (AG) versus no treatment (NT group) on post-prandial glucose (PPG) levels...This double-blind, controlled, randomized, three-way cross-over study evaluates the effect of 40 g (D1 group) and 20 g (D2 group) of acacia gum (AG) versus no treatment (NT group) on post-prandial glucose (PPG) levels in normal-weight and overweight subjects. Additionally, post-prandial insulin (PPI) levels as well as the safety and tolerability of gum acacia were assessed. 35 healthy subjects aged 25 - 60 years, body mass index 18.5 kg/m<sup>2</sup> - 29.9 kg/m<sup>2</sup>, received one treatment of 20 g, 40 g, or 0 g of AG each. Glucose and insulin values were determined at -15 min and prior to the intake (time “0”) as well as 15, 30, 45, 60, 90 120, and 180 min after the “0 min” blood draw. The mean PPG levels were lower (34% in D1 group, p = 0.003;35% in D2 group, p = 0.005) than in the NT group. PPI concentration was statistically significantly lower at all time points except baseline in both treatment groups compared to NT groups. Global benefit and tolerability were rated as “very good” or “good” by 100% of subjects in the treatment groups. This study provides robust evidence of the significant benefits of AG consumption on PPG and PPI levels in healthy subjects. Moreover, very good tolerability was demonstrated.展开更多
Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy ...Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy (IIT) (maintain glucose p = 0.628), ICU LOS (MD = -0.073 days, 95% CI = -0.324 to 0.178;p = 0.568), or hospital LOS (MD = 0.269, 95% CI = -2.158 to 2.696;p = 0.828). No difference in AF rates (RR = 0.887, 95% CI = 0.681 to 1.155;p = 0.375) or deep sternal infection (RR = 0.985, 95% CI = 0.357 to 2.720;p = 0.977) were observed. Conclusion: IIT targeting blood sugar levels of 80 - 120 mg/dl have no effect on perioperative outcomes in cardiac surgery patients. IIT is associated with similar mortality, ICU LOS, hospital LOS, AF rates, and deep sternal infection rates compared to more liberal glycemic strategies. IIT should not replace CIT as the standard of care in cardiac surgery patients.展开更多
A discrete insulin infusion based on long-time interval measurement is the classic technique for diabetes treatment. Nevertheless, in this research, a closed-loop control system was proposed for continuous drug infusi...A discrete insulin infusion based on long-time interval measurement is the classic technique for diabetes treatment. Nevertheless, in this research, a closed-loop control system was proposed for continuous drug infusion to overcome the drawbacks of these typical discrete methods and develop more practical diabetes therapy systems. A blood glucose-insulin system was implemented relying on continuous insulin injection model. Based on this model, two controllers were designed to deal with the control dilemma of the resulting highly nonlinear plant. The controllers designed in this paper are: proportional integral derivative (PID), and sliding table controllers. Simulation results have shown that the sliding table controller can outperform the PID controller even with severe circumstances of disturbance in glucose, such as exercise, delay or noise in glucose sensor and nutrition mixed meal absorption at meal times.展开更多
文摘This paper studies benefits of using simplified re-gime-switching adaptive control strategies in improving performance of insulin control for Type I diabetic patients. Typical dynamic models of glucose levels in diabetic patients are nonlinear. Using a linear time invariant controller based on an operating condition is a common method to simplify control design. On the other hand, adaptive control can potentially improve system performance, but it increases control complexity and may create further stability issues. This paper investigates patient models and presents a simplified switching control scheme using PID controllers. By comparing different switching schemes, it shows that switched PID controllers can improve performance, but frequent switching of controllers is unnecessary. These findings lead to a control strategy that utilizes only a small number of PID controllers in this scheduled adaptation strategy.
文摘Background: Iowa Care (Iowa Medicaid in State of Iowa, USA), switched insulin glargine to detemir in subjects with Diabetes Mellitus (DM) without the knowledge or approval of healthcare providers beginning 8/2006.Impact of this transition in subjects with Type 1 DM is recently reported. Objective: To examine the impact of this transition on various parameters of diabetes management in Type 2 DM. Subjects and Methods: A retrospective review of the records of subjects with Type 2 DM was conducted until 8/2007 in whom the transition had occurred. Only those subjects with adequate glycemic control while receiving insulin glargine [GI] and completing at least 3 months of therapy with insulin detemir [DI] are included in this report. Ten subjects with Type 2 DM, duration 7 ± 2 years with age, 55 ± 3 years who were switched from GI to DI (Group 1) fulfilled the criteria for inclusion. Subjects were switched from GI in Q AM to DI Q HS in the same daily dose. Glycemic control (HbA1c), body weight, daily insulin dose (Units) and severe hypoglycemic events during the last 2 weeks of the period, pre switch and again at the end of 3 months post switch were assessed. Records of 8 subjects matched for age, duration of DM, glycemic control while receiving GI for additional 3 months (Group 2) during the same period were examined for comparison. All subjects were followed in the outpatient clinic at intervals of 3 months. Results Glycemic control remained stable on continuing GI AM;HbA1c;7.1 ± 0.3 to 7.1 ± 0.3%, while it worsened on switching to DI Q HS;HbA1c, 7.1 ± 0.3 to 8.1 ± 0.5 [P < 0.01]. A mild weight loss was noted in subjects on transition. No severe hypoglycemic events were reported in any subject in either group. Conclusion Abrupt transition from insulin glargine to insulin detemir in subjects with Type 2 DM is likely to result in lapse of glycemic control which may cause decreased quality of life. Furthermore, use of insulin detemir may result in increased costs due to need of the higher daily dose as well as additional equipment required for probable twice daily administration to achieve adequate glycemic control. Therefore, insulin glargine and detemir appear to be far from being bioequivalent.
文摘The success of a specific treatment is traditionally judged according to parameters such as HbA1c. However, other, patient-reported outcomes (PRO) of (insulin) therapy, become increasingly more important. The introduction of (basal) insulin-analogues could possibly improve PRO, particularly “quality of life”. Direct comparative studies between once daily insulin glargine and once to twice or twice daily insulin detemir have previously shown differences in insulin dosage, dosing frequency and weight gain. Whether this leads to a difference in quality of life in patients who are transferred from insulin detemir to insulin glargine remains to be determined. To establish the effect of insulin glargine on quality of life and patient satisfaction in patients with DM2 who are in poor metabolic control with a (human) basal insulin, a large prospective, observational study in Dutch daily practice was performed. The results of the patient population switched from NPH-insulin to insulin glargine have been published previously. In this article the results of the group of patients treated with insulin detemir before the observation period are described. The results of this observational study show that changing basal insulin therapy to insulin glargine in patients with DM2 who are in poor glycemic control with insulin detemir leads to a clinically significant improvement of glycemic control as well as emotional wellbeing, despite a small increase in weight. Whether other factors such as decreased dosing frequency play a role remains to be determined by future studies.
文摘Background: The major effect of Exenatide is attributed to lowering of post-prandial glycemia, whereas insulin glargine mainly improves fasting glycemia [FPG]. Objective: Therefore, we assessed effect of Exenatide administration at 6 months and for at 1 year on glycemic control, lipids, body weight [BW], daily insulin dose and hypoglycemic events. Methods: Records of 164 subjects, 126 men and 38 women administered Exenatide between January 2011 and December 2013 are included in this report. Exenatide was initiated at 5 mcg subcutaneously twice daily [BID] in obese subjects, BMI > 30 kg/m2, with C-peptide > 1 ng/d, and HbA1c 7.5% - 9.5%, while receiving daily metformin 2000 mg, Sulfonylurea Glimepiride 8 mg and insulin Glargine [GLAR]. Exclusion criteria were creatinine > 1.5 mg/dL and liver enzymes > 2.5 times upper limit of normal. Indices of glycemic control include fasting plasma glucose levels and HbA1c. Lipids include serum concentrations of total, LDL and HDL cholesterol. Other endpoints are body weight, daily insulin dose and number of hypoglycemic events per patient during 4 weeks prior to initiation of Exenatide, at 6 months and 1 year of therapy. Results: In 37 subjects, Exenatide was discontinued within 1 - 3 weeks;29 due to onset of nausea and vomiting. Seven of these also complained of abdominal pain and in these, serum amylase and lipase were elevated indicating presence of acute pancreatitis. One subject discontinued because of chest pain. Fasting plasma Glucose remained unchanged following Exenatide administration. However, HbA1c declined significantly denoting improvement in overall glycemic control without significant changes in body weight, daily insulin dose and hypoglycemic events. Lipid panel improved as well. Conclusion: Exenatide may be an appropriate adjuvant option in obese subjects with Type 2 diabetes mellitus with lack of desirable glycemic control while receiving therapy with Metformin, Glimepiride, and insulin Glargine. Moreover, improvement in glycemic control is likely to be secondary to lowering of post prandial hyperglycemia induced by Exenatide.
文摘The term Diabetes Mellitus (DM) comprises a group of metabolic disorders characterized by chronic hyperglycemia resulting from defects in the secretion and/or action of insulin. The Insulin therapy constitutes the preferred treatment for DM, consisting of daily subcutaneous insulin injections to control blood glucose levels. The chitosan studied for Biomedicine is a biomaterial that can be used for controlled release of drugs whose release rate can be controlled by Sodium Tripolyphosphate (TPP), which is an ionic cross linker of the chitosan. Present study, therefore, was aimed to develop and evaluate membranes of chitosan and chitosan cross linked by TPP for use in controlled release of insulin system, with the purpose of obtaining an alternative to the injectable administration of this drug. The developed membranes were characterized by the techniques of Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), High Performance Liquid Chromatography (HPLC) and Evaluation of Cell Viability of Macrophages (MTT). With the FTIR technique the interaction between chitosan, tripolyphosphate and insulin was identified. Chemical elements present in chitosan, insulin and sodium tripolyphosphate membranes were detected by EDX technique. By SEM technique, the changes in the morphology of the membrane containing insulin, with the presence of granular particles of varying sizes, could be observed when compared to pure chitosan. With HPLC assay insulin was identified and it was shown that it gets separated from chitosan membrane even when the membrane was cross linked by the TPP, though at a reduced rate. The crosslinking agent was effective to control the rate of insulin release. The biocompatibility of the prepared membranes was confirmed by cell viability of macrophages using the MTT assay. The developed membranes, therefore, have potential for use as a biomaterial in controlled release systems for insulin.
文摘While the incidence of toddlers’ diabetes is soaring,their mainstay insulins were withdrawn,namely the weak 10% or 20% insulin mixtures (WIM),which were injected only once or twice daily.Consequently,toddlers are coerced to use an insulin pump,multi-dose insulin regime (MuDIR),mix or dilute insulins.This paper highlights the difficulties and proposes a simple solution.While an insulin pump is the best available option,it is not readily available for everyone.Mixing insulins is not sufficiently precise in small doses.Although diluting insulin would allow precise dosing and reduce the dose variability secondary to dribbling after injections,it,like insulin mixing,deprives children from using the pen and related child-friendly accessories.In MuDIR,we inject 4-5 small doses of insulin instead of 1-2 daily larger doses of WIM.Thus,on using a half unit (unit) insulin pen,a dose of 0.5,1,1.5 and 2 units are adjusted in steps of 100%,50%,33% or 25%;unlike the advisable 5%-20%.This does not easily match the tiny erratic meals of grazing toddlers.Maternal anxiety peaks on watching yo-yoing glycemia.Carers have to accept either persistently high sugar or wild fluctuation.The risks of such poor glycemic pattern are increasingly recognized.Using insulin U20 in a unit disposable pen allows deci-unit dosing,with 5%-20% dose-tuning,greater accuracy on delivering small doses and reduction of dose variability from dribbling.Deci-unit dosing may help avoid wide glycemic swings and provide the affordable alternative to insulin pumps for toddlers.Deci-unit pen materializes the Human Rights of Children,a safer and effective treatment.
文摘Diabetes therapy is normally based on discrete insulin infusion that uses long-time interval measurements. Nevertheless, in this paper, a continuous drug infusion closed-loop control system was proposed to avoid the traditional discrete approaches by automating diabetes therapy. Based on a continuous insulin injection model, two controllers were designed to deal with this plant. The controllers designed in this paper are: proportional integral derivative (PID), and fuzzy logic controllers (FLC). Simulation results have illustrated that the fuzzy logic controller outperformed the PID controller. These results were based on serious disturbances to glucose, such as exercise, delay or noise in glucose sensor and nutrition mixed meal absorption at meal time.
文摘Introduction: To assess the changes in glycemic control after initiating or switching to a basal insulin analogue in patients with diabetes mellitus. Methods: A retrospective, observational analysis was conducted using electronic data from a Hong Kong regional hospital. Data from adult patients with type 1 and 2 diabetes mellitus (T1DM and T2DM, respectively) who had been prescribed with basal insulin glargine in 2008-2010, with recorded HbA1c levels at the time of initiation, at 6 and 12 months thereafter, were analysed. Results: Data from 106 eligible patients were analysed. Substantial reduction in HbA1c and fasting sugar levels were reported in both T1DM (Δ HbA1c = 1.5%, Δ FBG = 1.3 mmol/L p < 0.05) and T2DM (Δ HbA1c = 1.2%, Δ FBG = 2.9 mmol/L p < 0.05) patients after 12 months of therapy. A total of 42% of T1DM and 26% of T2DM patients achieved HbA1c levels < 7.0%. After adjustment, T2DM patients who were insulin naive achieved a statistically greater HbA1c reduction (Δ = 1.7%) than those who previous treated with premixed or basal bolus insulin (Δ = 0.3%) (p < 0.05). Percentage of patients experiencing hypoglycaemia reduced from 69% to 62% in T1DM but increased from 26% to 36% in T2DM patients. All hypoglycaemic episodes recorded were either asymptomatic or mild and self-limiting. Only 4% of the patients discontinued treatment at the end of 12 months. Conclusions: In real life clinical practice, a single daily basal insulin analogue therapy provided effective glycemic control with an acceptable risk of mild hypoglycaemia.
文摘This paper aims at the development of an approach integrating the fuzzy logic strategy for a glucose and insulin in diabetic human optimal control problem. To test the efficiency of this strategy, the author proposes a numerical comparison with the indirect method. The results are in good agreement with experimental data.
文摘The effect of nutrition education using self-monitoring of blood glucose on glycemic control was investigated in the present study. Of 36 males and 25 females aged 30 - 69 years under outpatient treatment at 3 hospitals in Niigata prefecture, Japan, 61 non-insulin-treated obese type 2 diabetes patients with HbA1c of 6.9% - 9.3% and body mass index of 25 kg/m2 or higher were randomly allocated. Thirty and 31 patients were analyzed in intervention and control groups, respectively. The intervention group performed self-monitoring of blood glucose 2 hours after supper twice a week for 6 months and underwent nutrition education on the association between meals and postprandial blood glucose once every 2 months. The primary outcome was glycated hemoglobin, with the secondary outcome of body mass index. Stages of change for eating the appropriate supper amount were investigated to verify the process of the educational effect, and satisfaction with diabetes treatment and well-being were investigated to verify the continuity of treatment. On intention-to-treat analysis, glycated hemoglobin (mean ± SD) decreased from 7.9% ± 0.6% to 7.7% ± 0.6% in the intervention group but increased from 7.9% ± 0.6% to 8.1% ± 0.6% in the control group, showing a significant difference in the change after intervention between the groups (p = 0.027). In the intervention group, body mass index decreased from 28.9 ± 3.8 to 28.4 ± 3.7 kg/m2 (p = 0.019), the stages of change to learn the appropriate amount of supper progressed (p = 0.026), and satisfaction with diabetes treatment increased (p = 0.031).
基金supported by Ministry of Education 211 Project,Fudan UniversityProject of Innovation of Shanghai Municipal Committee of Science and Technology (No.08dj1400600)+6 种基金National Natural Science Foundation of China(No.81001574)Leading Medical Projects at Science and Technology Commission of Shanghai Municipality (No.12401905100)Three-year Projects to Promote Traditional Chinese Medicine,Shanghai(No.ZYSNXD-CC-ZDYJ050)Project of Shanghai Cerebrated TCM Doctor Workshop (No.ZYSNXD-CC-MZY034)Shanghai Association of Chinese Integrative Medicine(No.zxyQ-1245)The Fok Ying-Tong Education Foundation for Young Teacher of University(No.114036)the Foundation of Leading Academic Discipline Project of Shanghai Municipal Education Commission(No.J50307)
文摘BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE: To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES: Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbAlc), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. RESULTS: Compared with the control group, CHF treatment significantly decreased BMI (P〈0.05), WC (P〈0.01) and WHR (P〈0.01). Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P〈0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P〈0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P〉0.05), whereas it significantly increased with CHF treatment (P〈0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P〈0.01). However, there was no significant difference between the two groups (P〉0.05). CONCLUSION: Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.
文摘Hyperglycemia is common in critically ill patients and can be caused by various mechanisms, including nutrition, medications, and insufficient insulin. In the past, hyperglycemia was thought to be an adaptive response to stress, but hyperglycemia is no longer considered a benign condition in patients with critical illnesses. Indeed, hyperglycemia can increase morbidity and mortality in critically ill patients. Correction of hyperglycemia may improve clinical outcomes. To date, a definite answer with regard to glucose management in general intensive care unit patients, including treatment thresholds and glucose target is undetermined. Meta-analyses of randomized controlled trials suggested no survival benefit of tight glycemic control and a significantly increased incidence of hypoglycemia. Studies have shown a J- or U-shaped relationship between average glucose values and mortality; maintaining glucose levels between 100 and 150 mg/dL was likely to be associated with the lowest mortality rates. Recent studies have shown glycemic control < 180 mg/d L is not inferior to near-normal glycemia in critically ill patients and is clearly safer. Glycemic variability is also an important aspect of glucose management in the critically ill patients. Higher glycemic variability may increase the mortal-ity rate, even in patients with the same mean glucose level. Decreasing glucose variability is an important issue for glycemic control in critically ill patients. Continuous measurements with automatic closed-loop systems could be considered to ensure that blood glucose levels are controlled within a specific range and with minimal variability.
文摘In type 1 diabetes,flexible,intensive insulin management improves not only glycemic control but also dietary freedom and treatment satisfaction.Such flexibility has been made possible with the new insulin analogues(as part of a basal-bolus regime) and is now gaining wide applicability,especially among children and adolescents.This approach requires appropriate individualized patient education.Especially for adolescents,the clinician should be able to guarantee insightful participation in direct response to their attitudes,wishes and needs.This patient-and-doctor collaboration is an ever-challenging duty and has the potential to change the future of the individual diabetic patient.
文摘AIM: To assess the safety of enhanced recovery after surgery(ERAS) program in gastrectomy and influences on nutrition state and insulin-resistance. METHODS: Our ERAS program involved shortening the fasting periods and preoperative carbohydrate loading. Eighty gastrectomy patients were randomly assigned to either the conventional group(CG) or ERAS group(EG). We assessed the clinical characteristics and postoperative outcomes prospectively. The primary endpoint was noninferiority in timely discharge from the hospital within 12 d. Secondary endpoints were the incidence of aspiration at anesthesia induction, incidence of postoperative complications, health related quality of life(HRQOL) using the SF8 Health Survey questionnaire, nutrition state [e.g., albumin, transthyretin(TTR), retinal-binding protein(RBP), and transferrin(Tf)], the homeostasis model assessment-insulin resistance(HOMA-R) index, postoperative urine volume,postoperative weight change, and postoperative oral intake.RESULTS: The ERAS program was noninferior to the conventional program in achieving discharge from the hospital within 12 d(95.0% vs 92.5% respectively; 95%CI:-10.0%-16.0%). There was no significant difference in postoperative morbidity between the two groups. Adverse events such as vomiting and aspiration associated with the induction of general anesthesia were not observed. There were no significant differences with respect to postoperative urine volume, weight change, and oral intake between the two groups. EG patients with preoperative HOMA-R scores above 2.5 experienced significant attenuation of their HOMA-R scores on postoperative day 1 compared to CG patients(P = 0.014). There were no significant differences with respect to rapid turnover proteins(TTR, RBP and Tf) or HRQOL scores using the SF8 method.CONCLUSION: Applying the ERAS program to patients who undergo gastrectomy is safe, and improves insulin resistance with no deterioration in QOL.
文摘This double-blind, controlled, randomized, three-way cross-over study evaluates the effect of 40 g (D1 group) and 20 g (D2 group) of acacia gum (AG) versus no treatment (NT group) on post-prandial glucose (PPG) levels in normal-weight and overweight subjects. Additionally, post-prandial insulin (PPI) levels as well as the safety and tolerability of gum acacia were assessed. 35 healthy subjects aged 25 - 60 years, body mass index 18.5 kg/m<sup>2</sup> - 29.9 kg/m<sup>2</sup>, received one treatment of 20 g, 40 g, or 0 g of AG each. Glucose and insulin values were determined at -15 min and prior to the intake (time “0”) as well as 15, 30, 45, 60, 90 120, and 180 min after the “0 min” blood draw. The mean PPG levels were lower (34% in D1 group, p = 0.003;35% in D2 group, p = 0.005) than in the NT group. PPI concentration was statistically significantly lower at all time points except baseline in both treatment groups compared to NT groups. Global benefit and tolerability were rated as “very good” or “good” by 100% of subjects in the treatment groups. This study provides robust evidence of the significant benefits of AG consumption on PPG and PPI levels in healthy subjects. Moreover, very good tolerability was demonstrated.
文摘Introduction: Optimal glycemic control in cardiac surgery patients remains a laudable but confusing practice. Existing studies have primarily employed two maintenance strategies using either intensive insulin therapy (IIT) (maintain glucose p = 0.628), ICU LOS (MD = -0.073 days, 95% CI = -0.324 to 0.178;p = 0.568), or hospital LOS (MD = 0.269, 95% CI = -2.158 to 2.696;p = 0.828). No difference in AF rates (RR = 0.887, 95% CI = 0.681 to 1.155;p = 0.375) or deep sternal infection (RR = 0.985, 95% CI = 0.357 to 2.720;p = 0.977) were observed. Conclusion: IIT targeting blood sugar levels of 80 - 120 mg/dl have no effect on perioperative outcomes in cardiac surgery patients. IIT is associated with similar mortality, ICU LOS, hospital LOS, AF rates, and deep sternal infection rates compared to more liberal glycemic strategies. IIT should not replace CIT as the standard of care in cardiac surgery patients.
文摘A discrete insulin infusion based on long-time interval measurement is the classic technique for diabetes treatment. Nevertheless, in this research, a closed-loop control system was proposed for continuous drug infusion to overcome the drawbacks of these typical discrete methods and develop more practical diabetes therapy systems. A blood glucose-insulin system was implemented relying on continuous insulin injection model. Based on this model, two controllers were designed to deal with the control dilemma of the resulting highly nonlinear plant. The controllers designed in this paper are: proportional integral derivative (PID), and sliding table controllers. Simulation results have shown that the sliding table controller can outperform the PID controller even with severe circumstances of disturbance in glucose, such as exercise, delay or noise in glucose sensor and nutrition mixed meal absorption at meal times.