Development of a multi-parametric model predictive control algorithm for insulin delivery in type 1 diabetes mellitus using clinical parameters.

A multi-parametric model predictive control (mpMPC) algorithm for subcutaneous insulin delivery for individuals with type 1 diabetes mellitus (T1DM) that is computationally efficient, robust to variations in insulin sensitivity, and involves minimal burden for the user is proposed. System identification was achieved through impulse response tests feasible for ambulatory conditions on the UVa/Padova simulator adult subjects with T1DM. An alternative means of system identification using readily available clinical parameters was also investigated. A safety constraint was included explicitly in the algorithm formulation using clinical parameters typical of those available to an attending physician. Closed-loop simulations were carried out with daily consumption of 200 g carbohydrate. Controller robustness was assessed by subject/model mismatch scenarios addressing daily, simultaneous variation in insulin sensitivity and meal size with the addition of Gaussian white noise with a standard deviation of 10%. A second-order-plus-time-delay transfer function model fit the validation data with a mean (coefficient of variation) root-mean-square-error (RMSE) of 26 mg/dL (19%) for a 3 h prediction horizon. The resulting control law maintained a low risk Low Blood Glucose Index without any information about carbohydrate consumption for 90% of the subjects. Low-order linear models with clinically meaningful parameters thus provided sufficient information for a model predictive control algorithm to control glycemia. The use of clinical knowledge as a safety constraint can reduce hypoglycemic events, and this same knowledge can further improve glycemic control when used explicitly as the controller model. The resulting mpMPC algorithm was sufficiently compact to be implemented on a simple electronic device.

Exercise and diabetes.

Diet and exercise form the foundation of a healthy lifestyle. These are especially important for people living with diabetes mellitus, as they are the most practical non-pharmacological means by which patients may significantly improve their blood glucose levels. Exercise increases insulin sensitivity (both short and long term), lowers blood sugar levels, reduces body fat and improves cardiovascular (CV) function. Because of this, exercise offers enormous benefit to patients with diabetes. Blood glucose levels can significantly drop during and after physical activities, due to the increased utilisation of glucose as a fuel during exercise and the up-regulation of glucose transport into working muscles. Therefore, patients (especially those with type 1 diabetes) must account for the effects of exercise and adjust their medications and nutrition accordingly. Improvements in real-time continuous glucose monitoring and optimisation of basal insulin dosing may offer significant benefit to preventing hypoglycaemia in patients with type 1 diabetes who regularly exercise. Diverse exercise programmes and devices can also assist patients in monitoring their activities as well as motivating them to achieve their exercise goals. For patients with type 1 diabetes, questions such as how much, how long, how strenuous and what kind of exercise must be addressed in order for healthcare professionals to offer maximum benefit to their patients. Additionally, since patients with type 2 diabetes often have other significant co-morbidities such as obesity and CV disease, care providers must evaluate each patient's risk factors before designing an exercise programme. Several publications in the last year have addressed these issues and may serve as a valuable resource to provide safe and effective recommendations to patients and their healthcare providers. To be included in the Exercise and Diabetes chapter for the 2010 YEARBOOK, we reviewed leading peer-reviewed manuscripts that were published in the period July 2009 to June 2010. PubMed was used in the initial screening of articles.

Exercise equipment and diabetes.

Regular exercise is one of the most powerful treatments for the prevention and treatment of insulin resistance and type 2 diabetes mellitus. Exercise is also beneficial for those living with type 1 diabetes although challenges exist with its prescription as it can promote both hyperglycaemia and hypoglycaemia and motivating patients is always a challenge. Nonetheless, promoting regular exercise should be the cornerstone of all healthcare professionals working with these patients. In this year's review on exercise and exercise equipment, we highlight 10 publications that focus on topics ranging from exercise adherence to fuel metabolism. We also highlight some new innovative tools that facilitate exercise participation and evaluation.

Modular closed-loop control of diabetes.

Modularity plays a key role in many engineering systems, allowing for plug-and-play integration of components, enhancing flexibility and adaptability, and facilitating standardization. In the control of diabetes, i.e., the so-called "artificial pancreas," modularity allows for the step-wise introduction of (and regulatory approval for) algorithmic components, starting with subsystems for assured patient safety and followed by higher layer components that serve to modify the patient's basal rate in real time. In this paper, we introduce a three-layer modular architecture for the control of diabetes, consisting in a sensor/pump interface module (IM), a continuous safety module (CSM), and a real-time control module (RTCM), which separates the functions of insulin recommendation (postmeal insulin for mitigating hyperglycemia) and safety (prevention of hypoglycemia). In addition, we provide details of instances of all three layers of the architecture: the APS© serving as the IM, the safety supervision module (SSM) serving as the CSM, and the range correction module (RCM) serving as the RTCM. We evaluate the performance of the integrated system via in silico preclinical trials, demonstrating 1) the ability of the SSM to reduce the incidence of hypoglycemia under nonideal operating conditions and 2) the ability of the RCM to reduce glycemic variability.

Efficacy, safety and lack of immunogenicity of insulin aspart compared with regular human insulin for women with gestational diabetes mellitus.

AIM: The efficacy and safety of insulin aspart (IAsp), a rapid-acting human insulin analogue, were compared with regular human insulin (HI) as the bolus component of basal-bolus therapy for subjects with gestational diabetes mellitus (GDM). METHODS: In a randomized, parallel-group, open-labelled trial, 27 women with GDM (age 30.7 +/- 6.3 years, HbA(1c) < 7%) were randomized to receive IAsp (5 min before meal) or HI (30 min before meal). The trial period extended from diagnosis of GDM (18-28 weeks) to 6 weeks postpartum. RESULTS: Both treatment groups maintained good overall glycaemic control during the study (beginning and end of study HbA(1c)< or = 6%). During the meal test, mean glucose at week 6 (IAsp 4.2 +/- 0.57 mmol/l, HI 4.8 +/- 0.86 mmol/l) was slightly lower than at week 0 (IAsp 4.9 +/- 0.59 mmol/l, HI 5.1 +/- 0.36 mmol/l). However, change from baseline values for average glucose (IAsp -1.09 +/- 0.54 mmol/l, HI -0.54 +/- 0.74 mmol/l; P = 0.003) and C-peptide (IAsp -0.50 +/- 0.67 nmol/l, HI -0.30 +/- 0.70 nmol/l; P = 0.027) were significantly lower after IAsp treatment than HI treatment. No major hypoglycaemic events were reported during the study. Cross-reacting insulin antibody binding increased slightly from baseline in both treatments groups (end of study: IAsp 2.1 +/- 5.4%, HI 6.4 +/- 13.9%), whereas antibodies specific to IAsp or HI remained relatively low (< 1% binding). CONCLUSION: IAsp was more effective than HI in decreasing postprandial glucose concentrations. Duration of IAsp injection 5 min before a meal rather than 30 min prior to meals offers a more convenient therapy for subjects with GDM. Overall safety and effectiveness of IAsp were comparable to HI in pregnant women with GDM.