Web-based guided insulin self-titration in patients with type 2 diabetes: the Di@log study. Design of a cluster randomised controlled trial [TC1316]

<p>Abstract</p> <p>Background</p> <p>Many patients with type 2 diabetes (T2DM) are not able to reach the glycaemic target level of HbA1c < 7.0%, and therefore are at increased risk of developing severe complications. Transition to insulin therapy is one of the obstacles in diabetes management, because of barriers of both patient and health care providers. Patient empowerment, a patient-centred approach, is vital for improving diabetes management. We developed a web-based self-management programme for insulin titration in T2DM patients. The aim of our study is to investigate if this internet programme helps to improve glycaemic control more effectively than usual care.</p> <p>Methods/Design</p> <p>T2DM patients (n = 248), aged 35–75 years, with an HbA1c ≥ 7.0%, eligible for treatment with insulin and able to use the internet will be selected from general practices in two different regions in the Netherlands. Cluster randomisation will be performed at the level of general practices. Patients in the intervention group will use a self-developed internet programme to assist them in self-titrating insulin. The control group will receive usual care.</p> <p>Primary outcome is the difference in change in HbA1c between intervention and control group. Secondary outcome measures are quality of life, treatment satisfaction, diabetes self-efficacy and frequency of hypoglycaemic episodes. Results will be analysed according to the intention-to-treat principle.</p> <p>Discussion</p> <p>An internet intervention supporting self-titration of insulin therapy in T2DM patients is an innovative patient-centred intervention. The programme provides guided self-monitoring and evaluation of health and self-care behaviours through tailored feedback on input of glucose values. This is expected to result in a better performance of self-titration of insulin and consequently in the improvement of glycaemic control. The patient will be enabled to 'discover and use his or her own ability to gain mastery over his/her diabetes' and therefore patient empowerment will increase. Based on the self-regulation theory of Leventhal, we hypothesize that additional benefits will be achieved in terms of increases in treatment satisfaction, quality of life and self-efficacy.</p> <p>Trial registration</p> <p>Dutch Trial Register TC1316.</p

Modelling the biomechanics and control of sphincters

This paper reviews current mathematical models of sphincters and compares them with a new spatial neuromuscular control model based on known physiological properties. Almost all the sphincter models reviewed were constructed as a component of a more extensive model designed to mirror the overall behaviour of a larger system such as the lower urinary tract. This implied less detailed modelling of the sphincter component. It is concluded that current sphincter models are not suitable for mimicking detailed interactions between a neural controller and a sphincter. We therefore outline a new integrated model of the biomechanics and neural control of a sphincter. The muscle is represented as a lumped-mass model, providing the possibility of applying two- or three-dimensional modelling strategies. The neural network is a multi-compartment model that provides neural control signals at the level of action potentials. The integrated model was used to simulate a uniformly activated sphincter and a partially deficient innervation of the sphincter, resulting in a non-uniformly activated sphincter muscle. During the simulation, the pressure in the sphincter lumen was prescribed to increase sinusoidally to a value of 60kPa. In the uniformly activated situation, the sphincter muscle remains closed, whereas the partially denervated sphincter is stretched open, although the muscle is intact

A compatmental model of an External Urethral Sphincter Motoneuron of Onuf's Nucleus

This article discusses a model of the electrical behavior of an external urethral sphincter motoneuron, based on morphological parameters like soma size, dendritic diameters and spatial dendritic configuration, and several electrical parameters. Because experimental data about the exact ion conductance mix of external urethral sphincter neurons is scarce, the gaps in knowledge about external urethral sphincter motoneurons were filled in with known data of α-motoneurons. The constructed compartmental model of motoneurons of Onuf's nucleus contains six voltage-dependent ionic conductances: a fast sodium and potassium conductance and an anomalous rectifier in the soma; a fast delayed rectifier type potassium conductance and a fast sodium conductance in the initial axon segment; an L-type calcium channel in the dendritic compartments. This paper considers the simulation of external urethral sphincter motoneuron responses to current injections that evoke bistable behavior. Simulations show self-sustained discharge following a depolarizing pulse through the microelectrode; the firing was subsequently terminated by a short hyperpolarizing pulse. This behavior is highly functional for neurons that have to exhibit prolonged activation during sphincter closure. In addition to these 'on' and 'off' responses, we also observed a particular firing behavior in response to long-lasting triangular current pulses. When the depolarizing current was slowly increased and then decreased (triangular pulse) the firing frequency was higher during the descending phase than during the initial ascending phase

A Compartmental Model of an External Urethral Sphincter Motoneuron of Onuf's Nucleus

This article discusses a model of the electrical behavior of an external urethral sphincter motoneuron, based on morphological parameters like soma size, dendritic diameters and spatial dendritic configuration, and several electrical parameters. Because experimental data about the exact ion conductance mix of external urethral sphincter neurons is scarce, the gaps in knowledge about external urethral sphincter motoneurons were filled in with known data of α-motoneurons. The constructed compartmental model of motoneurons of Onuf's nucleus contains six voltage-dependent ionic conductances: a fast sodium and potassium conductance and an anomalous rectifier in the soma; a fast delayed rectifier type potassium conductance and a fast sodium conductance in the initial axon segment; an L-type calcium channel in the dendritic compartments. This paper considers the simulation of external urethral sphincter motoneuron responses to current injections that evoke bistable behavior. Simulations show self-sustained discharge following a depolarizing pulse through the microelectrode; the firing was subsequently terminated by a short hyperpolarizing pulse. This behavior is highly functional for neurons that have to exhibit prolonged activation during sphincter closure. In addition to these 'on' and 'off' responses, we also observed a particular firing behavior in response to long-lasting triangular current pulses. When the depolarizing current was slowly increased and then decreased (triangular pulse) the firing frequency was higher during the descending phase than during the initial ascending phase

Modelling the biomechanics and control of sphincters

This paper reviews current mathematical models of sphincters and compares them with a new spatial neuromuscular control model based on known physiological properties. Almost all the sphincter models reviewed were constructed as a component of a more extensive model designed to mirror the overall behaviour of a larger system such as the lower urinary tract. This implied less detailed modelling of the sphincter component. It is concluded that current sphincter models are not suitable for mimicking detailed interactions between a neural controller and a sphincter. We therefore outline a new integrated model of the biomechanics and neural control of a sphincter. The muscle is represented as a lumped-mass model, providing the possibility of applying two- or three-dimensional modelling strategies. The neural network is a multi-compartment model that provides neural control signals at the level of action potentials. The integrated model was used to simulate a uniformly activated sphincter and a partially deficient innervation of the sphincter, resulting in a non-uniformly activated sphincter muscle. During the simulation, the pressure in the sphincter lumen was prescribed to increase sinusoidally to a value of 60kPa. In the uniformly activated situation, the sphincter muscle remains closed, whereas the partially denervated sphincter is stretched open, although the muscle is intact

Synthesis and evaluation of (S)-4-(3-(2'-[C-11]isopropylamino)-2-hydroxy-propoxy)-2H-benzimidazol-2-one ((S)-[C-11]CGP 12388) and (S)-4-(3-((1'-[F-18]-fluoroisopropyl)amino)-2-hydroxypropoxy)-2H-benzimidazol-2-one ((S)-[F-18]Fluoro-CGP 12388) for visualization of beta-adrenoceptors with positron emission tomography

The beta-adrenoceptor antagonist (S)-[C-11]CGP 12177 (4-(3-(tert-butylamino)-2-hydroxypropoxy)- 2H-benzimidazol-2[C-11]-one) is a generally accepted radioligand for cardiac and pulmonary PET studies. The synthesis of [C-11]CGP 12177 is a laborious and often troublesome procedure. Therefore, (S)-C GP 12388 (4-(3-(isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one), 5, the isopropyl analogue of CGP 12177,has been labeled with carbon-11 in the isopropyl group via a reductive alkylation by [C-11]acetone (3) of the corresponding (S)-desisopropyl compound 2. The fluoro-substituted analogue of (S-CGP 12388 was prepared by reacting 2 with [F-18]fluoroacetone (4). (S)-[C-11]CGP 12388 (5) was easily prepared via a one-pot procedure. The radiochemical yield of (S)-[C-11]CGP 12388 (600-800 Ci/mmol, EOS) was 18% (EOB) with a total synthesis time of 35 min, whereas (S)-[F-18]fluoro-CGP 12388 (6)(>2000 Ci/mmol, EOS) was synthesized in 105 min with a radiochemical yield of 12% (EOB). Biodistribution studies in rats demonstrated specific binding to beta-adrenoceptors of (S)-[F-18]fluoro-CGP 12388 and (S)-[C-11]CGP 12388 in lung and heart. The lungs were clearly visualized with PET studies of rats. Total/nonspecific binding at 60 min postinjection was 5.6 for (S)-[C-11]CGP 12388 and 2.0 for the.(S)-F-18 compound. Due to its facile synthetic procedure and in vivo data, (S)-[C-11]CGP 12388 is a promising beta-adrenoceptor ligand for clinical PET