Mais la polymyxine n'est pas du tout absorbée dans le sang du système gastro-intestinal et n'a d'effet que dans l'intestin et est utile pour le traitement des infections intestinales amoxicilline prix Internet en y faisant des achats permettant d’économiser jusqu'à soixante-dix pour cent, tout en étant sûr de la qualité des produits pharmaceutiques.
Starting a basal insulin in primary care
Starting a basal insulin in primary care
15th April 2013
The long term vascular complications of diabetes can lead to significant
morbidity and premature death. The Microvascular complications (retinopathy,
nephropathy and neuropathy) can cause visual impairment and blindness,
CKD leading to end stage renal failure and impaired sensation, neuropathic
pain, pedal ulceration, autonomic neuropathy and Charcot neuroarthropathy.
The Macrovascular complications result in myocardial infarction, stroke,
peripheral vascular disease and CVD death. Both Microvascular and
Macrovascular complications can be prevented by controlling blood glucose.
The UKPDS clearly demonstrated that early intensive glycaemic control in
T2DM can reduce the incidence and retard the progression of Microvascular
disease (Lancet 1998;352:837-53), a finding that has been mirrored in
numerous subsequent studies. The Steno-2 (NEJM 2009;358:580-91)and
UKPDS Follow Up studies (NEJM 2008;359:1577-89) revealed that early
intensive glycaemic control can result in long-term sustained benefit, and can
significantly reduce the risk of Macrovascular diabetes complications 10 to 15
years later, introducing the concept of a “Metabolic Memory”.
In diabetes of 8-10 or more years which coexists with established CVD (as in
many of our patients) 3 studies help to guide practice. The VADT (NEJM
2009;360:129-39), ACCORD (NEJM 2008;2545-59) and ADVANCE (NEJM
2008;358:2560-72) investigators all observed no CVD benefit when aiming to
achieve a lower HbA1c target (42 mmol/mol vs 53 mmol/mol) in these
individuals with longstanding T2DM and established vascular disease. Indeed,
the ACCORD study was stopped early on account of an increased risk of CVD
death in the group randomised to the aggressive HbA1c target. Despite the
fact that there were still small benefits observed in all 3 studies with respect to
microvascular complications, these studies show that aggressive glycaemic
targets in longstanding T2DM and established vascular disease provides no
CVD benefit and may increase risk of CVD mortality.
When approaching the glycaemic management of T2DM it is therefore
important to identify an appropriate HbA1c target.
Unlike other important T2DM therapeutic targets like BP or Lipids, the HbA1c
target should be INDIVIDUALISED to reflect the patients age, life expectancy,
duration of diabetes, presence of complications, comorbidities and risk of
By the time that we diagnose T2DM around one half of the endogenous beta
cell insulin-secreting ability is lost, and a further 5 to 10% is lost each year
thereafter (Diabetes Res Clin Pract 1998;40:S21–25). Metformin is the first
line drug of choice in T2DM (Diabetes Care 2012;35:1364-1379) as it is a safe and effective weight neutral insulin sensitiser which may also reduce CVD events (NEJM 1998;359:1577-1589). Like HbA1c target additional diabetes medications should be individualised to suit the individual’s age, comorbidities, BMI and lifestyle, with no drug conferring significant advantage over others. New Zealand Guidelines Group Guidance on the Management of type 2 diabetes (2011) indicates which options are funded in New Zealand. It is important to regularly monitor HbA1c (6 monthly if at target, 3 monthly if outwith target) to ensure control remains at the individualised target. Even with strict adherence to dietary and lifestyle recommendations T2DM will progress. 80% of UKPDS participants required insulin by 9 years after diagnosis (www.dtu.ox.ac.uk/ukpds_trial/index.php). Most individuals with T2DM will therefore require insulin (if they live long enough). The time to consider the addition of insulin is when the individualised glycaemic target is not being achieved. There is no HbA1c threshold above or below which insulin should not be used. There are a number of various insulin products that can be prescribed to an individual with T2DM who is failing to achieve their individualised HbA1c target. Sometimes the choice can be confusing, but they can be split into simple groups based upon their action profile. Studies have shown that there is very little difference in outcome whether we use a basal insulin, a rapid-acting prandial insulin or a pre-mix (containing a fixed ratio of basal and prandial insulin) at insulin outset (NEJM 2009;361:1736-47). The risk of hypoglycaemia and weight gain is higher using a prandial or pre-mixed insulin, which also tend to be more complex regimens. Therefore guidelines suggest that a basal insulin is the first line choice. You only need to be familiar with 1 or 2 insulins. This will keep it simple and safe. Although endogenous insulin secretion is inadequate when supplemental insulin is required in T2DM, most patients retain some endogenous beta cell function capable of insulin production. This remaining beta cell function is impaired when blood glucose is elevated (so-called pancreatic glucotoxicity). Accordingly, the addition of a basal insulin alone will suppress hepatic glucose production thus controlling blood glucose between meals. In turn, this helps to restore endogenous postprandial insulin release, and euglycaemia is restored. There are two basal insulins funded by Pharmac for use in T2DM in New Zealand. NPH can be administered either once or twice daily. Lantus is generally used once daily in T2DM. Patients (and doctors!) are often reluctant to consider insulin use despite suboptimal glycaemic control. Attentive patient education at diabetes diagnosis and upon intensification of oral regimes can mitigate against insulin refusal when the time comes to consider injectable therapies. Insulin use should never be used as a threat or stimulus in an attempt to change behaviour. Individuals should be fully informed of what to expect when they
start insulin. Regular support by consultations, phone calls or email will help to build self-confidence. A confident and supportive doctor (and his/her team) will achieve successful insulin initiations. Poor diet choices and sedentary lifestyle are often significant contributors to high HbA1c. Unless contraindicated 30 minutes of moderate intensity physical activity daily should be recommended for everybody with T2DM. A healthy diet for T2DM and for non-DM are identical. In general individuals should aim for around 70g carbohydrate for each meal, preferrably comprised of low glycaemic index carbohydrate with avoidance of large amounts of refined carbs (sugars). Before deciding which insulin to start it is helpful to understand the individual’s glucose profile over the course of the day. After instructing the patient how to perform self-monitored blood glucose measurements using a capillary blood glucose monitor, ask them to record their blood glucose before breakfast (fasting) before lunch, before dinner and before bed in a blood glucose diary on 3 consecutive days. By examining the glucose profile an appropriate individualised insulin regimen can be suggested. For most individuals with T2DM failing to achieve HbA1c target the self-monitored capillary glucose profile will reflect fasting hyperglycaemia. In these cases the simplest and most effective method of improving glycaemic control is with addition of a basal insulin injected before bed, gradually adjusting the dose in order to achieve a fasting blood glucose target - “Fix the Fasting First”. When insulin is started metformin should always continue (unless eGFR <30ml/min). The insulin-sensitising effects of metformin will allow the insulin dose to be limited, which in turn helps to limit weight gain associated with addition of insulin. Moreover the metabolic benefits of metformin will continue. When adding a basal insulin ongoing benefit can be derived from continuing the sulfonylurea. In most cases Thiazoledinedione (Pioglitazone), Acarbose or DPP-IV inhibitors should be discontinued when insulin is added. By starting with a low dose of insulin the patient will become familiar with insulin use without risk of hypoglycaemia. 10 units would be a typical starting dose. It is important the patient is informed that the initial dose is a starting dose, and that daily fasting blood glucose measurements recorded in a diary are required to guide further dose increments. Moreover I tell patients the dose of insulin ultimately required is not important, whereas control of the fasting blood glucose is. Having a conservative target for fasting blood glucose of 6 or 7 allows an element of safety (lower risk of hypoglycaemia if the target is overshot by 1 or 2 mmol/l). In the example seen here the fasting blood glucose is outwith target, with measured capillary blood glucose readings that are relatively flat throughout the day, rising further after the evening meal. This is the typical pattern for
T2DM when the individualised HbA1c target is no longer maintained on oral agents alone. The recommended management for this case would be initiation of basal insulin at bed time. My normal practice is to start 10 units basal insulin before bed and ask the patient to check and record fasting glucose every morning. If the glucose is higher than the target of 6 or 7 for 3 days running I instruct them to add 2 units to the dose then repeat each step. It is advisable to have contact over the first week (or more depending upon the individual) to instil confidence and ensure compliance. This can be via a phone call or email from doctor or nurse. Larger increments can be suggested if hyperglycaemia remains despite increasing insulin doses. If any fasting hypoglycaemia (blood glucose <4 mmol/l) is observed the dose of bedtime insulin should be reduced by 2 units IMMEDIATELY without waiting for 3 consecutive similar readings. Although it can take many weeks to reach stability this method is simple to instruct and safe to implement. Once the patient has a clear understanding of the titration schedule intensive phone and email support can be withdrawn. It is important to continue with regular review of SMBG profiles and 3 monthly HbA1c. Bear in mind large basal insulin doses that may be required by the obese. Alongside the daily CBG diary these data will help to guide further insulin regime intensification. As a guide, prandial insulin is usually required in addition to basal insulin when total daily insulin dose is >0.5 u/kg. Prandial insulin is easiest to deliver as a premix. Help is available to assist in decision making from either Diabetes Specialist Nurses or Diabetes Specialist Physicians at your local Diabetes Centre.
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