Algorithm

Lifestyle intervention is the basis for all treatment of T2D [27]. The improvements of glucose metabolism obtained initially, specifically on body weight, may influence the results of the drug added later on (Fig. 4). Specifically, a change of diet is important as it has an immediate effect. The amount of calories should be reduced by reducing intake of not only fat, but also rapidly absorbed carbohydrates. The patient should remain on non-pharmacological treatment for a couple of months before starting drug treatment in order to obtain the full beneficial effect of lifestyle changes. The time spent on lifestyle changes alone of course depends on the achieved blood glucose values and the clinical situation.

The first drug of choice is Metformin, which should be titrated up to the highest dose tolerated. To start with a low dose is recommendable to avoid side-effects. However, most patients suffer some gastrointestinal side-effects, but these side-effects disappear in most subjects in time. If the goal for HbA1c - either the international goal or the individually decided goal

- is not reached within 2-3 months, another group of drugs may be added. As mentioned in Fig. 4,

Diagnosis

Diagnosis

Add Basal Insulin - Most effective

Add Sulfonylurea - Least expensive

Add Glitazone - No hypoglycemia

Add Basal Insulin - Most effective

Add Sulfonylurea - Least expensive

Add Glitazone - No hypoglycemia

Fig. 4. Algorithm for the metabolic management of type 2 diabetes [27].

Intensive insulin + Metformin +/- Glitazone

Fig. 4. Algorithm for the metabolic management of type 2 diabetes [27].

three possibilities exist: insulin, SU or glitazones. The choice depends on several factors: the level of HbAlc, body weight, age and phenotype. Furthermore, some drugs may be contraindicated. The patient's preference must also be taken into account, as the patient's compliance has immediate impact on the results obtained. Since T2D subjects need many drugs for treatment, individual education and motivation are important.

Insulin

Insulin treatment may be initiated earlier in young subjects, in lean subjects and in subjects with high HbAlc levels (>8.5%). Today, in addition to Metformin, intermediate-acting insulin once daily -often given at night - will be the regime to choose [24]. This regime is easy to handle, as the patients themselves can titrate the dose of insulin based on the fasting blood glucose values. The goal is a fasting blood glucose of <6 mmol/L. The patients may start with NPH insulin at night and titrate according to the individually given algorithm. The long-acting insulin analogues may be used instead of NPH insulin, since they have demonstrated the same potency as NPH [25], but with fewer hypogly-caemic attacks. However, more studies are needed before recommending the new insulins in general, but in subjects showing a tendency of hypogly-caemia or poor control, glargine or determir must be considered.

A few studies used rapid-acting insulin or rapid-acting insulin analogues at meal time instead of intermediate- or long-acting insulin at night, since it is important to treat postprandial blood glucose values as stated above (triple therapy). Only a few studies have been published until now investigating the combination of these fast-acting insulins with Metformin. The concept of treating postprandial blood glucose alone seems as effective as treating with long-acting or intermediate-acting insulin at night. The advantage is that the postprandial values will be lower. However, fasting blood glucose values may be higher, and therefore more long-term studies are needed before this change of concept can be recommended. The only obvious situation is lean, young T2D subjects with reduced beta-cell function indicated by C-peptide values fasting lower than 300 pmol/L. In this case the classical basal bolus regimes should be considered.

SU is another possibility as add-on medication to Metformin in cases where the metabolic goal is not obtained. These drugs may be considered in young and lean subjects and in T2D subjects with a HbAlc value lower than 8.5% after 2-3 months of monotherapy with Metformin. These drugs can induce severe hypoglycaemia and are therefore relatively contraindicated in subjects prone to hypo-glycaemia, that is, elderly subjects and subjects suffering from liver diseases [22]. It has been claimed that SU should not be given to T2D subjects with coronary arteriosclerosis, but data supporting this are not very solid. The three different SUs mentioned above have the same potency and, for the moment, no scientific evidence exists to choose one for the other, but the patient's individual phenotype must naturally be taken into account.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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