Treatment and Prevention of Diabetes in Spain

Because of variations in age, risk factors, lifestyle, socioeconomic status, and disease presentation, the needs of individual patients must be considered in the treatment and management of diabetes, and strategies must be tailored to the specific patient. The primary objective of the treatment of both type 1 and 2 of diabetes is to prevent chronic complications and reduce morbidity and mortality associated with the disease.[1] Other objectives include improvement of acute symptoms and avoidance of hypoglycemic episodes.[1] In patients with a longer life expectancy, strict regulation of blood glucose is necessary to reduce the chronic effects of hyperglycemia, though in patients with a limited life expectancy the danger of hypoglycemia may outweigh the value of stricter control.[1]

Diet and exercise are essential elements of therapy, not only in order to maintain biochemical normality and to ensure good nutrition, but also to maintain a normal weight and diminish the postprandial fluctuations of glycemia and risk of hypoglycemia.[1] The effective care of patients with diabetes in general should take into consideration several particular targets such as glycemic control, lifestyle modification and maintenance, and control of cardiovascular risk factors such as hypertension and lipid levels.

A full treatment and management plan for the person with diabetes, whether type 1 or type 2, is comprised of at least 6 areas of focus. According to the Spanish Ministry of Health and Consumption (Ministerio de Sanida y Consumo), these include:[2]

• Dietary management: individualized to the necessities of each person’s preferences, an effective diet must contemplate objectives related to the attainment of an optimal weight, socioeconomic situation, availabilities, and physical ability.[2]

• Physical activity plan: similar to dietary plan in the need for individualization, preferences, objectives, and ability. The ideal is to reach at least 30 minutes daily of active and preferably aerobic activity.[2]

• Medication: In addition to insulin, there are many medications used in the treatment of diabetes, and the patient must be aware of contraindications, interactions, the relation of the medication to food intake, precautions with alcohol, etc. Most of the treatments for diabetes can cause hypoglycemia, so patients must be aware of the warning signs.[2]

• Self-monitoring and regulation: All patients with diabetes must be instructed in the basic techniques used to monitor and regulate their disease; the modifications required during physical activity, dietary changes, and illness; and the signs of glycemic irregularity.[2]

• Regular follow-up and evaluation: A fundamental part of the treatment of diabetes is the regular checkup, not only in relation to the performance of analytical tests that may affect treatment but also those that may detect complications such as retinopathy, microalbuminuria, hypertension, and evaluation of global cardiovascular risk.[2]

• General health behaviors: Most importantly, the patient with diabetes should be advised to avoid smoking, which is an important cardiovascular risk factor in all individuals but presents an increased risk in the individual with diabetes. Also, developing habits that allow a regular and ordered life, with schedules of regular meals and time for physical exercise, is extremely advisable. Further, the care and hygiene of the feet and the skin in general is of considerable importance to the patient with diabetes.[2]

Global efforts to prevent complications and delay disease progression in patients with type 1 and type 2 diabetes have been considerably influenced by two often-cited major clinical trials.[3],[4] The Diabetes Control and Complications Trial (DCCT) showed that intensive therapy improved glycemic control and slowed the onset and progression of complications (diabetic retinopathy, nephropathy, and neuropathy) in patients with type 1 diabetes.[3] Patients received either conventional diabetes management or intensive insulin therapy. The latter group also received education and extensive support to assist them in achieving glycemic targets.[3] However, the reduction in diabetic complications was diminished by as much as a 3-fold increase in severe hypoglycemia. In addition, the study’s design did not allow for separation of the effects of education versus insulin therapy.[3] The United Kingdom Prospective Diabetes Study (UKPDS) examined the role of glycemic and blood pressure control in patients with type 2 diabetes.[3],[4] In the glycemic control component of the study, the intensive control group (treated with a sulfonylurea, insulin, or metformin) aimed for a fasting plasma glucose (FPG) <6 mmol/L, whereas the conventional control group (treated primarily with dietary modifications) aimed for an FPG of <15 mmol/L.[5] Similarly, blood pressure was tightly maintained with captopril or atenolol and a target of <150/85 mm Hg, or less tightly controlled without ACE inhibitors or β blockers and a target of <180/105 mm Hg.[4],[5] Intensive glycemic control reduced the risk of major diabetic eye disease by 25% and early kidney damage by 33%, and tighter blood pressure control reduced the risk of death from long-term complications of diabetes by up to 33%, strokes by more than 44%, and serious deterioration of vision by more than 47%.[4],[5] Several key points regarding the management of diabetes and hypertension can be extrapolated from the UKPDS:

• Diabetes progressed despite clinical management. Even with intensive initial treatment with insulin or a sulfonylurea, most patients require a combination of oral antidiabetic agents and/or insulin to optimize glycemic control[3]

• Intensive treatment with sulfonylureas or insulin carries a risk of hypoglycemia and weight gain[3]

• First-line use of metformin in overweight patients may reduce complications and death without causing significant weight gain, and reduces cardiovascular events. This effect was not seen when metformin was added to maximal dose sulfonylurea[3]

• Multiple drugs may be required to optimize blood pressure control. Three or more drugs were needed by 29% of the tightly controlled group, and only 56% of patients in the tightly controlled group attained the target blood pressure[3]

• Blood pressure level attained appears to be more important than the type of drug used[3]

Given the results of these and numerous other studies, Sociedad Española de Diabetes (SED) guidelines, as well as regional guidelines, all stress the importance of focusing on glycemic control and cardiovascular risk factors in the treatment and management of patients with diabetes in order to delay progression of disease and prevent the development of associated complications.[2],[6] Measurement of glycated hemoglobin (A1C) has been shown to be an effective indicator of average glycemia over the previous 60-day period, and both the UKPDS and the DCCT have demonstrated the importance of controlling blood glucose levels by targeting A1C levels for people with both type 1 and type 2 diabetes.

Treatment of Type 1 Diabetes

Insulin delivery methods, frequency of injections, insulin pharmacological profile, patient compliance, target control, severity of disease, and risk factors for complications and hypoglycemic episodes should be foremost in the mind of the clinician when managing patients with type 1 diabetes. Further, treatment regimens continue to evolve, potentially increasing in effectiveness and convenience as emerging forms of insulin; new and improved insulin delivery methods such as pumps, pens and inhaled forms; blood glucose monitoring technology; and procedures such as solid pancreas and islet cell transplantation are developed and improved.

In patients with type 1 diabetes, insulin therapy is initiated at diagnosis, accompanied by diabetic education (eg, diet, exercise, self-monitoring, self-administration of insulin) whether as an outpatient or as an inpatient in the case of ketoacidosis or other adverse condition[7] Currently, most insulins used in Spain are recombinant forms, having displaced those of animal origin, and are categorized typically based on onset and duration of action into short-acting, intermediate-acting, and long-acting, as well as premixed insulins.[7] There are 3 main insulin delivery systems in use in Spain at present. These are:

• Insulin syringes: the classic needle delivery, currently used with 40UI/mL concentration[7]

• Insulin pens: Automated mechanisms with replaceable insulin cartridges that work with 100 UI/mL concentration insulin[7]

• Preloaded syringes: Like the pen, these syringes come preloaded, are disposable, and are used with 100UI/mL insulin[7]

Table 1. Illustrates the various types of insulins and delivery systems generally used in Spain.

Table 1. Insulins avaiable in Spain[7]

*Cartridges for injector pen
†Preloaded syringe

Treatment of Type 2 Diabetes

The primary objectives in the treatment of type 2 diabetes are similar to those for type 1; according to the SED guidelines, these include:[8]

• Normalization of glycemia[8]

• Reduction/elimination of symptoms related to hyperglycemia[8]

• Avoidance of acute glycemic fluctuations[8]

• Avoidance or delay of the appearance or progression of chronic complications such as:

o        Microvascular complications: diabetic retinopathy, diabetic nephropathy, diabetic neuropathy[8]

o        Macrovascular complications: ischemic cardiopathy, cerebrovascular disease, peripheral arterial disease[8]

• Reduction of mortality[8]

• Maintenance of quality of life[8]

Dietary and lifestyle modifications are the initial treatment for patients with less severe type 2 diabetes.[7] Pharmacological intervention with metformin, sulfonylureas (SUs), α-glucosidase inhibitors (AGIs), thiazolidinediones (TZDs), insulin therapy, or combinations of these medications are indicated in more severe or chronically uncontrolled patients or if no improvement is seen in 3-6 months.[7] Stricter therapeutic objectives should be observed in younger patients to avoid the development of chronic complications of hyperglycemia, and in older and frailer patients, for whom the dangers of hypoglycemia are more pronounced.[1]

According to one 2004 study, about 25% of patients with diabetes in Spain are treated with diet alone.[9] The study looked at differences in treatment regimens during a 1-year period in 294 practices throughout the EU, and found the following patterns in the treatment and management of patients in Spain (Table 2). These patient groups, however, include both type 1 and type 2, though it may be assumed that no type 1 patients fall into the “diet alone”category.

Table 2. Diabetes treatment patterns in Spanish primary care practices (2004)[9]

Oral antidiabetic agents currently in general use in Spain include:[3],[6]

• Sulfonylurea

o        Clorpropamide

o        Glibenclamide

o        Gliclazide

o        Glimepiride

o        Glipizide

o        Gliquidone

o        Glisentide

o        Tolbutamide

• Biguanides

o        Metformin

• Meglitinides

o        Repaglinide

o        Nateglinide

• Glucosidase inhibitors

o        Acarbose

o        Miglitol

• Thiazolidinediones

o        Rosiglitazone

o        Pioglitazone

The following general guidelines are suggested when combining oral antidiabetic agents:[7]

• Two SUs are contraindicated[7]

• SUs + Acarbose: may be useful in controlling postprandial hyperglycemia[7]

• Metformin + SU: may be useful when patient fails the maximum dosage of metformin, only when there are no contraindications to both drugs[7]

• Metformin + acarbosa: insufficient evidence for this combination[7]

Clinicians should be guided by patient needs and accepted guidelines, such as the SED guidelines, when combining oral therapeutic agents, and when adding insulin to an oral regimen[7]

References

1. http://www.icf.uab.es/a_primaria/Capituls-Index-Cas/capi9cas.pdf. Accessed May 2006.
2. www.msc.es/en/ciudadanos/enfLesiones/enfNoTransmisibles/diabetes/diabetes.htm#prevencion. Accessed May 2006.
3. British Medical Association. Diabetes mellitus: an update for professionals. Available at: http://www.bma.org.uk/ap.nsf/Content/Diabetes/$file/diabetes.pdf. Accessed March 2006.
4. UK Prospective Diabetes Study. Available at: http://www.dtu.ox.ac.uk/index.html?maindoc=/ukpds/. Accessed March 2006.
5. NHS MeReC briefing. Type 2 diabetes (part 1):the management of blood glucose. Available at: http://www.npc.co.uk/MeReC_Briefings/2003/Briefing%20No%2025%20press%20RGB.pdf. Accessed: February 2006
6. http://www.feaed.org/biblioteca/documentos/andalucia/Mellitus_1.pdf. Accessed March 2006.
7. http://www.gobiernodecanarias.org/sanidad/scs/6/6_1/cardiovascular/diabetes/dbtes_tratamiento.jsp.
8. www.sediabetes.org/grupos_trabajo/doc_diabetes_tipo2_1.pdf. Accessed May 2006.
9. Donker G, et al. Differences in treatment regimes,consultation frequency and referral patterns of diabetes mellitus in general practice in five European countries. Family Practice. 2004;21:362-369.