International Diabetes Federation Global Guidelines for Diabetic Microvascular Complications

Introduction

Why develop global guidelines?

Evidence-based guidelines serve as cost-effective resources to standardize the care of diabetes patients.1^,2 Ample evidence exists to instruct physicians on improving the quality of life of diabetes patients by providing optimal diabetes care.¹ However, the evidence base is large, and diabetes care can be complex.¹ Evidence-based practice guidelines provide concise clinical practice recommendations based on rigorous analysis of the evidence.¹ In the Global Guideline for Type 2 Diabetes, the International Diabetes Federation (IDF) notes that many countries do not possess the resources to develop formal guidelines and would therefore benefit from a formal global guideline. In addition, development of guidelines by many countries would be a repetitive and inefficient effort.¹ The IDF therefore determined that it would be appropriate to develop a global guideline for the treatment of type 2 diabetes.  

What is included in the IDF Guideline for Type 2 Diabetes?

The IDF Guideline covers a wide variety of topics relevant to diabetes care. Five chapters are devoted to diabetes complications: retinopathy, nephropathy, foot care, neuropathy, and cardiovascular risk.¹ Each chapter is divided into 6 sections: practice recommendations, rationale, evidence base, special consideration, implementation, and evaluation. To address the differences in resource availability around the world and ensure applicability of the recommendations in diverse settings, the IDF Guideline describes 3 levels of care: standard, minimal, and comprehensive.¹ Standard care is the level of care that should be available to everyone. It is evidence-based and cost-effective in most nations with good service bases and significant healthcare funding.¹ Minimal care should reach major treatment goals of diabetes management in settings with limited resources.¹ Comprehensive care encompasses standard care but additionally considers more advanced technologies that may have less supporting evidence.¹

IDF Global Guidelines for Diabetic Microvascular Complications

Consequences of diabetic microvascular complications (DMC), such as blindness and amputation, are feared and contribute substantially to the social and financial burden of the disease.3 Diabetic retinopathy (DR) is the most important cause of vision loss in developed countries, diabetic nephropathy (DN) is a significant cause of renal failure, and diabetic peripheral neuropathy (DPN) increases the risk of foot ulceration and amputation.³ Guidelines for the treatment of these complications are therefore an important part of optimal patient care.

The IDF Guideline sections covering DMC focus on preventive therapy and routine assessment for early detection of complications. Early detection facilitates the use of treatment modalities that delay DMC development and progression, which in turn postpones the use of procedures required at later stages, such as laser surgery, amputation, and dialysis. Because these procedures are performed at great monetary and health costs, early detection and prevention are cost effective. Therefore, from the perspectives of patient health and resource utilization, it is important to be aware of the recommendations in the IDF Guideline.

Eye screening

At all 3 levels of care (standard, comprehensive, and minimal), the goal is to provide regular eye assessment using either ophthalmological expertise or camera technologies.¹ Eye examinations according to standard care recommendations should include retinopathy assessment and measurement and documentation of visual acuity. Retinopathy assessment may consist of retinal photography through dilated pupils performed by a trained professional or examination by an ophthalmic specialist. Seven-field stereoscopic color fundus (SSF) photography is the “gold standard” test for retinal screening, and as such, it is included in recommendations for comprehensive care. Although SSF photography is accurate and reproducible, it requires substantial labor and resources and is not considered essential to standard care.^1,4 In considering potential resource limitations (eg, lack of camera technologies and ophthalmologists), minimal care recommendations require only direct fundoscopy by a trained professional. This approach is less sensitive than photographic techniques but can detect many problems.¹ Review intervals and recommendations for specialist referral are the same for standard, comprehensive, and minimal care. Situations requiring specialist referral are detailed and provide examples of situations requiring referral the same day (eg, sudden vision loss, evidence of retinal detachment), within 1 week (eg, evidence of preretinal and/or vitreous hemorrhage, new vessel formation or rubeosis iridis), and within 1-2 months (eg, advanced retinal lesions, unexplained deterioriation of visual acuity, macular edema, unexplained retinal findings, cataract, inability to visualize fundus).¹ A summary of IDF recommendations for eye screening is provided in Table 1.

Table 1. IDF Eye Screening Recommendations for Patients with Type 2 Diabetes

The IDF Guideline provides information regarding the rationale, evidence base, and special considerations for the recommendations, as well as comments regarding implementation and evaluation of the guideline. For example, evidence indicates that the sensitivity/selectivity, feasibility, and opportunities for quality assurance make digital photography a better option for screening than direct ophthalmoscopy.¹ One special consideration in developing the guideline for eye screening is the lack of availability of laser treatment in many areas of the world. The guideline notes that, even when laser treatment is unavailable, regular examinations can promote preventive care by raising awareness of visual problems. In addition, records of visual problems can be used to justify establishment of laser service.¹ Comments on implementation of guideline recommendations indicated staff and equipment requirements. To evaluate implementation, the guideline suggests reviewing records to ensure eye examinations and appropriate referrals have been completed. In addition, screening services can be checked for appropriately trained personnel and evidence of quality checks.

Kidney damage

The IDF recommendations for preventing kidney damage focus on annual screening for microalbuminuria and specific steps for managing patients who progress to microalbuminuria/proteinuria. Specific recommendations for individuals with raised urine albumin or proteinuria differ for standard and minimal care levels. The differences reflect the consideration of resource limitations when developing minimal care recommendations. For standard care, individuals with raised urine albumin or proteinuria or reduced eGFR (<90 ml/min/1.73m²) should be managed as follows: use an angiotensin converting enzyme (ACE) inhibitor or angiotensin 2 receptor blocker (A2RB) at maximum tolerated dose; control blood pressure (target <130/80 mmHg) through drugs and dietary modification; intensify blood glucose management (A1C <6.5%); monitor progression by ACR or PCR, serum creatinine and potassium; advise limiting protein intake to 0.8 g/kg daily if proteinuric; intensify other renal and cardiovascular protection measures. Minimal care recommendations for people with proteinuria include behavioral changes (eg, avoiding risk factors and limiting protein intake); controlling blood pressure through accessible means, including salt limitation and any available antihypertensive agent; use of ACE inhibitors if available; blood glucose control; lipid control using available agents; and regular follow up. Comprehensive care recommendations are the same as for standard care with the inclusion of regular quantitative laboratory assessment of albuminuria (ACR) and investigation of other potential causes of renal disease through auto-antibody testing, ultrasound, or biopsy. Recommendations for preventing kidney damage are summarized in Table 2.

Table 2. IDF Recommendations for Prevention of Kidney Damage

The rationale for regular screening for kidney damage is based on evidence indicating that disease progression can be slowed with appropriate blood pressure treatment.¹ Slowing disease progression delays the need for dialysis or transplantation, which are expensive treatments with limited availability. Evidence also indicates added benefits for use of ACE inhibitors and A2RBs, if available, in delaying progression from micro- to macroalbuminuria. Treatment of anemia is recommended because mild anemia has been associated with risk of renal disease progression.¹ Implementation of these recommendations requires resources for repeated measurement and drug dose titration, access to laboratory microalbuminuria estimation, and availability of multiple agents for blood pressure control. Evaluation relies on the availability of records demonstrating that individuals received required testing, that action was taken to control blood pressure, and that patients were appropriately referred to a nephrologist.

Foot care

Foot ulceration and limb amputation impair health and increase healthcare costs among diabetes patients. Evidence-based reviews are consistent in recommending formal regular review to detect individuals at risk for foot ulceration, more frequent review of those at risk, and intensive management of those developing foot ulcers in order to reduce health and monetary costs. Education and revascularization are also commonly recommended. The IDF recommendations are very consistent with the recommendations of other clinical guidelines.¹

The standard, comprehensive, and minimal care recommendations for foot care do not differ significantly because foot inspection and sensorimotor assessment, key components of foot care, can easily be modified according to the given resource settings.¹  Standard care recommendations indicate the option of using a biothesiometer for quantitative detection of neuropathy, but sensory assessment using 10-g monofilament, tuning fork, or pin-prick are considered appropriate for standard, minimal, and comprehensive care. Sensory and vascular function are part of both standard and minimal care recommendations, although standard care recommendations provide for use of more quantitative measurement technologies.¹ In addition, vascular referral depends on available resources in a minimal care setting.¹ Comprehensive care is as standard and minimal care, although formation of a multidisciplinary on-site foot-care team is suggested as are foot pressure distribution measurements, vascular scanning, and angiography.¹ A summary of IDF recommendations for foot care is provided in Table 3.

Table 3. IDF Recommendations for Foot Care

Specifics of the IDF recommendations include classification of the patient’s status based on the annual foot review, management according to the patient’s status, and criteria to consider prior to amputation. The classifications for foot status are listed in Table 3. “No added risk” indicates no loss of sensation, signs of peripheral arterial or other risk factors. Patients in this category develop a foot care plan with their healthcare provider. “At risk” is assigned to patients with neuropathy or any other single risk factor. A 6-month review should be scheduled for patients in this category, including foot inspection, footwear evaluation, and enhanced education. Patients designated “at high risk” demonstrate diminished sensation with foot deformities or evidence of peripheral arterial disease. Individuals in this category receive the same care as those “at risk,” but review should be scheduled every 3-6 months, vascular assessment may be appropriate, and foot care education should be assessed. Previous ulceration or amputation is considered to be “very high risk.” Patients with ulceration or infection should be referred to a multidisciplinary foot care team within 24 hours. Amputation should not be considered unless: the patient has had a detailed vascular evaluation by by vascular staff; neither analgesia nor revascularization relieve ischemic rest pain; there are no other means to treat a life-threatening foot infection; the burden for amputation is lower than that for the presence of a non-healing ulcer.¹

Implementation and evaluation of these recommendations are straightforward. Healthcare staff involved in diabetes foot care need to be adequately trained. Evaluation of the effectiveness of these guidelines can be measured by the annual incidence of foot ulceration, foot hospitalization, foot ulceration healing rates, and amputation rates.

Nerve damage

Standard care recommendations rest on diagnosis of conditions that are the result of peripheral neuropathy. Exclusion of causes other than diabetes is important because non-diabetic causes may account for 10% of neuropathy cases among diabetes patients.¹ For standard care, diagnosis of sensorimotor nerve damage, painful DPN, erectile dysfunction, gastroparesis, and cardiovascular autonomic neuropathy is recommended. Suggestions for pharmacologic agents to treat painful DPN, erectile dysfunction, and gastroparesis are provided. In the case of painful DPN, referral to a pain control team is suggested when pharmacologic options fail. Comprehensive care is the same as standard care but includes provisions for quantitative sensory testing, electrophysiology, and autonomic function tests. For minimal care, only screening for sensorimotor nerve damage is recommended. A limited list of pharmacologic agents is provided for treatment of painful DPN, but referral to a pain control team is not included in the recommendations. Assessment of erectile dysfunction to consider possible contributions of other medications or disease is also suggested. Recommendations for managing diabetic neuropathy are summarized in Table 4.

Table 4. IDF Recommendations for Managing Diabetic Neuropathy

The rationale for developing this set of recommendations rests on the observations that, in addition to foot injury, diabetic neuropathy has other clinical consequences, including pain, gastrointestinal symptoms, bladder problems, and sexual problems.¹ Unfortunately, the assessment and care of these conditions are underrepresented in clinical practice guidelines.¹ In general, stabilizing glycemic control and treating with tricyclic drugs are the accepted approaches.¹ Consideration of the evidence revealed the cost of newer therapies to be too high to justify altering this approach.¹ Implementation of the guideline will require protocols for sensory testing and medical teams who are aware of the presentations of autonomic neuropathy. Evaluation consists of maintaining records that document regular surveillance for neuropathic symptoms.

Summary

The recommendations for standard care of DMC in the IDF Global Guideline for Type 2 Diabetes are comparable to those in the American Diabetes Association (ADA) Clinical Practice Recommendations.5 Both the IDF and ADA provide more detailed practice recommendations regarding DMC than other guidelines.6^,7 However, there are notable differences between the ADA and IDF guidelines. The ADA recommendations apply to both type 1 and type 2 diabetes, but the IDF Guideline is specific to type 2 diabetes. Unlike the ADA recommendations, the IDF guideline includes separate sections on foot care and diabetic neuropathy. However, the ADA addresses diabetic neuropathy in a separate statement.8 The IDF guideline also provides recommendations for practice in limited resource settings and for implementation and evaluation of guideline implementation. Recommendations for ensuring and monitoring implementation are important because guidelines are cost-effective resources if they are properly implemented.² The IDF Global Guideline for Type 2 Diabetes seems, as it was designed to be, a cost-effective resource that will be useful in many healthcare settings around the world.

References

1. IDF Clinical Guidelines Task Force. Global guideline for Type 2 diabetes. Brussels: International Diabetes Federation, 2005.

2. IDF Clinical Guidelines Task Force. Guide for guidelines: a guide for clinical guideline development. Brussels; International Diabetes Federation, 2003.

3. IDF. Diabetes atlas. 2^nd edition. Brussels; International Diabetes Federation, 2003.

4. Fong DS, Aiello LP, Ferris FL III, Klein R. Diabetic retinopathy. Diabetes Care. 2004;27(10):2540-2553.

5. ADA. Clinical practice recommendations 2006. Diabetes Care. 2006;29(suppl 1).

6. The American Association of Clincal Endocrinologists (AACE). Medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management – 2002 update. Endocr Pract. 2002;8(suppl 1):40-82.

7. Institute for Clinical Systems Improvement (ICSI). Health care guideline: management of type 2 diabetes mellitus. Available at: http://www.icsi.org. Accessed

8. Boulton A, Vinik A, Arezzo J, et al. Diabetic neuropathies: a statement of the American Diabetes Association. Diabetes Care. 2005;28:956-962.