U.S. Department of Health and Human Services

Principle 8: Detect & Monitor Microvascular Complications

Nephropathy

Diabetes is the leading cause of end-stage renal disease (ESRD). Intensive glucose control and blood pressure reduction have been shown to reduce onset and progression of nephropathy in type 1 and type 2 diabetes. 1, 3 While blood pressure control is important for all people with diabetes, it is particularly imperative to achieve blood pressure control in people with diabetic nephropathy, both to prevent progression of nephropathy and because nephropathy is a risk factor for cardiovascular disease (CVD). Early recognition of kidney damage in people with diabetes allows for preventive measures to slow or prevent progressive loss of kidney function.

Use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to lower systolic blood pressure in people with diabetes and albuminuria slows the rise in levels of albuminuria and the decline in glomerular filtration rate (GFR). ACE inhibitors also reduce major CVD outcomes in people with type 2 diabetes. 4

Persistent albuminuria is an early marker of diabetic kidney disease and is useful for monitoring progression and prognosis. Urine albumin excretion exceeding what is considered normal (< 30 mg/day), even when below what is detected by dipstick (equivalent to 300 mg/day), is an early marker of diabetic nephropathy and a risk factor for CVD. Albuminuria increases with diabetes progression. High levels of albuminuria are associated with rapid progression. However, decreased GFR can occur in the absence of albuminuria in people with diabetes. 4

Nephropathy assessment

  • Annually assess urine albumin excretion in adults and children with type 1 diabetes with diabetes duration of more than 5 years and in adults and children with type 2 diabetes starting at diagnosis. Use the albumin-to-creatinine ratio in a random spot urine collection to assess urine albumin excretion. Results are reported as albumin in mg/g creatinine and are equivalent to albumin excretion in mg/day.
  • Annually measure serum creatinine in all adults with diabetes regardless of the degree of urine albumin excretion. Use the serum creatinine to estimate GFR.

Nephropathy management

  • Hyperglycemia and hypertension are major risk factors for the onset and progression of nephropathy. Multiple drugs are often required to control blood pressure. Therapy should be individualized based on risks and benefits. For more information about blood glucose and blood pressure control, refer to Principles 6 and 7.
  • Use an ACE inhibitor or an ARB to manage nonpregnant people with hypertension and diabetes. Patients without hypertension and with urine albumin-to-creatinine ratio (UACR) higher than 300 mg/g should also receive an ACE inhibitor or ARB. Evidence for treatment of nonhypertensive people with lower levels of albuminuria (30–300 mg/g creatinine) is less well supported. Do not use these medications in pregnant women or women considering pregnancy.
  • Refer people to a registered dietitian/registered dietitian nutritionist specializing in kidney disease to help moderate intake of dietary sodium, phosphorus, potassium, and protein as necessary.
  • Screen for anemia, malnutrition (e.g., low serum albumin), and mineral and bone disease (potassium, bicarbonate, calcium, phosphorus, and vitamin D deficiency) when the estimated GFR is less than 60 mL per minute per 1.73 m 2.
  • Consider referral to a physician experienced in the care of kidney disease when there is uncertainty about the etiology of kidney disease (active urine sediment, heavy proteinuria, absence of retinopathy, or rapid decline in GFR), difficult management issues, or advanced kidney disease.
  • Educate people with diabetes about the progressive nature of kidney disease, the renal preservation benefits of optimal management of blood pressure and blood glucose, the importance of a low-sodium diet, and the potential need for renal replacement therapy.

Resources for nephropathy

Neuropathy

Early recognition and appropriate management of neuropathy is important because a number of symptomatic treatment options exist for diabetic neuropathy. 5 Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and autonomic neuropathy. Up to 50 percent of DPN patients may be asymptomatic and at risk of insensate injury to their feet. Autonomic neuropathy may involve every system in the body, and cardiovascular autonomic neuropathy causes substantial morbidity and mortality. Optimal glycemic control may slow progression of neuronal loss.

Neuropathy assessment

  • Screen all people with diabetes for DPN at diagnosis of type 2 diabetes and 5 years after diagnosis of type 1 diabetes and at least annually thereafter, using simple clinical tests such as monofilament pressure sensation, pinprick sensation, vibration perception, and ankle reflexes.
  • Assess people found to have peripheral neuropathy for vitamin deficiencies, alcoholism, hypothyroidism, and heavy metal or toxin exposure.
  • Screen for signs and symptoms of cardiovascular autonomic neuropathy (such as resting tachycardia and orthostatic hypotension) at diagnosis of type 2 diabetes and 5 years after diagnosis of type 1 diabetes.
  • Assess adults for symptoms of gastrointestinal neuropathy and genitourinary tract problems, including erectile dysfunction in men.

Foot assessment

Annually conduct a comprehensive foot examination, including skin (dryness, sweating, fungal infection, cracking, ulceration, calluses, and blistering), musculoskeletal, neurological, vascular, and footwear assessment. 6

Neuropathy management

  • Optimize the control of blood glucose to reduce the risk for or slow the progression of neuropathy.
  • Consider medications for the relief of specific symptoms related to DPN and autonomic neuropathy. Medication does not slow progression of neuropathy and must be carefully titrated, balancing reduction in symptoms against side effects with the goal of improving quality of life. 5
  • Educate all adults with DPN about self-care of the feet:
    • Daily foot inspection, skin and nail care, use of emollients, treatment for callus, and selection of footwear.
    • For those with significant DPN, provide enhanced foot care education about their risk factors and appropriate management as well as referral for special footwear.
  • Referral to specialists may improve the management of high-risk feet. When the patient or health care team detects a foot ulcer, prompt referral to a foot specialist may prevent the development of osteomyelitis. 7

Resources for neuropathy

Retinopathy

Diabetic retinopathy is the leading cause of blindness in working-age adults. Optimal glycemic management and blood pressure control can reduce risk of retinopathy or slow its progression. 1, 2, 8, 9 Regular screening for retinopathy is important to identify people with diabetes at risk for vision loss who can benefit from interventions.

Laser photocoagulation therapy reduces risk of vision loss in patients with high-risk proliferative diabetic retinopathy (PDR); clinically significant macular edema (CSME); and, in some cases, severe nonproliferative diabetic retinopathy (NPDR). The Diabetic Retinopathy Study 10 showed that panretinal photocoagulation surgery reduced the risk of severe vision loss from PDR from 15.9 percent in untreated eyes to 6.4 percent in treated eyes. The Early Treatment Diabetic Retinopathy Study 11 established the benefit of focal laser photocoagulation surgery in eyes with CSME. This study also verified the benefits of panretinal photocoagulation for high-risk PDR and in older-onset patients with severe NPDR or less-than-high-risk PDR. More recently, intravitreal treatment with a vascular endothelial growth factor (VEGF) inhibitor alone or in combination with laser therapy was shown to improve vision, retinal thickening, and patient quality of life more than laser alone in patients with CSME. 12

Retinopathy assessment

  • For adults and children over 10 with type 1 diabetes, provide an initial dilated and comprehensive eye examination by an eye care professional (optometrist or ophthalmologist) within 3 to 5 years after the onset of diabetes.
  • Provide people with type 2 diabetes with an initial dilated and comprehensive eye examination by an eye care professional shortly after the diagnosis of diabetes.
  • Repeat dilated comprehensive eye examinations at least annually for persons with established retinopathy. Individualize the frequency and type of professional follow-up referral (such as to a retinal specialist) as needed. Less-frequent examinations (every 2–3 years) may be considered following one or more normal eye examinations based on individual risk factors for development of retinopathy, including diabetes duration, glycated hemoglobin, blood pressure, and patient understanding of and compliance with principles of good diabetes self-care.
  • Because ocular complications of diabetes are myriad, including cataract, glaucoma, ocular surface disease, hypertensive retinopathy, retinal vascular occlusive disease, and ischemic optic neuropathy, all people with diabetes should have regular comprehensive eye examinations.
  • Eye care providers should stress the importance of early, good glycemic control as a protective factor against the onset and progression of diabetic retinopathy and other ocular complications of diabetes, and should promptly communicate eye examination findings to the patient’s PCP and/or endocrinologist.
  • The use of retinal photography with remote reading by experts may improve detection and management of sight-threatening diabetic retinopathy and has great potential in areas where qualified eye care professionals are not available. Photos are not a substitute for a comprehensive eye examination, which should be performed at least initially and at intervals thereafter as recommended by an eye care professional.

Retinopathy management

  • Optimize the control of blood glucose, blood pressure, and blood lipids to reduce the risk for or slow the progression of retinopathy.
  • Promptly refer patients with any level of macular edema, severe NPDR, or any PDR to an eye care professional experienced in the management of retinal disease.
  • Retinopathy is not a contraindication to low-dose aspirin use for CVD prevention.

References

1. de Boer IH, Sun W, Cleary PA, et al. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011;365(25):2366–76.

2. United Kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837–53.

3. Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376(9739):419–430.

4. National Kidney Foundation Kidney Disease Outcomes Quality Initiative. NKF KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. New York: National Kidney Foundation; 2007.

5. Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758–65.

6. Boulton AJ, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment. A report of the Task Force of the Foot Care Interest Group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Phys Ther. 2008;88(11):1436–43.

7. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. J Am Podiatr Med Assoc. 2013;103(1):2–7.

8. United Kingdom Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703–13.

9. Chew EY, Ambrosius WT, Davis MD, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363(3):233–44.

10. Diabetic Retinopathy Study Research Group. Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol. 1976;81(4):383–96.

11. Early Treatment Diabetic Retinopathy Study. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985;103(12):1796–806.

12. Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012;366(13):1227–39.