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Diagnosis and Management of Type 2 Diabetes, 10th Edition, Ch 15, Pt3

Feb 5, 2011
Long-Term Complications and Treatments


Steve V. Edelman, MD
Robert R. Henry, MD

Microvascular Complications


Retinopathy, nephropathy, and neuropathy are the major microvascular complications of Type 2 diabetes. Prevention, early detection, and aggressive treatment are essential to reduce associated morbidity and mortality. Good metabolic control has been clearly shown to prevent the development and delay the progression of these complications in both types of diabetes….

Diabetic Retinopathy

The development and progression of retinopathy depend on the duration of diabetes and the duration and severity of hyperglycemia. Because diabetic retinopathy does not cause symptoms until it has reached an advanced stage, early and frequent evaluation for vision problems is critical for patients with diabetes. The following findings also support the importance of early detection:

  • Diabetes is the leading cause of all new cases of blindness (13%).
  • Loss of vision associated with diabetic retinopathy and macular edema can be reduced by at least 50% with laser photocoagulation if identified in a timely manner.

Patients must be completely informed about the possible relationship between hyperglycemia and retinopathy, stressing the importance of promptly reporting any visual symptoms. They should be aware that hypertension can worsen retinopathy and therefore be encouraged to take any antihypertensive medications that have been prescribed. Most important, patients should understand the potential visual complications associated with diabetic retinopathy and how to prevent or reduce the severity of these problems.

The three categories of diabetic retinopathy that are part of a continuum are:

  • Nonproliferative or background
  • Preproliferative
  • Proliferative.

Background changes are the earliest stage of retinopathy and are characterized by microaneurysms and intraretinal “dot and blot” hemorrhages (Figure 15.1). If serous fluid leaks into the area of the maculae (where central vision originates), macular edema can occur and Macular edema cannot be observed directly but is suggested by the presence of hard exudates lose to the maculae. Any of these findings should prompt immediate referral to an ophthalmologist.

FIGURE 15.1 — Background Diabetic Retinopathy


Advanced background retinopathy with certain lesions is considered the preproliferative stage and indicates an increased risk of progression to proliferative retinopathy. This stage is characterized by “beading” of the retinal veins; soft exudates (also called “cotton-wool” spots that are ischemic infarcts of the inner retinal layers) (Figure 15.2); and irregular, dilated, and tortuous retinal capillaries or occasionally newly formed intraretinal vessels. Any one of these signs suggests the need for further evaluation by an ophthalmologist.

FIGURE 15.2 — Preproliferative Retinopathy


Proliferative retinopathy is the final stage of this degenerative condition and imparts the most serious threat to vision. Neovascularization typically covers more than one third of the optic disk and may extend into the posterior vitreous. These fragile new vessels, which are prone to bleeding, probably develop in response to ischemia. Bleeding that occurs in the vitreous or preretinal space can cause visual symptoms such as “floaters” or “cobwebs” or retinal detachment that results from contraction of fibrous tissue. Sudden and painless vision loss usually is related to a major retinal hemorrhage.

Evaluation and Referral

Because visual acuity frequently changes in response to fluctuations in glycemic control particularly extreme variations, eg, low-to-high and high-to-low), the reason for any vision changes should be thoroughly investigated. All patients with diabetes should have annual eye examinations with complete visual history, visual acuity examinations, and careful ophthalmoscopic examinations with dilated pupils. High-quality fundus photographs can detect most clinically significant diabetic retinopathy. Indications for referral to an ophthalmologist are shown in Table 15.8. Patients with Type 1 diabetes should begin having annual eye examinations after 5 years of diabetes. Patients with Type 2 diabetes should have annual eye examinations starting at the time of diagnosis because of the probability that glucose Intolerance was present for up to 4 to 7 years before the diagnosis of diabetes.

TABLE 15.8 — Reasons to Refer Patients with Type 2 Diabetes Mellitus to an Ophthalmologist


Treatment of nonproliferative and preproliferative retinopathy typically involves blood glucose control and blood pressure control. The only standard treatment for background retinopathy, in addition to optimizing metabolic control and blood pressure, is photocoagulation treatment. Results of the Early Treatment Diabetic Retinopathy Study revealed the effectiveness of argon laser photocoagulation applied focally (e.g., spot-welding the leaking micro aneurysms) intreating macular edema and stabilizing vision. Photocoagulation can slow the progression of vision loss in cases of macular edema and reduce visual loss by >50% when used as a preventive measure to limit neovascularization and vitreous hemorrhages. Pan retinal laser treatment has been proven effective and is the treatment of choice for patients with proliferative retinopathy and high-risk characteristics. A scatter pattern of 1200 to 1600 burns is applied throughout the periphery of the retina, avoiding the macular area.

Vitrectomy may be required to treat retinal detachment and large vitreous hemorrhages. This procedure generally is reserved for patients with poor vision in whom the benefits outweigh the risks.

Diabetic Nephropathy

Over 20% of adults who have had diabetes for >20 years have clinically apparent nephropathy. This disease is progressive, takes years to develop, and requires laboratory evaluation for early detection because it generally is asymptomatic in the early stages.

Structural and functional changes in the kidneys occur early in the course of poorly controlled diabetes but do not produce clinical symptoms. The first sign of nephropathy is microalbuminuria (30 to 300 mg albumin/24 hours), which may be apparent at the time of diagnosis in patients with Type 2 diabetes. The presence of microalbuminuria is not only a predictable marker of early diabetic nephropathy, but is also very strongly associated with coronary artery disease in patients with Type 2 diabetes. In addition, hypertiltration, indicated by an elevated CrCl, is also a finding in early diabetic nephropathy. The important clinical point is that in this early stage of nephropathy, aggressive management may reverse or completely stabilize any abnormalities. Overt nephropathy is defined as urinary protein excretion >0.5 g/24 hours and clinical proteinuria characterized by albumin excretion rates >300 mg (0.3g)/24 hours, typically accompanied by hypertension. The following conditions play a role in the development and acceleration of renal insufficiency:

  • Chronic uncontrolled hyperglycemia
  • Hypertension (virtually all patients who develop nephropathy also have hypertension [systolic blood pressure >135 mm Hg, diastolic blood pressure >85mm Hg])
  • Neurogenic bladder leading to hydronephrosis and infections
  • Urinary tract infection (UTI) and obstruction
  • Nephrotoxic drugs (nonsteroidal anti-inflammatory drugs, chronic analgesic abuse, radiocon trast dyes [should be performed only when adequate hydration and dieresis can be assured and if no other diagnostic alternatives are available]).

Patients with diabetes often develop uremia at lower creatinine levels than patients with renal insufficiency resulting from other causes. Second, even with dialysis, the prognosis for patients with diabetes is worse than that for nondiabetic patients. Patients with diabetes tend to start dialysis earlier because they develop symptoms sooner than other patients with renal disease. Therefore, a renal transplant is the preferred method of treatment, if possible, at this stage.


A routine urinalysis should be done at the time of diagnosis and then yearly. If the urinalysis is positive for protein (>300 mg of albumin or macroalbuminuria), then a 24-hour quantitative measure along with a CrCl is important to obtain. If the urinalysis is negative, a test for microalbuminuria is indicated. The easiest method is the albumin-to-creatinine ratio in a random spot collection. The gold standard is a 24-hour collection and can be used to accurately follow the patient over time and assess the success of therapy. If a UTI is present, it should be treated promptly before determining the significance of proteinuria. A positive result (>30 mg protein/24 hour) indicates the need for pharmacologic therapy with an ACE inhibitor or an ARB.

Annual screening is important for patients who have negative results (particularly those without microalbuminuria and hypertension), given that certain factors can interfere transiently with this evaluation (e.g., exercise, infections, fever, uncontrolled diabetes, and hypertension). The mean albumin excretion of three timed urine collections can be used to establish a diagnosis of microalbuminuria if the values are equivocal.

It is important for physicians to inform patients with diabetes about the relationship between high blood pressure and renal disease, and the benefits of maintaining glycemic control. Patients should be encouraged to have their blood pressure checked regularly (in addition to obtaining their own blood pressure cuff to measure blood pressure at home), take antihypertensive medications that have been prescribed, decrease their protein intake to approximately 10% of daily calories, and monitor glucose levels frequently with SMBG and take any other measures to improve glycemia. The importance of reporting symptoms of UTI should be emphasized, along with following proper treatment for this infection and avoiding nephrotoxic drugs.

Next Week: Treatment of Nephropathy and Diabetic Neuropathy
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