≥ 92% of participants will know the microvascular complications of diabetes, and the signs/symptoms, risk factors, and treatments for these complications.
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≥ 92% of participants will know the microvascular complications of diabetes, and the signs/symptoms, risk factors, and treatments for these complications.
After completing this module, the learner will be able to:
Diabetes mellitus (DM) is one of the most common chronic diseases in the United States (US), and approximately 37.3 million people, or 11.3% of the US population, have diabetes (Centers for Disease Control and Prevention [CDC], 2022b). Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) cause significant complications (Powers et al., 2022), and these complications are the primary cause of morbidity and mortality for diabetic patients (Limonte et al., 2022; Natarajan, 2021).
The course will discuss the microvascular complications of DM, including diabetic nephropathy or diabetic kidney disease, diabetic neuropathy, and diabetic retinopathy (Powers et al., 2022). These pathologies are considered microvascular because damage to the microvasculature of the kidneys, nerve cells, and eyes is a prominent finding and a cause of their signs and symptoms. These microvascular complications may seem to be an inevitable consequence of T1DM and T2DM; however, the risk factors for diabetic nephropathy, neuropathy, and retinopathy may be modifiable.
Note: DM also causes macrovascular complications, cerebrovascular disease, coronary heart disease, and peripheral arterial disease. These pathologies are quite common in people with DM, but they share pathophysiologic underpinnings with non-diabetic diseases (Powers et al., 2022). For this course, the term diabetes will refer to diabetes mellitus.
The terms that are used to discuss the renal damage caused by DM are used interchangeably and in a way that can be confusing.
The pathophysiologic mechanisms that cause DKD involve three basic factors: chronic hyperglycemia, genetics, and lifestyle factors (Guedes & Pecoits-Filho, 2022; Natarajan, 2021; Powers et al., 2022, Wu et al., 2021).
DKD occurs in 20-40% of patients who have diabetes (ElSayed et al., 2023a). Diabetes is the most common cause of CKD (Guedes & Pecoits-Filho, 2022), and in the US, DM is the leading cause of kidney failure or ESRD (Limonte et al., 2022). In addition, CKD caused by DM significantly increases the risk of developing cardiovascular disease and mortality from cardiovascular disease (Limonte et al., 2022). The risk increases as albuminuria and reduced eGFR worsen, and DM-associated CKD increases the risk of developing peripheral vascular disease and stroke (Limonte et al., 2022).
American Indian, Asian, Black, and Hispanic Americans have a higher prevalence of DM than white Americans (Limonte et al., 2022; Ngo-Metzger, 2022; Owoyemi & Balogun, 2022). Diabetic members of these populations have a higher risk of developing DKD, and the prevalence of DKD and kidney failure is higher (Limonte et al., 2022). Diabetes and hypertension, the two primary causes of CKD, and lifestyle factors that contribute to CKD are more prevalent among Black Americans (CDC, 2020; CDC, 2022a; CDC, 2022b). However, the comparatively higher risk for DKD, ESRD, and other diabetic complications in Black Americans is not fully explained by these factors (Owoyemi & Balogun, 2022).
Risk factors for DKD, and all DM microvascular complications, are considered modifiable or non-modifiable (Pelle et al., 2022).
Modifiable risk factors for DKD include cigarette smoking, hyperglycemia, hyperlipidemia, hypertension, and obesity (Guedes & Pecoits-Filho, 2022; Pelle et al., 2022). Non-modifiable risk factors include age, genetic susceptibility, ethnicity, and male gender (Pelle et al., 2022).
Gender differences that may affect the risk of developing DKD are still being researched. Giandalia et al. (2021) wrote that although the available information is still inconclusive, the overall epidemiological data indicate that the risk of developing DKD is higher in men with DM, who also have a higher risk of DKD progression (Giandalia et al., 2021).
Modifiable risk factors are very common in people with diabetes (CDC, 2022b). For example, it has been estimated that in US adults aged 18 years or older diagnosed with diabetes, 13.8% smoked cigarettes, 69.0% had hypertension, 89.8% were overweight or obese, and 49.4% had a glycated hemoglobin or A1C level ≥ 7.0 (CDC, 2022b).
Note: Hypertension can help cause diabetic nephropathy, and diabetic nephropathy can cause hypertension.
The American Diabetes Association recommends that at least once a year:
The albuminuria and the low eGFR are persistent, and the albuminuria is 30 mg to 300 mg albumin per g of creatine, and eGFR is <60 mL/min/1.73 m2 (Brutsaert, 2022; Maddukuri, 2022b; Selby & Taal, 2020; Suneja, 2021). The albumin level and the eGFR are used to diagnose DKD, and they are also used to help guide treatment decisions (ElSayed et al., 2023a).
Diabetic nephropathy causes structural damage to the glomeruli, resulting in hyperfiltration and reduced blood flow through the glomeruli (A/L B Vasanth Rao et al., 2019). Hyperfiltration is detected and measured by comparing the amount of urinary albumin to the amount of urinary creatinine. Reduced blood flow is detected and measured by the eGFR.
Treatment of DKD is intended to slow and hopefully stop the progression of the disease, and treatment of DKD includes glycemic control, blood pressure control, and nutritional modifications. Regarding the prevention of DKD, exercise, lipid control, weight loss, and smoking cessation can help prevent diabetic complications, but the “. . . only proven primary prevention interventions for CKD are blood glucose and blood pressure control” (ElSayed et al., 2023a).
The pharmacological treatment of DKD for glycemic control is discussed in the next section.
Two classes of antidiabetic medications are used for glycemic control and have been shown to decrease the progression of CKD (ElSayed et al., 2023b). Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1-RAs) lower blood glucose, slow CKD progression, and prevent cardiovascular complications caused by DM and CKD.
Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are the first-line treatment for diabetic patients who have hypertension, an eGFR <60 mL/min/1.73 m2, and a urinary albumin/creatinine ratio ≥300 mg/g (ElSayed et al., 2023a). The ACEs and the ARBs can prevent the progression of CKD, and they seem equally effective at doing so (ElSayed et al., 2023d). The American Diabetes Association Standard of Care recommends that in nonpregnant patients with diabetes and hypertension, either an ACE inhibitor or an ARB is recommended for those with modestly elevated urinary albumin-to-creatinine ratio (30–299 mg/g creatinine) and is strongly recommended for those with urinary albumin-to-creatinine ratio ≥ 300 mg/g creatinine and/or an eGFR <60 mL/min/1.73 m2” (ElSayed et al., 2023a).
There are interventions and lifestyle changes that can help prevent the progression of DKD, which will be discussed in a separate section.
The only interventions proven to prevent the development of DKD are glucose control and blood pressure control (ElSayed et al., 2023a). “There is no evidence that renin-angiotensin-aldosterone system (RAAS) inhibitors or any other interventions prevent the development” of DKD (ElSayed et al., 2023a)
A patient who has DKD should be closely monitored for changes in serum potassium, the dose of medications that need to be adjusted according to a patient’s eGFR should be periodically checked, nephrotoxic drugs should be avoided, and urinary albumin excretion and eGFR should periodically be measured (ElSayed et al., 2023a). In addition, these patients should be monitored for complications of CKD, such as anemia, electrolyte abnormalities, hypertension, metabolic acidosis, metabolic bone disease, and volume overload (ElSayed et al., 2023a).
Diabetic neuropathy is the most common complication of DM, occurring in approximately 10% of patients at the time they are diagnosed with DM (Samakidou et al., 2021), and it occurs in > 50% of all patients who have chronic T1DM and T2DM (Ang et al., 2022; Powers et al., 2022; Samakidou et al., 2021).
Diabetic neuropathy manifests in three basic forms: diffuse, mononeuropathy, and diabetic radiculoplexus neuropathy, also called radiculopathy/polyradiculopathy or diabetic amyotrophy (Pop-Busui et al., 2017; Powers et al., 2022). The most common diabetic neuropathies are diffuse neuropathies: distal symmetrical polyneuropathy (DSPN) and autonomic neuropathy or cardiovascular autonomic neuropathy (Samakidou et al., 2021; Sudo et al., 2022).
DSPN is considered the most common chronic complication of T1DM and T2DM (Ang et al., 2022). The lifetime prevalence of DSPN has been estimated to be > 50% (Ang et al., 2022), and because 20% to 50% of patients who have DSPN do not have pain or other symptoms, the prevalence is likely higher (Ang et al., 2022; Powers et al., 2022). Distal symmetrical polyneuropathy appears to be more common in patients who have T2DM (Ang et al., 2022).
Note: Distal symmetrical polyneuropathy is sometimes referred to as diabetic peripheral neuropathy or DPN; however, DSPN is the preferred term.
Three primary causes of DSPN initiate and sustain the mechanisms of injury by which DSPN affect the peripheral nerves and include elevated glucose, changes in insulin signaling, and dyslipidemia (Ang et al., 2022; James et al., 2022). These three factors cause multiple pathologic processes, including (but not limited to) decreased blood flow to the nerves and ischemic stress, inflammation, oxidative stress, changes in cell function, and DNA damage (Ang et al., 2022; Fan & Gordon Smith, 2022). Ang et al. (2022) wrote: “The most common form of nerve injury is a progressive distal-to-proximal peripheral nerve loss that typically presents as sensory predominant.” As with other diabetic microvascular complications, the nerves are “. . . susceptible to hyperglycemia due to their shared inability to balance intracellular glucose levels, resulting in diabetic neuropathy” (James et al., 2022; Smith et al., 2022a).
The American Diabetes Association defines DSPN as “. . . the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes.” (Pop-Busui et al., 2017).
Approximately 30% to 50% of patients who have DSPN are asymptomatic (Ang et al., 2022; Powers et al., 2022), and DSPN is often diagnosed many years after its onset when irreversible sensory damage has already occurred (James et al., 2022).
Sensory symptoms typically start first.
A physical examination usually reveals a decreased perception of vibration and temperature. The patient may have foot drop and muscular atrophy, unsteady gait, and the ankle deep-tendon reflexes may be absent (Powers et al., 2022; Smith et al., 2022b). The signs and symptoms of DSPN are considered chronic when they have been present for greater than three to six months (Bönhof et al., 2019).
The American Diabetes Association recommends that everyone who has T2DM should be screened for the presence of DSPN when the diagnosis is made, and everyone who has T1DM should be screened for DSPN five years after the diagnosis is made; after the initial screening, annual screening should be done for both groups (ElSayed et al., 2023e). Screening for DSPN is very important: “Up to 50% of diabetic peripheral neuropathy may be asymptomatic.
Everyone who has DM should be screened with a 10-g monofilament test once a year to determine if their feet are at risk for diabetic foot ulcers (DFU) and/or amputation (ElSayed et al., 2023e).
DSPN is a clinical diagnosis and a diagnosis of exclusion (Pop-Busui et al., 2017). The criteria for the diagnosis include the following:
The American Diabetes Association states that a combination of typical symptomatology and symmetrical distal sensory loss or typical signs in the absence of symptoms in a patient with diabetes is highly suggestive of DSPN and may not require additional evaluation or referral. A diagnosis may only be made on examination or, in some cases, when the patient presents with a painless foot ulcer (Pop-Busui et al., 2017).
Physical examination may include the following:
Symptoms may include burning, electric shock sensations, loss of balance, numbness, pain, stabbing sensation, and tingling.
If a patient has signs and symptoms of DSPN, but the clinician is unsure if DSPN is the cause, a consultation with a neurologist and nerve conduction studies can be done (Mishriky et al., 2022).
Factors that increase the risk of developing DSPN are listed in Table 1.
|(Ang et al., 2022; Fan & Gordon Smith, 2022)|
The importance of these risk factors in the progression to DSPN differs between T1DM and T2DM (Gibbons, 2020). For patients who have T1DM, hyperglycemia is the primary factor in DSPN development and progression. For patients who have T2DM, the risk factors for disease development and progression are hyperlipidemia, hyperglycemia, hypertension, insulin resistance, smoking, and body weight (Fan & Gordon Smith, 2022; Gibbons, 2020). In addition, research suggests that metabolic syndrome and obesity by themselves, independent of a patient’s level of glucose control, increase the risk of developing DSPN (Fan & Gordon Smith, 2022).
DFU is a very common and potentially dangerous complication of diabetic peripheral neuropathy. Charcot neuroarthropathy can also occur but is much less common than DFU.
Note: A discussion of the assessment and grading of DFU and the treatment of DFU would be long, complex, and beyond the scope of this module.
Three medications are FDA-approved as a treatment for painful diabetic peripheral neuropathy and include duloxetine (Cymbalta®), pregabalin (Lyrica®), and tapentadol (Nucynta®).
Other medications that are used successfully to treat painful peripheral neuropathy include the SNRI venlafaxine (Effexor®), tricyclic antidepressants (TCAs) like amitriptyline, other opioids, and topical therapy with capsaicin or lidocaine cream (James et al., 2022; Pop-Busui et al., 2022).
These medications can be effective, but they have limitations.
Nutraceutical is an informal term, a combination of nutrition and pharmaceuticals. Nutraceutical was originally defined as a dietary supplement or food that can prevent or treat disease (Aronson, 2017), and many dietary supplements, including (but not limited to) alpha-lipoic acid, vitamin B compounds, and other vitamins, have been used to try and prevent or treat DSPN (Pop-Busui et al., 2022).
Diabetic autonomic neuropathy is a diffuse neuropathy, a common complication of DM that can affect multiple organ systems, e.g., cardiovascular, gastrointestinal, genitourinary, and sudomotor (Cheshire, 2020; Pop-Busui et al., 2018; Powers et al., 2022; Sharma et al., 2020; Spallone et al., 2019).
Diabetic autonomic neuropathy is a common complication of DM, and in the US, DM is the most common cause of autonomic neuropathy (Pop-Busui et al., 2018). The incidence and prevalence of diabetic autonomic neuropathy are difficult to determine because:
However, for some of the sub-types, there is good documentation. For example, the prevalence of autonomic disorders in DM increases with the age of the patient (Lamotte & Sandroni, 2022), and 35% of patients who have T1DM and 65% of patients who have T2DM for > 20 years will have cardiovascular autonomic neuropathy (Pop-Busui et al., 2018). Diabetic autonomic neuropathy can be present alone, or a patient can have other diabetic neuropathies (Agochukwu-Mmonu et al., 2020; Lamotte & Sandroni, 2022), and > 50% of patients who have DSPN will develop CAN (Sudo et al., 2022). Symptoms of genitourinary dysfunction caused by diabetic neuropathy can affect as many as 50% of all patients with DM (Sharma et al., 2020).
The pathophysiologic mechanisms that cause diabetic autonomic neuropathy are the same as those that cause DSPN (Sharma et al., 2020; Sudo et al., 2022; Williams et al., 2022), i.e., oxidative stress, inflammation, and accumulation of AGEs. These pathophysiologic processes damage the parasympathetic and sympathetic branches of the autonomic nervous system, disrupting the normal balance between them and affecting the involuntary central nervous control of the cardiovascular, gastrointestinal, and genitourinary systems tract, and other organ systems (Lamotte & Sandroni, 2022).
Cardiovascular autonomic neuropathy is caused by damage to the autonomic nerve fibers that innervate the heart and vasculature (Duque et al., 2021), resulting in an imbalance of parasympathetic and sympathetic tone and impaired autonomic control of the cardiovascular system (Duque et al., 2021; Sudo et al., 2022; Williams et al., 2022). The pathophysiologic mechanisms that cause cardiovascular autonomic neuropathy are the same as those that cause DSPN (Duque et al., 2021; Sharma et al., 2020; Sudo et al., 2022; Williams et al., 2022).
Gastric: Diabetic gastrointestinal autonomic neuropathy is characterized by constipation or diarrhea, dysphagia, fecal incontinence, nausea, reflux, and vomiting.
Genitourinary: Genitourinary autonomic neuropathy is characterized by male and female sexual dysfunction and urinary dysfunction, e.g., neurogenic bladder (Agochukwu-Mmonu et al., 2020; Pop-Busui et al., 2017).
Sudomotor dysfunction: Sudomotor refers to the autonomic nerves that stimulate the production of sweat and perspiration (Cheshire, 2020). DM is the most common cause of autonomic sudomotor dysfunction (Cheshire, 2020), and this diabetic complication is characterized by anhidrosis, hypohidrosis (Pop-Busui et al., 2017), dry skin, and skin fissures (Shivaprasad et al., 2018).
Diabetic retinopathy is a chronic vascular disease of the retina (ElSayed et al., 2023e). It is a common complication of T1DM and T2DM (Bebu et al., 2023; Cai et al., 2023), and
The prevalence of diabetic retinopathy in patients with T1DM has been estimated to be > 33% (Bebu et al., 2023; Surowiec et al., 2022). The prevalence of diabetic retinopathy in patients who have T2DM has been estimated to be 13.1% (Cai et al., 2023). It should be noted that these are estimates, and Drinkwater et al. (2022) noted that recent (2018 to 2021) estimates of the prevalence of diabetic retinopathy have varied significantly, from 5% to 40%. The risk of developing diabetic retinopathy increases with age (Cai et al., 2023).
The pathophysiology of diabetic retinopathy is, like the other DM microvascular complications, very complex (Whitehead et al. 2018), and it involves multiple pathophysiological processes that cause inflammation, oxidative stress, and mitochondrial dysfunction that damage the retinal vasculature (Cai et al., 2023; Whitehead et al., 2018). The primary driver of diabetic retinopathy is chronic hyperglycemia (Powers et al., 2022; Whitehead et al., 2018).
The onset of diabetic retinopathy in patients who have T1DM has been estimated to be at least five years after hyperglycemia has begun (ElSayed et al., 2023e). The onset of diabetic retinopathy in patients with T2DM is likely to be much later (Cai et al., 2023), as many patients with T2DM have asymptomatic hyperglycemia late after the onset of the disease (ElSayed et al., 2023f).
Diabetic retinopathy can present with many ocular pathologies and is categorized into two stages, non-proliferative and proliferative (Mehta, 2022; Powers et al., 2022).
Factors that increase the risk of developing diabetic retinopathy include chronic hyperglycemia, hyperlipidemia, a high mean A1C, a high urinary albumin-creatinine ratio, hypertension, the duration of diabetic retinopathy (longer duration increases the risk), and nephropathy (Chou et al., 2020; Drinkwater et al., 2022; ElSayed et al., 2023e; Mehta, 2022; Powers et al., 2022; Whitehead et al., 2018). Factors that may increase the risk of diabetic retinopathy progressing include an elevated A1C, elevated systolic blood pressure, and total cholesterol (Tarasewicz et al., 2023).
These recommendations for diabetic retinopathy screening are from the American Diabetes Association.
Powers et al. (2022) wrote: “Most diabetic eye disease can be successfully treated if detected early. Routine, nondilated eye examinations by the primary care provider or diabetes specialist are inadequate to detect diabetic eye disease, which requires a dilated eye exam performed by an optometrist or ophthalmologist, and subsequent management by a retinal specialist.”
Hyperlipidemia (elevated low-density lipoprotein cholesterol [LDL-C], low high-density lipoprotein cholesterol [HDL-C], and very-low-density lipoprotein cholesterol [VLDL-C]) has been identified as a risk factor for developing diabetic retinopathy (Bryl et al., 2022; Chou et al., 2020). Treatment of hyperlipidemia with a statin and fenofibrate has been shown to reduce the incidence and progression of diabetic retinopathy (Bryl et al., 2022; Chou et al., 2020). Bryl et al. (2022) wrote that the relationship between lipids and diabetic retinopathy is not entirely understood, but “. . . lipid-reducing therapies can be considered one of the potential therapeutic agents with a beneficial effect on the course of diabetic retinopathy.”
Choosing a treatment, or treatments, for a patient who has diabetic retinopathy depends on what type the patient has, the presence of complications, risk factors for progression, and a patient’s signs and symptoms.
The four commonly used and effective therapies for treating diabetic retinopathy and macular edema are intravitreal anti-vascular endothelial growth factor (VEGF) inhibitor drugs, laser photocoagulation, intravitreal glucocorticoids, and vitrectomy. These can be used alone or as adjuncts to each other. The choice of treatment depends on the type of diabetic retinopathy, the severity of the disease, and whether there is macular damage.
A 55-year-old male with a past medical history of T2DM is admitted to a hospital for complaints of pain, decreased sensation in both feet, and occasional episodes of blurred vision. His medications include metformin and glipizide. His blood pressure is 172/88 mm Hg; his fasting serum glucose is 256 (Normal is < 100 mg/dL). His A1C is 9.5% (Normal is < 5.6%), he weighs 104 kg, and his BMI is 34.8, categorizing him as obese. His BUN is 19 mg/dL, and serum creatinine is 1.3 mg /dL. The eGFR is 64 mL/min/1.73 m2, and the urinary albumin-creatinine ratio is mildly elevated, 35 mg/g (Normal is < 30 mg/g). Examining his lower extremities and nerve conduction studies reveal decreased pain sensation and diminished nerve conduction. An ophthalmologic exam reveals a very slight level of decreased visual acuity and a very mild level of new retinal vascular growth. The physician prescribes insulin and an ACE inhibitor; the doses of glipizide and metformin are left unchanged. The patient is encouraged to exercise, and the dietary department provides him with a weight-reducing diet. At a follow-up nine months after discharge, the patient has lost 7 kg, his blood pressure is 152/78, his fasting serum glucose is 118 mg/dL, and his HbA1c is 7.0%. The retinal vascular growth has not diminished, but it has not extended, the visual acuity is unchanged, and the patient reports that he has increased sensation and decreased pain in both feet. The provider decides to leave the treatment regimen unchanged. The patient is scheduled for another ophthalmologic examination in six months, remeasurements of fasting glucose and A1C in three months, and remeasurements of BUN, serum creatinine, eGFR, and urinary albumin-creatinine ratio in three to six months; the urinary albumin-creatinine ratio will be scheduled depending on the patient’s progress at the three-month mark. In addition, the patient will have weekly online follow-ups with a diabetes nurse specialist.
Nursing care for a patient who has any of the DM microvascular complications should include the following:
Diabetic nephropathy, neuropathy, and retinopathy are common complications of DM; they cause significant morbidities like amputation and blindness, which, unfortunately, happen frequently to DM patients and increase mortality risk. There are treatments for these microvascular complications that can provide symptomatic relief, delay their onset, and slow their progression. However, the development of renal, neurological, and ocular DM pathologies is slow and progressive, and patients are often asymptomatic. The diagnosis is made after damage has been done.
The most effective treatment is prevention. Prevention involves 1) screening for DM and DM microvascular complications, and 2) glycemic control, control of hypertension, correction and treatment of hyperlipidemia, and changing other modifiable risk factors, e.g., weight loss, avoiding a sedentary lifestyle, and exercise. These interventions have been shown to prevent diabetic microvascular complications from developing and slow their onset and progression.
CEUFast, Inc. is committed to furthering diversity, equity, and inclusion (DEI). While reflecting on this course content, CEUFast, Inc. would like you to consider your individual perspective and question your own biases. Remember, implicit bias is a form of bias that impacts our practice as healthcare professionals. Implicit bias occurs when we have automatic prejudices, judgments, and/or a general attitude towards a person or a group of people based on associated stereotypes we have formed over time. These automatic thoughts occur without our conscious knowledge and without our intentional desire to discriminate. The concern with implicit bias is that this can impact our actions and decisions with our workplace leadership, colleagues, and even our patients. While it is our universal goal to treat everyone equally, our implicit biases can influence our interactions, assessments, communication, prioritization, and decision-making concerning patients, which can ultimately adversely impact health outcomes. It is important to keep this in mind in order to intentionally work to self-identify our own risk areas where our implicit biases might influence our behaviors. Together, we can cease perpetuating stereotypes and remind each other to remain mindful to help avoid reacting according to biases that are contrary to our conscious beliefs and values.