Chronic Diabetic Complications

Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus ( DM DM Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus) is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion (type 1 DM DM Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus), insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance (type 2 DM DM Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus), or both (latent autoimmune diabetes in adults (LADA)). The goal of diabetes management is to prevent chronic serious and potentially disabling complications due to damage to various organs. Adequate long-term control of blood glucose is crucial in the prevention of complications. Macrovascular complications include heart disease, stroke, peripheral vascular disease, and CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease in various stages, including end-stage renal disease that requires dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Overview and Types of Dialysis. Microvascular disease can cause retinopathy, neuropathy, or symptomatic cardiac disease, which are not seen during stress testing or angiogram that are used to diagnose large vessel diseases.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus ( DM DM Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus) is a common disease that can lead to multiple serious complications. Long-term glycemic control is imperative to prevent these complications.

  • Cardiovascular disease:
    • 60% of all individuals with diabetes die from cardiovascular disease.
    • MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction:
      • Men: 3.7 times higher risk than nondiabetic individuals
      • Women: 5.9 times higher risk than nondiabetic individuals
  • Diabetic nephropathy/ CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
    • The most common cause of renal failure in the US
    • Affects 20%–30% of individuals with diabetes
  • Diabetic retinopathy:
    • Approximately 90% of cases with type 1 diabetes and 25% of cases with type 2 diabetes develop retinopathy after 15 years of the disease.
    • The most common cause of visual impairment and blindness in individuals aged 25–74 years in the US
    • Classified as nonproliferative or proliferative based on retinal findings on examination
  • Neuropathy:
    • At the time of diagnosis, approximately 10%–20% of cases already have some extent of peripheral neuropathy.
    • Prevalence after 10 years of diagnosis: approximately 41%
    • Classification:
      • Distal symmetric polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy (most common)
      • Autonomic neuropathy
      • Mononeuropathy Mononeuropathy Neuropathy is a nerve pathology presenting with sensory, motor, or autonomic impairment secondary to dysfunction of the affected nerve. The peripheral nerves are derived from several plexuses, with the brachial and lumbosacral plexuses supplying the major innervation to the extremities. Mononeuropathies affect a single nerve. Mononeuropathy and Plexopathy
      • Polyradiculopathy
      • Mononeuropathy Mononeuropathy Neuropathy is a nerve pathology presenting with sensory, motor, or autonomic impairment secondary to dysfunction of the affected nerve. The peripheral nerves are derived from several plexuses, with the brachial and lumbosacral plexuses supplying the major innervation to the extremities. Mononeuropathies affect a single nerve. Mononeuropathy and Plexopathy multiplex

Pathophysiology

Chronic complications of diabetes have unique pathophysiological processes and are dependent on the organ system involved.

Cardiovascular

  • Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis:
    • Endothelial dysfunction:
      • Hyperglycemia leads to increased production of mitochondrial free-radical species → reduced NO levels
      • Low NO leads to vasoconstriction and reduced blood flow, leading to end-organ damage.
    • Increased inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation: diabetes is a proinflammatory state → known risk for atherosclerosis
  • Peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease: lipid accumulation in blood vessels → vasoconstriction and reduced blood flow, leading to end-organ damage
  • Macrovascular disease:
    • Heart: MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
    • Brain: cerebrovascular accident Cerebrovascular accident An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke/stroke, multi-infarct dementia
    • Kidney: diabetic nephropathy/ CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
  • Microvascular disease:
    • Eyes: diabetic retinopathy
    • Feet: diabetic neuropathy
    • Stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: gastroparesis
    • Intestines: mesenteric ischemia Mesenteric Ischemia Mesenteric ischemia is a rare, life-threatening condition caused by inadequate blood flow through the mesenteric vessels, which results in ischemia and necrosis of the intestinal wall. Mesenteric ischemia can be either acute or chronic. Mesenteric Ischemia
    • Legs: peripheral vascular disease/peripheral artery disease
    • Genitalia:  erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction

Renal

There are various forms of kidney disease in diabetes, including nonclassical glomerular lesions and tubulointerstitial disease.

  • “Diabetic kidney disease” is a clinical diagnosis based on the severity of albuminuria, GFR, or both, in individuals with diabetes.
  • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Deposits in the capillary membrane cause hyaline arteriosclerosis.
  • Diabetic nephropathy/ CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease:
    • Mesangial changes: increased permeability and hyperfiltration
    • Vascular lesions: arteriolosclerosis, especially in the efferent arterioles
    • Glomerular lesions:
      • Diffuse capillary basement membrane thickening is the earliest and most common finding.
      • Nodular: Kimmelstiel-Wilson nodules are pathognomonic.
    • Tubular lesions: tubular glycogen deposition

Neurological

  • Hyperglycemia causes glycation of axon proteins with subsequent development of neuropathy in the peripheral nerves.
  • Neuropathy:
    • Arteriolosclerosis of endoneurial arterioles resulting in ischemia and neuronal damage
    • Oxidative stress and osmotic damage

Clinical Presentation

Cardiovascular disease

  • In individuals with diabetes, MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction may present atypically due to concurrent diabetic neuropathy, instead of the typical presentation with chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain.
  • Other heart diseases:
    • Microvascular disease
    • Diabetic cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Overview of Cardiomyopathies
  • Carotid stenosis:
    • Arteriosclerosis in the large arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries of the neck may present with transient ischemic attacks (TIAs).
    • Physical exam: Carotid bruits may be heard.
  • Stroke/ TIA TIA Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA) Atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis in the cerebral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries presents with focal neurologic deficits.
  • Peripheral arterial disease:
    • Presents as intermittent claudication due to vascular occlusive disease in the legs
    • Decreased pedal pulses on physical exam

Diabetic nephropathy/ CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease

  • Usually asymptomatic
  • Affected individuals note “foamy urine.”
  • May have hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension or increased creatinine on laboratory testing

Diabetic retinopathy

  • Usually asymptomatic and diagnosed by routine screening
  • Affected individuals may complain of decreased visual acuity in advanced stages.
  • If complicated, individuals may present with:
    • Sudden, painless monocular loss of vision
    • Floaters
  • Fundoscopic exam:
    • Macular edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Cotton wool spots
    • Dot and blot hemorrhages
  • Additional eye complications due to hyperglycemia:
    • Sorbitol accumulation and increased osmotic pressure in the lens of the eye
    • Increased risk of cataracts
  • Women with diabetes who are planning pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care:
    • Should be comprehensively evaluated and treated
    • Counseled about the risk of progression

Neuropathy

  • Often asymptomatic and found on screening exams
  • Can be generalized focal, multifocal, or autonomic
  • Chronic distal symmetric polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy:
    • Presents with paresthesias in a “stocking glove” sensory-loss pattern
    • Affected individuals may complain of:
      • Numbness
      • Tingling
      • Burning
      • Pain in the feet
      • Worsening at night
    • Decreased sensation to light touch/monofilament on exam
    • Loss of pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain perception, leading to the potential for wounds
  • Autonomic neuropathy:
    • Cardiovascular manifestations:
      • Resting tachycardia
      • Orthostatic hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Gastroparesis due to the vagus nerve being affected:
      • Delayed gastric emptying
      • Risk of postprandial hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
      • Nausea
      • Bloating
      • Loss of appetite
      • Can result in excess weight loss
    • Genitourinary involvement can lead to erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction, although this condition is more likely due to a vascular etiology.
    • Cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. Overview of the Cranial Nerves:
      • Can lead to oculomotor nerve palsies
      • Ptosis
      • Spared pupillary function
    • Peripheral mononeuropathy: nerve palsies, such as common peroneal nerve causing foot drop
    • Mononeuritis multiplex: asymmetric neuropathy involving multiple peripheral and cranial nerves
Diabetic foot injury

Foot injury in an individual with peripheral neuropathy:
Peripheral neuropathy causes affected individuals to not feel small injuries to the extremities, which are often then untended. Combined with reduced blood flow to extremities, these injuries can lead to chronic foot ulcers that may even require surgical debridement in individuals with diabetes.

Image: “Pre-operative view of chronic recurrent ulcer under the fifth MT head” by Department of Orthopaedic Surgery, Assaf HaRofeh Medical Center, Zerrifin, Affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. License: CC BY 4.0

Skin manifestations

  • Acanthosis nigricans:
    • Dark, velvety plaques in the axillae or neck
    • Seen in individuals with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance
    • Can sometimes be a sign of underlying malignancy
  • Necrobiosis lipoidica:
    • Oval or irregular, indurated patches of central atrophy with yellow pigmentation and red-brown margins
    • Often asymptomatic, found on the shins
Acanthosis nigricans grade 1

Acanthosis nigricans: a common finding in individuals with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance (such as in diabetes). Acanthosis nigricans is described as velvety, thickened, and darkened areas of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin, often seen on the nape of the neck.

Image: “Acanthosis nigricans Grade 1” by Department of Clinical Medical Sciences, The University of West Indies, St Augustine, Trinidad & Tobago, WI. License: CC BY 2.0

Diagnosis

Cardiovascular disease

Coronary artery disease:

  • Medical history: inquiry about factors that impact cardiovascular risk:
    • Chest pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain or symptoms similar to those experienced in angina
    • Past history of heart disease or treatment
    • Lifestyle factors:
      • Level of physical activity and overall fitness
      • Dietary choices
      • Smoking
      • Intake of alcohol
      • Use of illicit drugs
      • Emotional stress
  • Screening tests:
    • Lab testing
    • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (ECG)
    • Stress testing
    • Note: Screening tests are not recommended for individuals who are asymptomatic or those with established cardiovascular disease or risk factors.
  • Testing is indicated for symptomatic individuals, and depends on the individual and the circumstances in which the test is being ordered.
    • Coronary calcium score: Due to false negatives, the test is not recommended for high-risk individuals.
    • Stress testing: exercise or pharmacologic, based on the ability of the individual:
      • With or without nuclear medicine imaging
      • Stress echocardiogram
    • CTA
    • Angiography in individuals with abnormal stress test results

Peripheral arterial disease:

  • Ankle-brachial index testing
  • Ultrasound
  • Angiogram

Carotid stenosis: ultrasound to evaluate the extent of occlusive disease

Diabetic nephropathy

Diabetic nephropathy is usually diagnosed during an annual screening urine test for microalbuminuria.

  • Microalbuminuria (30–299 mg/24 hours) is the earliest sign of diabetic nephropathy.
  • CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease is diagnosed on laboratory testing for creatinine.

Diabetic retinopathy

Diagnosed during annual screening eye examinations with an eye specialist (ophthalmologist or optometrist)

  • Proliferative:
    • Microaneurysms
    • Soft exudates (cotton wool exudate representing infarction)
    • Intraretinal hemorrhage
    • Occluded, dilated, tortuous vessels
  • Nonproliferative:
    • Neovascularization from the disc and/or retinal vessels
    • Periretinal and vitreous hemorrhage
    • Subsequent fibrosis and tractional retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment
  • Macular edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema:
    • Retinal thickening and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema involving the macula
    • Can occur during proliferative and nonproliferative retinopathy

Diabetic neuropathy

  • Physical exam:
    • Assess sensation using a monofilament.
    • Assess vibration sense using a 128-Hz tuning fork.
    • Deep tendon reflexes
    • Check for neuropathic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin ulcers or infections.
  • Diabetic neuropathic arthropathy (Charcot foot) is a severe complication:
    • Deformation of tarsometatarsal joints
    • Coexisting ulcers are common.
    • Presents as bony deformities with midfoot collapse

Management

All complications

With all diabetic complications, prevention is key, and glycemic control is the top priority.

  • Control comorbidities ( hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and hyperlipidemia).
  • Lifestyle modifications:
    • Smoking cessation
    • Aggressive blood pressure control
    • Treatment of dyslipidemia
    • Weight loss if overweight or obese
    • Moderate alcohol intake:
      • 1 drink/day on average for women
      • 2 drinks/day on average for men

Coronary artery disease

  • Low-dose aspirin for secondary prevention (in individuals with diabetes who have known macrovascular complications)
  • Colchicine: new recommendation for individuals with chronic coronary disease receiving other secondary preventive strategies

Nephropathy

  • Control comorbidities:
    • Hypertension: The blood pressure goal for all individuals with diabetes should be < 130/80 mm Hg.
    • Smoking cessation
    • Hyperlipidemia management
  • ACE inhibitors or ARBs act on efferent arterioles, which are the most affected.

Retinopathy

  • Nonproliferative type:
    • Usually untreated unless severe
    • Panretinal laser photocoagulation is the treatment of choice.
  • Proliferative type:
    • Panretinal laser photocoagulation
    • Medication: bevacizumab:
      • Monoclonal antibody that functions as an angiogenesis inhibitor
      • Targets vascular endothelial growth factor (VEGF)-A
      • Consider vitrectomy.
  • Macular edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema:
    • Focal laser photocoagulation
    • Bevacizumab
  • Serious potential complications:
    • Retinal detachment
    • Vitreous hemorrhage
    • Vision loss

Neuropathy

  • Instruct affected individuals to perform daily foot examinations.
  • Medications to alleviate neuropathic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain:
    • Anticonvulsants: gabapentin or pregabalin
    • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants: amitriptyline
    • Serotonin-norepinephrine reuptake inhibitors: duloxetine
    • Opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics are the last resort, but may be required for chronic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain relief.
  • Gastroparesis:
    • Small, frequent meals
    • Prokinetic medication: metoclopramide

Peripheral arterial disease

  • Periodic foot examination
  • Care to not cause wounds to extremities, as healing is delayed
  • Surgical revascularization in select cases
  • Amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation may be needed for some individuals with peripheral arterial disease.

Skin manifestations

  • Acanthosis nigricans does not require treatment and often resolves with glycemic control.
  • Necrobiosis lipoidica is treated using topical steroids.

References

  1. Aiello, L.M. (2003). Perspectives on diabetic retinopathy. Am J Ophthalmol. 136, 122-35. https://pubmed.ncbi.nlm.nih.gov/12834680/
  2. Frank, R.N. (2004). Diabetic retinopathy. N Engl J Med. 350, 48-58. https://pubmed.ncbi.nlm.nih.gov/14702427/
  3. Mogensen, C.E., Christensen, C.K. (1984). Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 311, 89-93. https://pubmed.ncbi.nlm.nih.gov/6738599/
  4. Perkins, B.A., Ficociello, L.H., Silva, K.H., Finkelstein, D.M., Warram, J.H., Krolewski, A.S. (2003). Regression of microalbuminuria in type 1 diabetes. N Engl J Med. 348, 2285-93. https://pubmed.ncbi.nlm.nih.gov/12788992/
  5. Smith, S.C. Jr., et al. (2011). AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: A guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. J Am Coll Cardiol. 58, 2432-46. doi: 10.1016/j.jacc.2011.10.824. Epub 2011 Nov 3. Erratum in: J Am Coll Cardiol. 65, 1495. Dosage error in article text. https://pubmed.ncbi.nlm.nih.gov/22055990/
  6. Diabetes Control and Complications Trial Research Group, Nathan, D., et al. (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 329, 977-86. https://pubmed.ncbi.nlm.nih.gov/8366922/
  7. Ismail-Beigi, F., et al., ACCORD trial group. (2010). Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 376, 419-30. doi: 10.1016/S0140-6736(10)60576-4. Erratum in: Lancet. (2010). 376, 1466. https://pubmed.ncbi.nlm.nih.gov/20594588/

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Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

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