Nursing 200 Foundations > Quiz 10 > Flashcards
Quiz 10 Flashcards
Vent
Ventilator
vfib
Ventricular fibrillation = not compatible for life. Allow intervene if no code (DNR)
v/o
Verbal order = not safe
VRE
Vancomycin resistance enterococci
VS
Vital signs
VSS
Vital signs stable
WBAT
Weight bearing as tolerated
WBC
White blood cell
W/C
Wheelchair
WHO
World Health Organization
WIC
Women, infants, and children
WNL
Within normal limits= can use for vital signs, or use for body systems/ rrr= rate, regular, rhythm
w/o
Without
x
Times
Dawn phenomenon
The “dawn phenomenon” refers to periodic episodes of hyperglycemia experienced by patients with diabetes in the early morning hours. This clinical entity differs from the Somogyi effect in that it is not preceded by an episode of hypoglycemia.
Diurnal variation in hepatic glucose metabolism has been well documented. The transient increase in both glycogenolysis and gluconeogenesis in the early morning hours can be responsible for hyperglycemia if unopposed by insulin
The dawn phenomenon has been documented in both type 1 and type 2 diabetes and has been demonstrated in all age groups, even patients with type 2 diabetes over 70 years of age. For both type 1 and type 2 diabetes mellitus, its prevalence is estimated to exceed 50 percent.[6] This affects a large patient population over a wide age range, and the dawn phenomenon should be an important consideration for any clinician who manages patients with diabetes.
Studies in populations without diabetes have shown that blood glucose, and plasma insulin levels remain steady through the night, with only a small increase in insulin secretion before dawn, which serves to achieve supression of the hepatic glucose production. Hyperglycemia is prevented by this physiologic surge of insulin. Hence, the dawn phenomenon does not occur in patients without diabetes because they can secrete normal amounts of insulin to prevent it. In patients without diabetes growth hormone exerts insulin-antagonistic effects. [7] Furthermore, exogenous insulin activity frequently begins to wane during the early morning hours (depending on the type of insulin and route of administration), so there is not enough opposition to hepatic activity to prevent hyperglycemia. Patients with type 2 diabetes are more likely affected by early morning dysregulation of hepatic glucose production because of the inability to produce compensatory insulin secretion
Patients with diabetes will manifest the dawn phenomenon clinically with persistent and worsening early morning hyperglycemia, which is difficult to control. Often found early in the disease process, this is associated with worsening HbA1c levels. The dawn phenomenon is not associated with nocturnal hypoglycemic episodes, and no specific physical findings are present.
By measuring blood glucose pre-breakfast, pre-lunch, and pre-dinner, then taking the difference between the pre-breakfast glucose and the average of the pre-lunch and pre-dinner glucose values to determine “X”, the presence of the dawn phenomenon in an individual, which has been defined as an upward variation in glucose of 20 mg/dl, can be detected with 71% sensitivity and 68% specificity. The magnitude of the dawn phenomenon can then be calculated by using the equation 0.49X +15
Treatments:
When the presence of the dawn phenomenon is detected, especially when associated with the extended dawn phenomenon, an individual patient should be considered for earlier and more aggressive control of glucose. The prevention of long-term sequelae by minimizing exposure to hyperglycemia is key early in the disease process. Optimal insulin therapy is important in type 1 diabetes, but also in type 2 diabetes. Oral hypoglycemic agents have failed to show adequate control of the dawn phenomenon, while insulin therapy has been shown to be much more effective.
Choosing an insulin regimen must, of course, be individualized for each patient, but research has indicated that the presence of the dawn phenomenon must be considered in selecting the type of insulin and the mechanism of delivery. In studies that have demonstrated superior glycemic control with continuous insulin infusion as opposed to long-acting insulin formulations, the dawn phenomenon is likely the reason. The ability for a continuous infusion to provide a bolus in the early morning hours to counteract the dawn phenomenon is a possible explanation, as long-acting insulin preparations have no ability to achieve this. For type 1 diabetes, tight control with insulin must take into account the dawn phenomenon to avoid nocturnal hypoglycemia before the onset of early morning glucose elevations. If insulin adjustments are made based on early morning fasting glucose levels, a larger dose of insulin might be administered than would be appropriate if the dawn phenomenon magnitude was considered.[12]
Management of morning hyperglycemia should be a part of the overall diabetes control strategy. Lifestyle modification is an important component to be considered. Better control of morning glucose levels has been demonstrated by increasing the amount of exercise in the evening and by increasing the protein to carbohydrate ratio of the evening meal. Consuming breakfast is also very important. While it seems counterintuitive, an early morning meal serves to decrease the secretion of insulin-antagonistic hormones.[13][2] In recent study the use of acarbose helped with dawn phenomenon treatment, but not the use of sulfonylurea
Diabetes mellitus
A chronic illness: Diabetes mellitus (DM) is a metabolic disease, involving inappropriately elevated blood glucose levels. DM has several categories, including type 1, type 2, maturity-onset diabetes of the young (MODY), gestational diabetes, neonatal diabetes, and secondary causes due to endocrinopathies, steroid use, etc. The main subtypes of DM are Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM), which classically result from defective insulin secretion (T1DM) and/or action (T2DM). T1DM presents in children or adolescents, while T2DM is thought to affect middle-aged and older adults who have prolonged hyperglycemia due to poor lifestyle and dietary choices. The pathogenesis for T1DM and T2DM is drastically different, and therefore each type has various etiologies, presentations, and treatments.
Etiology
In the islets of Langerhans in the pancreas, there are two main subclasses of endocrine cells: insulin-producing beta cells and glucagon secreting alpha cells. Beta and alpha cells are continually changing their levels of hormone secretions based on the glucose environment. Without the balance between insulin and glucagon, the glucose levels become inappropriately skewed. In the case of DM, insulin is either absent and/or has impaired action (insulin resistance), and thus leads to hyperglycemia.
-T1DM is characterized by the destruction of beta cells in the pancreas, typically secondary to an autoimmune process. The result is the absolute destruction of beta cells, and consequentially, insulin is absent or extremely low.
-T2DM involves a more insidious onset where an imbalance between insulin levels and insulin sensitivity causes a functional deficit of insulin. Insulin resistance is multifactorial but commonly develops from obesity and aging.
+Gestational diabetes is essentially diabetes that manifests during pregnancy. It is still unknown why it develops; however, some speculate that HLA antigens may play a role, specifically HLA DR2, 3, and 4. Excessive proinsulin is also thought to play a role in gestational diabetes, and some suggest that proinsulin may induce beta-cell stress. Others believe that high concentrations of hormones such as progesterone, cortisol, prolactin, human placental lactogen, and estrogen may affect beta-cell function and peripheral insulin sensitivity.[10]
+Several endocrinopathies, including acromegaly, Cushing syndrome, glucagonoma, hyperthyroidism, hyperaldosteronism, and somatostatinomas, have been associated with glucose intolerance and diabetes mellitus, due to the inherent glucogenic action of the endogenous hormones excessively secreted in these conditions. Conditions like idiopathic hemochromatosis are associated with diabetes mellitus due to excessive iron deposition in the pancreas and the destruction of the beta cells.
Pathophysiology
A patient with DM has the potential for hyperglycemia. The pathology of DM can be unclear since several factors can often contribute to the disease. Hyperglycemia alone can impair pancreatic beta-cell function and contributes to impaired insulin secretion. Consequentially, there is a vicious cycle of hyperglycemia leading to an impaired metabolic state. Blood glucose levels above 180 mg/dL are often considered hyperglycemic in this context, though because of the variety of mechanisms, there is no clear cutoff point. Patients experience osmotic diuresis due to saturation of the glucose transporters in the nephron at higher blood glucose levels. Although the effect is variable, serum glucose levels above 250 mg/dL are likely to cause symptoms of polyuria and polydipsia.
Insulin resistance is attributable to excess fatty acids and proinflammatory cytokines, which leads to impaired glucose transport and increases fat breakdown. Since there is an inadequate response or production of insulin, the body responds by inappropriately increasing glucagon, thus further contributing to hyperglycemia. While insulin resistance is a component of T2DM, the full extent of the disease results when the patient has inadequate production of insulin to compensate for their insulin resistance.
Chronic hyperglycemia also causes nonenzymatic glycation of proteins and lipids. The extent of this is measurable via the glycation hemoglobin (HbA1c) test. Glycation leads to damage in small blood vessels in the retina, kidney, and peripheral nerves. Higher glucose levels hasten the process. This damage leads to the classic diabetic complications of diabetic retinopathy, nephropathy, and neuropathy and the preventable outcomes of blindness, dialysis, and amputation, respectively
During patient history, questions about family history, autoimmune diseases, and insulin-resistant are critical to making the diagnosis of DM. It often presents asymptomatically, but when symptoms develop, patients usually present with polyuria, polydipsia, and weight loss. On physical examination of someone with hyperglycemia, poor skin turgor (from dehydration) and a distinctive fruity odor of their breath (in patients with ketosis) may be present. In the setting of diabetic ketoacidosis (DKA), clinicians may note Kussmaul respirations, fatigue, nausea, and vomiting. Funduscopic examination in a patient with DM may show hemorrhages or exudates on the macula. In frank diabetic retinopathy, retinal venules may appear dilated or occluded. The proliferation of new blood vessels is also a concern for ophthalmologists and can hasten retinal hemorrhages and macular edema, ultimately resulting in blindness. While T1DM and T2DM can present similarly, they can be distinguished based on clinical history and examination. T2DM patients are typically overweight/obese and present with signs of insulin resistance, including acanthosis nigricans, which are hyperpigmented, velvety patches on the skin of the neck, axillary, or inguinal folds. Patients with a longer course of hyperglycemia may have blurry vision, frequent yeast infections, numbness, or neuropathic pain. The clinicians must ask the patient bout any recent skin changes in their feet during each visit. The diabetic foot exam, including the monofilament test, should be a part of the routine physical exam.
Evaluation
The diagnosis of T1DM is usually through a characteristic history supported by elevated serum glucose levels (fasting glucose greater than 126 mg/dL, random glucose over 200 mg/dL, or hemoglobin A1C (HbA1c exceeding 6.5%) with or without antibodies to glutamic acid decarboxylase (GAD) and insulin.
Fasting glucose levels and HbA1c testing are useful for the early identification of T2DM. If borderline, a glucose tolerance test is an option to evaluate both fasting glucose levels and serum response to an oral glucose tolerance test (OGTT). Prediabetes, which often precedes T2DM, presents with a fasting blood glucose level of 100 to 125 mg/dL or a 2-hour post-oral glucose tolerance test (post-OGTT) glucose level of 140 to 200 mg/dL.[24][25]
According to the American Diabetes Association (ADA), a diagnosis of diabetes is through any of the following: An HbA1c level of 6.5% or higher; A fasting plasma glucose level of 126 mg/dL (7.0 mmol/L) or higher (no caloric intake for at least 8 hours); A two-hour plasma glucose level of 11.1 mmol/L or 200 mg/dL or higher during a 75-g OGTT; A random plasma glucose of 11.1 mmol/L or 200 mg/dL or higher in a patient with symptoms of hyperglycemia (polyuria, polydipsia, polyphagia, weight loss) or hyperglycemic crisis.[24] The ADA recommends screening adults aged 45 years and older regardless of risk, while the United States Preventative Service Task Force suggests screening individuals between 40 to 70 years who are overweight.[26].
To test for gestational diabetes, all pregnant patients have screening between 24 to 28 weeks of gestation with a 1-hour fasting glucose challenge test. If blood glucose levels are over 140mg/dL, patients have a 3-hour fasting glucose challenge test to confirm a diagnosis. A positive 3-hours OGTT test is when there is at least one abnormal value (greater than or equal to 180, 155, and 140 mg/dL for fasting one-hour, two-hour, and 3-hour plasma glucose concentration, respectively).[27]
Several lab tests are useful in the management of chronic DM. Home glucose testing can show trends of hyper- and hypoglycemia. The HbA1c test indicates the extent of glycation due to hyperglycemia over three months (the life of the red blood cell). Urine albumin testing can identify the early stages of diabetic nephropathy. Since patients with diabetes are also prone to cardiovascular disease, serum lipid monitoring is advisable at the time of diagnosis. Similarly, some recommend monitoring thyroid status by obtaining a blood level of thyroid-stimulating hormone annually due to a higher incidence of hypothyroidism.[24][25]
Go to:
Treatment / Management
The physiology and treatment of diabetes are complex and require a multitude of interventions for successful disease management. Diabetic education and patient engagement are critical in management. Patients have better outcomes if they can manage their diet (carbohydrate and overall caloric restriction), exercise regularly (more than 150 minutes weekly), and independently monitor glucose.[28] Lifelong treatment is often necessary to prevent unwanted complications. Ideally, glucose levels should be maintained at 90 to 130 mg/dL and HbA1c at less than 7%. While glucose control is critical, excessively aggressive management may lead to hypoglycemia, which can have adverse or fatal outcomes.
Since T1DM is a disease primarily due to the absence of insulin, insulin administration through daily injections, or an insulin pump, is the mainstay of treatment. In T2DM, diet and exercise may be adequate treatments, especially initially. Other therapies may target insulin sensitivity or increase insulin secretion by the pancreas. The specific subclasses for drugs include biguanides (metformin), sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, glucagonlike-peptide-1 agonist, dipeptidyl peptidase IV inhibitors (DPP-4), selective, amylinomimetics, and sodium-glucose transporter-2 (SGLT-2) inhibitors. Metformin is the first line of the prescribed diabetic medications and works by lowering basal and postprandial plasma glucose. Insulin administration may also be necessary for T2DM patients, especially those with inadequate glucose management in the advanced stages of the disease. In morbidly obese patients, bariatric surgery is a possible means to normalize glucose levels. It is recommended for individuals who have been unresponsive to other treatments and who have significant comorbidities.[29] The GLP-1 agonists liraglutide and semaglutide correlate with improved cardiovascular outcomes. The SGLT-2 inhibitors empagliflozin and canagliflozin have also shown to improve cardiovascular outcomes along with potential renoprotection as well as prevention for the development of heart failure.
Regular screenings are necessary since microvascular complications are a feared complication of diabetes. Regular diabetic retinal exams should be performed by qualified medical personnel to assess for diabetic retinopathy. Neurologic examination with monofilament testing can identify patients with neuropathy at risk for amputation. Clinicians can also recommend patients perform daily foot inspections to identify foot lesions that may go unnoticed due to neuropathy. Low-dose tricyclic antidepressants, duloxetine, anticonvulsants, topical capsaicin, and pain medications may be necessary to manage neuropathic pain in diabetes. Urine microalbumin testing can also assess for early renal changes from diabetes with albuminuria greater than 30mg/g creatinine along with the estimated GFR. The antiproteinuric effect of the angiotensin-converting enzyme (ACE) inhibitors and the angiotensin receptor blockers (ARBs) makes them the preferred agents to delay the progression from microalbuminuria to macroalbuminuria in patients with both Type 1 or Type 2 diabetes mellitus.
The FDA has approved pregabalin and duloxetine for the treatment of diabetic peripheral neuropathy. Tricyclic antidepressants and anticonvulsants have also seen use in the management of the pain of diabetic neuropathy with variable success.
The ADA also recommends regular blood pressure screening for diabetics, with the goal being 130 mmHg systolic blood pressure and 85 mmHg diastolic blood pressure.[30] Pharmacologic therapy for hypertensive diabetics typically involves angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, beta-blockers, and/or calcium channel blockers. The ADA recommends lipid monitoring for diabetics with a goal of low-density lipoprotein cholesterol (LDL-C) being less than 100 mg/dL if no cardiovascular disease (CVD) and less than 70 mg/dl if atherosclerotic cardiovascular disease (ASCVD) is present. Statins are the first-line treatment for the management of dyslipidemia in diabetics. The ADA suggests that low dose aspirin may also be beneficial for diabetic patients who are at high risk for cardiovascular events; however, the role of aspirin in reducing cardiovascular events in patients with diabetes remains unclear.
DKA (diabetic ketoacidosis)
Diabetic ketoacidosis (DKA) is a serious complication of diabetes that can be life-threatening. DKA is most common among people with type 1 diabetes. People with type 2 diabetes can also develop DKA.
DKA develops when your body doesn’t have enough insulin to allow blood sugar into your cells for use as energy. Instead, your liver breaks down fat for fuel, a process that produces acids called ketones. When too many ketones are produced too fast, they can build up to dangerous levels in your body.
Read on to learn more about DKA, how you can prevent DKA, and how to treat it if needed.
DKA Signs and Symptoms
DKA usually develops slowly. Early symptoms include:
Being very thirsty.
Urinating a lot more than usual.
If untreated, more severe symptoms can appear quickly, such as:
Fast, deep breathing.
Dry skin and mouth.
Flushed face.
Fruity-smelling breath.
Headache.
Muscle stiffness or aches.
Being very tired.
Nausea and vomiting.
Stomach pain.
Sometimes DKA is the first sign of diabetes in people who haven’t yet been diagnosed.
Causes of DKA
Very high blood sugar and low insulin levels lead to DKA. The two most common causes are:
Illness. When you get sick, you may not be able to eat or drink as much as usual, which can make blood sugar levels hard to manage.
Missing insulin shots, a clogged insulin pump, or the wrong insulin dose.
Other causes of DKA include:
Heart attack or stroke.
Physical injury, such as from a car accident.
Alcohol or drug use.
Certain medicines, such as some diuretics (water pills) and corticosteroids (used to treat inflammation in the body).
High ketones? Call your doctor ASAP
High ketones can be an early sign of DKA, which is a medical emergency. Checking your ketones at home is simple. Call 911 if your ketones are high and you can’t reach your doctor.
Test for Ketones
Anytime you’re sick or your blood sugar is 240 mg/dL or above, use an over-the-counter ketone test kit to check your urine or a meter to test your blood for ketones every 4 to 6 hours. You should also test for ketones if you have any of the symptoms of DKA. Call your doctor if your ketones are moderate or high. Elevated ketones are a sign of DKA, which is a medical emergency and needs to be treated immediately.
Go to the emergency room or call 911 right away if you can’t get in touch with your doctor and are experiencing any of the following:
Your blood sugar stays at 300 mg/dL or above.
Your breath smells fruity.
You are vomiting and can’t keep food or drinks down.
You’re having trouble breathing.
You have multiple signs and symptoms of DKA.
Treatment for DKA
If you have DKA, you’ll be treated in the emergency room or admitted to the hospital. Your treatment will likely include:
Replacing fluids you lost through frequent urination and to help dilute excess sugar in your blood.
Replacing electrolytes (minerals in your body that help your nerves, muscles, heart, and brain work the way they should). Too little insulin can lower your electrolyte levels.
Receiving insulin. Insulin reverses the conditions that cause DKA.
Taking medicines for any underlying illness that caused DKA, such as antibiotics for an infection.
Prevent DKA
DKA is a serious condition, but you can take steps to help prevent it:
Check your blood sugar often, especially if you’re sick.
Keep your blood sugar levels in your target range as much as possible.
Take medicines as prescribed, even if you feel fine.
Talk to your doctor about how to adjust your insulin based on what you eat, how active you are, or if you’re sick.
Diabetic peripheral neuropathy
Peripheral neuropathy (PN) encompasses a broad range of clinical pathologies potentially presenting with peripheral nervous system dysfunction.[1] Patients with PN often present with varying degrees of numbness, tingling, and/or burning in the extremities. While metabolic disorders represent the predominant etiology of extremity pain caused by an underlying PN clinical pathology, broad clinical consideration is given to many clinical conditions.
Although there are many possible causes of peripheral neuropathy, the most prevalent subtype, diabetic peripheral neuropathy, can lead to significant complications. Early assessment of symptoms of peripheral polyneuropathy helps avoid neuropathic foot ulcers to combat potential morbidity and mortality resulting from the pathophysiologic poor wound healing potential, which can lead to limb compromise, local to systemic infection, septicemia, and even death.
The exact cause of diabetic peripheral neuropathy is not known. Proposed theories include metabolic, neurovascular, and autoimmune pathways have been proposed. Mechanical compression (e.g., carpal tunnel), genetics, and social and lifestyle factors such as chronic alcohol consumption and smoking have all been implicated. Perpetually high blood serum glucose appears to lead to damaged small blood vessels, compromising oxygen and nutrients to the nerves. First, the distal sensory and autonomic nerve fibers are damaged; the damage then continues with proximal progression leading to a gradual loss of protective sensation in both the skin and foot joints. Half of the diabetic peripheral neuropathies may be asymmetric. If they are not recognized and preventative foot care is not implemented, patients have an increased risk of injury due to their insensate feet.
Etiology
Metabolic disorders represent the most common clinical category of etiologies, causing extremity pain from underlying PN conditions.
Several causes of PN exist, but diabetes mellitus (DM) is the most common etiology. Other underlying etiologies worth considering include:
Alcohol use disorder
Nutritional deficiencies (e.g., low B12, high B6)
Guillain-Barre syndrome
Toxins (chemotherapy) and overdose
Hereditary or genetic conditions (e.g., Charcot Marie Tooth disease, amyloidosis, porphyria)
Infection (HIV)
Inflammatory conditions (lupus, rheumatoid arthritis)
Hypothyroidism
Malignancy
Risk factors for PN include:
Advanced age
Hypertension
Peripheral vascular disease
Smoking
Dyslipidemia
Poor glucose control
A long duration of diabetes
Heavy intake of alcohol
Positive HLA-DR3/4 genotype
Clinically, about half of patients with diabetic PN can present with asymmetric sensory changes.[6][7] Obesity and genetic factors increase the risk of developing diabetes. Peripheral and autonomic neuropathies are one of the leading causes of morbidity in diabetes mellitus. At five years, the risk of death for patients with a diabetic foot ulcer is 2.5 times as high as the risk of death for a patient with diabetes who does not have a foot ulcer. The rate of emergency department visits for diabetic foot ulcers and associated infection exceeds the rates for congestive heart failure, renal disease, depression, and most forms of cancer.
Pathophysiology
Diabetic peripheral neuropathy encompasses sensory, motor, and autonomic neuropathy. Implicated causes of peripheral nerve damage include oxidate stress damage, accumulation of sorbitol, advanced glycosylation end products, and a disturbance of hexosamine, protein kinase C, and polymerase pathways. Neurovascular impairment with poor repair processes and endothelial dysfunction also have been implicated
Toxicokinetics
Transient hyperglycemia is often tolerated by normal compensatory physiological function and homeostatic mechanisms of blood sugar control. However, in chronically elevated states, it can have toxic effects such as neuropathy. For patients diagnosed early with type 1 diabetes mellitus, tight glucose control can reduce the risk of diabetic peripheral neuropathy by 78%.[11] In contrast, typically, with a later diagnosis of long-standing hyperglycemia or type 2 diabetes, tight glucose control only reduces the risk by 5% to 9%
History and Physical
Symptoms of burning, numbness, or tingling in the feet tend to worsen at night are characteristic. Patients with pedal paresthesias and dysesthesia often describe a nonspecific constellation of symptoms resulting in difficulty with ambulation and other basic activities of daily living (ADL). The characteristic polyneuropathy and distal sensory peripheral neuropathy are present in about 80% of DM PN patients. This is often described as a “stocking-glove distribution,” which can take several years to develop.[12]
Since the protective sensation is lost after sensory impairment, the standard Semmes-Weinstein 5.07 monofilament 10 grams of pressure protective sensation test may be accurately sensed even after a neurotrophic ulcer has developed. Simply timing the duration that a vibrating 128 Hz tuning fork is felt at the dorsal hallux interphalangeal joint (usually 18 seconds) can be used to detect sensory deficits earlier and quantify severity. Decreased light touch sensation or loss of ankle reflexes tend to occur earlier in the disease process, while the detectable loss of protective sensation tends to occur later in the disease, sometimes even after a neuropathic ulcer develops. Needle electromyography (EMG) and nerve conduction velocity testing can be both painful and expensive and mainly test the large myelinated fibers. Epidermal nerve fiber density testing can be performed to evaluate the small unmyelinated fibers.[13]
Autonomic Symptoms
Autonomic neuropathy is also very common in diabetes and can affect the gastrointestinal, cardiovascular, and genitourinary organs. Typical symptoms include:
GI: Abdominal discomfort, dysphagia, nausea, fecal incontinence, constipation, diarrhea
Cardiac: Hypotension, sinus tachycardia, variable heart rate, syncope
Bladder: Weak urinary stream, straining to void, incomplete emptying of bladder,
Skin: Heat intolerance, gustatory sweating, extreme diaphoresis
Nervous: Carpal tunnel syndrome, radiculopathy, lumbosacral, and cervical neuropathy. In addition, cranial nerves 3,4,6, and 7 may be affected.
Evaluation
The medical history review of systems and medications captures most of the causes of peripheral neuropathy. Electromyography and/or nerve conduction studies are suggested if there are severe or rapidly progressive symptoms or motor weakness. Minor symptoms may not need laboratory workup. Persistent unexplained symptoms may warrant laboratory investigation, including serum glucose, hemoglobin A1c, complete blood count, erythrocyte sedimentation rate, rapid plasma reagin, serum electrophoresis, and vitamin B1, B6, and B12 level. A lower extremity neurological physical exam should be performed to include muscle strength, reflex evaluation, and sensation evaluation (light touch with a monofilament, vibratory sensation, and proprioception). A dermatological exam demonstrating dry/cracked skin may point to autonomic neuropathy, while pedal deformities (hammertoes) suggest motor neuropathy.[12]
Measurement of epidermal nerve fiber density (ENFD) by skin biopsy can be considered in patients with idiopathic cases. The number and morphology of axons within the epidermis can be evaluated, and intraepidermal nerve fiber density is compared to age-dependent normal values.[14][15]
Treatment / Management
Many patients with neuropathy have mild to moderate numbness symptoms yet still retain protective sensations in their feet. They may only need reassurance and education as to the cause of the numbness. Periodic follow-up is essential. With improved glycemic control, paresthesias and dysesthesias may diminish within one year. After peripheral arterial disease and radiculopathy are ruled out, painful symptoms that disturb sleep or activities of daily living can be treated with pregabalin, gabapentin, or anti-depressants.[16] These medications have been shown to reduce the symptoms by 30% to 50% in many patients. Some patients also respond to the over-the-counter antioxidant alpha-lipoic acid. Additionally, although classified as a medical food, the prescription containing L-methyl folate, pyridoxal 5’-phosphate, and methylcobalamin for the dietary management of endothelial dysfunction has been shown to improve nerve fiber density and monofilament sensation significantly.[17]
Depleting substance P with topical capsaicin cream may help some patients who can tolerate the initially increased burning.[18][19][20] For patients with painful diabetic peripheral neuropathy, a capsaicin 8% patch in serial treatments can provide modest improvements in pain and sleep quality.[21][16]
Diabetic gastroparesis may be managed with erythromycin and metoclopramide. Tegaserod is a newer agent but is only available on an emergency basis because of serious adverse cardiac effects.
Some patients may benefit from the use of vitamins, especially zinc.
Erectile dysfunction is managed with phosphodiesterase inhibitors, but not everyone has a response. A penile prosthesis may be of benefit.
Orthostatic hypotension may be managed by increased salt and fluid intake and compression stockings. If that fails, steroids may be required. Glycopyrrolate is used to manage sweating but often does not work.
All infected diabetic foot ulcers need debridement or amputation
Gastroparesis may be managed by a jejeunostomy tube, especially in patients losing weight.
A pancreas transplant is an option and has been shown to stabilize autonomic function.
Physical therapy is a must for all patients with PN, especially those with muscle pain and weakness. Also, occupational therapy may be necessary when there is a functional loss. Speech therapy is needed to help patients with dysphagia and the risk of aspiration.
Differential Diagnosis
Alcohol-associated neuropathy
Nutritional linked neuropathy
Uremic neuropathy
Vasculitic linked neuropathy
Vitamin B-12 deficiency
Toxic metal neuropathy
Gestational diabetes mellitus
Follow a healthy eating plan to nourish you and your baby.
Gestational diabetes is a type of diabetes that can develop during pregnancy in women who don’t already have diabetes. Every year, 2% to 10% of pregnancies in the United States are affected by gestational diabetes. Managing gestational diabetes will help make sure you have a healthy pregnancy and a healthy baby.
What Causes Gestational Diabetes?
Gestational diabetes occurs when your body can’t make enough insulin during your pregnancy. Insulin is a hormone made by your pancreas that acts like a key to let blood sugar into the cells in your body for use as energy.
During pregnancy, your body makes more hormones and goes through other changes, such as weight gain. These changes cause your body’s cells to use insulin less effectively, a condition called insulin resistance. Insulin resistance increases your body’s need for insulin.
All pregnant women have some insulin resistance during late pregnancy. However, some women have insulin resistance even before they get pregnant. They start pregnancy with an increased need for insulin and are more likely to have gestational diabetes.
Preventing Type 2 Diabetes
About 50% of women with gestational diabetes go on to develop type 2 diabetes, but there are steps you can take to prevent it. Talk to your doctor about how to lower your risk and how often to have your blood sugar checked to make sure you’re on track.
Symptoms and Risk Factors
Gestational diabetes typically doesn’t have any symptoms. Your medical history and whether you have any risk factors may suggest to your doctor that you could have gestational diabetes, but you’ll need to be tested to know for sure.
Related Health Problems
Having gestational diabetes can increase your risk of high blood pressure during pregnancy. It can also increase your risk of having a large baby that needs to be delivered by cesarean section (C-section).
If you have gestational diabetes, your baby is at higher risk of:
Being very large (9 pounds or more), which can make delivery more difficult
Being born early, which can cause breathing and other problems
Having low blood sugar
Developing type 2 diabetes later in life
Your blood sugar levels will usually return to normal after your baby is born. However, about 50% of women with gestational diabetes go on to develop type 2 diabetes. You can lower your risk by reaching a healthy body weight after delivery. Visit your doctor to have your blood sugar tested 6 to 12 weeks after your baby is born and then every 1 to 3 years to make sure your levels are on target.
Testing for Gestational Diabetes
It’s important to be tested for gestational diabetes so you can begin treatment to protect your health and your baby’s health.
Gestational diabetes usually develops around the 24th week of pregnancy, so you’ll probably be tested between 24 and 28 weeks.
If you’re at higher risk for gestational diabetes, your doctor may test you earlier. Blood sugar that’s higher than normal early in your pregnancy may indicate you have type 1 or type 2 diabetes rather than gestational diabetes.
Prevention
Before you get pregnant, you may be able to prevent gestational diabetes by losing weight if you’re overweight and getting regular physical activity.
Don’t try to lose weight if you’re already pregnant. You’ll need to gain some weight—but not too quickly—for your baby to be healthy. Talk to your doctor about how much weight you should gain for a healthy pregnancy.
Treatment for Gestational Diabetes
You can do a lot to manage your gestational diabetes. Go to all your prenatal appointments and follow your treatment plan, including:
Checking your blood sugar to make sure your levels stay in a healthy range.
Eating healthy food in the right amounts at the right times. Follow a healthy eating plan created by your doctor or dietitian.
Being active. Regular physical activity that’s moderately intense (such as brisk walking) lowers your blood sugar and makes you more sensitive to insulin so your body won’t need as much. Make sure to check with your doctor about what kind of physical activity you can do and if there are any kinds you should avoid.
Monitoring your baby. Your doctor will check your baby’s growth and development.
If healthy eating and being active aren’t enough to manage your blood sugar, your doctor may prescribe insulin, metformin, or other medication.
Glucosuria
Glycosuria is a term that defines the presence of reducing sugars in the urine, such as glucose, galactose, lactose, fructose, etc. Glucosuria connotes the presence of glucose in the urine and is the most frequent type of glycosuria and is the focus of this review. It happens when the glomerulus filters more glucose than the proximal tubule can reabsorb. In normal individuals, glucosuria can be up to 0.25 mg/ml. More than 0.25 mg/ml in random fresh urine is considered increased glucosuria and can be due to elevated plasma glucose or renal glucose absorption impairment, or both.[1][2] Physiologic glucosuria is a condition where individuals consume an excessive amount of carbohydrates.
Small amounts of glucose present in the urine are considered normal, but the term glucosuria usually refers to pathologic conditions where the amounts of urine glucose are more than 25 mg/dl in random fresh urine. Normally, the renal tubule will reabsorb almost all (leaving less than 25 mg/dl urine glucose) glucose present in the normal glomerular filtrate. When the glucose filtrated by glomerular exceeds the capacity of the renal tubule to absorb it, the loss of balance occurs. It can happen due to elevated plasma glucose as in diabetes mellitus or when the ability of the tubule to absorb glucose is impaired, e.g., Fanconi syndrome with impairment in the absorption of phosphate, amino acids, or isolated glucosuria as an inherited disorder termed Familial Renal glucosuria.
Go to:
Issues of Concern
Some limitations of urine glucose testing are the ability of most commercial semiquantitative urine tests to detect glucose in the urine only until it reaches a level of 50 to 250 mg/dl. Also, errors can stem from an altered renal threshold. There are known variations in the renal threshold among individuals that can lead to significantly misleading data.
Go to:
Organ Systems Involved
The renal tubule plays a significant role in glucose reabsorption. If the plasma glucose rises, renal tubular reabsorption of glucose will increase linearly until it reaches its maximum tubular resorptive capacity. The capacity of the proximal tubule to reabsorb glucose to prevent its passing to the urine is known as the renal threshold.[2][3]
Membrane proteins responsible for glucose reabsorption in the proximal convoluted tubule (PCT) from the glomerular filtrate are sodium-glucose cotransporters SGLT1 and SGLT2, located in the apical membrane of proximal tubular cells, and GLUT2, a uniporter, located in the basolateral membrane. The first stage is glucose being transported across the apical membrane by SGLTs. These transporters bind to Na before they bind to glucose; the electrochemical sodium gradient generated by the Na/K-ATPase is the driving force for the symporter activity, leading to glucose accumulation in the epithelium. It causes a glucose concentration gradient between the cell and plasma, driving to the second stage, which is a passive exit of glucose through the basolateral membranes via GLUT2. SGLT1 functions in segments 1 and 2 of the PCT and SGLT1 functions in segment 3.[4][5]
Go to:
Mechanism
In healthy individuals, the renal system filters approximately 180 g of glucose daily. The glucose that entered the tubular system is reabsorbed along with the segments of the proximal convoluted tubule (PCT). In diabetic patients, as a result of the increase in plasma glucose, the filtered glucose exceeds the capacity of the tubular system and results in glucosuria. The majority of glucose uptake of greater than 90 percent occurs in the proximal tubule, mediated by SGLT2, a low-affinity/high capacity transporter. The remaining glucose will then be reabsorbed by the distal parts of the proximal tubule via the high-affinity/low-capacity SGLT1.[6]
Kidneys play a significant role in maintaining glucose homeostasis and preventing an individual from developing hypoglycemia. The maintenance of glucose homeostasis by the kidney includes glucose reabsorption in the PCT, gluconeogenesis, and the clearance of important hormones such as insulin.[7]
Go to:
Related Testing
In a patient with glucosuria, diabetes is confirmed by measuring fasting or random plasma glucose and glycated hemoglobin(HbA1c). In Fanconi syndrome, a generalized defect of the PCT, there is hypophosphatemia with metabolic acidosis (due to bicarbonate wasting) in the presence of phosphaturia, aminoaciduria, and glucosuria.
Go to:
Pathophysiology
Glucose filters through glomeruli, and then it is reabsorbed by the proximal renal tubule. Less than 0.1% of glucose is not reabsorbed by the kidneys (less than 0.25 mg/ml), and most of the standard test does not detect this level. The causes of glucosuria can be grouped under two classes: the inability of PCT to reabsorb glucose and an increase in the concentration of glucose in the circulating blood.[8]
Defects in the PCT, either primary or secondary, can result in glucosuria. Examples include pregnancy, Fanconi syndrome, and acute tubular necrosis. In a normal condition, when the plasma glucose level is increasing, renal tubular reabsorption of glucose will rise linearly until its maximum is reached (ranges from 0.9 to 2.0 mmol/min).[2] As mentioned before, SGLT1, SGLT2, and GLUT2 are the membranes protein that is responsible for glucose reabsorption; mutations in one of these membrane proteins will cause glucosuria. Mutation in SGLT1 is associated with glucose-galactose malabsorption, a mutation in SGLT2 is associated with familial renal glucosuria (FRG), and mutation in GLUT2 is associated with Fanconi-Bickel syndrome.[5]
Glucosuria can also occur in an increased concentration of glucose in the circulating blood. This phenomenon can also occur in normal individuals who consume excess carbohydrates, known as ‘alimentary glycosuria.’ It also presents in diabetic patients.[8] In diabetes mellitus, with increasing duration, glomeruli can be damaged, resulting in albuminuria and a decrease in the glomerular filtration rate. In diabetic patients, the kidneys are more susceptible to the effects of hyperglycemia; many of the kidney cells are unable to decrease glucose transport rates and unable to prevent intercellular hyperglycemia in an increased glucose concentration state.[7]
Some conditions are known to raise the renal threshold for glucose, such as age, renal disease (diabetic glomerulosclerosis), heart failure, and chronic hyperglycemia. Also, some conditions are known to decrease it, such as hyperthyroidism, pregnancy, fever, and exercise. Normal aging and glomerulosclerosis in long-standing diabetes are associated with an increased renal threshold for glucose, and because of that, urine glucose testing becomes of little value, if any.
A number of substances are also known for their capability to cause glucosuria, such as chloride, iodide, bromide, and nitrate of sodium. Glucosuria can also occur in a condition where there is a lack of oxygenation of the PCT.[8]
Go to:
Clinical Significance
A study comparing the urine and plasma response 60 minutes after a 50 g oral glucose challenge for patients with potential gestational diabetes mellitus (GDM) screening showed that post-load glycosuria is a poor predictor of GDM, pre-eclampsia, and newborn size at birth. It has a limited clinical benefit.[9]
In diabetes mellitus type 2, there appears to be a maladaptive upregulation of SGLT2 that contributes to hyperglycemia. A significant advance in the treatment of diabetes is the ushering in of the SGLT2 inhibitor class of drugs. These drugs have been demonstrated to improve glycemic control with weight loss by inducing glycosuria with calorie loss. They also promote natriuresis resulting in a decrease in blood pressure. However, they can increase the risk of genital and urinary tract infections and dehydration.[10]
Hemoglobin A1c (Hg A1c)= mostly not use for hemodialysis pt bed it only lasts for 90 days
The A1C test—also known as the hemoglobin A1C or HbA1c test—is a simple blood test that measures your average blood sugar levels over the past 3 months. It’s one of the commonly used tests to diagnose prediabetes and diabetes, and is also the main test to help you and your health care team manage your diabetes. Higher A1C levels are linked to diabetes complications, so reaching and maintaining your individual A1C goal is really important if you have diabetes.
What Does the A1C Test Measure?
When sugar enters your bloodstream, it attaches to hemoglobin, a protein in your red blood cells. Everybody has some sugar attached to their hemoglobin, but people with higher blood sugar levels have more. The A1C test measures the percentage of your red blood cells that have sugar-coated hemoglobin.
Who Should Get an A1C Test, and When?
Testing for diabetes or prediabetes:
Get a baseline A1C test if you’re an adult over age 45—or if you’re under 45, are overweight, and have one or more risk factors for prediabetes or type 2 diabetes:
If your result is normal but you’re over 45, have risk factors, or have ever had gestational diabetes, repeat the A1C test every 3 years.
If your result shows you have prediabetes, talk to your doctor about taking steps now to improve your health and lower your risk for type 2 diabetes. Repeat the A1C test as often as your doctor recommends, usually every 1 to 2 years.
If you don’t have symptoms but your result shows you have prediabetes or diabetes, get a second test on a different day to confirm the result.
If your test shows you have diabetes, ask your doctor to refer you to diabetes self-management education and support services so you can have the best start in managing your diabetes.
Managing diabetes:
If you have diabetes, get an A1C test at least twice a year, more often if your medicine changes or if you have other health conditions. Talk to your doctor about how often is right for you.
How to Prepare for Your A1C Test
The test is done in a doctor’s office or a lab using a sample of blood from a finger stick or from your arm. You don’t need to do anything special to prepare for your A1C test. However, ask your doctor if other tests will be done at the same time and if you need to prepare for them.
Your A1C Result
Diagnosing Prediabetes or Diabetes
Normal
Below 5.7%
Prediabetes 5.7% to 6.4%
Diabetes 6.5% or above
A normal A1C level is below 5.7%, a level of 5.7% to 6.4% indicates prediabetes, and a level of 6.5% or more indicates diabetes. Within the 5.7% to 6.4% prediabetes range, the higher your A1C, the greater your risk is for developing type 2 diabetes.
Managing Diabetes
Your A1C result can also be reported as estimated average glucose (eAG), the same numbers (mg/dL) you’re used to seeing on your blood sugar meter:
A1C %
eAG mg/dL
7
154
8
183
9
212
10
240
What Can Affect Your A1C Result?
A patient using a Glucometer
Get your A1C tested in addition to—not instead of—regular blood sugar self-testing if you have diabetes.
Several factors can falsely increase or decrease your A1C result, including:
Kidney failure, liver disease, or severe anemia.
A less common type of hemoglobin that people of African, Mediterranean, or Southeast Asian descent and people with certain blood disorders (such as sickle cell anemia or thalassemia) may have.
Certain medicines, including opioids and some HIV medications.
Blood loss or blood transfusions.
Early or late pregnancy.
Let your doctor know if any of these factors apply to you, and ask if you need additional tests to find out.
Your A1C Goal
The goal for most people with diabetes is 7% or less. However, your personal goal will depend on many things such as your age and any other medical conditions. Work with your doctor to set your own individual A1C goal.
Younger people have more years with diabetes ahead, so their goal may be lower to reduce the risk of complications, unless they often have hypoglycemia (low blood sugar, or a “low”). People who are older, have severe lows, or have other serious health problems may have a higher goal.
Hyperglycemia
What is hyperglycemia?
Hyperglycemia means high blood glucose. It most often affects people who have diabetes. When you have diabetes, your body doesn’t make enough insulin or can’t use it the right way. Too much glucose stays in your blood and doesn’t reach your cells.
What causes hyperglycemia?
A key part of managing diabetes is controlling your blood glucose levels. To do this, you need to follow a diabetes meal plan and get regular physical activity. You might also need to take diabetes medicines. You have to balance all of these to keep your blood glucose at the right levels. But if you eat too much food or the wrong foods, don’t take your medicines correctly, or don’t get physical activity, you can get hyperglycemia. It can also happen if you are stressed or sick.
Less commonly, people who don’t have diabetes can also get hyperglycemia. It can be caused by conditions that can affect insulin or glucose levels in your blood. They include problems with your pancreas or adrenal glands, certain medicines, and severe illnesses.
What are the symptoms of hyperglycemia?
The symptoms of hyperglycemia include:
Feeling thirsty
Feeling tired or weak
Headaches
Urinating (peeing) often
Blurred vision
If you are diabetic and you often have high blood glucose levels or the symptoms of hyperglycemia, talk with your health care team. You may need a change in your diabetes meal plan, physical activity plan, or diabetes medicines.
If you don’t have diabetes and you are having these symptoms, see your provider to find out the cause and how to treat it.
What other problems can hyperglycemia cause?
If hyperglycemia is not treated, it can cause other problems. In people with diabetes, long-term hyperglycemia can lead to serious health problems (diabetes complications).
If your blood glucose levels get very high, you can develop diabetes-related ketoacidosis (DKA). It happens when your body doesn’t have enough insulin to allow blood glucose into your cells for use as energy. Instead, your liver breaks down fat for fuel. This process produces acids called ketones. When too many ketones are produced too fast, they can build up to dangerous levels in your body. This can be life-threatening.
The symptoms of DKA may include:
Trouble breathing
Nausea or vomiting
Pain in your abdomen (belly)
Confusion
Feeling very tired or sleepy
If you have an an at-home test for ketones, check your ketone level every 4 to 6 hours when your blood glucose is very high or when you are having these symptoms. If the test shows that your ketones are moderate or high, or if you don’t have a ketones test, contact your health care provider right away or get emergency medical help.
How is hyperglycemia diagnosed?
If you have diabetes, you’ll most likely need to check your blood glucose every day and make sure that it’s not too high. You can do this with a blood glucose meter or continuous glucose monitoring (CGM) system.
There are also blood tests that providers can use to check if your blood glucose is too high.
What are the treatments for hyperglycemia?
If you have diabetes and often have high blood glucose, your health care team may make changes to your diabetes meal plan, physical activity plan, and/or diabetes medicines.
If you have severe hyperglycemia and are having symptoms of DKA, you will need treatment at the hospital. The treatment often includes I.V. (intravenous) fluids and insulin.
Can hyperglycemia be prevented?
If you have diabetes, managing your diabetes can help prevent hyperglycemia. To manage your diabetes, it’s important to:
Follow your diabetes meal plan
Get regular physical activity
If you need diabetes medicines, take them correctly
Regularly check your blood glucose level
Get regular checkups with your health care team
Hypoglycemia
Low Blood Sugar (Hypoglycemia)
Español (Spanish) | Print
Young woman checks her blood sugar
Have low blood sugar without symptoms? You may need to check your blood sugar more often.
Blood sugar levels change often during the day. When they drop below 70 mg/dL, this is called having low blood sugar. At this level, you need to take action to bring it back up. Low blood sugar is especially common in people with type 1 diabetes.
Knowing how to identify low blood sugar is important because it can be dangerous if left untreated. Read more about what causes low blood sugar and common symptoms.
Causes of Low Blood Sugar
There are many reasons why you may have low blood sugar, including:
Taking too much insulin.
Not eating enough carbs for how much insulin you take.
Timing of when you take your insulin.
The amount and timing of physical activity.
Drinking alcohol.
How much fat, protein, and fiber are in your meal.
Hot and humid weather.
Unexpected changes in your schedule.
Spending time at a high altitude.
Going through puberty.
Menstruation.
Symptoms of Low Blood Sugar
How you react to low blood sugar may not be the same as how someone else with low blood sugar reacts. It’s important to know your signs. Common symptoms may include:
Fast heartbeat
Shaking
Sweating
Nervousness or anxiety
Irritability or confusion
Dizziness
Hunger
Hypoglycemia Unawareness
If you’ve had low blood sugar without feeling or noticing symptoms (hypoglycemia unawareness), you may need to check your blood sugar more often to see if it’s low and treat it. Driving with low blood sugar can be dangerous, so be sure to check your blood sugar before you get behind the wheel.
You may not have any symptoms when your blood sugar is low (hypoglycemia unawareness). If you don’t have symptoms, it will be harder to treat your low blood sugar early. This increases your risk of having severe lows and can be dangerous. This is more likely to happen if you:
Have had diabetes for more than 5-10 years.
Frequently have low blood sugar.
Take certain medicines, such as beta blockers for high blood pressure.
If you meet one or more of the above and you have hypoglycemia unawareness, you may need to check your blood sugar more often to see if it’s low. This is very important to do before driving or being physically active.
Types of Low Blood Sugar
Nighttime low blood sugar
While low blood sugar can happen at any time during the day, some people may experience low blood sugar while they sleep. Reasons this may happen include:
Having an active day.
Being physically active close to bedtime.
Taking too much insulin.
Drinking alcohol at night.
Eating regular meals and not skipping them can help you avoid nighttime low blood sugar. Eating when you drink alcohol can also help. If you think you’re at risk for low blood sugar overnight, have a snack before bed.
You may wake up when you have low blood sugar, but you shouldn’t rely on that. A continuous glucose monitor (CGM) can alert you with an alarm if your blood sugar gets low while you’re sleeping.
Severe low blood sugar
As your low blood sugar gets worse, you may experience more serious symptoms, including:
Feeling weak.
Having difficulty walking or seeing clearly.
Acting strange or feeling confused.
Having seizures.
Severe low blood sugar is below 54 mg/dL. Blood sugar this low may make you faint (pass out). Often, you’ll need someone to help you treat severe low blood sugar.
People with diabetes may experience low blood sugar as often as once or twice a week, even when managing their blood sugar closely. Knowing how to identify and treat it is important for your health. Learn how to treat low blood sugar.
Hypoglycemic unawareness
Hypoglycemia unawareness (HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms. It is a major limitation to achieving tight diabetes and reduced quality of life. HU occurs in approximately 40% of people with type 1 diabetes mellitus (T1DM) and with less frequency in T2DM. Though the aetiology of HU is multifactorial, possible mechanisms include chronic exposure to low blood glucose, antecedent hypoglycaemia, recurrent severe hypoglycaemia and the failure of counter-regulatory hormones. Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms, but the mechanisms and mediators remain largely unknown. Prevention and management of HU is complex, and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team. Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes. Several medications are thought to worsen or promote HU, whereas others may have an attenuating effect on the problem. This article reviews recent advances in how the brain senses and responds to hypoglycaemia, novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses. The consequences that HU has on the person with diabetes and their family are also described. Finally, it examines the evidence for prevention and treatment of HU, and summarizes the effects of medications that may influence it.
Hypoglycemia is usually defined as a plasma glucose level < 70 mg/dL (3.9 mmol/L)[1]. Since the brain is permanently dependent on glucose, strong counter-regulatory mechanisms exists to quickly increase glucose levels to protect the human body from the negative consequences of hypoglycemia. Counter-regulatory response to hypoglycemia (Figure (Figure1)1) includes inhibition of the endogenous insulin secretion and stimulation of glucagon, catecholamines (norepinephrine, epinephrine), cortisol and growth hormone secretion, which all together stimulate hepatic glucose production and cut down glucose utilization in peripheral tissues, increasing in this way plasma glucose levels. As glycaemia comes down, the activation of the autonomic nervous system leads to neurogenic symptoms (palpitations, sweating, hunger, anxiety, tremors, etc.), which allows the perception of hypoglycaemia (hypoglycaemia awareness
Hypoglycemia unawareness (HU) is defined as the onset of neuroglycopenia before the appearance of autonomic warning symptoms[2] or as the failure to sense a significant fall in blood glucose below normal levels[3]. In patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM), recurrent hypoglycemia has been shown to reduce the glucose level that precipitates the counter-regulatory response necessary to restore euglycemia during a subsequent episode of hypoglycemia[4,5].
HU was observed in 40% T1DM patients[6] and less frequently in T2DM patients with low C-peptide levels. The presence of HU increases the risk of severe hypoglycaemia (six-fold for T1DM[7] and 17-fold for T2DM[8]). HU is more common in individuals with longer duration of diabetes, history of recent and/or recurrent hypoglycaemic events, patients with intensive glycemic therapy and in advanced age
Catecholamines: Previous hypoglycemia leads to a blunted catecholamine response to a following episode of hypoglycemia. These has been demonstrated in several studies; for example Ramanathan et al[17] showed that intravenous infusion of adrenergic blockers on one day of a hypoglycemia prevent the counter-regulatory failure in the response on the next day of hypoglycemia. This study implicates that HAAF needs a previous hypoglycemia (with its sympathoadrenal responses). If we use this hypothesis to think in a possible pharmacologic treatment, we can concluded that blocking the action of catecholamines we can limit the development of HAAF and protect against subsequent hypoglycemias; but unfortunately, blocking the action of catecholamines in periphery we would tend to an increase in the severity of hypoglycemia. We would need to develop a selective adrenergic receptor modulators that favourably change central nervous system response without modify the beneficial peripheral effects of the sympathoadrenal response.
Sleep: Sleep is a peripheral mediator of HAAF linked with catecholamine response. Patients with T1DM, while they are sleeping, they have a significantly decreased epinephrine response to hypoglycemia[18], and also a reduced awakening from sleep during hypoglycemia[19]. So, because of the HU and the impaired adrenomedullary response, we can explain some of the overnight deaths of healthy young people with T1DM.
Cortisol: Hypoglycemia is associated with an elevation in systemic corticosteroids, and this has been proposed to feedback to the hypothalamus contributing to HAAF[20-22]. However it remains controversial if the endogenous hypercortisolemia is of sufficient magnitude to blunt de counter-regulatory response to hypoglycemia[23,24]. It have been shown that corticotrophin releasing hormone agonist impair the counter-regulatory response to a subsequent hypoglycemia, suggesting a possible role in HAAF[25].
Opioids: Preclinical and clinical studies with opioids demonstrated a rise in endogenous opioids during hypoglycemia, for example naloxone (an opioid receptor blocker), increased the sympathoadrenal response to hypoglycemia, and when is infused during previous hypoglycemia, it prevent HAAF[26,27]. Hence there is a potential therapeutic function for opioid receptor blockade to protect against HAAF.
Exercise: The inability to reduced circulating insulin during exercise, lead T1DM patients, at an increased risk for hypoglycemia during or after exercise. In addition to, during exercise the opioid beta endorphin is released to activate the sympathoadrenal response. In a recent study, healthy individuals who exercised and elevated endorphin levels, they had reduced catecholamine response during hypoglycemia in the next day[28], suggesting that endogenous opioids, again, play a role in HAAF, and that blocking their action may protect against exercise-autonomic failure.
Hyperosmolar hyperglycemic syndrome (HHS)
Hyperosmolar hyperglycemic syndrome (HHS) is a clinical condition that arises from a complication of diabetes mellitus. This problem is most commonly seen in type 2 diabetes. Won Frerichs and Dreschfeld first described the disorder around 1880. They described patients with diabetes mellitus with profound hyperglycemia and glycosuria without the classic Kussmaul breathing or acetone in the urine seen in diabetic ketoacidosis. This clinical condition was formerly called non-ketotic hyperglycemic coma, hyperosmolar hyperglycemic non-ketotic syndrome, and hyperosmolar non-ketotic coma (HONK).[1]
Diabetes mellitus is a clinical condition associated with hyperglycemia as the main metabolic disorder.[2] This is a result of an absolute or relative deficiency of insulin. Insulin is an anabolic hormone produced by the beta cells of the islets of Langerhans in the pancreas. The main function of this hormone is to lower the level of glucose in the blood by promoting the uptake of glucose by the adipose tissue and skeletal muscle, known as glycogenesis. Insulin also inhibits the breakdown of fat in the adipose tissue, known as lipolysis. The metabolic effect of insulin is countered by hormones such as glucagon and catecholamines.[3]
In type 1 diabetes, there is the autoimmune destruction of the beta cells in the pancreas. Only about 5% to 10% of all diabetes falls into this category. The most common complication of type 1 diabetes is diabetic ketoacidosis (DKA).
Type 2 diabetes accounts for about 90% to 95% of diabetes cases.[4] It is most commonly seen in patients with obesity. As a consequence of obesity and high body mass index (BMI), there is resistance of the peripheral tissue to the action of insulin. The beta-cell in the pancreas continues to produce insulin, but the amount is not enough to counter the effect of the resistance of the end organ to its effect.
HHS is a serious and potentially fatal complication of type 2 diabetes.
The mortality rate in HHS can be as high as 20%, which is about 10 times higher than the mortality seen in diabetic ketoacidosis.[5][6] Clinical outcome and prognosis in HHS are determined by several factors: age, the degree of dehydration, and the presence or lack of other comorbidities.[7][8][9]
Go to:
Etiology
In children and young adults with type 1 and type 2 diabetes, infectious diseases and disorders of the respiratory, circulatory, and genitourinary systems can cause HHS. Obesity and incessant consumption of carbohydrate-rich beverages have led to an increase in the incidence of HHS.[10][11]
This is particularly true in the pediatric population, where the incidence of type 2 diabetes is on the rise.
As stated earlier, HHS is most commonly seen in patients with type 2 diabetes. If diabetes mellitus is well controlled, the chance of developing HHS is minimal. However, under certain conditions, some factors might initiate the development of HHS. The most frequent reason for this complication is infection. The infectious process in the respiratory, gastrointestinal, and genitourinary systems can act as the causative factor. The reason for this is the insensible water loss and the release of endogenous catecholamines. Approximately 50% to 60% of HHS is attributable to an infectious etiology.[11][12][13]
Some medications for the treatment of other ailments and conditions in elderly patients with type 2 diabetes can trigger HHS. Examples of such medications are thiazide diuretics, beta-blockers, glucocorticoids, and some atypical antipsychotics.[14][15]
A cardiovascular insult like stroke, angina pectoris, and myocardial infarction can also trigger a stress response. This leads to the release of counterregulatory hormones with the resultant effect of an increased level of blood glucose, causing osmotic diuresis and dehydration, with the final result being HHS.
Go to:
Epidemiology
There is insufficient data on the epidemiology of HHS. Based on some studies, close to 1% of all hospital admission for diabetes is related to HHS.[16][17]
Most cases of HHS are seen in patients in the fifth and sixth decades of life. Typically DKA is more common in the younger population, with the peak age around the fourth decade of life.[17][18]
In the United States, because of the increase in childhood obesity which is related to the consumption of high amounts of carbohydrate-rich diet, there is a significant increase in the incidence of type 2 diabetes. This may lead to an increased incidence of HHS in the pediatric population.
There is a disproportionally high number of African Americans, Native Americans, and Hispanics who are afflicted with HHS. This might be related to a high prevalence of type 2 diabetes in these particular population groups. HHS can be fatal in morbidly obese African American males.
Go to:
Pathophysiology
HHS has similar pathophysiology to DKA but with some mild dissimilarities. The hallmark of both conditions is the deficiency of insulin. As a consequence of deficiency of this key hormone, there is a decrease in glucose utilization by the peripheral tissue causing hyperglycemia.[19] The peripheral tissues enter a state of “starvation.”The release of counterregulatory hormones like glucagon, growth hormone, cortisol, and catecholamines stimulates gluconeogenesis and glycogenolysis.[19][20] This creates a system of vicious cycle where there is an increased level of glucose in the serum but decreased uptake by the peripheral tissues for tissue metabolism. The serum osmolality is determined by the formula 2Na + Glucose /18 + BUN / 2.8. The resultant hyperglycemia increases the serum osmolarity to a significant degree. The glucose level in HHS is usually above 600 mg/dL. Hyperglycemia also creates an increase in the osmotic gradient, with free water drawn out of the extravascular space due to the increased osmotic gradient. Free water with electrolytes and glucose is lost via urinary excretion producing glycosuria, causing moderate to severe dehydration. Dehydration is usually more severe in HHS as compared to DKA, and there is more risk for cardiovascular collapse.[21][22][23][24]
Compared to DKA, the production of ketone bodies is scant in HHS. As a result of the deficiency of insulin, there is increased lipolysis that causes an increased release of fatty acid as an alternative energy substrate for the peripheral tissues. Beta oxidation of fatty acids produces ketone bodies: acetone, acetoacetate, and beta oxybutyric acid. Accumulation of these substrates produces ketonemia and acidemia. Acidemia from ketone bodies stimulates the kidney to retain bicarbonate ions to neutralize the hydrogen ions. This accounts for the low serum bicarbonate level in DKA.
In HHS, however, because insulin is still being produced by the beta cells in the pancreas, the generation of ketone bodies is minimal. Insulin inhibits ketogenesis. That aside, in HHS, there is a higher level of insulin with an associated lower level of glucagon. Therefore, ketonemia and acidemia, if they happen, they are very mild in HHS.[20][25][26]
The effect of the increased serum osmolarity on the brain can be very profound. To preserve the intracellular volume, the brain produces idiogenic osmoles. Idiogenic osmoles are substances that are osmotically active. The net effect of the production of these substances is to prevent fluid from moving from the intracellular space into the extracellular space and maintain a balanced equilibrium.[24]
The risk of developing cerebral edema is mostly related to how fast the serum osmolarity is decreasing. If the decline is too rapid and the brain is not able to eliminate idiogenic osmoles at the same rate as the decline in serum osmolarity, then the chances of fluid moving into the brain cell and causing swelling are higher. Hence, in the treatment of HHS, the goal of treatment is a slow correction of hyperglycemia.
Go to:
History and Physical
The history and physical examination are very important in the diagnosis of HHS. In many instances, there is a significant overlap in the signs and symptoms seen in HHS and DKA. In the history taking and the initial assessment, particular attention should be focused on the insulin regimen, missed dosages of oral hypoglycemic agents, overconsumption of carbohydrate-rich diet, or simultaneous use of medications that can trigger hyperglycemia or cause dehydration.
If an infectious process precedes HHS, signs and symptoms include:
Fever
Malaise
General weakness
Tachypnea
Tachycardia
If the precipitating factor is a cardiac or vascular condition, signs and symptoms will include:
Chest pain
Chest tightness
Headache
Dizziness
Palpitations
The typical clinical presentation of patients with HHS is increased urination (polyuria) and increased water intake (polydipsia). This is a result of the stimulation of the thirst center in the brain from severe dehydration and increased serum osmolarity. Weakness, malaise, and lethargy can also be part of the complaints.
Severe dehydration from HHS can also affect the skin and integumentary system. Typically, the skin and the oral mucosa are dry with a delayed capillary refill.
The most important distinguishing factor in HHS is the presence of neurological signs. Decreased cerebral blood flow from severe dehydration can cause:
Focal neurological deficit
Disturbance in visual acuity
Delirium
Coma
A system-based approach is necessary for the physical assessment:
General appearance: Patients with HHS are generally ill-appearing with altered mental status
Cardiovascular: Tachycardia, orthostatic hypotension, weak and thready pulse
Respiratory: Rate can be normal, but tachypnea might be present if acidosis is profound
Skin: Delayed capillary refill, poor skin turgor, and skin tenting might not be present even in severe dehydration because of obesity
Genitourinary: Decreased urine output
Central Nervous System (CNS): Focal neurological deficit, lethargy with low Glasgow coma score, and in severe cases of HHS, the patient might be comatose.
The physical examination should also focus on other comorbidities associated with diabetes mellitus. Acanthosis nigricans, oral thrush, vulvovaginitis, and multiple pustular skin lesions might all indicate poor glycemic control. This is particularly important if HHS is the initial presentation of type 2 diabetes.
Go to:
Evaluation
The diagnostic criteria for HHS were developed as a result of cases series reported by Gerich et al. Arieff and Carroll also contributed to this work in a separate study, both of which were published in 1971.[27]
According to the recommendation of the American Diabetic Association and current international guidelines, HHS is defined by plasma glucose level greater than 600 mg/dL, plasma effective osmolarity greater than 320 mOsm/L, and absence of significant ketoacidosis.[28]
Hyperosmolar hyperglycemic non-ketotic coma is no longer accepted as a diagnostic nomenclature because not all patients with HHS will present with coma, even in the presence of significant hyperglycemia and hyperosmolarity.
The evaluation of HHS requires a detailed history and physical examination. The onset of symptoms and the precipitating factors are very important to elicit from patients. That apart, ancillary studies are also necessary as part of the diagnostic workup.
The first test in HHS is a fingerstick to determine the serum glucose level. The value is usually between 600 to 1200 mg/dl. The higher the level of glucose, the greater the serum osmolarity and the higher the degree of dehydration.
Glucose
The glucose level should be monitored hourly to guard against a sudden and precipitous drop during treatment with isotonic fluid and insulin. This is to prevent the development of cerebral edema, which is the most dreaded complication in both DKA and HHS. The risk of cerebral edema is higher in HHS.
Hemoglobin A1C
This is a measure of long-term glycemic control and is a useful tool in the assessment of new-onset diabetes mellitus.
Serum Osmolarity
The serum osmolality is very high in HHS. Levels between 320 to 400mOsm/kg are very common in HHS. Normal serum osmolarity is around 280 -290 mOsm/kg. Higher serum osmolarity is associated with alteration in the level of consciousness and might eventually lead to a coma.
The comprehensive metabolic panel allows for the determination of electrolyte derangements seen in HHS.
Sodium
The sodium level is falsely low (pseudohyponatremia). The hyperglycemic state creates an osmotic gradient, drawing water from the intracellular space into the extracellular space. The correct or true sodium level is usually calculated using the formula:
Corrected Sodium = Measured sodium + (((Serum glucose - 100)/100) x 1.6)
Potassium
The level of potassium might be high or low. A low level of insulin can cause an extracellular shift of potassium. However, because of ongoing urinary losses, the total body potassium is low in both HHS and DKA. Care must be taken to avoid aggressive correction of hypokalemia in HHS because of decreased glomerular filtration rate from dehydration.
Bicarbonate
Bicarbonate level is usually close to normal in HHS, around 8 to 12 mmol/L, because the production of ketone bodies is minimal as compared to DKA, where the bicarbonate level is usually very low. The anion gap in HHS is normal or close to normal. On the contrary, the anion gap is usually above 12 mmol/L in DKA. The anion gap is determined by the formula:
(Na +K) - (Cl +HC0)
If the anion gap is high in HHS, it is usually because of the production of lactic acid from tissue hypoperfusion and decreased circulation.
Magnesium
The magnesium level might be low in HHS.
Phosphorus
Hyperphosphatemia is common in HHS, especially if rhabdomyolysis is a complication. This is a result of muscular tissue breakdown. Administration of insulin and hydration with fluid might lower the phosphorus level as it is driven back into cells. Some of the phosphorus also get excreted by the kidneys as end-organ perfusion improves.
Ketones
Ketonemia is very minimal in HHS. Electrolytes should be monitored serially every 2 to 3 hours in the management of HHS.
Arterial Blood Gases
The role of blood gas is to determine the level of acidosis. In HHS, pH is usually above or around 7.30. The pC0 might be low from hyperventilation. In DKA, serum pH is usually much lower ranging from 6.8 to around 7.2 on initial presentation. Acidosis in HHS is mainly a result of dehydration and compromised end-organ perfusion.
Arterial blood gases should be monitored every 2 to 3 hours in HHS.
Renal Function
The BUN and creatine levels are usually elevated, reflecting prerenal azotemia. As hydration and insulin therapy are initiated, these values will usually drop and eventually normalize.
Serum Enzymes
The level of serum enzymes like creatinine kinase, aldolase, and transaminases is usually high from hemoconcentration and dehydration.
Complete Blood Count
The white blood cell count might be high because of the stress response or as a result of an infectious process triggering HHS. In most cases, hemoglobin and hematocrit levels are elevated. If the white count is elevated, blood culture, urine culture, and a chest X-ray might be needed to find the source of infection.
Urine Analysis
Urine-specific gravity is high in HHS. Glycosuria and ketonuria are also present.
Go to:
Treatment / Management
Treatment of HHS requires a multidisciplinary approach. Consultations with an endocrinologist and an intensive care specialist are recommended. Appropriate resuscitation with attention to the principle of Airway, Breathing, Circulation (ABC) should be initiated. Patients with HHS can present with altered mental status as a result of significant fluid depletion and decreased cerebral perfusion. A good rule of thumb is to secure the airway if the Glasgow coma score is less than 8.
Aggressive hydration with isotonic fluid with electrolyte replacement is the standard practice in the management of HHS. An initial fluid bolus of 15 to 20 ml/kg followed by an infusion rate of 200 to 250 ml/hour are the recommended rates for adults. In pediatric patients, the infusion should run at about twice the maintenance rate. Hydration with isotonic fluid has been shown to help in reducing the amount of counterregulatory hormones produced during HHS. The use of this alone can reduce serum glucose by about 75 to 100 mg/hour. The serum potassium in HHS is usually high, but the total body potassium is low as a result of the extracellular shift from lack of insulin. Potassium replacement should be started when the serum potassium is between 4 to 4.5 mmol/L.[29]
Care should be taken to avoid starting insulin drip in the initial stage of treatment as this might cause a rapid drop in serum glucose levels leading to cerebral edema. It is recommended to try to keep the glucose level around 300 mg/dL to prevent the development of cerebral edema.
In pediatrics, rehydration and electrolyte correction over a longer period of 48 hours may help in the prevention of cerebral edema.[29][30]
Polyphagia
Polyphagia, also called hyperphagia, is the medical term for a feeling of extreme, insatiable hunger. It’s a symptom of certain health conditions. Eating typically doesn’t make polyphagia go away, except in the case of low blood sugar (hypoglycemia).
Excess eating as a result of this feeling may or may not lead to weight gain depending on the underlying cause. In some cases, it’s associated with unexplained weight loss.
An increase in hunger is a normal bodily response to situations like fasting or strenuous exercise. But intense, insatiable hunger like polyphagia is often a sign of a health condition that needs medical treatment, such as diabetes.
What causes polyphagia (hyperphagia)?
Polyphagia (extreme hunger) is a relatively uncommon symptom. It’s most often associated with undiagnosed or undertreated diabetes.
Other causes include:
Other hormone-related conditions.
Mental health conditions.
Rare medical conditions.
Malnutrition in the form of undernutrition can also cause polyphagia. Undernutrition is a deficiency of nutrients. You may be undernourished if you don’t have an adequate diet, or if your body has trouble absorbing enough nutrients from your food.
Certain medications, such as corticosteroids and cannabinoids (cannabis-related drugs), can cause polyphagia, as well. Talk to your healthcare provider if you experience extreme hunger after starting a new medication.
Diabetes and polyphagia
Diabetes mellitus is a condition in which your body doesn’t make enough or any insulin or your body doesn’t use the insulin properly. Insulin is an essential hormone that helps regulate your blood glucose (sugar) level. Without enough insulin, glucose builds up in your blood, causing hyperglycemia (high blood sugar).
Glucose (sugar) is the main form of energy your body uses from the food you eat. Without enough insulin, your body can’t use glucose for energy. This lack of energy usage causes an increase in hunger.
The three main types of diabetes include:
Type 1 diabetes (T1D): This is an autoimmune disease. In T1D, your immune system attacks the insulin-producing cells in your pancreas, destroying them. Your pancreas can no longer make insulin, so glucose builds up in your blood. Your body can’t use this glucose without insulin, so it starts rapidly breaking down fat and muscle for energy instead. This causes polyphagia with weight loss.
Type 2 diabetes (T2D): If you have T2D, your body either doesn’t make enough insulin or your body’s cells don’t respond normally to the insulin (insulin resistance). This is the most common type of diabetes. Polyphagia in T2D usually isn’t as apparent as it is in T1D because the hyperglycemia isn’t as extreme.
Gestational diabetes: This type of diabetes results when hormones your placenta produces during your pregnancy make your body’s cells more resistant to insulin. Your pancreas can’t make enough insulin to overcome this resistance. You may not notice symptoms of gestational diabetes, like increased hunger and more frequent peeing.
Polyphagia is one of the main three signs of diabetes:
Polyphagia (extreme hunger).
Polydipsia (extreme thirst).
Polyuria (frequent urination).
Healthcare providers often call these the “three Ps of diabetes.” Seek medical care as soon as possible if you’re experiencing these symptoms, especially if you’ve also experienced rapid weight loss. Untreated and undiagnosed Type 1 diabetes is fatal.
People with diabetes (especially T1D) can also experience polyphagia due to hypoglycemia (low blood sugar) episodes. Hypoglycemia needs to be treated by consuming sugar (glucose) in order to get your blood sugar back into a healthy range. People without diabetes can experience hypoglycemia, as well.
Somogi effect
The Somogyi effect, also known as the “chronic Somogyi rebound” or “posthypoglycemic hyperglycemia,” was a theory proposed in the 1930s by Dr. Michael Somogyi, a Hungarian-born professor at Washington University, St. Louis, MO, United States.[1] He described the paradoxical tendency of the body to react to hypoglycemia by producing hyperglycemia. Somogyi proposed that when blood glucose levels drop too low during the late evening, activation of counterregulatory hormones such as adrenaline, corticosteroids, growth hormone, and glucagon may be observed, leading to activation of gluconeogenesis and resultant hyperglycemia in the early morning.[2]
However, more recent studies involving continuous glucose monitoring (CGM) have disputed this theory. Also, clinicians have observed that patients with early morning hyperglycemia tend to have high blood glucose measurements at night rather than low.[1] As a result, the debate continues in the scientific community regarding Somogyi’s theory. Moreover, recently proposed mechanisms of morning hyperglycemia include nocturnal growth hormone secretion, hypoinsulinemia, and insulin resistance associated with metabolic syndrome.[3]
Go to:
Issues of Concern
Somogyi Phenomenon vs. Dawn Phenomenon
A phenomenon known as the dawn phenomenon was introduced by Dr. Schimdt in the 1980s, stating that morning hyperglycemia is due to the decreased levels of endogenous insulin secreted at night.[1] The dawn phenomenon also contributes to morning hyperglycemia to increased concentrations of insulin-antagonist hormones. The dawn phenomenon is comparable to the Somogyi phenomenon, which attributes morning hyperglycemia to counterregulatory hormones from low glucose. The dawn phenomenon has been noted to occur more commonly than the Somogyi phenomenon.[1] While the two theories are not seen in all cases of insulin-dependent diabetics, it is important to note that the best way to prevent either is optimal diabetes control with the proper insulin therapy.[1]
The Somogyi phenomenon states that early morning hyperglycemia occurs due to a rebound effect from late-night hypoglycemia. However, the dawn phenomenon does not include hypoglycemic episodes to be a factor.
Insulin Release and Insulin Resistance
With recent studies attributing early morning hyperglycemia to hypoinsulinemia, there is an observable pattern in which the body secretes insulin. The theory is insulin gets secreted in a circadian pattern, with the lowest concentrations between midnight and 6 AM and the highest concentrations between noon and 6 PM.[4] This pattern of insulin secretion is the opposite of melatonin from the pineal gland. The circadian pattern of insulin secretion provides evidence for the dawn phenomenon.
The Somogyi phenomenon has been a proposed phenomenon in insulin-dependent diabetic patients. The thinking is that these patients should monitor their blood glucose levels and adjust insulin dosages as necessary to prevent hypo- or hyperglycemic episodes.
In an individual that does not have diabetes, the blood glucose and insulin concentrations stay flat and constant throughout the night, with a transient increase in insulin just before dawn to prevent hepatic glucose production through gluconeogenesis and prevent hyperglycemia.[5] This explains why non-diabetic patients do not exhibit the dawn phenomenon, as their insulin levels follow the circadian pattern necessary for optimal glucose control.
Insulin resistance, seen in diabetes or metabolic syndrome, has been associated with constant exposure to high insulin levels.[6] As patients get diagnosed with diabetes or metabolic syndrome at an earlier age, there is more exogenous insulin exposure that leads to this resistance. Because of this, the normal regulation and pattern of insulin levels make it difficult for insulin-dependent diabetics to control their blood glucose levels during their sleep. Not only is insulin necessary to regulate glucose levels, but it is also the primary hormone that inhibits gluconeogenesis.[7] Gluconeogenesis in the morning gets inhibited in a non-diabetic due to the transient increase in insulin right before dawn. As a patient becomes more and more resistant to insulin, the key inhibitor of gluconeogenesis is no longer working; this allows the body to produce more glucose, leading to a hyperglycemic state.
Go to:
Clinical Significance
The Somogyi phenomenon had been considered in the past; an essential consideration for the proper diagnosis and management of blood glucose levels is vital for the body’s metabolic demands. The post-hypoglycemic hyperglycemia raises the question of whether a patient’s insulin levels should be adjusted in the evening to prevent hyperglycemia in the morning. As this is something ideally avoided, the Somogyi phenomenon occurs too infrequently to make this standardized practice.
Hypoglycemia vs. Hyperglycemia
Glucose control is vital for brain metabolism and function, as it is the primary substrate for proper brain activity. The body has different regulatory molecules that act to decrease the likelihood of low blood glucose. The first response thought to activate due to low blood glucose is the counterregulatory hormone mechanism.[8] Other mechanisms include glycogenolysis, the breakdown of glycogen into glucose, and gluconeogenesis, de novo production of glucose, which occur in the liver.[7] The ideal plasma glucose concentration ranges from 70 to 140 mg/dL throughout the day.[9] Both glycogenolysis and gluconeogenesis can activate when levels fall below this range. Another mechanism induced by hypoglycemia includes a decrease in the pancreatic beta-cell secretion of insulin and an increase in the pancreatic alpha-cell secretion of glucagon. Glucagon, epinephrine, and glucocorticoid production will increase to induce glucose production in the body.[10] A hypoglycemic episode puts patients at risk for neurological dysfunction, coma, or even death.[10] With repeated hypoglycemia, the counterregulatory system that is supposed to keep blood glucose levels in range will start to fail.[10] Signs of hypoglycemia that patients must be aware of include diaphoresis, hunger, irritability, loss of consciousness, seizures, and confusion.[10]
Hyperglycemic episodes are also to be avoided. Symptoms to look out for include polyuria, polydipsia, weakness, tachycardia, and hypotension.[11] The hyperglycemia will worsen the cytokine and inflammatory response, causing even more hyperglycemia.[11] Consequences of hyperglycemia include renal failure, polyneuropathy, retinopathy, and arrhythmias.[11] Hyperglycemia produces an increase in advanced glycation end products (AGEs), which deposit in the body, causing connective tissue crosslinking, fibrosis, and impaired relaxation of the heart.[12] People with diabetes become insulin-resistant, which keeps blood glucose levels elevated, causing an even more increase in AGEs.[12] With the failure to keep blood glucose levels at a normal range, the hyperglycemic episodes also induce the renin-angiotensin-aldosterone system (RAAS), increasing vascular resistance and arterial pressure in the body.[12]
In an interprofessional team, there are many things to consider in managing a patient’s blood glucose concentrations. Theoretically, the risks of adjusting a patient’s insulin in case they undergo the Somogyi phenomenon could risk the potential consequence of increasing a patient’s chance of becoming severely hypoglycemic.
It is essential to coordinate care by involving the patient in discussions regarding proper glucose management. Lifestyle modifications and being aware of the symptoms of hypoglycemia or hyperglycemia require discussion in great detail with the patient. It will allow them to make well-informed decisions regarding their food choices, lifestyle habits, and activity levels.
Controversy
The importance of maintaining proper blood glucose levels in any patient is apparent from both ends of blood glucose level abnormalities. Using the Somogyi phenomenon as a precaution for standard in practice does not have enough evidence. Instead, this theory can be used to help monitor patients’ blood glucose levels throughout different times of the day to see if they fit the theory.
Clinical studies suggest that underdosing of insulin from the previous night fails to prevent hyperglycemia.[2] Another study on Type 1 Diabetes patients suggested that nocturnal hypoglycemia is usually associated with early morning hypoglycemia, not hyperglycemia.[13] In clinical practice, patients with hypoglycemic episodes at night do not wake up in the morning with hyperglycemia, hence refuting Somogyi Phenomenon.
In a study done at the Washington University School of Medicine to test the hypothesis of the Somogyi phenomenon, the conclusion was that the nocturnal hypoglycemia did not cause daytime hyperglycemia.[14] It showed no correlation between increased daytime glucose levels with the concentrations of counterregulatory hormones such as glucagon, epinephrine, growth hormone, or cortisol.[14] This study disproved the theory of Dr. Somogyi.
Go to:
Nursing, Allied Health, and Interprofessional Team Interventions
All interprofessional healthcare team members who interact with patients with diabetes should be aware of the Somogyi phenomenon and the dawn effect and be able to explain them to their patients if it comes up during patient counseling, as patients may have heard of it and ask questions. Interprofessional healthcare team members can explain that it is no longer considered valid and direct the patients toward more scientifically back resources to help manage their condition.
