Diabetes Mellitus: A Quick Review

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Course Purpose   

To provide healthcare professionals an overview of Diabetes Mellitus, symptoms, diagnosis, and management options.

Overview

Diabetes mellitus (DM) refers to a group of diseases that affects how the body uses glucose, an important source of energy for muscle and tissue cells. Subclassifications of DM include Type 1 DM, Type 2 DM, gestational diabetes, maturity-onset diabetes of the young (MODY). This online learning activity provides an overview of the various types of DM, symptoms, diagnosis, and treatment options.

Objectives

  • Describe the various forms of diabetes mellitus
  • Identify common symptoms associated with diabetes mellitus
  • Review how diabetes mellitus is diagnosed
  • Identify common treatment and management options available

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Fast Facts: Diabetes Mellitus: A Quick Review

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Definitions
Diabetes MellitusA disease in which the body’s ability to produce or respond to insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated blood and urine glucose levels.
Diabetic KetoacidosisA complication of diabetes that results from increased levels of ketones in the blood, causing fatigue, frequent urination, increased thirst, and vomiting.
Gestational Diabetes MellitusDiabetes that is diagnosed for the first-time during pregnancy.
Hyperosmolar Hyperglycemic SyndromeA condition that causes extremely high blood glucose levels for long periods of time, usually occurs in people with type 2 diabetes mellitus, and. is often triggered by illness or infection.
Mature Onset Diabetes of the YoungA group of disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes that presents in adolescence or young adults.
Type 1 Diabetes MellitusA chronic condition in which the pancreas produces little or no insulin.
Type 2 Diabetes MellitusA chronic condition that results in high blood sugar, insulin resistance, and relative lack of insulin.
Introduction

Diabetes Mellitus (DM) is a metabolic disease that involves abnormally elevated blood glucose levels. There are several types of diabetes mellitus, including Type 1, Type 2, gestational diabetes, and maturity-onset diabetes of the young (MODY)¹. The main types of DM are Type 1 Diabetes Mellitus (T1DM), Type 2 Diabetes Mellitus (T2DM), and gestational diabetes. ¹¹ Type 1 diabetes mellitus is often caused by an autoimmune response and type 2 diabetes mellitus is a progressive disease that results from insulin resistance. Type 1 diabetes mellitus is most often diagnosed in children and adolescents, while T2DM is thought to affect middle-aged and older adults who have prolonged hyperglycemia due to sedentary lifestyles and poor dietary choices. ¹² The pathogenesis for T1DM and T2DM is drastically different, and therefore each type has various etiologies, presentations, and treatments.

Diabetes Types

There are two main subclasses of endocrine cells in the pancreas’s islets of Langerhans: glucagon secreting alpha cells and insulin-producing beta cells. Alpha and Beta cells constantly change their hormone levels to balance glucose levels. Without the balance between glucagon and insulin, the glucose levels can become skewed, resulting in hyperglycemia and diabetes mellitus. 

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia. It may be due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Diabetes Mellitus is mainly classified into three types based on cause and clinical presentation: type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM). ¹³ Other types of diabetes that are less common include mature onset diabetes of the young (MODY).

Stages of Type 1 Diabetes Mellitus

Type 1 diabetes mellitus develops in three stages¹³: 

Stage OneIn this stage, the person may be asymptomatic and have a normal fasting glucose, normal glucose tolerance, and may have the presence of two pancreatic autoantibodies.
Stage TwoIn this stage, the person will still be asymptomatic, but may have two pancreatic autoantibodies, elevated fasting glucose levels, elevated glucose tolerance test, and elevated hemoglobin A1c levels.
Stage ThreeIn this stage, the person will experience clinical symptoms of diabetes or hyperglycemia in addition to two or more pancreatic autoantibodies. 

In children and adolescents, the symptoms of T1DM can develop rapidly and may lead to health decline if not treated promptly. Symptoms associated with T1DM include¹²:

  • Blurred vision from osmotic swelling on the lens
  • Nocturnal enuresis from abnormal sensory pathways to the bladder
  • Polydipsia from dehydration caused by increased urination
  • Polyphagia from sustained elevated glucose levels
  • Polyuria from osmotic diuresis
  • Weight loss from the breakdown of muscle and fat, and ketone production

Type 1 diabetes mellitus is also associated with high morbidity and mortality. Close to 50% of people with T1DM will develop at least one serious complication over their lifetime. ¹³ For instance, some will lose eyesight, and others will develop end-stage renal disease. For those who have no complications 20 years after diagnosis, the prognosis is good. However, T1DM has no cure, and with time, an individual may develop the following complications:

  • Cardiomyopathy
  • Diabetic foot disease
  • Diabetic ketoacidosis
  • Hypoglycemia
  • Nephropathy
  • Retinopathy

Type 2 Diabetes Mellitus

Different from Type 1 diabetes mellitus that is an insulin-resistance condition with associated beta-cell dysfunction, Type 2 diabetes mellitus is characterized by a more subtle onset where an imbalance between insulin levels and insulin sensitivity (how sensitive the body is to the effects of insulin) causes a functional deficit of insulin. Insulin resistance is the diminished response to insulin and often develops from aging and obesity that is distributed mainly in the abdominal region. Although age-related T2DM typically occurs in those over age 45, its frequency has increased in children, adolescents, and younger adults due to rising levels of obesity, lack of physical activity, and high carbohydrate diets. ¹⁴ Type 2 diabetes mellitus is also seen in women with a previous diagnosis of gestational diabetes and in those diagnosed with hypertension or dyslipidemia.

Metformin is the first-line medication that is prescribed for T2DM. Insulin administration may also be necessary, especially in those with inadequate glucose management or who are in the advanced stages of the disease. In people who are morbidly obese, bariatric surgery may be recommended when glucose levels are unresponsive to other treatments, as weight loss may normalize glucose levels.

Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is any degree of glucose intolerance with an onset or first recognition during pregnancy, is related to the pancreatic beta-cell dysfunction or the delayed response of the beta cells to the glycemic levels and has marked insulin resistance secondary to placental hormonal release. ⁶ The human placental lactogen is a hormone released by the placenta and induces important metabolic changes during pregnancy to support fetal nutrition. It is also capable of provoking alterations and modifications in the insulin receptors. In gestational diabetes mellitus, maternal high glucose levels cross the placenta and produce fetal hyperglycemia. The fetal pancreas gets stimulated in response to the hyperglycemia, and insulin anabolic properties cause fetal tissues to grow at an increased rate, resulting in increased size and weight of the fetus (macrosomia).

Although gestational diabetes mellitus can occur anytime, it is usually diagnosed during the second and third trimesters of pregnancy. Women with GDM have an increased risk of developing type 2 diabetes mellitus in the future. In addition, a pregnant woman who has advanced maternal age, obesity, excessive gestational weight gain, history of congenital anomalies in previous pregnancies, stillbirth, or a family history of diabetes is at risk for developing GDM. ⁷

Gestational diabetes mellitus can be classified into two groups⁶; managed without medication and responsive to nutritional therapy, namely diet-controlled gestational diabetes (A1GDM), and gestational diabetes managed with medication to achieve adequate glycemic control (A2GDM).

A woman’s diagnosis of gestational diabetes mellitus can be complicated by hypertension, preeclampsia, and hydramnios, and may also lead to increased incidences of cesarean sections due to macrosomia of the fetus, and congenital anomalies. Even after birth, infants with macrosomia may be diagnosed with respiratory distress syndrome, and subsequent childhood and adolescent obesity. Risk factors for gestational diabetes mellitus include ⁵:

  • A first degree relative with diabetes mellitus
  • Abnormal oral glucose tolerance test
  • Any significant marker of insulin resistance (acanthosis nigricans)
  • Decreased physical activity
  • Hemoglobin A1C greater than 5.7
  • Increased body weight (a body mass index greater than 25)
  • Low HDL
  • Past medical history of cardiovascular diseases
  • Polycystic ovarian syndrome
  • Prior history of gestational diabetes or a newborn with macrosomia, or metabolic comorbidities like hypertension
  • Triglycerides greater than 250

The 50 g 1-hour oral glucose tolerance test is a reliable method of a screening for gestational diabetes, and it is used by approximately 95% of obstetricians as a method for screening GDM during pregnancy.

Mature Onset Diabetes of the Young

Mature onset diabetes of the young (MODY) is a heterogeneous disorder that is usually diagnosed in individuals under the age of 40.³ It is the most common form of monogenic diabetes and exhibits autosomal dominant transmission. Mature onset diabetes of the young is a non-ketotic disorder, and people with it do not have pancreatic autoantibodies, but they do have beta-cell insulin secretion dysfunction that is caused by a single gene mutation. It is caused by defects in pancreatic islet cell development, resulting in impaired insulin secretion. People with MODY can sometimes be mistaken for having either T1DM or T2DM. Recognizing and understanding MODY is important because it has autosomal dominant traits, and because certain genetic subtypes respond differently to treatment and have different complication rates. The genetics of MODY are unclear. Some people with mutations will never develop MODY, and others will develop clinical symptoms of MODY but have no identifiable mutation.

Genetic testing for MODY should be done in cases where there is a high index of suspicion that the individual does not have T1DM or T2DM. A diagnosis of MODY may change the understanding of the course of the disease and the optimal treatment, if necessary. Indications for genetic testing include³:

  • Autoantibody negative
  • Children diagnosed with T1DM who are antibody-negative and exhibit elevated C peptide levels
  • Features inconsistent with T1DM or T2DM such as:
    • A large increase in blood sugar in the oral glucose tolerance test
    • Low renal threshold
    • Lower than expected CRP levels
  • High insulin sensitivity
  • Leanness
  • Lower than expected HDL-C
  • People with a strong family history of diabetes mellitus

Molecular genetic testing helps to identify which mutation is involved. The type of testing performed depends on the healthcare provider’s pretest probability of knowing which gene is involved. Should an individual have characteristics of a specific subtype such as typical associated extra-pancreatic features, single-gene testing or serial single-gene testing can be performed. If an individual’s phenotype cannot be differentiated from other subtypes, one may opt to perform a MODY multigene panel which tests for 14 known genes to be associated with MODY. Additionally, if an individual has clinically suggestive features but the mutation cannot be found utilizing conventional testing, the healthcare provider may consider comprehensive genomic testing.

The best treatment for diabetes associated with MODY is based on the gene mutation. Thus, knowing the genetic subtype is important in understanding the treatment and prognosis.

Obtaining the History and Physical

Individuals with diabetes mellitus most commonly present with increased thirst, increased urination, lack of energy and fatigue, bacterial and fungal infections, and delayed wound healing. Some people may also complain of numbness or tingling in hands or feet or blurred vision.

When obtaining an individual’s medical history, questions about family history, social history, surgical history, autoimmune diseases, and insulin-resistance are critical to making the diagnosis of diabetes mellitus. ¹ It often presents asymptomatically, but when symptoms do develop, individuals usually present with polyuria, polydipsia, polyphagia, and weight loss. They may also have poor skin turgor from dehydration and a distinctive fruity odor on their breath resulting from diabetic ketoacidosis. Often, a diabetic ketoacidosis coma is the first clinical presentation in about 30% of people with T1DM.

Symptoms of diabetic ketoacidosis (DKA) can develop rapidly and include¹⁴: 

  • Blurred vision
  • Confusion
  • Drowsiness
  • Frequent urination
  • Fruity-scented breath
  • Hot, dry skin
  • Hyperventilation
  • Increased thirst
  • Lack of appetite
  • Nausea and vomiting
  • Pain in abdomen
  • Shortness of breath or rapid, deep breathing
  • Weakness or fatigue

In addition to the previous mentioned information, obtaining history of prior diabetes education, including monitoring of blood glucose and ketones, proper administration of insulin or oral medication usage, recognition and treatment of hypoglycemia, nutrition, and foot care should also be obtained. The healthcare provider should also pay particular attention to any prior treatments, and history of acute conditions including hypoglycemia and severe episodes of DKA, and chronic conditions, including skin disorders, dental problems, retinopathy, macular edema, neuropathy, kidney disease, cardiovascular disease, peripheral arterial disease, stroke, foot ulcers, or any other diabetic-related complications.

A physical exam should include a funduscopic examination in an individual with diabetes mellitus, which may show hemorrhages in the center of the retina (macula). In diabetic retinopathy, retinal venules may appear dilated or occluded. Blindness can occur because of retinal hemorrhages and macular edema. A healthcare provider should also measure an individual’s height, weight, and blood pressure. The thyroid should be palpated, because people with T1DM are at increased risk of developing autoimmune thyroid disease. ² The skin should also be examined, especially at sites of insulin injection. If lipodystrophy is evident, the healthcare provider should educate the individual on the importance of rotating insulin injection sites. The skin should also be checked for acanthosis nigricans, which are hyperpigmented, velvety patches on the skin of the neck, axillary, or inguinal folds. The heart, chest, and abdomen should also be assessed.  A foot exam should also be performed to examine pedal pulses, foot deformities, pre-ulcerative lesions, ulcerations, callus, and onychomycosis, and peripheral neuropathy. 

As with T1DM and T2DM, the healthcare provider should obtain a thorough medical history from a woman with GDM. When obtaining the health history of a woman with gestational diabetes mellitus, any information on past medical obstetric outcomes and family history of diabetes mellitus are important to obtain, in addition to the previous mentioned medical information. The clinical features of gestational diabetes mellitus can be varied, however, having disproportionate weight gain, obesity, and an elevated body mass index can be suggestive features of GDM. A diagnosis is usually made through laboratory screening at 24 to 28 weeks of pregnancy.

Like T1DM, T2DM, and GDM, the healthcare provider should obtain a full medial history of someone with mature onset diabetes of the young. The diabetes diagnosis characteristic of MODY occurs in adolescence or early adulthood, making the details surrounding their diabetes diagnosis of utmost importance. A further personal medical history should include a full review of systems as described with other forms of diabetes mellitus, and an inquiry regarding any known medical problems involving other organ systems should be obtained. In addition, gaining information on family history is vital and provides some of the most useful information. People with MODY have a strong family history of diabetes spanning at least 3 generations. ¹⁰ Details surrounding the diabetes diagnosis for each family member should include the age of onset, their body habitus at diagnosis, and history of insulin use. Information of prior genetic testing in the family can be very helpful.  Some forms of MODY can be associated with extra-beta cell manifestations including renal, hepatic, genitourinary, exocrine pancreatic or intestinal effects. ⁹

Diagnosis

The diagnosis of diabetes mellitus is usually made through a health history that is supported by elevated serum glucose levels (fasting glucose greater than 126 mg/dL, random glucose over 200 mg/dL, or hemoglobin A1C exceeding 6.5%, with or without antibodies to glutamic acid decarboxylase (GAD) and insulin. The types of laboratory tests used to diagnose diabetes mellitus include¹⁴:

Fasting Plasma Glucose (FPG)A blood sample is taken after an 8 hour overnight fast. A fasting plasma glucose (FPG) level of more than 126 mg/dL is consistent with diabetes mellitus.
Two-Hour Oral Glucose Tolerance Test (OGTT)The plasma glucose level is measured before the ingestion of 75 gm of glucose, and 2 hours after it is consumed. Diabetes mellitus is diagnosed if the plasma glucose level in the 2-hour sample is more than 200 mg/dL.
Glycated Hemoglobin (Hb) A1CProvides an average of blood glucose over the previous 2 to 3 months. People with a Hb A1C greater than 6.5% are diagnosed as having diabetes mellitus. 

People exhibiting classic symptoms of hyperglycemia (increased thirst, increased hunger, increased urination) in addition to a random plasma glucose level of more than 200 mg/dL are also considered to have diabetes mellitus. ¹

Pregnant women who have no history of diabetes should be tested for GDM between 24 and 28 weeks of gestation. The American Diabetes Association (ADA) and the American College of Obstetrics and Gynecology (ACOG) recommend using either a 1-step or 2-step approach for diagnosing GDM, including¹:

One-Step Strategy75 gm oral glucose tolerance test (OGTT) is performed after an overnight fast. Blood samples are collected at fasting for 1 hour and 2 hours. Gestational diabetes mellitus is diagnosed if the fasting glucose meets or exceeds 92 mg/dL, the 1-hour serum glucose exceeds 180 mg/dL, or the 2-hour serum glucose exceeds 153 mg/dL.
Two-Step StrategyStep one: Perform a 50-gram glucose challenge test irrespective of the last meal. If the glucose level is greater than or equal to 140mg/dL after 1 hour, proceed to step 2.Step 2: 100 gm glucose OGTT is performed after overnight fasting. GDM is diagnosed if the fasting glucose is greater than 105 mg/dL, 180 mg/dL after 1 hour, 155 mg/dL after 2 hours, or 140 mg/dL after 3 hours. At 4 to 12 weeks post-partum, a woman should have a 75g oral glucose tolerance test to rule out the possibility of the development of type 2 diabetes mellitus.
Treatment and Management

The treatment and management of diabetes is complex and requires an array of interventions for successful disease management. Diabetic education and active engagement are critical in diabetes management. People have better outcomes if they can manage their diet through carbohydrate and caloric restriction, by exercising at least 30 minutes a day, and independently monitoring glucose levels. Lifelong treatment is often necessary to prevent unwanted complications. Ideally, glucose levels should be maintained between 90 and 130 mg/dL and the HbA1c should be less than 7%. ¹ While glucose control is critical, excessively aggressive management may lead to hypoglycemia, which can have adverse or fatal outcomes.

Type 1 Diabetes Mellitus

Since T1DM is a disease primarily due to the absence of insulin, administering insulin daily by injections pump is the mainstay of treatment. To calculate the insulin total daily dose, the individual’s weight in kilograms is multiplied by 0.5 units. In general, 40% to 50% of the total daily dose comprises the individual’s long-acting insulin needs, and the other half approximates the daily short-acting insulin needs. ¹Dosing is modified based on many factors, including diet and physical activity. Adjustments can also be made based on blood glucose monitoring results. If using insulin pump therapy, a continuous infusion of rapid-acting insulin will be used. Individuals should also be taught which foods contain carbohydrates and could benefit from meeting with a dietician.

It is important to note that insulin requirements vary across the lifespan, and under specific circumstances. For example, larger doses of insulin are normally needed during puberty, pregnancy, when steroids are given, and with the development of obesity. Individuals often need less insulin when they are engaged in aerobic exercise and during the honeymoon period, the time period soon after diagnosis when there is a temporary recovery of beta-cell function.

Multiple types of insulin can be used for diabetes management, including¹²:

InsulinOnsetPeakDuration
Rapid Acting Insulin

Humalog (lispro)
Novolog (apart)
Aprida (glulisine)
10-30 minutes30-90 minutes3-5 hours
Short Acing Insulin

Regular Insulin
30 minutes to 1 hour2-4 hours6-8 hours
Humulin 70/30 (combination regular and NPH insulin)

Novolog 70/30 (combination of insulin aspart and insulin aspart protamine)
30-60 minutes   10-20 minutes2-12 hours   2 hours18-24 hours   24hours
Intermediate Acting Insulin
Humulin-N (NPH)
1.5 to 4 hours4-10 hours12-18 hours
Long-Acting Insulin

Lantus (glargine)

Xultophy (degludec)

Levemir (detemir)
Lantus: 1.5 hours

Xultophy: 30-90 minutes

Levemir: 1-2 hours
Lantus: 6 hours

Xultophy: no peak

Levemir: 6-8 hours
Lantus: 20-24 hours

Xultophy: 24 hours

Levemir: up to 42 hours

Type 2 Diabetes Mellitus

In T2DM, diet and exercise may initially be adequate treatments, however in uncontrolled or advanced disease, insulin administration may be required. Other therapies may target insulin sensitivity or increase insulin secretion by the pancreas. The specific subclasses for drugs include¹³:

MedicationMechanism of ActionSide Effects
Biguanides

Fortamet
Glucophage
Glucophage XR
Glumetza
Riomet
(Metformin)  
Prevent the production of glucose in the liver, improves insulin sensitivity and reduces the amount of sugar absorbed by the intestines.  Nausea, upset stomach, and diarrhea, lactic acidosis
Sulfonylureas  

DiaBeta, Glynase, Micronase (glyburinde, glibenclamide)  

Amaryl (glimepiride)  

Diabinese (chlorpropamide)  

Glucotrol (glipizide)  

Tolinase (tolazamide)  

Orinase, Tol-Tab (tolbutamide)  
Work by increasing the release of insulin from the pancreas.Signs of low blood sugar such as sweating, dizziness, confusion, or nervousness Hunger Weight gain Skin reactions Upset stomach Dark-colored urine  
Meglitinides

Prandin (repaglinide)  

Starlix (nateglinide)  
Work by stimulating the pancreas to release insulin in response to a meal.Low blood sugar symptoms including sweating, shakiness, lightheadedness, and confusion.  
Alpha-Glucosidase Inhibitors

Glyset (miglitol)  

Precose (acarbose)
Work by slowing the digestion of carbohydrates and delaying glucose absorption.Flatulence, diarrhea, low blood sugar symptoms including sweating, shakiness, lightheadedness, and confusion.  
Thiazolidinediones

Actos (pioglitazone)  

Avandia (rosiglitazone)  
Improve sensitivity to insulin by reducing circulating fat concentrations.Anemia, swelling, heart failure, increased LDL, low blood sugar symptoms including sweating, shakiness, lightheadedness, and confusion.  
Glucagonlike-Peptide-1 Agonist

Trulicity (dulaglutide)

Bydureon, Byetta (exenatide)

Ozempic, Rybelsus (semaglutide)  

Victoza (liraglutide)  

Adlyxin (lixisenatide)  
Injectable medications that work by stimulating insulin secretion after meal consumption, decreasing glucagon secretion, decreasing gastric emptying, and decreasing appetite.Nausea, vomiting, constipation, and diarrhea, local skin reactions at injection sites.
Dipeptidyl Peptidase IV Inhibitors (DPP-4)

Januvia (sitagliptin)  

Onglyza (saxagliptin)  

Tradjenta (linagliptin)  

Nesina, Vipidia (alogliptin)
Work by slowing the inactivation and degradation of GLP-1, a hormone involved in glucose removal from the gut.Headache, urinary tract infection, arthralgia, pancreatitis, low risk for hypoglycemia
Amylinomimetics

Symlin (pramlintide)
Injectable medication that is used with insulin to lower blood sugar by slowing gastric emptying, and reducing glucose absorptionNausea, low blood sugar symptoms including sweating, shakiness, lightheadedness, and confusion.  
Sodium-Glucose Transporter-2 (SGLT-2) Inhibitors

Jardiance (empagliflozin)  

Invokana (canagliflozin)  

Farxiga (dapaglifozin)  

Steglatro (ertugliflozin)
Work by reducing the renal absorption of renal glucoseLow risk of hypoglycemia when used as monotherapy.  Dehydration and genital and urinary tract infections because of the increase in urinary glucose.

Gestational Diabetes Mellitus

Gestational diabetes mellitus management usually begins with nonpharmacologic measurements like diet modifications, exercise, and glucose monitoring. The American Diabetes Association recommends nutritional counseling by a registered dietitian and development of a personalized plan based on the body mass index (BMI). The amount of exercise recommended for women with GDM is 30 minutes of moderate-intensity aerobic exercise at least five days a week or a minimum of 150 minutes per week. ⁶If glucose control is not obtained despite strict adherence to diet and exercise, pharmacologic treatment, namely insulin, is a first line of treatment for GDM to help achieve adequate glucose control. During the first trimester, the total daily insulin requirement is 0.7 units/kg/day, followed by 0.8 units/kg/day in the second semester, and 0.9 to 1.0 units/kg/day in th third semester.

The total daily dose of insulin should be divided into two halves; one half given as basal insulin at bedtime, and the other half divided between three meals and given as rapid-acting, or regular insulin before meals. Humalog and Novolog are short acting insulins that are approved for use in pregnancy, and Levemir, a long-acting insulin, is also approved for use in pregnancy.

Diabetes Complications

One of the most emergent complications of diabetes mellitus is diabetic ketoacidosis (DKA). This condition usually occurs in people diagnosed with T1DM, and results from inadequate insulin dosing, missed insulin doses, or chronic infections. In DKA, the lack of insulin causes tissues to not be able to obtain glucose from the bloodstream. ² To substitute as an energy source, lipids are metabolized into ketones, which causes systemic acidosis. The combination of hyperglycemia and ketosis causes acidemia, diuresis, and vomiting, which can lead to life threatening dehydration and electrolyte abnormalities. Hyperosmolar hyperglycemic syndrome (HHS) is another emergent condition that is most often associated with T2DM. It presents similarly to DKA with dry mouth, elevated blood glucose, excessive thirst, polyuria, tachycardia, and tachypnea. However, unlike DKA, HHS usually does not present with excessive urinary ketones because insulin is still produced by pancreatic beta cells. The treatment for DKA and HHS involves insulin administration and aggressive intravenous hydration. Careful management of electrolytes, particularly potassium, is critical in the management of both emergent conditions. ²

American Diabetes Association Considerations

Regular screenings are necessary for diabetes mellitus because of microvascular, macrovascular, and neuropathic complications. Microvascular and macrovascular complications vary according to the degree and the duration of poorly controlled diabetes mellitus, and include nephropathy, retinopathy, and atherosclerotic cardiovascular disease events, especially if it is associated with other comorbidities like dyslipidemia and hypertension. ⁸

Regular diabetic retinal exams should be performed by qualified healthcare professionals to assess for diabetic retinopathy, because diabetes is a common cause of blindness in adults between the ages of 20 and 75.  Neurologic examinations can identify individuals with neuropathy at risk for amputation. In addition, healthcare professionals should also recommend people with diabetes mellitus perform daily foot inspections to identify foot lesions that may go unnoticed due to neuropathy. If neuropathy is present, low-dose tricyclic antidepressants, duloxetine, anticonvulsants, topical capsaicin, and pain medications may be necessary to manage neuropathic pain. Urine microalbumin testing can also detect early renal changes from diabetes with albuminuria greater than 30mg/g creatinine. Renal disease is a significant cause of morbidity and mortality in people with diabetes and is the leading contributor to end-stage renal disease (ESRD) resulting in dialysis and kidney transplant. 

The American Diabetes Association (ADA) also recommends regular blood pressure monitoring for diabetics, with the goal of systolic blood pressure being less than 130 mmHg and the diastolic blood pressure being less than 85 mmHg. Pharmacologic therapy for hypertensive diabetics usually involves angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), diuretics, beta-blockers (BB), and/or calcium channel blockers (CCB). In addition to blood pressure monitoring, 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 is present and less than 70 mg/dl if atherosclerotic cardiovascular disease is present. Statins are the first-line treatment for the management of dyslipidemia in diabetics. ¹The ADA suggests that low dose aspirin also be considered for people with diabetes mellitus who are at risk for cardiovascular events; however, the role of aspirin in reducing cardiovascular events in diabetic remains unclear. ⁸ 

Blood glucose readings should be monitored throughout the day. People with diabetes mellitus should check their blood glucose before meals, 2 to 3 hours after meals (when dosages are being adjusted), before bedtime, and when they suspect hypoglycemia.  People with diabetes mellitus should be educated on the symptoms of hypoglycemia, including diaphoresis, tachycardia, lightheadedness, confusion, visual changes, and tremors.  Glucagon should be prescribed for emergency use for whenever an individual with diabetes mellitus has a severe hypoglycemic episode and is unable to consume carbohydrates by mouth.

Health Screening Considerations

People older than 40 years of age should be screened for diabetes mellitus at least every three years. More frequent screening is recommended for individuals with additional risk factors for diabetes, including: 

  • Certain races/ethnicities (Native American, African American, Hispanic, Asian American, or Pacific Islander)
  • Conditions associated with insulin resistance, such as acanthosis nigricans
  • Have previously birthed an infant weighing 4000 grams or more
  • HDL level less than 35mg/dL
  • Hemoglobin A1c greater than 5.7%
  • History of cardiovascular disease or hypertension
  • Immediate relative with diabetes mellitus
  • Impaired fasting glucose
  • Impaired glucose tolerance test
  • Other clinical conditions associated with insulin resistance
  • Overweight or obese with a BMI greater than or equal to 25 kg/m2 
  • Physical inactivity
  • Previous gestational diabetes or hypertension
  • Triglyceride level greater than 250 mg/dL
  • Women with polycystic ovarian syndrome

Women diagnosed with gestational diabetes mellitus (GDM) should have lifelong testing at least every three years. Everyone else should begin testing at age 40, and if results are normal, they should be tested at a minimum of every 3 years. The same tests are used to screen for and diagnose diabetes. These tests also detect individuals with prediabetes.

Conclusion

Persistent hyperglycemia in uncontrolled diabetes mellitus can cause several complications, both acute and chronic. Diabetes mellitus is one of the leading causes of cardiovascular disease, blindness, kidney failure, and amputation of lower limbs. Controlling glucose levels and treating high blood pressure, high cholesterol, and exercising regularly are of great importance in reducing the risk of complications. Acute complications include hypoglycemia, diabetic ketoacidosis, hyperglycemic hyperosmolar state, and hyperglycemic diabetic coma. Chronic microvascular complications are nephropathy and retinopathy, whereas chronic macrovascular complications are coronary artery disease, peripheral artery disease, and cerebrovascular disease. Healthcare professionals should educate individuals with diabetes on the symptoms of hypoglycemia, including confusion, sweating, tremors, and tachycardia , and how to treat it by consuming 15-20 grams of carbohydrates. The HbA1c should also be evaluated every 3 to 6 months. Having good management of diabetes management reduces the risk of complications, morbidity, and mortality that is associated with the disease.

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