Diabetes mellitus (Type 1): Clinical sciences

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Diabetes mellitus (Type 1): Clinical sciences

Block 2

Block 2

Pentose phosphate pathway
Diabetes mellitus
Disorders of carbohydrate metabolism: Pathology review
Amino acid metabolism
Disorders of amino acid metabolism: Pathology review
Dyslipidemias: Pathology review
Drug misuse, intoxication and withdrawal: Alcohol: Pathology review
Diabetes mellitus (Type 2): Clinical sciences
Fatty acid synthesis
Wernicke-Korsakoff syndrome
Alcohol-induced hepatitis: Clinical sciences
Diabetes mellitus: Clinical
Diabetes mellitus (Type 1): Clinical sciences
Fetal alcohol syndrome
Diabetes mellitus: Pathology review
Alcohol use disorder
Alcohol-associated liver disease
Enterococcus
Staphylococcus epidermidis
Mycobacterium tuberculosis (Tuberculosis)
Neisseria gonorrhoeae
Corynebacterium diphtheriae (Diphtheria)
Water-soluble vitamin deficiency and toxicity: B1-B7: Pathology review
Water-soluble vitamin deficiency and toxicity: B9, B12 and vitamin C: Pathology review
Vitamin D
Klebsiella pneumoniae
Vitamin B12 deficiency
Folate (Vitamin B9) deficiency
Streptococcus viridans
Clostridium perfringens
Chlamydia trachomatis
Staphylococcus saprophyticus
Staphylococcus aureus
Mycobacterium leprae
Clostridium botulinum (Botulism)
Bacillus anthracis (Anthrax)
Actinomyces israelii
Clostridium tetani (Tetanus)
Streptococcus agalactiae (Group B Strep)
Bacillus cereus (Food poisoning)
Listeria monocytogenes
Pseudomonas aeruginosa
Nocardia
Haemophilus influenzae
Neisseria meningitidis
Treponema pallidum (Syphilis)
Human papillomavirus
Herpes simplex virus
Neuraminidase inhibitors
Human herpesvirus 6 (Roseola)
Borrelia burgdorferi (Lyme disease)
Adenovirus
Yersinia pestis (Plague)
Rhinovirus
Rubella virus
Influenza virus
Mumps virus
Measles virus
Human herpesvirus 8 (Kaposi sarcoma)
Herpesvirus medications
Plasmodium species (Malaria)
Coxiella burnetii (Q fever)
Ehrlichia and Anaplasma
Bartonella henselae (Cat-scratch disease and Bacillary angiomatosis)
Rickettsia rickettsii (Rocky Mountain spotted fever) and other Rickettsia species
Anthelmintic medications
Antimalarials
Trypanosoma cruzi (Chagas disease)
Francisella tularensis (Tularemia)
Candida
Anti-mite and louse medications
Miscellaneous antifungal medications
Azoles
Cytokines
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Hyper IgM syndrome
Leukocyte adhesion deficiency
Chronic granulomatous disease
X-linked agammaglobulinemia
Wound healing
Complement deficiency
Inflammation
Pulmonary corticosteroids and mast cell inhibitors
Selective immunoglobulin A deficiency
Necrosis and apoptosis
Ischemia
Wiskott-Aldrich syndrome
Immunodeficiencies: Clinical
Non-corticosteroid immunosuppressants and immunotherapies
Intrinsic hemolytic normocytic anemia: Pathology review
Heme synthesis disorders: Pathology review
Blood groups and transfusions
Macrocytic anemia: Pathology review
Cytomegalovirus infection after transplant (NORD)
Glucocorticoids
Blood products and transfusion: Clinical
Acute intermittent porphyria
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Aplastic anemia
Sideroblastic anemia
Microcytic anemia: Pathology review
Erythropoietin
Post-transplant lymphoproliferative disorders (NORD)
Platelet disorders: Pathology review
Thrombotic thrombocytopenic purpura
Neonatal jaundice: Clinical
Jaundice: Clinical
Mixed platelet and coagulation disorders: Pathology review
Von Willebrand disease
Immune thrombocytopenia
Hemolytic-uremic syndrome
Extrinsic hemolytic normocytic anemia: Pathology review
Jaundice
Iron deficiency anemia
Anemia: Clinical
Graft-versus-host disease
Iron deficiency anemia: Clinical sciences
Autoimmune hemolytic anemia
Severe chronic neutropenia (NORD)
Anemia of chronic disease: Year of the Zebra
Jaundice: Pathology review
Blood transfusion reactions and transplant rejection: Pathology review
Anemia of chronic disease
Non-hemolytic normocytic anemia: Pathology review
Antimetabolites: Sulfonamides and trimethoprim
Cell wall synthesis inhibitors: Cephalosporins
DNA synthesis inhibitors: Fluoroquinolones
Protein synthesis inhibitors: Aminoglycosides
Nucleotide metabolism
Adenosine deaminase deficiency
Purine and pyrimidine synthesis and metabolism disorders: Pathology review
Gout
Gout and pseudogout: Pathology review
Lesch-Nyhan syndrome
Gout: Clinical sciences
Oncogenes and tumor suppressor genes
Anti-tumor antibiotics
Blood histology
DNA synthesis inhibitors: Metronidazole
Deep vein thrombosis
Disseminated intravascular coagulation
Factor V Leiden
Protein C deficiency
Protein S deficiency
Miscellaneous cell wall synthesis inhibitors
Miscellaneous protein synthesis inhibitors
Protein synthesis inhibitors: Tetracyclines
Antithrombin III deficiency
Heparin-induced thrombocytopenia
Antiphospholipid syndrome
Hemophilia
Hemophilia: Year of the Zebra
Protease inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs)
Hepatitis medications
HIV and AIDS: Pathology review
Thrombosis syndromes (hypercoagulability): Pathology review
Mechanisms of antibiotic resistance
Coagulation disorders: Pathology review
Integrase and entry inhibitors
Leukemias: Pathology review
Myeloproliferative disorders: Pathology review
Lymphomas: Pathology review
Chronic leukemia
Acute leukemia
Non-Hodgkin lymphoma
Polycythemia vera (NORD)
Myelodysplastic syndromes
Hodgkin lymphoma
Essential thrombocythemia (NORD)
Waldenstrom macroglobulinemia
Multiple myeloma: Clinical sciences
Mastocytosis (NORD)
Plasma cell disorders: Pathology review
Plasma cell disorders: Clinical
Spleen histology
Myelofibrosis (NORD)
Lymphoma: Clinical
Varicella zoster virus
Coxsackievirus
Congenital TORCH infections: Pathology review
Streptococcus pyogenes (Group A Strep)
Lyme disease: Clinical sciences
Cortisol
Hematopoietic medications
Parvovirus B19
HIV (AIDS)
Zika virus

Decision-Making Tree

Transcript

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Diabetes mellitus is a chronic condition where tissue cells can’t properly absorb and use glucose, so it stays and builds up in the blood. Normally, pancreatic islet beta cells produce insulin, which acts on insulin receptors on tissue cells to promote uptake and storage of glucose, amino acids, and triglycerides, as well as stimulate glycolysis, protein synthesis, and lipogenesis.

Now, there are two types of diabetes, type 1 and type 2. In type 1 diabetes, there’s autoimmune destruction of the pancreatic islet beta cells, resulting in severe insulin deficiency and, ultimately, hyperglycemia. This is in contrast to type 2 diabetes mellitus, where the pancreatic islet beta cells stop properly responding to stimulation to produce insulin, combined with insulin resistance, meaning that the tissue cells aren’t able to appropriately respond to the little insulin that’s still being produced.

In either disease type, the resulting hyperglycemia can cause clinical manifestations ranging from prediabetes and diabetes mellitus, to severe life-threatening conditions, like diabetic ketoacidosis, or DKA, most commonly seen in patients with type 1 diabetes, and, hyperosmolar hyperglycemic state, or HHS, most commonly in type 2 diabetes.

Now, if you suspect type 1 diabetes mellitus, you should first perform an ABCDE assessment to determine if your patient is unstable or stable. If the patient is unstable, stabilize the airway, breathing, and circulation. This means that you might need to intubate the patient. Next, obtain IV access and, if your patient is hypotensive, start IV fluids for volume resuscitation. Finally, put your patient on continuous vital sign monitoring, such as pulse oximetry, blood pressure, and heart rate.

Next, you want to assess for DKA or, less frequently, HHS. Obtain a focused history and physical exam, and order labs, such as point-of-care blood glucose, serum osmolality, BMP, urinalysis, hemoglobin A1c, as well as ABG or VBG.

Patients typically present with fatigue, headache, or dry mouth, polyuria, and polydipsia. They may also be so confused they cannot give an accurate history, so be sure to speak with caretakers and review the chart thoroughly to get an accurate history. Your patient may also have had a precipitating illness or infection, or have a known history of diabetes mellitus with or without disruption to their diabetes treatment plan.

On the other hand, physical exam might reveal tachypnea, tachycardia, and hypotension in a confused, somnolent patient. The mucous membranes are often dry. Let’s start by using our labs to help us distinguish between DKA and HSS. In HHS, lab results typically reveal a significantly elevated random blood glucose, more so than DKA, often exceeding 600 milligrams per deciliter. BMP may reveal hyponatremia and hypokalemia, as well as elevated BUN and creatinine. The serum osmolality is high, usually greater than 320 milliosmoles per kilogram. Finally, there will be an elevated hemoglobin A1c.

On the other hand, DKA, lab results reveal a significantly elevated random blood glucose, exceeding 250 milligrams per deciliter. BMP may reveal hyponatremia and hypokalemia, as well as elevated BUN and creatinine. There is a normal serum osmolality. Finally, there will be an elevated hemoglobin A1c, and the ABG or VBG will confirm elevated anion gap metabolic acidosis. You may also see decreased bicarbonate, hinting at a metabolic acidosis. Urinalysis will show ketones.

In either case, HHS or DKA, management of these individuals includes IV fluid resuscitation to correct dehydration and hyperosmolality, as well as electrolyte repletion. Additionally, you can start an IV insulin drip, if indicated, and carefully monitor potassium levels. Don’t forget to treat any underlying or precipitating causes!

Now that we're done with unstable patients, let’s go back to the ABCDE assessment and discuss stable ones. If your patient is stable, first obtain a focused history and physical examination. Your patient might report unintentional weight loss, polydipsia, polyuria, and blurred vision, while family history often reveals autoimmune disorders such as thyroid disease or celiac disease.

On physical exam, you may notice oral thrush or dry mucous membranes. At this point, you should suspect diabetes mellitus, and proceed with labs, such as hemoglobin A1c, a fasting blood glucose, a 2-hour oral glucose tolerance test, or OGTT, and a random blood glucose test. Keep in mind that not all patients require an OGTT; this is often used when the other values are inconclusive or unclear in making a diagnosis.

Now let’s look at lab results to determine a diagnosis. Now, if the hemoglobin A1c is less than 5.7%, fasting blood glucose is less than 100 mg/dL, blood glucose after the 2-hour OGTT is less than 140 mg/dL, and random blood glucose is less than 200 mg/dL, then you should consider an alternative diagnosis.

On the other hand, you should consider prediabetes if the hemoglobin A1c is between 5.7 and 6.5%, fasting blood glucose is between 100 and 126 mg/dL, or blood glucose after the 2-hour OGTT is between 140 and 199, and a random blood glucose is under 200 mg/dL. Keep in mind that prediabetes typically precedes type 2 diabetes mellitus, and only rarely precedes type 1.

Sources

  1. "American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update" Endocr Pract (2022)
  2. "The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)" Diabetes Care (2021)
  3. "Type 1 diabetes" Lancet (2018)
  4. "Harrison's Principles of Internal Medicine, 21e." McGraw Hill (2022)