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Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance, as well as relative insulin deficiency. Genetically determined causes of diabetes (e.g., maturity-onset diabetes of the young and late autoimmune diabetes in adults) are being increasingly recognized, but they make up a small portion of cases. There is no definitive cure for DM. The objective of management is the prevention of complications, which may include coronary artery disease, CKD, retinopathy, and neuropathy. Long-term monitoring and maintenance of optimal blood glucose levels are key to preventing complications. Treatment is specific to the type of diabetes, with glycemic control as the goal in all types; insulin replacement is essential in type 1, and a healthy diet, lifestyle changes, and medications are important in type 2.

Last updated: September 15, 2024 810 views

Type 1 VS Type 2
Features Type 1 DM Type 2 DM
Genetics
  • Positive HLA-DR4 and HLA-DR3 association
  • Weak familial predisposition
  • Polygenic
    • Negative HLA association
    • Strong familial predisposition
    • Polygenic
    Pathogenesis
    • Autoimmune destruction of β cells → absolute insulin deficiency
    • Insulin resistance, progressive destruction of pancreatic β-cells
      Association with obesity
      • No
      • Yes
      Onset
      • Childhood onset typically < 20 years but can occur at any age
      • Peaks at age 4–6 years and 10–14 years
      • Gradual; usually at age > 40 years
      C-peptide (insulin)
      • Decreased or absent
      • Initially elevated, decreased in advanced stage
      Glucose intolerance
      • Severe
      • Mild to moderate
      Insulin sensitivity
      • High
      • Low
      Risk of ketoacidosis
      • High
      • Low
      β-cells in the islets
      • Decreased
      • Variable (with amyloid deposits)
      Classic symptoms (i.e., polyuria, polydipsia, polyphagia, weight loss)
      • Common
      • Sometimes
      Histology
      • Leukocyte infiltration of islets
      • Amyloid polypeptide (IAPP) deposits in islets
      Treatment
      • Insulin therapy
      • Lifestyle changes
      • Oral antidiabetic drugs
      • Insulin therapy

      • Autoimmune destruction of pancreatic β cells by glutamic acid decarboxylase (GAD) antibodies leading to insulin deficiency
      • Typically presents in children (4-6 & 10-14) or adults < 25 years of age
      • Genetic predisposition
        • HLA-linked (HLA-DQ, HLA-DR3, and HLA-DR4)
      • Associated with other autoimmune conditions
      • Autoantibodies (not always detectable):
        • GAD autoantibodies:
          • Target insulin-producing pancreatic β cells
          • Autoimmune destruction of 80%–90% of cells
          • Leads to insulin deficiency and hyperglycemia.
      • Pathophysiology:
        • Genetic susceptibility and environmental triggers; (often associated with previous viral infection) → autoimmune response with production of autoantibodies, e.g., anti-glutamic acid decarboxylase antibody (anti-GAD), anti-islet cell cytoplasmic antibody (anti-ICA) → progressive destruction of β cells in the pancreatic islets → absolute insulin deficiency → decreased glucose uptake in the tissues
      Type 1 diabetes mellitus ملخص
      Pathophysiology
      • Autoimmune destruction of pancreatic beta cells → low/absent insulin → hyperglycemia
      Epidemiology
      • Peak onset at ages 4-6 & 10-14
      • Often thin habitus but up to 25% are overweight
      Clinical
      manifestations
      • Polyuria, enuresis (osmotic diuresis)
      • Polydipsia (hypovolemia & hyperosmolality)
      • Weight loss & fatigue (ketosis from impaired glucose use)
      • DKA: severe symptoms + abdominal pain, vomiting, fruity-smelling breath
      Diagnosis
      • Fasting glucose ≥126 mg/dL
      • Oral glucose tolerance test or random glucose ≥200 mg/dL
      • Hemoglobin A1c ≥6.5%
      DKA = diabetic ketoacidosis.

      • Caused by insulin resistance → يكون الجسم مقاوم لعمل الأنسولين
      • Relative insulin deficiency → يوجد انسلوين لكن بكمية غير كافية
      • Strong family history/genetic component
        • A child with one diabetic parent has a ∼ 40% lifetime risk of developing T2DM.
        • The concordance between monozygotic twins is significant, with some studies finding rates of > 75%.
      • Adult onset typically > 40 years (Insulin production decreases with age)
      • Gender: ♂ > ♀
      • Risk factors
        • Positive family history
        • Physical inactivity
        • History of cardiovascular disease
        • Conditions associated with insulin resistance : e.g., severe obesity and high-calorie diet
        • Hypertension  
        • Dyslipidemia  
        • History of gestational diabetes
      • Pathophysiology
        • Peripheral insulin resistance
          • Central obesity → increased plasma levels of free fatty acids → impaired insulin-dependent glucose uptake into hepatocytes, myocytes, and adipocytes
        • Pancreatic β cell dysfunction:

      Type 1

      1. DKA
        Type 1 DM often presents urgently with DKA :
        • Usually precipitated by a “tipping” event (e.g., viral illness, trauma, emotional stress)
        • Depressed mental status
        • Abdominal pain
        • Vomiting
        • Fruity “acetone” breath
      2. Hyperglycemia:
        Type 1 DM can also present with classic symptoms of hyperglycemia:
        • Polydipsia
        • Polyphagia
        • Polyuria (can present as enuresis and nocturia in children)
        • Weight loss
        • Blurred vision

       

      Type 2

      Type 2 DM has a gradual onset, initially remaining asymptomatic for several years:

      1. High glucose levels often detected on screening tests before symptoms appear
      2. Can present with classic symptoms of hyperglycemia, as in type 1 DM
      3. Sometimes diagnosed with hyperosmolar hyperglycemic state or signs of long-term complications before the diagnosis is known
      4. Rarely, DKA present
      5. Nonspecific symptoms due to hyperglycemia:
        • Fatigue
        • Malaise
        • Anorexia
        • Amenorrhea
        • Erectile dysfunction
        • Headache
        • Blurred vision
        • Dehydration
      6. Skin manifestations:
        • Recurrent cellulitis or fungal infections
        • Poor or delayed wound healing
        • Generalized pruritus
        • Acanthosis nigricans: hyperpigmented velvet-like plaques on the skin of the axilla or neck or between the digits

      Diagnosis of DM can be achieved using any of the 2 following criteria:

      1. Random glucose ≥ 200 mg/dL along with classic symptoms (polyuria, polydipsia, and polyphagia)
        يعني لازم يكون مع المريض أعراض السكري بالإضافة لنتيجة الفحص
      2. OR ≥ 2 abnormal test results for hyperglycemia in asymptomatic individuals
        فحصين أو أكثر من الفحوصات التالية يجب أن تكون غير طبيعية
      Interpretation of diagnostic tests
        Fasting plasma glucose 2-hour glucose value after OGTT HbA1c
      Random blood sugar

       

       

      Classic hyperglycemic symptoms plus a random plasma glucose > 200 mg/dL
      Diabetes mellitus

      ≥ 126 mg/dL (≥ 7.0 mmol/L)

      ≥ 200 mg/dL (≥ 11.1 mmol/L)

      ≥ 6.5%
      Prediabetes

      100–125 mg/dL (5.6–6.9 mmol/L) = impaired fasting glucose

      140–199 mg/dL (7.8–11.0 mmol/L) = impaired glucose tolerance

      5.7–6.4%
      Normal

      < 100 mg/dL (< 5.6 mmol/L)

      < 140 mg/dL (< 7.8 mmol/L)

      < 5.7%

       

      الملخص: إما أن يكون المريض لديه أعراض السكري ويكون فحص الــ RBS أكثر من 200 أو أن يكون لديه نتيجة فحصين مرتفعين من الفحوصات الموجودة في الجدول

      ملاحظة: يمكن أيضاً إجراء بعض الفحوصات الأخرى والتي تساعد على معرفة أي نوع من أنواع السكري يوجد لدى المريض
      مثل

      C-peptide, Antibody testing

      No definitive cure exists for diabetes. Management centers around correcting high blood glucose with insulin (type 1) or oral medication (type 2), avoiding low blood glucose , and treating the clinical effects of chronic hyperglycemia.

      Multidisciplinary approach

      Initial management is with patient education and support.

      • Lifestyle modifications (Balanced diet, Regular exercise, Weight loss with reduced caloric intake if overweight or obese)
      • Smoking cessation to decrease the risk of comorbid complications
      • Stress management
      • Pharmacologic therapies to meet individualized glycemic goals:
        • Choice of medication depends on the level of HbA1c at the time of diagnosis
        • Need to be adjusted with CKD or intolerance

      Oral medications

      Classes of oral medications used to treat insulin -resistant diabetes (usually type 2):

      • Biguanide ( metformin ): 1st-line drug of choice
      • Sodium – glucose cotransporter-2 (SGLT-2) inhibitors: demonstrated benefit for cardiorenal outcomes, especially for heart failure hospitalization , risk of kidney disease progression, and mortality
      • Dipeptidyl peptidase-4 (DPP-4) inhibitors
      • Sulfonylureas
      • Thiazolidinediones

      Insulin therapy

      Insulin therapy is used to treat type 1 DM and sometimes type 2 DM when oral medications alone are no longer sufficient.

      • Rapid-acting insulins: start working in 10–15 minutes
        • Glulisine 
        • Lispro 
        • Aspart
      • Short-acting insulin :
        • Starts working in 30 minutes, peaks at 2–3 hours
        • Rapid-acting and short-acting insulins are used in combination with longer-acting insulins or in insulin pumps for type 1 diabetes
      • Long-acting insulin : last 12–24 hours
        • NPH
        • Glargine
        • Detemir

      Noninsulin injectable therapies

      • Glucagon-like peptide-1 (GLP-1) receptor agonists: preferred in patients who already have cardiac or renal comorbidities :
        • Exenatide
        • Dulaglutide
        • Liraglutide 
        • Semaglutide  — also available in tablet form (Rybelsus)
      • Amylin mimetic pramlintide (not often used):
        • Suppresses plasma glucagon secretion
        • Slows gastric emptying
        • Promotes satiety

      Special considerations with insulin use

      The dawn phenomenon:

      • Early in the morning, the effect of exogenous insulin injected the day before disappears.
      • Insulin-antagonistic hormones increase physiologically in the morning.
      • May cause morning hyperglycemia

      The Somogyi effect:

      • Rebound morning hyperglycemia
      • Response to hypoglycemia during the night after excessive amounts of exogenous insulin the evening before