Understanding Diabetes Mellitus

Diabetes Mellitus Definition

• Group of metabolic diseases featuring hyperglycemia
• Hyperglycemia is a product of ineffective insulin secretion, action, or both
• Chronic hyperglycemia links to lasting harm and diminished performance in eyes, kidneys, nerves, heart, and blood vessels
• Insulin and glucagon interplay to regulate blood glucose

High Blood Glucose Levels

• Insulin is prompted by Glucose, GLP-1, and vagal tone
• Insulin fosters glucose uptake by muscle and adipose tissues
• Insulin is anabolic, synthesizing carbs, proteins, lipids, and nucleic acids
• Insulin encourages glycogen formation (glycogenesis)
• Insulin impedes glucose production (gluconeogenesis)
• Lipogenesis increases and lipolysis decreases as a result of insulin
• Insulin enriches metabolic substrates in the CNS, offering neuroprotection
• Insulin controls appetite

Low Blood Glucose Levels

• Glucagon promotes glycogen breakdown (glycogenolysis)

Insulin Insufficiency

• Absolute: Genetic disorders, autoimmune damage to β-cells, viral damage (mumps, Coxsackie B4), toxic influence on β-cells, pancreatic gland diseases
• Relative: Issues with β-cells, insulin transport defects, receptor insensitivity

Clinical Manifestations of Diabetes Mellitus

• Polyuria occurs when blood glucose exceeds 180 mg/dl, leading to glucosuria
• Polydipsia results from more water excretion and water intake
• Polyphagia is linked to increased catabolic activity and lack of energy
• Pruritus (itching) of the skin may occur
• Paraesthesia involves tingling, burning, prickling, or numbness (pins and needles)

Further effects of diabetes mellitus

• Loss of weight and energy (calories) occurs as glucose is shed in urine
• Water loss adds to weight loss
• Increased breakdown of proteins and amino acid movement results in protein catabolism and loss of muscle mass
• Decreased glucose use and electrolyte abnormalities are the cause of Fatigue and weakness
• High lipolysis yields FFA release, metabolized into ketones, causing Acidosis
• Blurred vision is triggered by loss of clearness of vision

Diabetes Classification

• Type 1 diabetes stems from autoimmune β-cell destruction, often causing absolute insulin deficiency (including LADA), with common onset in childhood and early adulthood
• Type 2 diabetes, the main presentation, shows varying β-cell dysfunction and insulin resistance, commonly associated with excess weight and obesity
• Monogenic diabetes syndromes are inclusive of neonatal diabetes and maturity-onset diabetes of the young (MODY), exhibiting monogenic flaws in insulin action
• Late Autoimmune DM of Adult (LADA) has evolving type 1 traits in adults
• It shows metabolic syndrome features, retains great β-cell function, and has a single GAD autoantibody
• Gestational diabetes mellitus is diagnosed during the second or third pregnancy trimester, absent evident diabetes prior to gestation
• Specific diabetes types include:
  • Diseases of the exocrine pancreas such as cystic fibrosis and pancreatitis
  • Endocrine disorders
  • Drug- or chemical-induced cases like glucocorticoid use, in HIV/AIDS
  • Infection-related diabetes
  • Rare immune-mediated diabetes variants

Type 1 Diabetes Mellitus

• Previously known as insulin-dependent or juvenile diabetes, this chronic condition signifies a marked decline in the pancreas's ability to produce insulin
• It's defined through autoimmune pancreatic islet beta cell destruction by Anti-GAD, Anti-ICA, and Anti-insulin antibodies
• This is prompted by environmental factors in genetically susceptible individuals, causing absolute insulin deficiency and Low C peptide; insulin is the only treatment

Type 1 Diabetes Mellitus Epidemiology

• The onset of Type 1 DM commonly is between ages 5-7 or as individuals reach puberty
• It is a prevalent chronic childhood disease, more commonly found in men, and affecting 5-10% of diabetes cases

Type 1 Diabetes Mellitus Pathophysiologic Features

• Blood glucose levels, rather than A1C, aid in diagnosing acute onset of type 1 diabetes individuals displaying symptoms of hyperglycemia
• Blood glucose measurement is sufficient for diagnosing diabetes with classic symptoms
• Hyperglycemia or hyperglycemic crisis plus random plasma glucose ≥200 mg/dL [11.1 mmol/L] signals this
• Autoantibody association: Anti-GAD, Anti-ICA, Anti-insulin antibodies, and Low C peptide

Stages of T1DM

• Honeymoon period involves upgraded function of residual beta cells and reversal of insulin resistance with unregulated diabetes
• Initiating insulin treatment improves secretory function of residual beta cells, reversing insulin resistance and glucotoxicity

T1DM Honeymoon period

• A remission (honeymoon period) heralds
• Patients generally reduce daily dose to avoid hypoglycemia
• Normoglycemia sustains in a small number of children (<5% of patients) without administered insulin
• Insulin treatment may persist unless a daily dose of 0.1 U/kg causes hypoglycemia