Diabetes Mellitus: Types, Mechanisms, and Diagnosis

Diabetes Mellitus

• Diabetes Mellitus, a chronic disease, presents in various types.
• Type 1 Diabetes (T1D) is characterized by insulin deficiency (10% of cases).
• Type 2 Diabetes (T2D) is characterized by insulin resistance (90% of cases).
• Glucose levels in the body increase (hyperglycemia).
• Glucose non-enzymatically glycosylates protein, causing pathology.
• Long-term complications lead to increased mortality.
• Significant resource use is associated with the disease.

Learning Outcomes

• Define Diabetes Mellitus
• Compare and contrast the pathophysiology of type 1 and type 2 diabetes.
• Discuss diagnosis and classification principles of diabetes.
• List cardinal symptoms and signs of diabetes
• Identify risk factors for the rising prevalence of Type 2 Diabetes:
• Recognize the importance of prevention and early intervention in the management of type 2 diabetes:
• Outline overarching principles of diabetes investigation and management:
• Evaluate the implications of diabetes, including its impact on quality of life and healthcare costs
• Identify the role of interdisciplinary care in the management of diabetes

Learning Case Study (Patient MF ):

• A 22-year-old male at a hospital's emergency room showed worsening polyuria, polydipsia, fatigue, and unintentional weight loss.
• Despite drinking high volumes of soda and fruit punch daily
• The patient's height and weight, resulting in a BMI of 21.5 kg/m2, were documented.
• No family history of diabetes was reported. The patient's mother exhibited hypothyroidism.
• The patient's plasma glucose measured 26 mmol/L, an abnormally high level.

Definition of Diabetes Mellitus

• A chronic disease characterized by high levels of blood glucose.
• Two main types: Type 1 and Type 2 diabetes.
• Type 1 is mainly autoimmune, while Type 2 results from insulin resistance.

Pathophysiology of Diabetes

• Multiple factors contribute to the development of diabetes.
• Environmental influences, genetics, and lifestyle choices all play roles.

Type 1 Diabetes (T1D)

• Autoimmune process: The body's immune system attacks insulin-producing beta cells in the pancreas.
• Beta cells are destroyed, leading to little or no insulin production.

Pathogenesis of Type 1 Diabetes (T1D)

• The process begins with an autoimmune reaction triggered by environmental factors.
• Inflammation, mediated by lymphocytes, damages the beta cells.
• Continued damage leads to the complete destruction of beta cells.
• This destruction prevents insulin production, leading to high blood sugar levels.
• The body, unable to efficiently use glucose, breaks down fats (lipolysis) which produce ketone bodies leading to acidosis.
• The cascade of events are crucial in an individual's diagnosis who may experience high blood sugar levels in the presence of ketones.

Causes of Type 1 Diabetes

• Precise causes are not fully understood.
• Likely a combination of individual's genetic susceptibility and environmental triggers such as a viral infection.
• The disease frequently develops in children and young adults.

Beta Cell Destruction (Mechanism)

• Lymphocytes (cells within the immune system) enter the pancreas
• Beta cells are identified as targets and destroyed.
• The area repairs with fibrosis.

Pancreas (Structure and Function)

• The pancreas is an organ that controls blood sugar levels.
• Islets of Langerhans are clusters of cells within the pancreas
• Islets contain specialised cells that secrete hormones essential for regulating blood sugar levels.

Insulin

• A hormone produced by beta cells within the pancreas.
• Critical for normal glucose metabolism, lipid, protein synthesis, and growth.
• Islet function depends on islet beta cell mass, insulin synthesis, insulin signalling and glucose dependent insulin secretion.

Importance of Beta Cells

• They detect glucose levels.
• They produce insulin to lower those levels.
• In Type 1, beta cells are progressively destroyed, thereby halting these processes.
• In Type 2, the body may fail to respond appropriately or the pancreas cannot produce adequate insulin.

Classification of DM

• Type 1
• Type 1a (autoimmune) and Type 1b (non-autoimmune)
• Type 2
• Gestational Diabetes.
• Other specific types: Autoimmune, Monogenic

T1D vs T2D

• Type 1: Absolute insulin deficiency.
• Type 2: Insulin resistance with relative insulin deficiency.

Symptoms of Diabetes Mellitus

• The cardinal symptoms are the classic 3 P's: Polyuria (excessive urination), Polydipsia (extreme thirst), Polyphagia (constant hunger)
• Other symptoms include unexplained weight loss, blurred vision, fatigue and wounds that won't heal.

Diagnosing Diabetes

• Fasting plasma glucose (FPG)
• Oral glucose tolerance test (OGTT)
• HbA1c
• Random plasma glucose, measured along with accompanying symptoms such as unexplained weight loss.

Complications of Diabetes

• Microvascular problems (e.g., retinopathy, nephropathy, neuropathy)
• Macrovascular problems (e.g., coronary artery disease, peripheral arterial disease, stroke).
• Diabetic ketoacidosis

Epidemiology of T1D

• Most common in Northern Europe.
• Peak age at diagnosis is between 5 and 7 years and at puberty.
• Increased incidence noted in winter (cold) months
• Incidence is increasingly noted worldwide

Relationship of Autoantibodies to Diabetes Type

• Several autoantibodies can be detected in the preclinical phase of Type 1 Diabetes.
• These include islet-cell antibodies (ICA), insulin autoantibodies (IAA), glutamic acid decarboxylase 65 (GAD65) antibodies, and antibodies to tyrosine phosphatase-like proteins like insulinoma-associated protein (IA-2) or Zinc Transporter (ZnT8) antibody.

Pathogenesis of Type 1 Diabetes

• Genetic predisposition (polygenic) plays a role
• Environmental factors (e.g., viruses) are involved.
• Autoimmune destruction of β-cells in the pancreas, resulting in impaired insulin production.

Pathogenesis of Type 2 Diabetes

• Genetic and environmental factors play a role.
• Key defects include impaired insulin secretion, insulin resistance, and increased hepatic glucose output.

Risk factors for Type 2 Diabetes

• Family history.
• Overweight/obesity.
• Physical inactivity.
• Race/ethnicity (e.g., African Americans, Hispanics).
• Prior history of IFG or IGT.

T2D and Age

• Typically a disease of middle age or older.

Screening for T2DM

• Adults with overweight/obesity along with 1 or more risk factors should be screened.
• Those without risk factors should be screened beginning at age 45.
• Regular screening, with HbA1c, FPG, or OGTT, should be repeated depending on risk factors.

Glycemic Targets

• The recommended A1C levels are <7.0% for adults.
• Pre-prandial capillary plasma glucose should range from 80 to 130 mg/dL.
• Peak postprandial levels should be below 180 mg/dL.

Goals of Treatment

• Aggressive treatment early to reduce microvascular damage.
• Prevention and remission of early T2DM
• Controlling A1C levels to reduce complications.

Treatment Strategies

• Lifestyle changes (diet, exercise, weight loss)
• Oral medications (in combination with a lifestyle change program)
• Non-insulin injections
• Insulin replacement
• Additional weight loss strategies (e.g., medications, bariatric surgery)
• Cardiovascular risk factor modification (e.g., blood pressure control, aspirin, statins)

Bariatric Surgery

• A weight-loss surgery involving the stomach.
• It can help in those with a high BMI, failing lifestyle change and medical treatments.
• Effective long-term remission.

Interdisciplinary Care

• Important in comprehensively managing diabetes.
• Endocrinologist/general practitioner coordinates treatment.
• Dietitian provides nutritional counseling.
• Diabetes educator guides self-management.
• Podiatrist ensures foot health.
• Ophthalmologist monitors eye conditions.
• Psychologist/psychiatrist addresses emotional & psychological needs

Prediabetes

• Condition with impaired glucose tolerance/impaired fasting glucose levels, often impacting the onset of type 2 diabetes within 5 years.

Diabetes Prevention

• Lifestyle changes remain the main method of prevention.
• Diet and exercise changes can lower risk by 58%

Summary of T1 and T2 Diabetes

• Overview of Type 1 and Type 2 diabetes.
• Their pathogenesis's
• Typical symptoms during diagnosis

Explore the underlying mechanisms of Type 1 and Type 2 Diabetes, including the consequences of hyperglycemia and the impact on life expectancy. Investigate the histological events in the pancreas during Type 1 Diabetes and the significance of HbA1c in diagnosis.