Diabetes: What You Need to Know and Keep in Mind

Diabetes is a chronic condition characterized by a disorder in carbohydrate metabolism leading to persistent high blood sugar levels. While it commonly affects older adults, it can also occur in children and adolescents.

I. Causes and Pathogenesis:

• Factors Increasing Insulin Resistance:

• Genetic Predisposition: Individuals with a family history of diabetes are at a higher risk.

• Obesity (Abdominal Obesity): Increased abdominal fat elevates insulin resistance, hindering insulin’s entry into cells.

• Aging: Insulin production capacity in the pancreas declines with age.

• Insufficient Physical Activity: Lack of exercise makes the body less sensitive to insulin.

• Other Mechanisms Leading to Type 2 Diabetes:

• Reduced Incretin Secretion: Incretins are hormones that stimulate insulin secretion after meals. Reduced secretion disrupts glucose metabolism.

• Increased Glucagon Secretion: Glucagon raises blood sugar levels. Increased glucagon secretion leads to hyperglycemia.

• Increased Glucose Reabsorption in the Kidneys: When kidney function declines, less glucose is excreted in urine, resulting in elevated blood sugar levels.

• Gestational Diabetes:

• Diabetes developing or first diagnosed during pregnancy.

• After delivery, it can lead to three possibilities:

• True diabetes.

• Impaired glucose tolerance.

• Return to normal but reoccur in subsequent pregnancies.

II. Clinical Features:

• Type 1 Diabetes:

• Onset usually under 30 years old.

• Thin or average physique.

• Prominent clinical presentation, often with ketoacidotic coma as a complication.

• Family history of diabetes or autoimmune disease.

• Laboratory tests:

• HLA-DR3,4 (+)

• Increased anti-islet antibodies (++)

• Blood insulin levels near zero.

• C-peptide < 0.3 nmol/l.

• Oral medications (SU) ineffective.

• Type 2 Diabetes:

• Onset usually over 30 years old.

• Obese.

• Less prominent clinical presentation.

• History: Gestational diabetes in women.

• Laboratory tests:

• HLA-DR3,4 (-)

• Anti-islet antibodies (-)

• C-peptide > 1 mmol/l.

• Certain Medications Causing Secondary Diabetes:

• Corticosteroids.

• Nicotinic acid, beta-adrenergic agonists, thiazides, interferons.

III. Diagnosis:

• ADA 2019 Criteria for Definitive Diabetes Diagnosis:

• a. Random blood glucose >= 11.1 mmol/l + symptoms of hyperglycemia (increased hunger, thirst, frequent urination, weight loss).

• b. Fasting blood glucose (>= 8-14 hours) >= 7 mmol/l on two separate mornings.

• c. Oral glucose tolerance test >= 11.1 mmol/l after 2 hours.

• d. HbA1c >= 6.5%.

• Note: b, c, d should be performed twice.

• What is an Oral Glucose Tolerance Test?

• Assessing blood sugar levels 2 hours after consuming 75g of glucose.

• Conditions for Conducting the Test:

• Fasting for 8-14 hours.

• High-carbohydrate diet for 3 days prior to the test.

• Avoid conducting the test during acute illness, malnutrition, or medication use: Corticosteroids, thiazides.

• No strenuous exercise before or during the test.

• Indications for Performing an Oral Glucose Tolerance Test:

• Fasting hyperglycemia (7 > G > 5.6).

• Normal + risk factors:

• Obesity in men.

• Family history, history of delivering babies > 4kg.

• Dyslipidemia.

• Presence of chronic complications.

• Glucosuria.

• Prediabetes:

• Impaired fasting glucose: 5.6 <= G < 7.

• Impaired glucose tolerance: 7.8 <= [G] < 11.1 after 2 hours of the test.

IV. Complications:

• Acute Complications:

• Diabetic Ketoacidotic Coma:

• Clinical presentation: Preceding hyperglycemia, dehydration, altered consciousness, symptoms of metabolic acidosis: Kussmaul breathing, fruity odor.

• Laboratory tests: Blood glucose > 13.9, pH < 7.3, HCO3- < 18 mmol/l, anion gap > 12, ketonuria, ketonemia (+).

• Hyperosmolar Hyperglycemic State (HHS):

• Clinical symptoms of hyperglycemia and dehydration.

• Laboratory tests: Blood glucose > 33.3 mmol/l, serum osmolality > 320 mOsm/L.

• Chronic Complications:

• Retinopathy:

• Non-proliferative retinopathy in the early stage and proliferative retinopathy in the later stage.

• Cataracts: Hyperglycemia leads to increased sorbitol, affecting the osmotic properties of the lens.

• Open-angle glaucoma.

• Nephropathy:

• Diabetic nephropathy: Focal or diffuse sclerosis or both.

• Progression to end-stage renal failure.

• Treatment: Blood glucose control, protein restriction, blood pressure control < 130/80, urinary tract infection management if present.

• Peripheral Vascular Disease:

• Symptoms: Intermittent claudication, cold feet, cyanosis of lower extremities and toes, necrosis.

• Two forms: Dry and wet necrosis, dry necrosis without infection has a better prognosis.

• Diagnosis: Doppler ultrasound.

• Neuropathy:

• Polyneuropathy:

• Bilateral symmetry, sensory disturbances, progressing to Charcot’s foot.

• Reduced or absent tendon reflexes, loss of vibratory sensation.

• Treatment: Blood glucose control, nerve pain medications like amitriptyline, gabapentin.

• Mononeuropathy: Radial, peroneal, or cranial nerve palsy.

• Diabetic Foot:

• A complication of peripheral neuropathy + peripheral vascular disease + infection.

• Diabetic foot stages:

• Stage 0: Calluses only.

• Stage 1: Superficial ulcers at major pressure points.

• Stage 2: Deep ulcers with infection, nerve damage, no osteomyelitis.

• Stage 3: Cellulitis, abscess formation, potential osteomyelitis.

• Stage 4: Necrosis of toes, forefoot, or heel.

• Stage 5: Extensive necrosis.

• Infections:

• Skin and mucous membranes: Boils, myositis, perianal infections.

• Lungs: Pulmonary tuberculosis, pneumonia.

• Genitourinary:

• Cystitis, urethritis, prostatitis.

• Pyelonephritis.

• Genital infections.

V. Treatment:

• Treatment Goals for Non-pregnant Adults:

• HbA1c < 7%.

• Fasting blood glucose (before meals) 4.4-7.2.

• Postprandial blood glucose 1-2h < 10.

• Blood pressure < 130/80 if there are kidney complications or high cardiovascular risk factors.

• LDL cholesterol < 2.6 if no cardiovascular complications, < 1.8 if there are complications or high risk.

• Weight management.

• Control Goals for Older Adults:

• Healthy: HbA1c < 7.5%, fasting blood glucose 4-7.

• Multimorbidity, moderate health: HbA1c < 8%, fasting blood glucose 4-8.3.

• Frail: HbA1c < 8.5%, fasting blood glucose < 10.

• Indications for Insulin Use:

• Type 1 diabetes, gestational diabetes, diabetes due to chronic pancreatitis.

• Acute complications.

• Type 2 diabetes but oral medications are not achieving desired blood glucose levels or random blood glucose >= 16.7 or HbA1c > 10% or contraindications to oral medications.

• Need for rapid blood glucose control.

VI. Types of Medications for Treatment:

• Metformin:

• 3 forms: 500mg, 850mg, 1000mg.

• Mechanism: Primarily reduces hepatic glucose production, reduces intestinal glucose absorption, and enhances glucose uptake in skeletal muscle.

• Advantages: Inexpensive, does not cause weight gain, does not induce hypoglycemia, may reduce cardiovascular events.

• Disadvantages: Gastrointestinal side effects, intolerance, lactic acidosis, vitamin B12 deficiency with long-term use.

• Contraindications: Type 1 diabetes, ketoacidosis, tissue hypoxia, liver failure, renal failure with an estimated glomerular filtration rate (eGFR) < 45ml/min for new users and < 30ml/min for existing users, heart failure.

• Oral Stimulators of Beta-cell Insulin Secretion (SU):

• Gliclazid XR 30-60mg, once daily, 24-hour effect.

• Advantages: Inexpensive, reduces HbA1c by 1-1.5%, reduces microvascular complications.

• Disadvantages: Weight gain, hypoglycemia.

• Contraindications: Type 1 diabetes, ketoacidosis, severe liver or kidney failure, pregnancy.

• Non-SU Insulin Secretagogues:

• Repaglinide 0.5-1.2mg.

• Short half-life, suitable for elderly, renal insufficiency.

• Disadvantages: Weight gain, hypoglycemia.

• TZD (Thiazolidinedione):

• Pioglitazone 15-45mg/day, once daily, independent of meals.

• Mechanism: Activates PPAR gamma receptor, increases GLUT1,4 expression, enhances insulin sensitivity in muscle and fat cells.

• Advantages: Does not induce hypoglycemia when used alone, reduces triglycerides, increases HDL.

• Disadvantages: Weight gain, edema, increased risk of fractures, anemia, cystitis.

• Contraindications: Heart failure stages III, IV, active liver disease, ALT elevated > 2.5 times the upper limit.

• Alpha-glucosidase Inhibitors:

• Acarbose 50mg, three times daily before meals.

• Mechanism: Slows down glucose absorption in the intestines.

• Advantages: Does not induce hypoglycemia when used alone, local effect, reduces postprandial blood glucose.

• Disadvantages: Gastrointestinal disturbances, minimal reduction in HbA1c (0.5-0.8%).

• DPP-4 Inhibitors:

• Sitagliptin, Saxagliptin (2.5-5mg).

• Indications: Type 2 diabetes, postprandial hyperglycemia.

• Advantages: Does not induce hypoglycemia alone, well-tolerated.

• Disadvantages: Allergies, itching, nasal congestion, acute pancreatitis.

• GLP-1RA (GLP-1 Receptor Agonists):

• Injectable form, reduces HbA1c by 0.6-1.5%.

• Advantages: Improves beta-cell function, prevents atherosclerotic plaque progression, weight loss, lowers blood pressure, reduces cardiovascular events, suitable for individuals with mild kidney or liver failure.

• Disadvantages: Nausea, vomiting, acute pancreatitis, contraindicated in those with a family history of medullary thyroid cancer.

• SGLT-2 Inhibitors:

• Dapagliflozin (Forxiga) 5, 10mg.

• Mechanism: Inhibits the channel that increases glucose excretion in urine.

• Advantages: Weight loss, lowers blood pressure, minimal hypoglycemia, reduces cardiovascular events, slows progression of kidney disease.

• Disadvantages: Fungal and urinary tract infections, expensive, minimal HbA1c reduction (0.5%), postural hypotension.

VII. Insulin:

• Initiating Basal/Mixed Insulin, Combination:

• Basal insulin: 10 units/day or 0.1-0.2 IU/kg/day.

• Mixed/combination insulin:

• If once daily: 12 units at dinner.

• If twice daily: 6 units in the morning, 6 units at night.

• Adjust by 10-15% until the target is achieved.

• If HbA1c is not achieved with basal/mixed insulin:

• Consider 1/3:

• 1. + 1 injection of rapid-acting insulin before the largest meal: 4 units, 0.1 IU/kg/day or 10% of the basal dose.

• If still high, switch to rapid-acting basal: + >= 2 injections of rapid-acting insulin before meals.

• 2. + GLP-1RA.

• 3. Mixed/combination insulin: Divide 2/3 in the morning and 1/3 in the afternoon (before meals).

• If HbA1c still not achieved:

• Use mixed/combination analog insulin three times daily.

• Dose of 30 units divided into three doses per day (breakfast, lunch, dinner).

• Indications for Insulin Pump:

• Type 1 diabetes.

• Type 2 diabetes but currently experiencing acute illness or during pregnancy.

• Difficult-to-control diabetes: Unpredictable hypoglycemia, nocturnal hypoglycemia.

VIII. Types of Insulin:

• Rapid-acting, Short-acting Insulin:

• Aspart, Lispro, Glulisine.

• Onset after 30 minutes, peak at 1 hour, lasts 3-4 hours.

• Intermediate-acting Insulin:

• NPH: Onset after 2-4 hours, peak at 6-10 hours, and lasts 10-16 hours.

• Long-acting Insulin:

• Lantus, Degludec.

• Lantus: Onset after 2-3 hours, lasts 24 hours.

• Mixed/Combination Insulin:

• Mixtard (NPH/Regular 70/30, 80/20).

• Humalog mix (Lispro/Lispro protamine).

IX. Insulin Complications:

• Hypoglycemia.

• Somogyi Phenomenon: Rebound hyperglycemia, often occurring at night due to an increased response of hyperglycemic hormones.

• Insulin Resistance.

• Lipodystrophy.

• Allergies.

X. Weight Loss in Overweight, Obese Individuals:

• 5-10% of body weight.

• Avoid rapid weight loss, as it disrupts lipid metabolism.

Note:

• This article provides general information only.

• Consult an endocrinologist for accurate diagnosis and treatment.

• Good blood glucose control is crucial to minimize the complications of the disease.

• Maintain a positive attitude and collaborate closely with your doctor during treatment.

This draft provides a basic overview of diabetes. Please remember that this is just a starting point and you should always seek medical advice from a healthcare professional for personalized guidance and treatment.