Internal exam (endocrinology)

E-1. Pathogenetic classification of diabetes mellitus

1. Type 1 DM: autoimmune destruction of pancreatic β-cells → absolute insulin deficiency

2. Type 2 DM: insulin resistance + impaired β-cell insulin secretion → relative insulin deficiency

3. Gestational DM: impaired glucose tolerance first diagnosed during pregnancy

4. Genetic defects:

   • β-cell function defect → MODY

   • insulin synthesis defect

5. Pancreatogenic DM: destruction/removal of pancreas or islets

   • chronic pancreatitis, pancreatic cancer, pancreatectomy

6. Endocrinopathies: Cushing syndrome, acromegaly

7. Drug-induced DM: especially corticosteroids

8. Infections: e.g. congenital rubella

9. Rare immune causes: stiff-person syndrome

E-2. Diabetes diagnostic and metabolic compensation criteria

Diagnostic criteria for diabetes:

• Classic symptoms: polyuria, polydipsia, polyphagia, weight loss, poor wound healing

• *Random plasma glucose ≥11.1 mmol/L with symptoms

• *Fasting plasma glucose ≥7.0 mmol/L

• *OGTT: 75 g glucose → 2h plasma glucose ≥11.1 mmol/L

• *HbA1c ≥6.5%

Good metabolic compensation:

• HbA1c <6.5%

• Fasting glucose 4.4–6.7 mmol/L

• No glucosuria

• TAG <1.7 mmol/L

• Total cholesterol <5.0 mmol/L

• BMI: male <25, female <24

• BP <135/85 mmHg

can be divided into good, sufficient, and insufficient

E-3. Type 1 and type 2 DM differences: pathogenesis, clinical picture, therapy strategy

Type 1 DM

• Pathogenesis: genetic/environmental factors → autoimmune β-cell destruction → absolute insulin deficiency

• Clinical picture: usually <20 years, sudden onset, often thin, ketoacidosis common

• Symptoms: polyuria, polydipsia, polyphagia, weight loss, poor wound healing, visual disturbances

• Therapy: lifelong insulin therapy

  • basal insulin + prandial insulin or insulin pump

  • regular glucose/HbA1c monitoring

  • diet, exercise, cardiovascular risk control

Type 2 DM

• Pathogenesis: insulin resistance + progressive β-cell dysfunction → relative insulin deficiency

• Risk factors: obesity, glucotoxicity, lipotoxicity, genetic/environmental factors

• Clinical picture: usually >30 years, gradual onset, often obese, initially asymptomatic, ketoacidosis uncommon

• Therapy: lifestyle + oral antidiabetics

  • metformin first-line, SGLT2 inhibitors etc.

  • insulin if decompensated

  • BP/statins/smoking control

E-4. Late complications of diabetes: pathogenesis, types, therapy principles

Microvascular complications:

Pathogenesis: Chronic hyperglycemia → glycation of proteins/lipids → basement membrane thickening + vascular/tissue damage

• Diabetic nephropathy: glucose + BP control, ACEi/ARB for proteinuria, lifestyle, RRT if end-stage

• Diabetic retinopathy: non-proliferative/proliferative/macular edema; glucose + BP control, laser photocoagulation, anti-VEGF

• Diabetic neuropathy: glucose + BP control, pain control e.g. gabapentin

Macrovascular complications = accelerated atherosclerosis:

Pathogenesis: Metabolic risk factors (obesity, dyslipidemia, and arterial hypertension)

• Coronary artery disease - MI

• Cerebrovascular disease - Stroke

• Peripheral artery disease - Peripheral occlusions

Therapy/prevention:

• Strict glucose and BP control

• Statins

• Antiplatelet therapy/aspirin when indicated

• Smoking cessation, weight control, physical activity

• Treat metabolic risks: weigh control, lipid control, AH control

E-5. Diabetic sensorimotor polyneuropathy: symptoms, diagnosis, therapy principles

Diabetic neuropathy can be peripheral + autonomic.

Peripheral sensorimotor neuropathy

• Common DM complication → neuropathic pain + ↑ risk of foot ulceration.

• Symptoms: distal symmetric sensory loss with proximal progression, numbness, tingling, burning, sharp/shooting pain in feet or legs, hyperalgesia, ↓ vibration sense, ↓ reflexes, late: ↓ pain + temperature sensation, motor weakness, ataxia/balance problems, foot deformity/ulcers

Autonomic neuropathy

• Small-fiber autonomic nerve damage → many organ systems affected.

• Symptoms: gastropathy, sweating abnormalities, constipation, cardiopathy, urinary retention, erectile dysfunction, hypoglycemia unawareness

Diagnosis

• Symptoms + known DM

• Physical exam:

  • tuning fork vibration test

  • 5-point measurement

  • reflexes

  • pain + temperature sensation

• EMG / MRI neurography / neurometry if needed

Treatment

• First line: optimal glycemic control

• Foot care: daily self-checks, proper footwear, treat ulcers

• Pain management: gabapentin; also anticonvulsants, antidepressants/SNRIs, opioids if needed

• B vitamins: B1, B6, B12

• Antioxidants

• TENS

• Physiotherapy: strength, balance, coordination

E-6. Diabetic macroangiopathy: symptoms and diagnostic principles

• Definition: accelerated large-vessel atherosclerosis development in DM → CAD, cerebrovascular disease, PAD.

• CAD: chest pain, dyspnea, MI/HF; dx ECG, echo, coronary angiography.

• Cerebrovascular: speech disturbance, confusion, facial signs, poor balance, hemiparesis; dx CT/CT Angiography/MRI.

• Peripheral Artery Disease: claudication (muscle pain due to lack of O2), cold leg, ulcers/gangrene/necrosis; dx ABI ≤0.9, MR angiography if revascularization planned.

• Core idea: macroangiopathy = atherosclerotic complications, main morbidity/mortality risk in diabetes.

E-7. Basic groups of insulin preparations (with examples and pharmacokinetic differences)

E-8. Oral antidiabetic drug groups, preparations, and their mechanism of action.

• Biguanides: metformin → ↓ hepatic gluconeogenesis + ↑ insulin sensitivity; 1st line.

• Thiazolidinediones: pioglitazone, rosiglitazone → ↑ peripheral insulin sensitivity, ↓ hepatic gluconeogenesis.

• Sulfonylureas: glipizide, glimepiride → ↑ β-cell insulin secretion via SUR1/KATP closure; hypoglycemia risk.

• Meglitinides: repaglinide, nateglinide → ↑ insulin secretion, shorter acting than sulfonylureas.

• GLP-1 agonists: exenatide, liraglutide/semaglutide → ↑ insulin, ↓ glucagon, slow gastric emptying.

• DPP-4 inhibitors: sitagliptin, saxagliptin → prolong GLP-1 → ↑ insulin, ↓ glucagon.

• α-glucosidase inhibitors: acarbose, miglitol → ↓ intestinal carbohydrate absorption.

• SGLT2 inhibitors: dapagliflozin, empagliflozin → ↓ renal glucose reabsorption → glucosuria.